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Atherosclerosis is a lipid-driven inflammatory disease, in which both lipids and inflammation can be considered treatment targets. The CANTOS-trial, using the IL-1β monoclonal antibody canakinumab, has proven the concept of targeting inflammation to reduce cardiovascular risk. In contrast, the anti-inflammatory drug methotrexate failed to show cardiovascular benefit. Colchicine is a drug used in gout patients, acting as a non-selective inflammasome inhibitor. The COLCOT-trial uncovered a significant reduction in ischemic cardiovascular events in subjects following an acute myocardial infarction, which was recently confirmed in the larger LoDoCo2-trial in stable coronary heart disease. Guideline committees will have to decide whether the trials have supplied sufficient evidence to implement the routine use of colchicine in the guidelines for cardiovascular risk management. These convincing endpoint trials have paved the way for tailored treatment regimens, comprising anti-inflammatory agents besides currently established treatment modalities in CVRM.

Diabetes is a risk factor for increased mortality after a myocardial infarction. Whether this applies for patients with hyperglycemia during the acute phase of a acute myocardial infarction is unclear. Therefore we determined the relation between admission plasma glucose level and mortality in a prospectively collected series of 336 consecutive AMI patients. Patients were divided in four groups based on WHO criteria for glucose levels: I: <5.6 mmol/l, II: 5.6--8.3 mmol/l, III: 8.4--11.0 mmol/l, IV: 11.1 mmol/l. The average age was 68+/-11 years with a peak CK of 1378+/-160 U/l, 34% were anterior wall AMIs and 52% were treated with thrombolysis. All patients had a long-term follow-up control at an average of 14.2 months. One year mortality rate was 19.3% and rose to 44% in patients with glucose levels >11.1 mmol/l. The mortality was higher in diabetic patients than in non-diabetic patients (40 vs. 16%; P<0.05). Multivariate analysis revealed an independent effect of glucose level on mortality. In conclusions, our study in an unselected patient population demonstrates that admission plasma glucose level independently predicts 1 year mortality even in absence of diagnosed diabetes mellitus. Further studies evaluating the effect of acute insulin intervention in reducing mortality are warranted.

There is a controversy regarding the functional significance of stress-induced ST-segment elevation (STE) in Q leads. However, the effect of revascularization on the induction of STE was not investigated. We studied 35 patients with old Q-wave myocardial infarction who underwent coronary artery bypass grafting (CABG) of the infarct-related artery with dobutamine (up to 40 microg/kg per minute) stress echocardiography before and 3 months after CABG. Ischemia was defined as new or worsened wall motion abnormalities. Functional recovery was defined as a reduction of regional wall motion score of 1 or more in 2 or more segments from the pre-CABG to post-CABG resting echocardiogram with the use of the 16-segment/5-grade score model. STE (>/=0.1 mV J-point elevation lasting 80 ms in >/=2 Q leads) occurred in 20 (57%) patients. There was no significant difference between patients with and those without STE before CABG with regard to the prevalence of peri-infarction ischemia (85% vs 80%) or index of improvement of regional function after CABG (0.26 +/- 0.26 vs 0.29 +/- 0.33). STE was reinduced to the same level in 4 patients after CABG, whereas 16 patients showed absent reinduction (8 patients) or reduced level (8 patients) of STE. Functional changes associated with absent reinduction or less STE after CABG were absence of reinduction of regional ischemia in 13 patients, improvement of resting regional function in 5 patients, and resection of scarred segments in 4 patients. Among the 4 patients with persistent dobutamine-induced STE, 1 patient had persistent ischemia and 2 showed worsening of resting regional function. Although dobutamine-induced STE in patients with old Q-wave infarction referred for CABG cannot identify patients with a higher prevalence of ischemia, the lack of reinduction of this pattern after CABG correlates with absent reinduction of ischemia in most of patients.

