Effects of basal insulin glargine and omega-3 on lower limb arterial disease outcome in patients with dysglycaemia: An analysis of the Outcome Reduction with an Initial Glargine INtervention (ORIGIN) trial.

The impact of insulin or omega-3 supplements on the incidence and progression of peripheral artery disease (PAD) in patients with dysglycaemia has not been well studied. The Outcome Reduction with an Initial Glargine INtervention (ORIGIN) trial randomized participants with dysglycaemia and cardiovascular risk factors to titrated insulin glargine vs standard care, and to either 1 g of omega-3 per day or placebo. We assessed incident PAD, defined as the composite of either asymptomatic or symptomatic PAD according to the randomized interventions in the 11 119 ORIGIN participants whose baseline ankle-brachial index (ABI) was >0.9 (no PAD), and PAD progression in the 971 ORIGIN participants whose baseline ABI was ≤0.9. Hazard ratios (HR) were adjusted for confounders. During a 6.2-year follow-up period, allocation to insulin glargine vs standard care had a neutral effect on the composite of PAD incidence (HR, 0.99; 95% CI, 0.86-1.15) and progression (HR, 0.88; 95% CI, 0.63-1.22). Similar findings were noted for allocation to omega-3 vs placebo for PAD incidence (HR, 1.02; 95% CI, 0.89-1.18) and progression (HR, 0.93; 95% CI, 0.67-1.28). In this large study, neither insulin glargine nor omega-3 affected the incidence or progression of PAD.

Transfer of patients with ST-elevation myocardial infarction for primary percutaneous coronary intervention: a province-wide evaluation of "door-in to door-out" delays at the first hospital.

BACKGROUND: Interhospital transfer of patients with ST-elevation myocardial infarction (STEMI) for primary percutaneous coronary intervention (PPCI) is associated with longer delays to reperfusion, related in part to turnaround ("door in" to "door out," or DIDO) time at the initial hospital. As part of a systematic, province-wide evaluation of STEMI care, we examined DIDO times and associations with patient, hospital, and process-of-care factors. METHODS AND RESULTS: We performed medical chart review for STEMI patients transferred for PPCI during a 6-month period (October 1, 2008, through March 31, 2009) and linked these data to ambulance service databases. Two core laboratory cardiologists reviewed presenting ECGs to identify left bundle-branch block and, in the absence of left bundle-branch block, definite STEMI (according to both cardiologists) or an ambiguous reading. Median DIDO time was 51 minutes (25th to 75th percentile: 35-82 minutes); 14.1% of the 988 patients had a timely DIDO interval (≤30 minutes as recommended by guidelines). The data-to-decision delay was the major contributor to DIDO time. Female sex, more comorbidities, longer symptom duration, arrival by means other than ambulance, arrival at a hospital not exclusively transferring for PPCI, arrival at a center with a low STEMI volume, and an ambiguous ECG were independently associated with longer DIDO time. When turnaround was timely, 70% of patients received timely PPCI (door-to-device time ≤90 minutes) versus 14% if turnaround was not timely (P<0.0001). CONCLUSIONS: Benchmark DIDO times for STEMI patients transferred for PPCI were rarely achieved. Interventions aimed at facilitating the transfer decision, particularly in cases of ECGs that are difficult to interpret, are likely to have the best impact on reducing delay to reperfusion.

Information on myocardial ischemia and arrhythmias added by prehospital electrocardiograms.

