E. Boersma

Dobutamine stress echocardiography for assessment of perioperative cardiac risk in patients undergoing major vascular surgery.

BackgroundThe purpose of this study was to determine the predictive value of dobutamine stress echocardiography for perioperative cardiac events in patients scheduled for elective major noncardiac vascular surgery. Methods and ResultsPatients (N = 136; mean age, 68 years) unable to exercise underwent a dobutamine stress test before surgery (incremental dobutamine infusion [10-40 μg. kg-1. min-1] continued with atropine [0.25-1 mg i.v.] if necessary to achieve 85% of the age-predicted maximal heart rate without symptoms or signs of ischemia). The clinical risk profile was evaluated by Detskys modification Goldmans risk factor analysis. Echocardiographic images were evaluated by two observers blinded to the clinical data of the patients, and results of the test were not used for clinical decision making. Technically adequate images were obtained in 134 of 136 patients, one major complication occurred (ventricular fibrillation), and three tests were discontinued prematurely because of side effects. Finally, data from 131 patients were analyzed with univariate and multivariate methods. The dobutamine stress test was positive (new or worsened wall motion abnormality) in 35 of 131 patients. In the postoperative period, five patients died of myocardial infarction, nine patients had unstable angina, and one patient developed pulmonary edema. All patients with cardiac complications (15 patients) had a positive dobutamine stress test. cardiac events occurred in patients with negative tests. Five patients with a technically inadequate prematurely stopped test were operated on without complications. By multivariate analysis (logistic regression), only age >70 years and new wall motion abnormalities during the dobutamine test were significant predictors of perioperative cardiac events. ConclusionsDobutamine stress echocardiography is a feasible, safe, and useful method for identifying patients at high or low risk of perioperative cardiac events. The test yields additional information, beyond that provided by clinical variables, in patients who are scheduled for major noncardiac vascular surgery.

A meta-analysis comparing the prognostic accuracy of six diagnostic tests for predicting perioperative cardiac risk in patients undergoing major vascular surgery

Objective: To evaluate the discriminatory value and compare the predictive performance of six non-invasive tests used for perioperative cardiac risk stratification in patients undergoing major vascular surgery. Design: Meta-analysis of published reports. Methods: Eight studies on ambulatory electrocardiography, seven on exercise electrocardiography, eight on radionuclide ventriculography, 23 on myocardial perfusion scintigraphy, eight on dobutamine stress echocardiography, and four on dipyridamole stress echocardiography were selected, using a systematic review of published reports on preoperative non-invasive tests from the Medline database (January 1975 and April 2001). Random effects models were used to calculate weighted sensitivity and specificity from the published results. Summary receiver operating characteristic (SROC) curve analysis was used to evaluate and compare the prognostic accuracy of each test. The relative diagnostic odds ratio was used to study the differences in diagnostic performance of the tests. Results: In all, 8119 patients participated in the studies selected. Dobutamine stress echocardiography had the highest weighted sensitivity of 85% (95% confidence interval (CI) 74% to 97%) and a reasonable specificity of 70% (95% CI 62% to 79%) for predicting perioperative cardiac death and non-fatal myocardial infarction. On SROC analysis, there was a trend for dobutamine stress echocardiography to perform better than the other tests, but this only reached significance against myocardial perfusion scintigraphy (relative diagnostic odds ratio 5.5, 95% CI 2.0 to 14.9). Conclusions: On meta-analysis of six non-invasive tests, dobutamine stress echocardiography showed a positive trend towards better diagnostic performance than the other tests, but this was only significant in the comparison with myocardial perfusion scintigraphy. However, dobutamine stress echocardiography may be the favoured test in situations where there is valvar or left ventricular dysfunction.

Predictors of pregnancy complications in women with congenital heart disease

AIMSnData regarding pregnancy outcome in women with congenital heart disease (CHD) are limited.nnnMETHODS AND RESULTSnIn 1802 women with CHD, 1302 completed pregnancies were observed. Independent predictors of cardiac, obstetric, and neonatal complications were calculated using logistic regression. The most prevalent cardiac complications during pregnancy were arrhythmias (4.7%) and heart failure (1.6%). Factors independently associated with maternal cardiac complications were the presence of cyanotic heart disease (corrected/uncorrected) (P < 0.0001), the use of cardiac medication before pregnancy (P < 0.0001), and left heart obstruction (P < 0.0001). New characteristics were mechanical valve replacement (P = 0.0014), and systemic (P = 0.04) or pulmonary atrioventricular valve regurgitation related with the underlying (moderately) complex CHD (P = 0.03). A new risk score for cardiac complications is proposed. The most prevalent obstetric complications were hypertensive complications (12.2%). No correlation of maternal characteristics with adverse obstetric outcome was found. The most prevalent neonatal complications were premature birth (12%), small for gestational age (14%), and mortality (4%). Cyanotic heart disease (corrected/uncorrected) (P = 0.0003), mechanical valve replacement (P = 0.03), maternal smoking (P = 0.007), multiple gestation (P = 0.0014), and the use of cardiac medication (P = 0.0009) correlated with adverse neonatal outcome.nnnCONCLUSIONnIn our tertiary CHD cohort, cardiac, obstetric, and neonatal complications were frequently encountered, and (new) correlations of maternal baseline data with adverse outcome are reported. A new risk score for adverse cardiac complications is proposed, although prospective validation remains necessary.

