European Heart Journal: Acute Cardiovascular Care

Intravenous sedation and analgesia are important therapies during mechanical ventilation (MV). However, daily interruption of these medications is associated with improved outcomes in mechanically ventilated patients. We tested a clinical pathway for the use of sedation and analgesia during MV in a cardiac intensive care unit (CICU).

We evaluated all mechanically ventilated patients in a CICU during two phases: phase 1 prior to pathway implementation (PRE) and phase 2 post-pathway implementation (POST). A total of 198 patients (98 PRE and 100 POST) and 1012 days of intubation (574 PRE and 434 POST) were included in this analysis. We found an increase in the frequency of daily interruptions of sedation post-implementation (49.3% PRE and 58.4% POST, p=0.0041). There was a significant decrease in the mean duration of MV in the POST vs PRE periods (5.0±2.3 vs 6.1±2.8 days, p=0.015). There was also a significant decrease in total neuroimaging studies (9 vs 49, p=0.001) and a trend toward a decrease in tracheostomies (3.0% vs 6.1%, p=0.33). Mean CICU length of stay (LOS) and hospital LOS respectively were 10.4 days and 16.8 days PRE and 10.4 days and 17.9 days POST (p=0.99 and p=0.55). Mortality did not differ (PRE 36.7% vs POST 32.0% p=0.55).

Implementation of a pragmatic pathway for sedation and analgesia in a CICU was associated with an increase in the daily interruption of sedation and a corresponding decrease in the duration of MV days and the need for neuroimaging.

Hyperglycemia is associated with increased mortality in cardiac patients. However, the predictive value of admission- and average glucose levels in patients admitted to an intensive cardiac care unit (ICCU) has not been described.

Observational study of patients admitted to the ICCU of a tertiary medical center in whom glucose levels were measured at and during admission. Over a 19-month period, 1713 patients were included. Mean age was 63±14 years, 1228 (72%) were male, 228 (17%) had known diabetes. Median (interquartile) glucose levels at admission were 7.9 (6.5–10.1) mmol/l; median glucose levels during ICCU admission (873 patients with three or more measurements) were 7.3 (6.7–8.3) mmol/l. Cox regression analysis was performed including the variables age, gender, admission diagnosis, length of stay, prior (cardio)vascular disease and diabetes.

A 1 mmol/l increase in admission glucose level (above 9 mmol/l) was associated with a 10% (95% confidence interval (CI): 7 –13%) increased risk for all-cause mortality. A 1 mmol/l higher average glucose level (above 8 mmol/l) was an additional independent predictor of mortality (HR 1.11, 95% CI: 1.03 – 1.20). At 30 days, 16.8% (97/579) of the patients with an admission glucose level in the highest tertile (>9.8 mmol/L) had died vs 5.2% (59/1134) of those with a lower admission glucose level.

In a high risk ICCU population, both high admission glucose levels as well as high average glucose levels during hospitalization were independently associated with increased mortality, even when accounting for other risk factors and parameters of disease severity.

Current ESC guidelines for the diagnosis of myocardial infarction consider a rise and/or fall of cardiac biomarkers. However, whether rising or falling patterns of high-sensitivity cardiac troponin T (hs-cTnT) improve the discrimination of ST-elevation myocardial infarction (non-STEMI) from non-acute coronary syndromes (ACS) has not been evaluated yet.

We compared protocols of rising and falling absolute and relative hs-cTnT changes in an unselected emergency department population.