BACKGROUND: The prehospital electrocardiogram (ECG) allows earlier identification of acute ST-segment elevation myocardial infarction (STEMI). Its utility for detection of other acute cardiac events, as well as for transient ST-segment abnormalities no longer present when the first hospital ECG is performed, is not well characterized. OBJECTIVE: We sought to examine whether the prehospital ECG adds supplemental information to the first ECG obtained in hospital, by comparing data on possible cardiac ischemia and arrhythmias provided by the two ECGs, in ambulance patients later diagnosed as having cardiac disorders, including STEMI. METHODS: Ambulance personnel acquired 12-lead ECGs for patients suspected of having an acute ischemic event, prior to transport to hospital. The first emergency department 12-lead ECG was provided by medical records at the receiving hospital, and the principal hospital diagnosis for the event was extracted from chart data. Two cardiologists, blinded to the hospital diagnosis, provided their consensus interpretation of 1,209 pairs of ECGs, noting the presence or absence of specific abnormalities on each tracing. RESULTS: Among the 82 patients who had an eventual hospital diagnosis of STEMI, the study cardiologists identified 71 with ST-segment elevations on the ECGs they examined. The vast majority of these (97%) were observed on both ECGs, but the prehospital ECG showed ST-segment elevation for two additional patients (3%). No additional instances were seen only on the hospital ECG. Among the 116 patients with a hospital diagnosis of non-ST-segment elevation myocardial infarction (NSTEMI), the cardiologists identified 36 with ST-segment depressions: 28 (78%) of these were present on both ECGs, seven (19%) only on the prehospital ECG, and one (3%) only on the hospital ECG. Among the 567 patients with any cardiac hospital diagnosis, the cardiologists identified 87 with arrhythmias: 73 (84%) on both ECGs, 12 (14%) only on the prehospital ECG, and two (2%) only on the hospital ECG. CONCLUSIONS: Beyond identifying ST-segment elevation earlier, prehospital ECGs detect important transient abnormalities, information not otherwise available from the first emergency department ECG. These data can expedite diagnosis and clinical management decisions among patients suspected of having an acute cardiac event. The prehospital ECG should be fully integrated into emergency medicine practice.

Routine invasive management after fibrinolysis in patients with ST-elevation myocardial infarction: a systematic review of randomized clinical trials.

BACKGROUND: Patients with ST-elevation myocardial infarction (STEMI) treated with fibrinolysis are increasingly, and ever earlier, referred for routine coronary angiography and where feasible, undergo percutaneous coronary intervention (PCI). We sought to examine the randomized clinical trials (RCTs) on which this approach is based. METHODS: We systematically searched EMBASE, Medline, and references of relevant studies. All contemporary RCTs (published since 1995) that compared systematic invasive management of STEMI patients after fibrinolysis with standard care were included. Relevant study design and clinical outcome data were extracted. RESULTS: Nine RCTs that randomized a total of 3320 patients were identified. All suggested a benefit from routine early invasive management. They were individually reviewed but important design variations precluded a formal quantitative meta-analysis. Importantly, several trials did not compare a routine practice of invasive management after fibrinolysis with a more selective 'ischemia-guided' approach but rather compared an early versus later routine invasive strategy. In the other studies, recourse to subsequent invasive management in the usual care group varied widely. Comparison of the effectiveness of a routine invasive approach to usual care was also limited by asymmetric use of a second anti-platelet agent, differing enzyme definitions of reinfarction occurring spontaneously versus as a complication of PCI, a preponderance of the 'soft' outcome of recurrent ischemia in the combined primary endpoint, and an interpretative bias when invasive procedures on follow-up were tallied as an endpoint without considering initial invasive procedures performed in the routine invasive arm. CONCLUSIONS: Due to important methodological limitations, definitive RCT evidence in favor of routine invasive management following fibrinolysis in patients with STEMI is presently lacking.

Association between timeliness of reperfusion therapy and clinical outcomes in ST-elevation myocardial infarction.

CONTEXT: Guidelines emphasize the importance of rapid reperfusion of patients with ST-elevation myocardial infarction (STEMI) and specify a maximum delay of 30 minutes for fibrinolysis and 90 minutes for primary percutaneous coronary intervention (PPCI). However, randomized trials and selective registries are limited in their ability to assess the effect of timeliness of reperfusion on outcomes in real-world STEMI patients. OBJECTIVES: To obtain a complete interregional portrait of contemporary STEMI care and to investigate timeliness of reperfusion and outcomes. DESIGN, SETTING, AND PATIENTS: Systematic evaluation of STEMI care for 6 months during 2006-2007 in 80 hospitals that treated more than 95% of patients with acute myocardial infarction in the province of Quebec, Canada (population, 7.8 million). MAIN OUTCOME MEASURES: Death at 30 days and at 1 year and the combined end point of death or hospital readmission for acute myocardial infarction or congestive heart failure at 1 year by linkage to Quebec's medicoadministrative databases. RESULTS: Of 1832 patients treated with reperfusion, 392 (21.4%) received fibrinolysis and 1440 (78.6%) received PPCI. Fibrinolysis was untimely (>30 minutes) in 54% and PPCI was untimely (>90 minutes) in 68%. Death or readmission for acute myocardial infarction or heart failure at 1 year occurred in 13.5% of fibrinolysis patients and 13.6% of PPCI patients. When the 2 treatment groups were combined, patients treated outside of recommended delays had an adjusted higher risk of death at 30 days (6.6% vs 3.3%; odds ratio [OR], 2.14; 95% confidence interval [CI], 1.21-3.93) and a statistically nonsignificant increase in risk of death at 1 year (9.3% vs 5.2%; OR, 1.61; 95% CI, 1.00-2.66) compared with patients who received timely treatment. Patients treated outside of recommended delays also had an adjusted higher risk for the combined outcome of death or hospital readmission for congestive heart failure or acute myocardial infarction at 1 year (15.0% vs 9.2%; OR, 1.57; 95% CI, 1.08-2.30). At the regional level, after adjustment, each 10% increase in patients treated within the recommended time was associated with a decrease in the region-level odds of overall 30-day mortality (OR, 0.80; 95% CI, 0.65-0.98). CONCLUSION: Among patients in Quebec with STEMI, reperfusion delivered outside guideline-recommend delays was associated with significantly increased 30-day mortality, a statistically nonsignificant increase in 1-year mortality, and significantly increased risk of the composite of mortality or readmission for acute myocardial infarction or heart failure at 1 year.