Reprinted Article “A Combination of Statins and Beta-blockers is Independently Associated with a Reduction in the Incidence of Perioperative Mortality and Nonfatal Myocardial Infarction in Patients Undergoing Abdominal Aortic Aneurysm Surgery”

OBJECTIVEnTo investigate the combined beneficial effect of statin and beta-blocker use on perioperative mortality and myocardial infarction (MI) in patients undergoing abdominal aortic aneurysm surgery (AAA).nnnBACKGROUNDnPatients undergoing elective AAA-surgery identified by clinical risk factors and dobutamine stress echocardiography (DSE) as being at high-risk often have considerable cardiac complication rate despite the use of beta-blockers.nnnMETHODSnWe studied 570 patients (mean age 69 ±9 years, 486 males) who underwent AAA-surgery between 1991 and 2001 at the Erasmus MC. Patients were evaluated for clinical risk factors (age>70 years, histories of MI, angina, diabetes mellitus, stroke, renal failure, heart failure and pulmonary disease), DSE, statin and beta-blocker use. The main outcome was a composite of perioperative mortality and MI within 30 days of surgery.nnnRESULTSnPerioperative mortality or MI occurred in 51 (8.9%) patients. The incidence of the composite endpoint was significantly lower in statin users compared to nonusers (3.7% vs. 11.0%; crude odds ratio (OR): 0.31, 95% confidence interval (CI): 0.13-0.74; pxa0=xa00.01). After correcting for other covariates, the association between statin use and reduced incidence of the composite endpoint remained unchanged (OR: 0.24,95% CI: 0.10-0.70; pxa0=xa00.01). Beta-blocker use was also associated with a significant reduction in the composite endpoint (OR: 0.24, 95% CI: 0.11-0.54). Patients using a combination of statins and beta-blockers appeared to be at lower risk for the composite endpoint across multiple cardiac risk strata; particularly patients with 3 or more risk factors experienced significantly lower perioperative events.nnnCONCLUSIONSnA combination of statin and beta-blocker use in patients with AAA-surgery is associated with a reduced incidence of perioperative mortality and nonfatal MI particularly in patients at the highest risk.

Noninvasive evaluation of ischaemic heart disease: myocardial perfusion imaging or stress echocardiography?

Stress echocardiography and myocardial perfusion imaging are commonly used noninvasive imaging modalities for the evaluation of ischaemic heart disease. Both modalities have proved clinically useful in the entire spectrum of coronary artery disease.1–29 Both techniques can detect coronary artery disease and provide prognostic information.1–21 Both techniques can identify low-risk and high-risk subsets among patients with known or suspected coronary artery disease and thus guide patient management decisions.18–21 In patients with acute myocardial infarction, both techniques have been used to identify residual viable tissue and predict improvement of function over time.22–26 In patients with chronic ischaemic left ventricular (LV) dysfunction, viability assessment with either modality can be used to predict improvement of function after revascularisation and thus guide patient treatment.27–29nnHence, the use of noninvasive cardiac imaging can help guide management and potentially reduce healthcare costs.30 The question remains what is the optimal noninvasive cardiac imaging method in which setting? This article evaluates the value of the two modalities in: (1) the detection of coronary artery disease, (2) the prognosis of coronary artery disease in patients with known or suspected coronary artery disease, (3) prediction of functional recovery following acute myocardial infarction and (4) prediction of functional recovery after revascularisation in patients with chronic ischaemic LV dysfunction. To provide the most objective information, only direct comparative studies on stress echocardiography and perfusion imaging in the same patients are included and pooled analysis of the data was performed.nnThe available studies were identified by MEDLINE searches using the following key words: noninvasive imaging, stress echocardiography, dobutamine, dipyridamole, adenosine, myocardial perfusionimaging, technetium-99m sestamibi, technetium-99m tetrofosmin and thallium-201. In addition, a manual search of eight cardiology and nuclear medicine journals (American Heart Journal, American Journal of Cardiology, Circulation, European Heart Journal, Heart, Journal of the American College of …

