Jorik R. Timmer

Prognostic Value of Admission Glycosylated Hemoglobin and Glucose in Nondiabetic Patients With ST-Segment–Elevation Myocardial Infarction Treated With Percutaneous Coronary Intervention

Background— In nondiabetic patients with ST-segment–elevation myocardial infarction, acute hyperglycemia is associated with adverse outcome. Whether this association is due merely to hyperglycemia as an acute stress response or whether longer-term glycometabolic derangements are also involved is uncertain. It was our aim to determine the association between both acute and chronic hyperglycemia (hemoglobin A1c [HbA1c]) and outcome in nondiabetic patients with ST-segment–elevation myocardial infarction. Methods and Results— This observational study included consecutive patients (n=4176) without known diabetes mellitus admitted with ST-segment–elevation myocardial infarction. All patients were treated with primary percutaneous intervention. Both glucose and HbA1c were measured on admission. Main outcome measure was total long-term mortality; secondary outcome measures were 1-year mortality and enzymatic infarct size. One-year mortality was 4.7%, and mortality after total follow-up (3.3±1.5 years) was 10%. Both elevated HbA1c levels (P<0.001) and elevated admission glucose (P<0.001) were associated with 1-year and long-term mortality. After exclusion of early mortality (within 30 days), HbA1c remained associated with long-term mortality (P<0.001), whereas glucose lost significance (P=0.09). Elevated glucose, but not elevated HbA1c, was associated with larger infarct size. After multivariate analysis, HbA1c (hazard ratio, 1.2 per interquartile range; P<0.01), but not glucose, was independently associated with long-term mortality. Conclusions— In nondiabetic patients with ST-segment–elevation myocardial infarction, both elevated admission glucose and HbA1c levels were associated with adverse outcome. Both of these parameters reflect different patient populations, and their association with outcome is probably due to different mechanisms. Measurement of both parameters enables identification of these high-risk groups for aggressive secondary risk prevention.

Long-term impact of multivessel disease on cause- specific mortality after ST-elevation myocardial infarction treated with reperfusion therapy

Objectives: To investigate the long-term impact of multivessel coronary artery disease (MVD) on cause-specific mortality in patients with ST elevation myocardial infarction (STEMI) treated with reperfusion therapy. Methods and results: Patients with STEMI (n  =  395) treated with primary angioplasty or thrombolysis in the setting of a randomised clinical trial were enrolled in the study. Follow up was 8 (2) years. For patients who died all available records were reviewed to assess the specific cause of death. MVD was present in 57% of patients. Patients with MVD were older and more of them had diabetes and previous myocardial infarction. Compared with the non-MVD group, residual left ventricular ejection fraction was lower (45.9% v 49.6%, p  =  0.001) and total mortality was higher in patients with MVD (32% v 19%, p  =  0.002). After adjustment for potential confounders this association was not significant (hazard ratio 1.4, 95% confidence interval (CI) 0.9 to 2.2). When the specific cause of death was considered, sudden death was comparable between patients with and without MVD (10% v 8%, p  =  0.49) but death caused by heart failure was significantly higher in patients with MVD (hazard ratio 7.4, 95% CI 1.7 to 32.2). Conclusion: Patients with STEMI and MVD have a higher long-term mortality than do patients with non-MVD. MVD is not an independent predictor of long-term total mortality or sudden death. However, MVD is a very strong and independent predictor of long-term death caused by heart failure.