Nonrandomized comparison of coronary artery bypass surgery and percutaneous coronary intervention for the treatment of unprotected left main coronary artery disease in octogenarians.

BACKGROUND: The objective of the present study was to compare the midterm follow-up results of percutaneous coronary intervention (PCI) and coronary bypass graft surgery (CABG) for the treatment of unprotected left main coronary artery disease in octogenarians. METHODS AND RESULTS: A total of 249 consecutive patients > or =80 years of age diagnosed with left main coronary artery disease underwent coronary revascularization in our center between January 2002 and January 2008; 145 patients underwent CABG, and 104 patients had PCI. Major adverse cardiac and cerebrovascular events (MACCE [cardiac death, myocardial infarction, cerebrovascular event, revascularization]) were evaluated at a mean follow-up of 23 +/- 16 months. Patients who underwent PCI were older; had higher creatinine levels, lower ejection fraction, and higher EuroSCORE; and presented more frequently with an acute coronary syndrome. Drug-eluting stents were used in 48% of PCI patients. A propensity score analysis was performed to adjust for baseline differences between the 2 groups. Survival free of cardiac death or myocardial infarction (PCI, 65.4%; CABG, 69.7%) and MACCE-free survival (PCI, 56.7%; CABG, 64.8%) at follow-up were similar between the groups (adjusted hazard ratio for survival free of cardiac death or myocardial infarction, 1.28; 95% CI, 0.64 to 2.56; P=0.47; adjusted hazard ratio for MACCE-free survival, 1.11; 95% CI, 0.59 to 2.0; P=0.73). The EuroSCORE value was an independent predictor of MACCE regardless of the type of revascularization (hazard ratio, 1.17 for each EuroSCORE increase of 1 point; 95% CI, 1.09 to 1.25; P<0.0001). CONCLUSIONS: In this single-center, nonrandomized study, there were no significant differences in cardiac death or myocardial infarction and MACCE between CABG and PCI for the treatment of left main coronary artery disease in octogenarians after a mean follow-up of 2 years. Baseline EuroSCORE was the most important predictor of MACCE regardless of the type of revascularization. Randomized studies comparing both revascularization strategies in this high-risk coronary population are warranted.

Atherosclerotic burden findings in young cryptogenic stroke patients with and without a patent foramen ovale.

BACKGROUND AND PURPOSE: To further determine the mechanisms of cryptogenic stroke or transient ischemic attack in young patients, we evaluated indices of atherosclerosis in patients

Comparison of prognosis for men with type 2 diabetes mellitus and men with cardiovascular disease.

BACKGROUND: People with type 2 diabetes mellitus are at high risk for cardiovascular disease. In some studies, the mortality rate among people with this condition has been equivalent to that among people with cardiovascular disease. We compared cardiovascular mortality between incident cases of diabetes and cardiovascular disease. METHODS: The study population was part of a random sample of 4376 men from Quebec, Canada, aged 35 to 64 years, who did not have cardiovascular disease in 1974 and who were followed until 1998. Three groups of incident cases were identified: diabetes without cardiovascular disease, first cardiovascular event (myocardial infarction, unstable angina or stroke) without diabetes, and both cardiovascular disease and diabetes. These cases were age-matched to a control group without diabetes or cardiovascular disease. RESULTS: During the 24-year follow-up period, new diabetes without cardiovascular disease was documented in 137 men. A first cardiovascular event without diabetes was documented in 527 men. Relative to the 627 controls, men with 1 of the 2 diseases of interest had higher cardiovascular mortality (age-adjusted relative risk [RR] 3.11, 95% confidence interval [CI] 1.96-4.92) for those with diabetes and 4.46 (95% CI 3.15-6.30) for those with cardiovascular disease). However, within the first 5 years after diagnosis, men with cardiovascular disease had higher cardiovascular mortality than men with diabetes (age-adjusted RR 2.03, 95% CI 1.01-4.08). INTERPRETATION: Men with isolated type 2 diabetes and men with isolated cardiovascular disease had similar cardiovascular mortality rates several years after initial diagnosis of either condition. These findings reinforce the need to prevent and optimally manage diabetes and cardiovascular disease.