Long-Term Results After the Glycoprotein IIb/IIIa Inhibitor Abciximab in Unstable Angina : One-Year Survival in the GUSTO IV-ACS (Global Use of Strategies To Open Occluded Coronary Arteries IV - Acute Coronary Syndrome) Trial

Background—This study was designed to investigate long-term effects of the glycoprotein IIb/IIIa inhibitor abciximab in patients with acute coronary syndrome without ST elevation who were not scheduled for coronary intervention. Methods and Results—A total of 7800 patients were included with an acute coronary syndrome without ST elevation, documented by either elevated cardiac troponin or transient or persistent ST-segment depression. They were randomized to abciximab bolus and 24-hour infusion, abciximab bolus and 48-hour infusion, or matching placebo. The overall 1-year mortality rate was 8.3% (649 patients). One-year mortality was 7.8% in the placebo group and 8.2% in the 24-hour and 9.0% in the 48-hour abciximab infusion group. Compared with placebo, the hazard ratio for the 24-hour infusion of abciximab was 1.1 (95% CI 0.86 to 1.29), and for the 48-hour infusion, it was 1.2 (95% CI 0.95 to 1.41). The lack of benefit of abciximab was observed in every subgroup studied. Patients with negative troponin or elevated C-reactive protein had a higher mortality rate after treatment with abciximab for 48 hours than with placebo: 8.5% versus 5.8% in those with negative troponin (P =0.02), 16.3% versus 12.1% in those with elevated C-reactive protein (P =0.04). Conclusions—Compared with placebo, abciximab did not provide any survival benefit at 1 year in patients admitted with an acute coronary syndrome with ST depression and/or elevated troponin who were not scheduled to undergo early coronary revascularization. In subgroups of patients, in particular those with low cardiac troponin or elevated C-reactive protein, abciximab was associated with excess mortality.

Genetic determinants of treatment benefit of the angiotensin-converting enzyme-inhibitor perindopril in patients with stable coronary artery disease

AIMSnThe efficacy of angiotensin-converting enzyme (ACE)-inhibitors in stable coronary artery disease (CAD) may be increased by targeting the therapy to those patients most likely to benefit. However, these patients cannot be identified by clinical characteristics. We developed a genetic profile to predict the treatment benefit of ACE-inhibitors exist and to optimize therapy with ACE-inhibitors.nnnMETHODS AND RESULTSnIn 8907 stable CAD patients participating in the randomized placebo-controlled EUROPA-trial, we analysed 12 candidate genes within the pharmacodynamic pathway of ACE-inhibitors, using 52 haplotype-tagging-single nucleotide polymorphisms (SNPs). The primary outcome was the reduction in cardiovascular mortality, non-fatal myocardial infarction, and resuscitated cardiac arrest during 4.2 years of follow-up. Multivariate Cox regression was performed with multiple testing corrections using permutation analysis. Three polymorphisms, located in the angiotensin-II type I receptor and bradykinin type I receptor genes, were significantly associated with the treatment benefit of perindopril after multivariate adjustment for confounders and correction for multiple testing. A pharmacogenetic score, combining these three SNPs, demonstrated a stepwise reduction of risk in the placebo group and a stepwise decrease in treatment benefit of perindopril with an increasing scores (interaction P < 0.0001). A pronounced treatment benefit was observed in a subgroup of 73.5% of the patients [hazard ratio (HR) 0.67; 95% confidence interval (CI) 0.56-0.79], whereas no benefit was apparent in the remaining 26.5% (HR 1.26; 95% CI 0.97-1.67) with a trend towards a harmful effect. In 1051 patients with cerebrovascular disease from the PROGRESS-trial, treated with perindopril or placebo, an interaction effect of similar direction and magnitude, although not statistically significant, was observed.nnnCONCLUSIONnThe current study is the first to identify genetic determinants of treatment benefit of ACE-inhibitor therapy. We developed a genetic profile which predicts the treatment benefit of ACE-inhibitors and which could be used to optimize therapy.

Management of patients with heart failure in clinical practice: differences between men and women.

Objectives: This study evaluated gender differences in clinical characteristics, treatment and outcome among patients with heart failure, and to what extent these differences are due to age and differences in left ventricular (LV) function. Although gender differences are observed among heart failure patients, few studies have been adequately powered to investigate these differences. Methods: A total of 8914 (out of 10u2009701) patients (47% women) from the Euro Heart Survey on Heart Failure with confirmed diagnosis of heart failure were included in the analyses. Results: Women were older (74.7 vs 68.3 years, p<0.001), and less often had evidence of coronary artery disease (56% vs 66%, age-adjusted odds ratio (OR) 0.62; 95% CI 0.57 to 0.68). Women were more likely to have hypertension, diabetes, or valvular heart disease. Fewer women had an investigation of LV function (59% vs 74%, age-adjusted OR 0.67; 95% CI 0.61 to 0.74), and, among those investigated, fewer had moderate/severe left ventricular systolic dysfunction (44% vs 71%, age-adjusted OR 0.35; 95% CI 0.32 to 0.39). Drugs with a documented impact on survival, that is ACE-inhibitors and β-blockers, were given less often to women, even in the adjusted analysis (OR 0.72; 95% CI 0.61 to 0.86 and OR 0.76; 95% CI 0.65 to 0.89, respectively). 12-week mortality was similar for men and women. Conclusions: Fewer women had an assessment of LV function, but, when investigated, women had better ventricular function. Women were less often treated with evidence-based drugs, even after adjustment for age and important clinical characteristics. Clinicians need to be aware of deficiencies in the treatment of women with heart failure and measures should be taken to rectify them.