Coronary Artery Calcium Scoring to Exclude Flow-Limiting Coronary Artery Disease in Symptomatic Stable Patients at Low or Intermediate Risk

PURPOSE To assess the capability of a zero coronary artery calcium (CAC) score to help exclude flow-limiting coronary artery disease (CAD) in a homogeneous population with stable anginal complaints and a low-to-intermediate pretest likelihood. MATERIALS AND METHODS The study protocol had institutional ethics committee approval, with written informed consent from all patients. Between 2009 and 2011, a total of 3501 consecutive stable patients without known CAD underwent prospectively simultaneous myocardial perfusion imaging and CAC scoring on a hybrid, 64-section single photon emission computed tomography (SPECT)/computed tomography (CT) scanner. In 868 (25%) of 3501 patients, the CAC score was zero, and these patients constituted the current study population. When feasible, additional coronary CT angiography was performed in those with abnormal SPECT findings. Clinical follow-up was recorded with regard to invasive coronary angiography, coronary revascularization, nonfatal myocardial infarction, or death. Results were analyzed by using descriptive statistics. RESULTS In 868 patients (mean age, 54 years ± 11 [standard deviation]; 610 [70%] female, 258 [30%] male), SPECT findings were normal in 766 (88%) and abnormal in 102 (12%), with equivocal results in 41 (5%), persistent defect in 35 (4%), and ischemia in 26 (3%). In the group with abnormal SPECT findings, additional coronary CT angiography was performed in 93 patients (91%), showing nonobstructive CAD in eight patients (9%) and normal coronary arteries in 85 patients (91%). In the other nine patients (9%), invasive angiography was used to exclude obstructive CAD. At a median follow-up of 17 months (25th percentile, 11; 75th percentile, 24 months), no coronary events were recorded. CONCLUSION A CAC score of zero in stable patients at low or intermediate risk excludes flow-limiting CAD. These findings support the possibility of CAC scoring as a simple and safe tool to select patients for additional testing or discharge, as recommended in the literature.

Myocardial scar characteristics based on cardiac magnetic resonance imaging is associated with ventricular tachyarrhythmia in patients with ischemic cardiomyopathy

OBJECTIVES We hypothesized that myocardial scar characterization using cardiac magnetic resonance imaging (CMR) may be associated with the occurrence of ventricular tachyarrhythmia (VT), appropriate implantable cardioverter-defibrillator (ICD) therapy and mortality. BACKGROUND Since a minority of patients with prophylactic ICD implantation receive appropriate ICD therapy, there is a need for more effective risk stratification for primary prevention in patients with ischemic cardiomyopathy. METHODS AND RESULTS In 99 patients with ischemic cardiomyopathy, CMR was performed prior to ICD implantation. We assessed if CMR indices (cardiac mass, LVEF) and CMR scar characteristics (infarct core mass, peri-infarction mass and the ratios between left ventricular mass, infarct core mass and peri-infarction mass) were associated with outcome. The primary endpoint was sustained VT and/or appropriate ICD therapy. The secondary endpoint was all-cause mortality. During a median follow-up of 5.4 years (IQR 4.5-6.6 years), 34 patients reached the primary end-point (17 appropriate ICD shocks) and 26 patients died. In multivariable Cox regression analysis, peri-infarction to core-infarction ratio (HR 2.01, 95%CI: 1.17-3.44, p=0.01) was independently and significantly associated with the primary endpoint, whereas NYHA-class and lower LVEF were not. Conversely, age (HR 1.06, 95% CI: 1.01-1.12, p=0.02) and lower LVEF (HR 0.95, 95% CI: 0.91-1.00, p=0.04) were independently associated with all-cause mortality, mainly due to heart failure. CONCLUSION A relatively large peri-infarction mass is associated with sustained VT and/or appropriate ICD therapy, whereas age and lower LVEF are associated with mortality. CMR based tissue characterization could aid in the prediction of specific outcome measures and in clinical decision making.

Prognostic Value of Coronary Artery Calcium Scoring in Addition to Single-Photon Emission Computed Tomographic Myocardial Perfusion Imaging in Symptomatic Patients.

