Maarten de Mulder

EuroHeart score for the evaluation of in-hospital mortality in patients undergoing percutaneous coronary intervention

AIMS The applicability of currently available risk prediction models for patients undergoing percutaneous coronary interventions (PCIs) is limited. We aimed to develop a model for the prediction of in-hospital mortality after PCI that is based on contemporary and representative data from a European perspective. METHODS AND RESULTS Our analyses are based on the Euro Heart Survey of PCIs, which contains information on 46 064 consecutive patients who underwent PCI for different indications in 176 participating European centres during 2005-08. Patients were randomly divided into a training (n = 23 032) and a validation (n = 23 032) set with similar characteristics. In these sets, 339 (1.5%) and 305 (1.3%) patients died during hospitalization, respectively. On the basis of the training set, a logistic model was constructed that related 16 independent patient or lesion characteristics with mortality, including PCI indication, advanced age, haemodynamic instability, multivessel disease, and proximal LAD disease. In both the training and validation data sets, the model had a good performance in terms of discrimination (C-index 0.91 and 0.90, respectively) and calibration (Hosmer-Lemeshow P-value 0.39 and 0.18, respectively). CONCLUSION In-hospital mortality in PCI patients was well predicted by a risk score that contains 16 factors. The score has strong applicability for European practices.

Elevated admission glucose is associated with increased long-term mortality in myocardial infarction patients, irrespective of the initially applied reperfusion strategy

BACKGROUND It is uncertain if elevated admission plasma glucose (APG) remains an independent determinant of longer-term mortality in myocardial infarction (MI) patients with early restoration of coronary reperfusion by primary percutaneous coronary intervention. The objective of the study was to describe the relation between elevated APG and long-term mortality in MI patients undergoing invasive management. METHODS We studied 1,185 consecutive MI patients treated in the Medical Center Alkmaar in the separate years 1996 and 1999 (preinvasive era) and 2003 and 2006 (invasive era). In both eras, APG was derived according to a standard protocol. A multivariate Cox regression model was created to study the relation between APG, reperfusion era, and 5-year mortality. RESULTS During a median follow-up of 63 months, 261 patients had died. Mortality was lower in the invasive (19%) than in the preinvasive era (28%). Increased APG was associated with increased mortality, irrespective of the initial reperfusion strategy, although the relation was more pronounced in the preinvasive era (P value for heterogeneity of effects < .001). Each millimole-per-liter APG increase corresponded to a 7% increased mortality (adjusted hazard ratio 1.07, 95% CI 1.04-1.10). Patients with an APG >11 mmol/L had nearly 2-fold higher mortality (hazard ratio 1.9, 95% CI 1.3-2.7) than those with lower values. CONCLUSION Elevated APG remains a determinant of long-term mortality in MI patients, irrespective of the advances that have been made in reperfusion therapy.

Comparison of diagnostic criteria to detect undiagnosed diabetes in hyperglycaemic patients with acute coronary syndrome.

Background Elevated plasma glucose levels on admission (APG) are very common in patients with acute coronary syndrome (ACS) and can be the first indication of diabetes mellitus. Objective To provide insight into the prevalence of previously undiagnosed diabetes and to compare different methods of diagnosing diabetes in patients with ACS. Methods Patients with ACS with elevated APG who participated in the BIOMArCS 2 glucose trial underwent an oral glucose tolerance test (OGTT) prior to discharge. 130 patients were included who underwent metabolic assessment. Of these, 109 had an OGTT and 13 patients had pre-existing diabetes. Results The OGTT results were categorised as (previously) undiagnosed diabetes in 35% of patients (fasting plasma glucose (FPG) ≥7.0 mmol/l or 2-h post-load glucose ≥11.1 mmol/l) and impaired glucose metabolism in 44% (FPG 6.1–6.9 mmol/l or post-load glucose 7.8–11.0 mmol/l), so only 21% had a normal glucose metabolism. Undiagnosed diabetes could not be adequately predicted with APG, FPG or HbA1c (area under the ROC curve 0.61, 0.75 and 0.72, respectively). Patients with abnormal glucose metabolism were significantly older, had higher admission HbA1c values, a higher Killip classification and more often had a prior stroke than patients with normal glucose metabolism. Conclusion 79% of hyperglycaemic patients with ACS were found to have abnormal glucose metabolism. As APG, HbA1c and FPG had a low sensitivity to detect undiagnosed diabetes, an OGTT appears to be the best test to assess the presence of previously undiagnosed diabetes or impaired glucose metabolism in hyperglycaemic patients with ACS.

Admission glucose does not improve GRACE score at 6 months and 5 years after myocardial infarction

Objective: Admission plasma glucose (APG) is a biomarker that predicts mortality in myocardial infarction (MI) patients. Therefore, APG may improve risk stratification based on the GRACE risk score. Methods: We collected data on baseline characteristics and long-term (median 55 months) outcome of 550 MI patients who entered our hospital in 2003 and 2006. We determined the GRACE risk score at admission for each patient, which was entered in a logistic regression model, together with APG, to evaluate their prognostic value for 6-month and 5-year mortality. Results: Patients with APG ≧7.8 mmol/l had a higher mortality than those with APG levels <7.8 mmol/l; 6 months: 13.7 versus 3.6%, p value <0.001; 5 years: 20.4 versus 11.1%, p value 0.003. After adjustment for the GRACE risk score variables, APG appeared a significant predictor of 6-month and 5-year mortality, adjusted OR 1.17 (1.06-1.29) and 1.12 (1.03-1.22). The combination of the GRACE risk score and APG increased the models performance (discrimination C-index 0.87 vs. 0.85), although the difference was not significant (p = 0.095). Combining the GRACE risk score and APG reclassified 12.9% of the patients, but the net reclassification improvement was nonsignificant (p = 0.146). Conclusion: APG is a predictor of 6-month and 5-year mortality, each mmol/l increase in APG being associated with a mortality increase of 17 and 12%, respectively, independent of the GRACE risk score. However, adding APG to the GRACE model did not result in significantly improved clinical risk stratification.