A total of 635 patients with unstable angina pectoris (UAP), non-STEMI, or acute symptoms and increased hs-cTnT (>99th percentile) were enrolled. Of these, 572 patients met the inclusion criteria of consistently rising patterns (n=254, 44.4%), consistently falling patterns (n=224, 39.2%), or falling patterns after an initial rise (n=94, 16.4%). Final diagnoses included 66 (11.5%) patients with UAP, 141 (24.7%) patients with non-STEMI, and 365 (63.8%) patients with hs-cTnT elevations not due to ACS. Rising values were found more frequently in patients with non-STEMI, as compared to non-ACS (OR 3.69, 95% CI 2.46–5.53; p<0.0001), and falling patterns were observed more frequently in patients with non-ACS conditions (OR 3.56, 95% CI 2.24–5.63; p<0.001). Addition of rising but not falling changes increased diagnostic performance of hs-cTnT concentrations at presentation: positive: AUC 0.680 (95% CI 0.618–0.742) vs. 0.861 (95% CI 0.822–0.900; p<0.0001), negative: AUC 0.678 (95% CI 0.545–0.812) vs. 0.741 (95% CI 0.635–0.847). A 20% criterion as proposed by ESC guidelines performed equally for positive and negative changes only when admission hs-cTnT values were considered: AUC 0.785 (95% CI 0.726–0.845) vs. AUC 0.763 (95% CI 0.681–0.845); p=ns.

Detection of rising but not falling hs-cTnT values improves discrimination of non-STEMI from non-ACS in an unselected emergency department population.

Criteria for diagnosing myocardial infarction (MI) after coronary artery bypass grafting (CABG) are controversial. Uncertainties remain around the optimal threshold for biomarker elevation and the need for associated criteria. There are no studies of high-sensitivity troponin (hs-TnT) after CABG. We assessed whether using hs-TnT to define MI after CABG was associated with 30-day and medium-term mortality and evaluated the utility of adding to the troponin criteria new Q-waves or imaging evidence of new wall motion abnormality as suggested in the Universal Definition of MI.

Isolated CABG was performed in 818 patients from July 2010 to June 2012 and hs-TnT was measured 12–24 hours after CABG. Patients with rising baseline or missing troponins (n=258) were excluded. Thresholds of 140 ng/l (10-times 99th percentile upper reference limit) and 500 ng/l (10-times coefficient of variation of 10% for fourth-generation troponin T applied to hs-TnT) were prespecified.

Mean follow up was 1.8±0.6 years. On multivariate analyses, isolated hs-TnT rise >140 ng/l (n=360) or >500 ng/l (n=162) were not associated with mortality. Additional ECG and/or echocardiographic criteria plus hs-TnT >140 ng/l was associated with 30-day mortality (hazard ratio, HR, 4.92, 95% CI 1.34–18.1; p=0.017) and medium-term mortality (HR 3.44, 95% CI 1.13–10.5; p=0.030), whereas ECG and/or echocardiographic abnormalities with hs-TnT >500 ng/l was not (p=0.281 and p=0.123 for 30-day and medium-term mortality, respectively).

A definition for MI following CABG using hs-TnT with a cut point of 10-times 99th percentile upper reference limit and ECG and/or echocardiographic criteria predicts 30-day and medium-term mortality. These findings validate the Third Universal Definition of type 5 MI.

Poorer outcomes in women with ST-elevation myocardial infarction (STEMI) are often attributed to gender differences in baseline characteristics. However, these may be age dependent. We examined the importance of gender in separate age groups of patients with STEMI undergoing primary percutaneous coronary intervention (PPCI).

Data of 6746 consecutive patients with STEMI admitted for PPCI between 1998 and 2008 in our hospital were evaluated. Age was stratified into two groups, <65 years (young group) and ≥65 years (elderly). Endpoints were enzymic infarct size as well as 30-day and 1 year mortality. We studied a total of 4991 (74.0%) men and 1755 (26.0%) women; 40% of women were <65 years and 60% of men were <65 years of age. In the elderly group (≥65 years), women had more frequently diabetes and hypertension while they smoked less frequently than men. Younger women smoked more often than similarly aged men and had more hypertension. At angiography, single-vessel disease and TIMI 3 flow before PPCI was more present in younger women than men, whereas these differences were not found in the older age group. Patient delay before admission was shorter in men at all ages, while women had lower creatine kinase levels. Younger women had a higher mortality after 30 days (HR 2.1, 95% CI 1.3−3.4) and at 1 year (HR 1.7, 95% CI 1.2−2.6), whereas in the older age group women mortality rates were higher at 30 days (HR 1.5, 95% CI 1.1−2.0) but not at 1 year (HR 1.2, 95% CI 0.9−1.5). After multivariate analysis, 1-year mortality remained significantly higher in women at younger age (HR 1.7, 95% CI 1.1−2.5). Patient delay before admission was shorter in men in both age groups. Creatine kinase levels were in both age groups higher in men.