Background—The prognostic value of coronary artery calcium (CAC) scoring on top of myocardial perfusion imaging with single-photon emission computed tomography (SPECT) in patients suspected for coronary artery disease is not well established. Methods and Results—Four thousand eight hundred ninety-seven symptomatic patients without a history of coronary artery disease referred for SPECT and CAC scoring were included. Major adverse cardiac events (MACEs) were defined as late revascularization (>90 days after scanning), nonfatal myocardial infarction, and all-cause mortality. The frequency of abnormal SPECT increased with higher CAC scores, from 12% in patients with CAC scores of 0 to 19%, 32%, 37%, and 50% among those with CAC scores 1 to 99, 100 to 399, 400 to 999, and ≥1000, respectively (P<0.001). During a median follow-up of 940 days (25th to 75th percentile, 581–1377), a total of 278 MACEs were observed. Overall incidence of MACE was 2.3% per year. A stepwise increase of MACE was present with increasing CAC scores, both in patients with normal SPECT (annual event rate CAC score 0: 0.6%; CAC score ≥1000: 5.5%) and abnormal SPECT (annual event rate CAC score 0: 0.4%; CAC score ≥1000: 7.6%). After multivariate analysis, both SPECT and CAC score were independent predictors of MACE (CAC score ≥1000: hazard ratio, 7.7; P<0.001 and large perfusion defect on SPECT: hazard ratio, 3.7; P<0.001). Conclusions—CAC score and SPECT are independent predictors of MACE in patients suspected for coronary artery disease. Our findings strongly support performing a CAC score in addition to SPECT in symptomatic patients to better define the risk of events during follow-up.

Pre-hospital administration of tirofiban in diabetic patients with ST-elevation myocardial infarction undergoing primary angioplasty: a sub-analysis of the On-Time 2 trial

AIMS Glycoprotein IIb/IIIa blocking agents seem to improve percutaneous coronary intervention (PCI) results in patients with ST-elevation myocardial infarction (STEMI). We aimed to compare the effect of pre-hospital administration of tirofiban in STEMI patients with and without diabetes mellitus (DM) treated with primary PCI. METHODS AND RESULTS We performed a pre-specified sub-analysis of the randomised On-Time II trial (n=984) and its open label run-in phase (n=414), which investigated pre-hospital administration of high dose tirofiban in STEMI patients treated with primary PCI. Two-hundred and twenty (16%) diabetic patients (known DM or Hba1C ≥6.2%) were included, 101 in the placebo group and 119 in the tirofiban group. In patients with DM, randomisation to tirofiban resulted in a lower residual ST deviation (5.1±8.5 mm vs. 6.2±5.6 mm, p=0.003), a reduced infarct size (CK 1694±1925 U/L vs. CK 2040±1829 U/L, p=0.02) and a trend towards lower one-year mortality (4.6% vs. 11.6%, p=0.07). The beneficial effects of tirofiban were more pronounced in diabetic patients compared to patients without diabetes. CONCLUSIONS Pre-hospital administration of tirofiban in diabetic STEMI patients treated with primary PCI improves ST resolution and reduces myocardial infarct size. Tirofiban seems particularly beneficial in patients with diabetes.

Age-dependent differences in diabetes and acute hyperglycemia between men and women with ST-elevation myocardial infarction: a cohort study

BackgroundBoth acute hyperglycemia as diabetes results in an impaired prognosis in ST-elevation myocardial infarction (STEMI) patients. It is unknown whether there is a different prevalence of diabetes and acute hyperglycemia in men and women within age-groups.MethodsBetween 2004 and 2010, 4640 consecutive patients (28% women) with STEMI, were referred for primary PCI. Patients were stratified into two age groups, < 65 years (2447 patients) and ≥65 years (2193 patients). Separate analyses were performed in 3901 patients without diabetes. Diabetes was defined as known diabetes or HbA1c ≥6.5 mmol/l at admission.ResultsThe prevalence of diabetes was comparable between women and men in the younger age group (14% vs 12%, p = 0.52), whereas in the older age group diabetes was more prevalent in women (25% vs 17% p < 0.001). In patients without diabetes, admission glucose was comparable between both genders in younger patients (8.1 ± 2.0 mmol/l vs 8.0 ± 2.2 mmol/l p = 0.36), but in older patients admission glucose was higher in women than in men (8.7 ± 2.1 mmol/l vs 8.4 ± 2.1 mmol/l p = 0.028). After multivariable analyses, the occurrence of increased admission glucose was comparable between men and women in the younger age group (OR 1.1, 95%CI 0.9-1.5), but increased in women in the older age group (OR 1.3, 95% CI 1.1-1.7). Both diabetes and hyperglycemia were associated with a higher one-year mortality in both men and women.ConclusionsThe differences between men and women in hyperglycemia and diabetes in patients with STEMI are age dependent and can only be observed in older patients. This may have implications for medical treatment and should be investigated further.