Background: Pharmacological stress echocardiography and myocardial perfusion scintigraphy are used frequently for risk stratification in patients with suspected myocardial ischemia. However, their relative prognostic strength has never been explored., Methods and Results: Two hundred twenty consecutive patients with chest pain (mean age, 60 +/- 12 years; 124 men, 115 with previous myocardial infarction) were studied with dobutamine-atropine stress echocardiography (ECHO) and simultaneous 99mTc sestamibi single photon emission computed tomography imaging (MIBI). Ischemia was defined as deterioration in left ventricular wall motion and reversible perfusion defects, respectively. ECHO was positive for ischemia in 76 and MIBI in 91 patients (agreement, 77%; kappa = .51). During follow-up of 31 +/- 15 months, 24 patients had hard cardiac events (nonfatal myocardial infarction or cardiac death). By univariate analysis, age, history of congestive heart failure, and any abnormality or ischemia on ECHO or MIBI were associated with cardiac events. Multivariate analysis revealed that age, abnormal ECHO (odds ratio [OR], 18.9; 95% CI, 2.5 to 146.0) or MIBI (OR, 12.8; 95% CI, 1.7 to 98.3), and ischemia on ECHO (OR, 4.0; 95% CI, 1.6 to 9.9) or MIBI (OR, 3.0; 95% CI, 1.2 to 7.4) had independent predictive values. When ECHO was used as a first option, the addition of MIBI to all nonischemic ECHO studies decreased the OR from 4.0 (95% CI, 1.6 to 9.9) to 3.8 (95% CI, 1.4 to 10.2). Addition of MIBI confined to nonischemic ECHO studies in which target heart rate was not attained (nondiagnostic studies) increased the OR to a maximal 5.7 (95% CI, 2.2 to 15.0). In contrast, the addition of ECHO to nondiagnostic MIBI studies was not useful., Conclusions: Dobutamine-atropine ECHO and MIBI provide comparable prognostic information. The addition of MIBI to ECHO may be useful in patients with nondiagnostic ECHO studies.

The use of 18F-fluorodeoxyglucose (FDG) imaging with single photon emission computed tomography (SPECT) has been introduced recently to assess myocardial viability. Several centres have now gained experience with cardiac FDG SPECT imaging, and this report is a summary of the currently available FDG SPECT data. Three studies have compared FDG SPECT with FDG positron emission tomography and demonstrated good agreement between them. Initial results in patients undergoing revascularization suggest that FDG SPECT can predict improvement in contractile function after revascularization. Although the initial results are promising, larger studies are needed to determine the precise role of FDG SPECT in the assessment of myocardial viability.

The aim of this study was to assess the influence of the severity of coronary artery stenosis and the grade of collateral circulation on myocardial viability in patients with chronic left ventricular (LV) dysfunction undergoing coronary artery bypass grafting. Forty patients (age 59 +/- 8 years) with old myocardial infarction were studied by dobutamine stress echocardiography (DSE) before coronary artery bypass grafting. LV function was assessed using a 16-segment, 5-grade score model. Viability and functional recovery were respectively defined as a reduction in wall motion score > or = 1 at low-dose DSE and at follow-up echocardiograms obtained 3 months after surgery. There were 56 stenotic coronary arteries subtending severely dyssynergic myocardial segments, of which 38 were occluded. Among 186 severely dyssynergic segments, functional recovery occurred in 42 (23%). There was no significant difference between myocordial regions with patent or occluded coronary arteries with respect to prevalence of viability or functional recovery and percentage of viable or recovered segments relative to the total number of dyssynergic segments. In patients with total occlusion, these parameters were not different between regions with different collateral grades. Sensitivity, specificity, and accuracy of low-dose DSE for prediction of regional functional recovery were 71%, 90%, and 86%, respectively. It is concluded that in patients with chronic LV dysfunction, the presence of total occlusion of coronary arteries supplying severely dyssynergic regions does not imply a lower prevalence or extent of functional recovery after revascularization, regardless of the grade of angiographically visualized collaterals. Low-dose DSE can identify myocardial regions with a high probability of functional improvement after revascularization regardless of the severity of underlying coronary stenosis or collateralization of the involved coronary vessel.