Differences in mortality between men and women with STEMI treated with PPCI are age dependent. Although young women have less obstructive coronary artery disease and more often TIMI 3 flow before PCI (suggesting a lower risk), survival was worse compared to similarly aged men. Women had a longer patient delay compared to men, but this was not related to gender-specific mortality.

Data on temporal trends in outcomes, gender differences, and adherence to evidence-based therapy (EBT) of diabetic patients with ST-segment elevation myocardial infarction (STEMI) are sparse.

We performed a retrospective analysis of prospectively acquired data on 3565 diabetic (2412 males and 1153 females) STEMI patients enrolled in the Swiss AMIS Plus registry between 1997 and 2010 and compared in-hospital outcomes and adherence to EBT with the nondiabetic population (n=15,531).

In-hospital mortality dramatically decreased in diabetic patients, from 19.9% in 1997 to 9.0% in 2010 (p_trend<0.001) with an age-adjusted decrease of 6% per year of admission. Similar trends were observed for age-adjusted reinfarction (OR 0.86, p<0.001), cardiogenic shock (OR 0.88, p<0.001), as well as death, reinfarction, or stroke (OR 0.92, p<0.001). However, the mortality benefit over time was observed in diabetic males (p_trend=0.006) but not females (p_trend=0.082). In addition, mortality remained twice as high in diabetic patients compared with nondiabetic ones (12.1 vs. 6.1%, p<0.001) and diabetes was identified as independent predictor of mortality (OR 1.23, p=0.022). Within the diabetic cohort, females had higher mortality than males (16.1 vs. 10.2%, p<0.001) and female gender independently predicted in-hospital mortality (OR 1.45, p=0.015). Adherence to EBT significantly improved over time in diabetic patients (p_trend<0.001) but remained inferior – especially in women – to the one of nondiabetic individuals.

In-hospital mortality and morbidity of diabetic STEMI patients in Switzerland improved dramatically over time but, compared with nondiabetic counterparts, gaps in outcomes as well as EBT use persisted, especially in women.

This study examined clinical factors associated with sex differences in the use of acute reperfusion therapy (fibrinolysis or primary percutaneous coronary intervention) in ST-elevation myocardial infarction (STEMI) patients, and the interaction between sex and these factors in Sweden and Canada.

Patients with STEMI in Sweden (n=32,676 from the Register of Information and Knowledge about Swedish Heart Intensive Care Admissions) were compared with similar patients in Canada (n=3375 from the Canadian Global Registry of Acute Coronary Events) for the period 2004–2008.

Unadjusted vs. age-adjusted odds ratios (OR) for no reperfusion (women vs. men) were for Sweden 1.57 (95% CI 1.49–1.64) vs. 1.14 (95% CI 1.08–1.20), and for Canada 1.61 (95% CI 1.39–1.87) vs. OR 1.18 (95% CI 1.01–1.39). Sex differences persisted after multivariable adjustments (including prehospital delay, atypical symptoms, diabetes), factors for which no interaction with sex was found. Among women <60 years, adjusting for atypical symptoms in Canada and angiographic data in Sweden made the greatest contribution to explaining observed sex differences.

In both countries, acute reperfusion therapy in STEMI was used less often in women than in men. Factors associated with these sex differences appear to differ between older and younger women. Targeted interventions are needed to optimize care for women with STEMI, as well as sex- and age-stratified reporting of quality indicators to assess their effectiveness.