Impact of diabetes on outcome in patients with non-ST-elevation myocardial infarction

BACKGROUND Diabetes mellitus contributes to the increase of cardiovascular deaths worldwide. Despite continuous treatment evolution, patients with diabetes suffering from an acute coronary syndrome still have a high morbidity and mortality. We aimed to analyze the impact of diabetes on one-year outcome in an unselected patient population with non-ST-elevation myocardial infarction (non-STEMI). METHODS Retrospective analysis of 847 unselected patients with non-STEMI. We compared the baseline characteristics, treatment and outcome of patients versus those without diabetes. RESULTS A total of 138 patients had diabetes (16%) and 709 (84%) had no diabetes. Patients with diabetes were older, often had hypertension, hyperlipidemia, previous myocardial infarction and Killip class ≥2 on admission. Approximately 80% of both patients, with and without diabetes, underwent diagnostic coronary angiography. Multivessel disease was more present among patients with diabetes, but patients with diabetes were treated more often conservatively. At one-year follow up rates of death and major adverse cardiac events were significantly higher in patients with diabetes compared to those without diabetes (8% vs. 3%; P=0.001 and 23% vs. 14%; P=0.008, respectively). Even after adjustment for differences in baseline characteristics, diabetes remained an independent predictor of mortality (OR: 2.25; CI95%: 1.05-3.91). CONCLUSIONS In an unselected patient population with non-STEMI, patients with diabetes have higher risk factors on admission, less often undergo coronary revascularisation and have worse outcome at one-year follow-up. Diabetes is an independent predictor of one-year mortality in patients with non-STEMI.

Early or late intervention in patients with transient ST-segment elevation acute coronary syndrome: Subgroup analysis of the ELISA-3 trial

To investigate incidence and patient characteristics of transient ST‐segment elevation (TSTE) ACS and to compare outcome of early versus late invasive treatment.

Impact of image processing in the detection of ischaemia using CZT-SPECT/CT

BackgroundThe new multipinhole cardiac single photon emission computed tomography/computed tomography (SPECT/CT) cameras with cadmium–zinc–telluride (CZT) detectors are highly sensitive and produce images of high quality but rely on complex dedicated reconstruction algorithms. The aim of this study was to determine the impact of various processing steps on image formation and in the detection of ischaemia in CZT-SPECT/CT both with and without attenuation correction (AC). Materials and methodsData on 20 consecutive patients who underwent a 1-day protocol stress–rest SPECT/CT using 99mTc-tetrofosmin were processed twice by three experienced operators, yielding 120 AC and 120 noncorrected (NC) data sets. Processing steps included selection and determination of myocardial axes, manual SPECT/CT coregistration for AC and myocardial masking. Using the 17-segment cardiac model, differences between stress and rest segmental uptake (%) were calculated for NC and AC image sets. Both interoperator and intraoperator variations were considered significant for the diagnosis of ischaemia when greater than 5%. ResultsThe mean interoperator variations were 2.4±1.4% (NC) and 3.8±1.9% (AC) (P<0.01). In 6% (NC) and 23% (AC) of the 120 processed cases, operator variation was larger than 5% and therefore potentially clinically interfering with the diagnosis of ischaemia. Differences between interoperator and intraoperator variations were nonsignificant. ConclusionOperator variations in the processing of myocardial perfusion image data using CZT-SPECT/CT are significant and may influence the diagnosis of ischaemia, especially when AC is applied. Clearer guidelines for image processing are necessary to improve the reproducibility of the studies and to obtain a more reliable diagnosis of ischaemia.