Variability in High-Sensitivity Cardiac Troponin T Testing in Stable Patients With and Without Coronary Artery Disease.

BACKGROUND: High-sensitivity cardiac troponin T (hs-cTnT) is used to diagnosis acute myocardial infarction, often based on values exceeding the 99th percentile threshold (14 ng/L) of normal populations. The short- and long-term variability of hs-cTnT in stable patients with or without coronary artery disease (CAD) is unknown. METHODS: Prospective cohort study of 75 stable patients with CAD and 3 differing clinical profiles (stable angina [SA]; remote myocardial infarction [MI]; repetitive acute coronary syndrome [ACS]) and 25 controls without angiographic CAD, each with 15 hs-cTnT measurements over 1 year. RESULTS: Individual results (1491 measurements) did not vary over within-day, daily, weekly, monthly, seasonal, or yearly time windows. The overall median was 2.8 ng/L (interquartile range [IQR] 5.2 ng/L) with the highest median (6.3 ng/L) and variability (IQR 6. 9 ng/L) in the repetitive ACS group. Diabetes, impaired renal function, and raised C-reactive protein were independent predictors of higher hs-cTnT values (average increase by 8.5 ng/L [95% CI, 5.0-11.9], 5.0 ng/L [95% CI, 2.0-8.1] and 4.0 ng/L (95% CI, 1.0-7.0), respectively). The 99th percentile value of all hs-cTnT measurements in the combined stable patients with CAD was 39 ng/L compared with 14 ng/L in the non-CAD patients. CONCLUSIONS: Individual hs-cTnT readings in both patients with and without CAD were stable over hours, days, weeks, and months. Diabetes, poor renal function, and elevated C-reactive protein were independent predictors of higher median and IQR hs-cTnT values, often exceeding conventional thresholds. These findings highlight the need for caution and clinical contextualization in the interpretation of hs-cTnT results.

Paradoxical low-flow, low-gradient severe aortic stenosis despite preserved ejection fraction is associated with higher afterload and reduced survival.

BACKGROUND: Recent studies and current clinical observations suggest that some patients with severe aortic stenosis on the basis of aortic valve area may paradoxically have a relatively low gradient despite the presence of a preserved left ventricular (LV) ejection fraction. The objective of the present study was to document the prevalence, potential mechanisms, and clinical relevance of this phenomenon. METHODS AND RESULTS: We retrospectively studied the clinical and Doppler echocardiographic data of 512 consecutive patients with severe aortic stenosis (indexed aortic valve area < or = 0.6 cm2 x m(-2)) and preserved LV ejection fraction (> or = 50%). Of these patients, 331 (65%) had normal LV flow output defined as a stroke volume index > 35 mL x m2, and 181 (35%) had paradoxically low-flow output defined as stroke volume index < or = 35 mL x m(-2). When compared with normal flow patients, low-flow patients had a higher prevalence of female gender (P<0.05), a lower transvalvular gradient (32+/-17 versus 40+/-15 mm Hg; P<0.001), a lower LV diastolic volume index (52+/-12 versus 59+/-13 mL x m(-2); P<0.001), lower LV ejection fraction (62+/-8% versus 68+/-7%; P<0.001), a higher level of LV global afterload reflected by a higher valvulo-arterial impedance (5.3+/-1.3 versus 4.1+/-0.7 mm Hg x mL(-1) x m(-2); P<0.001) and a lower overall 3-year survival (76% versus 86%; P=0.006). Only age (hazard ratio, 1.04; 95% CI, 1.01 to 1.08; P=0.025), valvulo-arterial impedance > 5.5 mm Hg x mL(-1) x m(-2) (hazard ratio, 2.6; 95% CI, 1.2 to 5.7; P=0.017), and medical treatment (hazard ratio, 3.3; 95% CI, 1.8 to 6.7; P=0.0003) were independently associated with increased mortality. CONCLUSION: Patients with severe aortic stenosis may have low transvalvular flow and low gradients despite normal LV ejection fraction. A comprehensive evaluation shows that this pattern is in fact consistent with a more advanced stage of the disease and has a poorer prognosis. Such findings are clinically relevant because this condition may often be misdiagnosed, which leads to a neglect and/or an underestimation of symptoms and an inappropriate delay of aortic valve replacement surgery.