Objective: To assess the relation between ST segment elevation during the dobutamine stress test and late improvement of function after acute Q wave myocardial infarction., Patients and Design: 70 patients were studied a mean (SD) 8 (3) days after acute myocardial infarction with high dose dobutamine-atropine stress echocardiography and a follow up echocardiogram at 85 (10) days. A score model based on 16 segments and four grades was used to assess left ventricular function. Functional improvement was defined as a reduction of wall motion score > or = 1 in > or = 1 segments at follow up., Intervention: Myocardial revascularisation was performed in 23 patients (33%) before follow up studies., Results: ST segment elevation occurred in 40 patients (57%). Late functional improvement occurred in 35 patients (50%). Functional improvement was more common in patients with ST segment elevation (68% v 30%, P < 0.005) and they had a higher mean (SD) number of improved segments at follow up (1.9 (2.2) v 0.5 (1.1), P < 0.005). The wall motion score index decreased between baseline and follow up in patients with ST segment elevation (1.54 (0.50) v 1.48 (0.43), P < 0.05) but not in patients without ST segment elevation (1.39 (0.60) v 1.45 (0.47)). The accuracy of ST segment elevation for the prediction of functional improvement was similar to that of low dose dobutamine echocardiography in patients with anterior infarction (80% v 83%) and in patients who underwent revascularisation (78% v 83% respectively)., Conclusion: In patients with a recent Q wave myocardial infarction, dobutamine-induced ST segment elevation is a valuable marker of myocardial viability particularly when the test is performed without or with suboptimal echocardiographic imaging.

Unlabelled: This study assessed the value of dobutamine 201Tl scintigraphy for detecting significant disease of infarct-related and remote coronary arteries in myocardial infarction patients., Methods: Dobutamine (up to 40 micrograms/kg/min)/atropine (up to 1 mg) stress test in conjunction with stress-reinjection 200Tl SPECT was performed in 71 symptomatic patients with left ventricular dysfunction > 3 mo after myocardial infarction. Ischemia was defined as reversible perfusion defects., Results: Significant coronary artery stenosis (> or = 50% luminal diameter stenosis) was detected in all patients. Sensitivity, specificity and accuracy of regional ischemia for the diagnosis of remote coronary artery stenosis were 74% (95% Cl 63-86), 80% (Cl 70-90) and 76% (Cl 65-87), respectively. Those for infarct-related artery stenosis were 71% (Cl 60-81), 83% (Cl 75-92) and 72% (Cl 61-82), respectively. Ischemic perfusion score was higher in patients with multiversus single-vessel disease (1056 +/- 1021 versus 423 +/- 633, p < 0.01)., Conclusion: Dobutamine thallium scintigraphy is valuable for assessing the extent of coronary stenosis on the basis of reversible hypoperfusion in symptomatic patients late after myocardial infarction.

Objectives: This study investigated the prognostic value of dobutamine-atropine technetium-99m (Tc-99m) sestamibi single-photon emission computed tomographic (SPECT) myocardial perfusion imaging., Background: Dobutamine-atropine Tc-99m sestamibi SPECT imaging is an accurate method for the detection of coronary disease. However, the prognostic value of this stress modality has not been assessed., Methods: Three hundred ninety-two consecutive patients with chest pain (mean [+/- SD] age 60 +/- 12 years; 220 men, 190 with a previous myocardial infarction) underwent a dobutamine-atropine Tc-99m sestamibi SPECT scintigraphic study. Patients were followed up for 22 +/- 13 months to determine the univariate and multivariate variables associated with hard cardiac events (cardiac death, nonfatal myocardial infarction), to define their event-free survival and to determine whether the extent and severity of reversible perfusion defects correlated with events., Results: Forty-four patients (11%) had hard cardiac events. Multivariate models demonstrated that older age (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.0 to 4.4), history of heart failure (OR 2.6, 95% CI 1.3 to 5.2), abnormal sestamibi scan results (OR 10.0, 95% CI 2.3 to 43.0) and reversible perfusion defects (OR 3.2, 95% CI 1.6 to 6.4) had independent predictive value. Patients without perfusion defects, with fixed defects alone, reversible defects alone and fixed plus reversible defects had annual hard cardiac event rates of 0.8%, 6.8%, 8.1% and 11.6%, respectively. Patients with increasing reversible defect scores had increasing annual event rates of 2.1%, 5.0%, 5.5%, 13.0% and 14.6%, respectively., Conclusions: Dobutamine-atropine stress Tc-99m sestamibi SPECT imaging provides excellent prognostic information. The single most important independent predictor for future hard cardiac events is an abnormal pattern, and a reversible defect provides additional, independent prognostic information. Moreover, the extent and severity of reversible defects are major determinants for prognosis.