Current management of hyperglycemia in acute coronary syndromes: A national Dutch survey

Hyperglycemia is common among patients admitted with acute coronary syndromes (ACS) and is associated with less favorable clinical outcomes. Guidelines for the treatment of hyperglycemia in myocardial infarction are confusing, partly because of lack of sufficient evidence. Neither do we know what the everyday practice on hyperglycemia in ACS is. Therefore the aim of our study is to describe current glucose management in ACS patients in The Netherlands. We designed a multiple-choice questionnaire that was emailed to all 94 independent cardiology departments of each of the 114 hospitals within The Netherlands. We interviewed cardiologists about their specific hospital setting, the presence, content, and actual use of a dedicated hyperglycemia protocol in the setting of ACS. Ninety-four questionnaires were returned (response rate 100%). Only 32% of the respondents reported to have a routinely applied, dedicated hyperglycemia protocol in the setting of ACS. An admission glucose of 13.0 mmol/L is considered a stress value by 60% of respondents. Treatment of hyperglycemia is postponed until after the acute phase (ie, after >6 hours) in 41% of the cardiology departments and in 76% HbA1c is not routinely measured before discharge. Only a minority of Dutch cardiology departments have a routinely applied, dedicated hyperglycemia protocol for patients admitted with ACS. Different views exist on the interpretation of admission hyperglycemia in patients without previously diagnosed diabetes. Dedicated protocols with well-established treatment goals allow early treatment and are mandatory to improve timely metabolic regulation.

Long-term follow-up of the randomized (BIOMArCS-2) glucose trial

In the BIOMArCS-2 Glucose (Randomized Trial to Evaluate the Clinical Value of Intensive Glucose Monitoring and Regulation in Myocardial Infarction) trial, intensive glucose control (IGC) did not reduce myocardial infarction (MI) size in ST-segment–elevation MI or non–ST-segment–elevation MI patients presenting with hyperglycemia. In fact, IGC was associated with excess in-hospital death or MI (8 versus 1 event).1 Because these findings were unexpected, we executed a longer-term extension of the original trial cohort. In BIOMArCS-2 Glucose, 280 MI patients with admission blood glucose 140 to 288 mg/dL were randomly assigned to either IGC with intravenous insulin for 48 hours aiming for plasma levels of 85 to 110 mg/dL versus conventional management (control).1 The protocol was approved by the local Medical Ethics committee, and all patients provided written informed consent. In January 2016, median follow-up was 5.1 years (interquartile range, 4.0–6.2). We obtained data on vital status from municipal registries and on MI by reviewing medical records. MI was defined as typical chest pain accompanied by a rise of troponins. Follow-up on all-cause death and MI was 99.3% and 97.5% of patients, respectively. Patients with incomplete follow-up data were censored after their last hospital …

INCREASED ADMISSION GLUCOSE RELATES WITH INCREASED 5-YEAR MORTALITY IN MYOCARDIAL INFARCTION PATIENTS, IRRESPECTIVE OF THE INITIALLY APPLIED REPERFUSION STRATEGY

Results During 5-year f-up, 261 pts (22%) had died. Mortality was lower in the invasive (19%) than in the pre-invasive era (28%), p 11 mmol/l had 2-fold higher mortality (HR 2.0 and 95% CI 1.4 to 2.7) than patients with a lower APG. No significant interaction between APG and treatment era for 5-yr mortality was found (p 0.08).

Response to `Insulin therapy in acute coronary syndromes'

Corresponding author: M de Mulder, Department of Cardiology, Medical Centre Alkmaar, The Netherlands. Tel: +31 725484444 Fax: +31 725482156 Email: m.de.mulder@mca.nl In the November 2008 issue of this journal Goyal et al. gave a good overview of past and present studies concerning glucose regulation in acute coronary syndromes. We would like to extend the observational overview with the BIOMArCS 2 glucose study. In July 2008 we started a single centre prospective randomised open-label clinical trial to systematically evaluate hyperglycaemia in ACS patients. We aim to randomise 300 ACS patients with an admission glucose > 7.7 mmol/L and no previous use of insulin. They either receive intensive or expectative hyperglycaemia management. In the intensive treatment group we aim for normoglycaemia using intravenous insulin; naturally caution is warranted to avoid hypoglycaemia. We hypothesise that systematic, frequent and intensive glucose level control, in those with abnormal levels, will improve LV haemodynamics; it will preserve myocardial tissue and LV function in ACS patients. We expect that the beneficial effects of this strategy will be modified by treatment delay (i.e. early treatment results in better outcomes), especially in ST segment elevation-ACS patients. Our primary endpoint is infarct size defined by cardiac Troponin T at 72 h after randomisation. Secondary endpoints include ST segment resolution, NT pro-BNP levels and LVEF and infarct size determined by using a 99mTc-sestamibi SPECT 6 weeks after randomisation. Furthermore we expect that the effects of intensive glucose level control will result in a more favourable wash out pattern of biomarkers of (vascular) inflammation, hypercoagulability and neurohumoral activation.