Clinical and angiographic outcome of patients with mild coronary lesions treated with balloon angioplasty or coronary stenting. Implications for mechanical plaque sealing

AIMSnTo investigate the clinical and angiographic outcome of patients with mild coronary lesions treated with balloon angioplasty or coronary stenting (coronary plaque sealing, i.e. dilatation of angiographically non-significant lesions) compared to moderate and severe stenoses.nnnMETHODS AND RESULTSnPatients with chronic stable angina and a single de novo lesion in a native coronary vessel scheduled to undergo percutaneous coronary intervention (PCI) were selected from 14 different studies. Off-line analysis of angiographic outcomes was assessed in all patients using identical and standardised methods of data acquisition, analysis and definitions. Clinical endpoints were adjudicated by independent clinical events committees. All quantitative coronary angiographic (QCA) analyses were performed in the same core laboratory. Stenosis severity prior to PCI was categorised into three groups: <50% diameter stenosis (DS), 50-99%DS and >99%DS pre. A total of 3812 patients were included in this study; 1484 patients (39%) were successfully treated with balloon angioplasty (BA) only and stented angioplasty was performed in 2328 patients (61%).One-year mortality and rate of non-fatal myocardial infarction (MI) (Kaplan-Meier) did not differ between BA and stented angioplasty for any of the stenosis severity categories. Following BA, the combined event rate (death and non-fatal MI) was 4.8, 4.6 and 0% in the <50, 50-99 and >99%DS categories, respectively. Following stented angioplasty, the combined event rate was 3.1, 4.4 and 4.8% in the same categories. The need for repeat revascularisation corrected for stenosis severity in the Cox proportional-hazards regression model was reduced by 20% after stented angioplasty (hazard ratio (HR) 0.80, 95%CI 0.69-0.93).nnnCONCLUSIONnThe concept of plaque sealing is appealing from the theoretical point of view. However, with current technology, plaque sealing cannot prevent death and future non-fatal MIs in the long-term because 1-year event rates after PCI of non-significant stenoses remain unacceptably elevated when compared with the estimated 1-year probability of a non-fatal MI in lesions with a <50%DS. Moreover, major adverse cardiac events at 1-year after PCI are not directly related to the degree of pre-procedural stenosis severity.

Elevated troponin T and C-reactive protein predict impaired outcome for 4 years in patients with refractory unstable angina, and troponin T predicts benefit of treatment with abciximab in combination with PTCA

AIMSnTreatment with the glycoprotein IIb/IIIa receptor antagonist abciximab before and during coronary intervention in refractory unstable angina improves early outcome. We collected 4-year follow-up data to assess whether this benefit is sustained. Additionally, we investigated the predictive value of baseline troponin T and CRP for long-term cardiovascular events.nnnMETHODS AND RESULTSnOf 1265 patients enrolled in the CAPTURE trial follow-up was available in 94% of the patients alive after 6 months (median 48 months). Survival was similar in both groups. Both elevated troponin T and CRP were associated with impaired outcome, independently of other established risk factors, but with a different time course. Elevated troponin was associated with increased procedure related risk, and elevated CRP with increased risk for subsequent events. Lower rates of the composite end-point of death or myocardial infarction with abciximab vs. placebo were sustained during long-term follow up: 15.7% vs 17.2% at 4 years (P=ns), particularly in patients with elevated troponin T: 16.9% with abciximab vs 28.4% with placebo: P=0.015. Elevated CRP was not associated with specific benefit of abciximab.nnnCONCLUSIONnTroponin T as a marker of thrombosis and CRP as a marker of inflammation are independent predictors of impaired outcome at 4 years follow-up. The initial benefit from abciximab with regard to death and myocardial infarction was preserved at 4 years. No specific benefit with abciximab was observed for patients with elevated CRP, suggesting that a chronic inflammatory process is not affected by abciximab. In contrast the benefit of treatment in patients with elevated troponin T implies that the acute thrombotic process in refractory unstable angina is treated effectively.