Spontaneous improvement of contraction and perfusion occurs after acute myocardial infarction. The relative merit of low-dose dobutamine stress echocardiography (LDDE) and rest-redistribution thallium scintigraphy (RR TI) in this setting has not been evaluated. We studied 30 patients at 7 +/- 3 days after acute myocardial infarction with LDDE (5 to 10 micrograms/kg/min) and RR TI single photon emission computed tomography. Viability was defined as improvement of wall thickening at LDDE in the presence of redistribution or a defect with uptake > or = 50% of peak activity at RR TI. Baseline echocardiography and RR TI were repeated after 3 months. In 112 dyssynergic segments, viability was detected in 60 (54%) by RR TI and in 39 (35%) by LDDE (p < 0.005). Spontaneous improvement of function was detected in 35 (31 %) segments. In the same regions, thallium uptake increased significantly. The sensitivity, specificity, and accuracy of LDDE for predicting late improvement of wall motion were 77%, 84%, and 82%, respectively. Those of RR TI were 77%, 57%, and 63%, respectively. Specificity and accuracy of LDDE were higher than RR TI (p < 0.005). We conclude that a myocardial viability pattern after acute myocardial infarction is more frequently detected by RR TI than by LDDE. Both techniques are equally sensitive, but LDDE is a more specific predictor of spontaneous recovery of regional left ventricular function.

Unlabelled: Conflicting results in a heterogenous patient population have been described on the functional significance of stress-induced T wave normalization in the ECG. The aim of this study was to evaluate the relationship between T wave normalization during dobutamine stress testing and stress-induced ischaemia evaluated by echocardiography and myocardial perfusion scintigraphy in patients with previous non-Q wave myocardial infarction. Among 520 patients who underwent dobutamine stress, testing in conjunction with simultaneous echocardiography and 201 thallium or sestamibi SPECT for evaluation of suspected myocardial ischaemia, 36 were selected according to the following criteria: previous non-Q wave myocardial infarction, normal QRS, negative T waves in two or more ECG leads and no significant ST segment depression or elevation at rest or during stress. Diagnosis of ischaemia relied upon the occurrence of reversible perfusion defects by scintigraphy and stress-induced wall motion abnormalities by echocardiography. During the test, T wave normalization (defined as a resting negative T wave becoming upright in one or more ECG leads during stress) occurred in 20 patients (group 1), while in 16 patients the T waves remained negative (group 2). The prevalence of ischaemia was higher in group 1 than in group 2 both by scintigraphy (85% vs 38%, P = 0.004) and by echocardiography (70% vs 32%, P = 0.02). The sensitivity, specificity and accuracy of T wave normalization in the detection of ischaemia were 74%, 77% and 75% by SPECT and 74%, 65% and 69% by echocardiography respectively., Conclusion: In patients with non-Q wave myocardial infarction and suspected myocardial ischaemia, T wave normalization without concomitant ECG changes during dobutamine stress testing is associated with a higher prevalence of ischaemia compared to patients with persistent T wave inversion. This ECG finding should not be disregarded as a marker of ischaemia in that particular patient population.

This study was performed to assess the prevalence of spontaneous improvement of regional left ventricular function in patients after acute myocardial infarction, and to evaluate the role of low-dose dobutamine stress echocardiography for its prediction. In 57 patients with a first acute myocardial infarction (thrombolysis, n = 27; Q-wave, n = 49), regional wall motion was evaluated with 2-dimensional echocardiography at rest, during a low-dose dobutamine stress test performed within 1 week after hospital admission, and at 3-month follow-up. Myocardial viability was considered if there was an improvement of > or = 1 grade in dyssynergic segments from rest to low-dose dobutamine infusion; recovery of regional function was defined as an improvement of > or = 1 grade between rest and follow-up echocardiograms. Wall motion score index decreased from rest to low-dose dobutamine echocardiography (1.46 +/- 0.29 to 1.39 +/- 0.30, p < 0.0001), and this change persisted at follow-up study (1.37 +/- 0.30). No differences were found between patients who did and did not undergo thrombolyis, or between those who had Q-wave and non-Q-wave infarction. At baseline echocardiography, 189 of 627 segments were dyssynergic (85 hypokinetic, 104 akinetic). Viability at low-dose dobutamine stress echocardiography was more frequent in hypokinetic than in akinetic segments (30 of 85 vs 12 of 104, odds ratio 4.18, 95% confidence interval [CI] 1.87 to 9.48).(ABSTRACT TRUNCATED AT 250 WORDS)