Effects of exogenous metabolic substrate modulation on exercise-induced myocardial ischemia.

BACKGROUND: The aim of the study is to compare the impact of intravenous glucose versus lipid versus saline on exercise-induced myocardial ischemia in patients with stable angina. METHODS: Twelve men with coronary artery disease and positive exercise tests performed a symptom-limited, modified Bruce electrocardiogram (ECG) exercise test at 3 sessions, 3 weeks apart. They randomly received, in double-blind design, at each session equal intravenous volumes of 10% glucose/insulin or Intralipid plus heparin or saline. We assessed the effects on (1) ischemic threshold (heart rate x systolic pressure at 1-mm ST-segment depression [STD]) and (2) maximum ST-depression (Max STD) corresponding to the highest heart rate x systolic pressure common to the 3 tests. RESULTS: During glucose infusion, glycemia increased from 5.7 +/- 0.4 to 9.4 +/- 3.0 mmol/L but did not change during lipid or saline infusion. During lipid infusion, free fatty acids increased from 0.32 +/- 0.19 to 1.44 +/- 0.46 mmol/L but decreased during glucose infusion from 0.39 +/- 0.21 to 0.04 +/- 0.03 mmol/L and did not change during saline. Exercise times were 10.0 +/- 3.4, 9.8 +/- 3.4, and 10.3 +/- 3.5 minutes, during glucose, lipid, and saline infusions, respectively. Ischemic thresholds (x 10(-3)) were 16.5 +/- 2.8, 16.8 +/- 2.7, and 16.6 +/- 2.6, respectively. MaxSTD was 2.5 +/- 1.4, 2.5 +/- 1.0, and 2.5 +/- 1.0 mm, respectively. CONCLUSION: Neither glucose-insulin nor lipid infusion modified exercise ischemic parameters compared with saline control, suggesting that marked and acute changes in exogenous energy substrate are unlikely to affect exercise-induced myocardial ischemia.

Effects of Lipid-Lowering and Antihypertensive Treatments in Addition to Healthy Lifestyles in Primary Prevention: An Analysis of the HOPE-3 Trial.

BACKGROUND: It is not clear whether the effects of lipid-lowering or antihypertensive medications are influenced by adherence to healthy lifestyle factors. We assessed the effects of both drug interventions in subgroups by the number of healthy lifestyle factors in participants in the HOPE-3 (Heart Outcomes Prevention Evaluation) trial. METHODS AND RESULTS: In this primary prevention trial, 4 healthy lifestyle factors (nonsmoking status, physical activity, optimal body weight, and healthy diet) were recorded in 12 521 participants who were at intermediate risk of cardiovascular disease (CVD) and were randomized to rosuvastatin, candesartan/hydrochlorothiazide, their combination, or matched placebos. Median follow-up was 5.6 years. The outcome was a composite of CVD events. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models. Participants with ≥2 healthy lifestyle factors had a lower rate of CVD compared with those with fewer factors (HR: 0.85; 95% CI, 0.73-1.00). Rosuvastatin reduced CVD events in participants with ≥2 healthy lifestyle factors (HR: 0.74; 95% CI, 0.62-0.90) and in participants with <2 factors (HR: 0.79; 95% CI, 0.61-1.01). Consistent results were observed with combination therapy (≥2 factors: HR: 0.74; 95% CI, 0.57-0.97; <2 factors: HR: 0.61; 95% CI, 0.43-0.88). Candesartan/hydrochlorothiazide tends to reduce CVD only in participants with <2 healthy lifestyle factors (HR: 0.78; 95% CI, 0.61-1.00). CONCLUSIONS: Healthy lifestyles are associated with lower CVD. Rosuvastatin alone and combined with candesartan/hydrochlorothiazide is beneficial regardless of healthy lifestyle status; however, the benefit of antihypertensive treatment appears to be limited to patients with less healthy lifestyles. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00239681.