Sestamibi is a Tc labeled radiotracer particularly suitable for myocardial perfusion studies, providing similar information as thallium scintigraphy for the diagnosis of coronary artery disease. In comparison with thallium, sestamibi has the advantage of improved imaging properties due to its higher gamma emission. This is particularly relevant when SPECT imaging is considered. The myocardial uptake of sestamibi is partially passively, related to the myocardial flow, and is also related to the metabolic cellular activity, as it is proportional to the electrochemical gradient generated at cell membrane level. While the role for sestamibi in diagnosing coronary artery disease is well accepted, it is still controversial for the assessment of myocardial viability. Clinical studies reported by others and results from our own institution will be described both in the setting of a recent myocardial infarction (myocardial stunning) and of longstanding left ventricular dysfunction (hibernating myocardium). The results concordantly suggest that sestamibi underestimates myocardial viability, compared to the accepted standards of thallium (rest-redistribution or stress-reinjection protocols), 18-F FDG PET and also in the prediction of left ventricular functional recovery after revascularisation. However, the data available at present are very limited, particularly after revascularisation. Furthermore, according to new promising results, the role of sestamibi in the setting of myocardial viability has potential for improvement, if the injection at rest will be performed during nitrates. It is also foreseen that the combined use of sestamibi perfusion/wall motion scan (first pass and/or gated perfusion studies) and the development of new softwares for attenuation correction might improve the results in the setting of myocardial viability.

BACKGROUND Cardiovascular events frequently recur after acute myocardial infarction, and low cholesterol efflux — a process mediated by apolipoprotein A1, which is the main protein in high-density lipoprotein — has been associated with an increased risk of cardiovascular events. CSL112 is human apolipoprotein A1 derived from plasma that increases cholesterol efflux capacity. Whether infusions of CSL112 can reduce the risk of recurrent cardiovascular events after acute myocardial infarction is unclear. METHODS We conducted an international, double-blind, placebo-controlled trial involving patients with acute myocardial infarction, multivessel coronary artery disease, and additional cardiovascular risk factors. Patients were randomly assigned to receive either four weekly infusions of 6 g of CSL112 or matching placebo, with the first infusion administered within 5 days after the first medical contact for the acute myocardial infarction. The primary end point was a composite of myocardial infarction, stroke, or death from cardiovascular causes from randomization through 90 days of follow-up. RESULTS A total of 18,219 patients were included in the trial (9112 in the CSL112 group and 9107 in the placebo group). There was no significant difference between the groups in the risk of a primary end-point event at 90 days of follow-up (439 patients [4.8%] in the CSL112 group vs. 472 patients [5.2%] in the placebo group; hazard ratio, 0.93; 95% confidence interval [CI], 0.81 to 1.05; P=0.24), at 180 days of follow-up (622 patients [6.9%] vs. 683 patients [7.6%]; hazard ratio, 0.91; 95% CI, 0.81 to 1.01), or at 365 days of follow-up (885 patients [9.8%] vs. 944 patients [10.5%]; hazard ratio, 0.93; 95% CI, 0.85 to 1.02). The percentage of patients with adverse events was similar in the two groups; a higher number of hypersensitivity events was reported in the CSL112 group. CONCLUSIONS Among patients with acute myocardial infarction, multivessel coronary artery disease, and additional cardiovascular risk factors, four weekly infusions of CSL112 did not result in a lower risk of myocardial infarction, stroke, or death from cardiovascular causes than placebo through 90 days. [ABSTRACT FROM AUTHOR]

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved.Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death.Results: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P=0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P=0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P=0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P=0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P=0.31).Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846 .). [ABSTRACT FROM AUTHOR]