Detailed data on patients admitted for acute myocardial infarction (AMI) on a European-wide basis are lacking. The Euro Heart Survey 2009 Snapshot was designed to assess characteristics, management, and hospital outcomes of AMI patients throughout European Society of Cardiology (ESC) member countries in a contemporary ‘real-world’ setting, using a methodology designed to improve the representativeness of the survey.

Member countries of the ESC were invited to participate in a 1-week survey of all patients admitted for documented AMI in December 2009. Data on baseline characteristics, type of AMI, management, and complications were recorded using a dedicated electronic form. In addition, we used data collected during the same time period in national registries in Sweden, England, and Wales. Data were centralized at the European Heart House.

Overall, 4236 patients (mean age 66±13 years; 31% women) were included in the study in 47 countries. Sixty per cent of patients had ST-segment elevation myocardial infarction, with 50% having primary percutaneous coronary intervention and 21% fibrinolysis. Aspirin and thienopyridines were used in >90%. Unfractionated and low-molecular-weight heparins were the most commonly used anticoagulants. Statins, beta-blockers, and angiotensin-converting enzyme inhibitors were used in >80% of the patients. In-hospital mortality was 6.2%. Regional differences were observed, both in terms of population characteristics, management, and outcomes.

In-hospital mortality of patients admitted for AMI in Europe is low. Although regional variations exist in their presentation and management, differences are limited and have only moderate impact on early outcomes.

Current guidelines prefer primary percutaneous coronary intervention (pPCI) over fibrinolysis in the treatment of acute ST-elevation myocardial infarction (STEMI). Pre-hospital fibrinolysis followed by early invasive evaluation is an alternative that we have used in patients presenting within three hours of symptom onset. We made a survey of patients suffering an acute STEMI over one year to assess mortality and adverse events following either pPCI or fibrinolysis.

Of the 448 consecutive STEMI patients, 194 were treated with pPCI and 176 underwent fibrinolysis; 78 patients received no reperfusion treatment within 12 hours (NRT group). The median TIMI risk scores were 4.0, 3.0 and 4.0 in the pPCI, fibrinolysis and NRT groups, respectively (p<0.001). Mortality at one year was 14.4% following pPCI, 5.1% following fibrinolysis and 12.8% in the NRT group (p=0.011 across all groups and p=0.003 between pPCI and fibrinolysis, adjusted for differences in risk factors). The one-year composite of cardiovascular death, stroke, reinfarction and new revascularization was 20.1%, 18.2% and 26.9% for the pPCI, fibrinolysis and NRT groups, respectively (p=NS). In patients presenting within three hours of symptom onset, one-year mortality was 3.7% in the fibrinolysis group (n=163) and 15.3% in the pPCI group (n=118) (adjusted p =0.001), while the composite of adverse events was 16.6% in the former group and 19.5% in the latter (p=NS).

Pre-hospital fibrinolysis followed by routine early invasive evaluation provides an excellent reperfusion strategy for low-risk STEMI patients presenting early after symptom onset.

Persistent oxidative stress may play a key role in microvascular obstruction (MVO). We aimed at assessing the role of platelet gp91phox (NOX2), the catalytic subunit of NADPH oxidase in MVO.

We enrolled 40 patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention within 12 h from symptoms onset, either with angiographic MVO (n=20) or good angiographic myocardial reperfusion (MR) (n=20). Angiographic MVO was defined as a final thrombolysis in myocardial infarction (TIMI) flow ≤2 or TIMI flow of 3 with myocardial blush grade <2. NOX2 and isoprostanes (8-iso-PGF_2α) levels, as assessed by enzyme-linked immunoadsorbent assay (ELISA) or by an enzyme immunoassays, respectively, were measured on admission, at 24 h and pre-discharge.

NOX2 levels increased from baseline to pre-discharge in patients with angiographic MVO (20.25 (15–24.75) pg/ml vs 25.50 (17–29.25) pg/ml, p=0.02), but not in MR patients (p=0.45), with a significant interaction between baseline and pre-discharge levels among the two groups (p=0.04). The levels of 8-iso-PGF_2α showed a trend to increase from baseline to pre-discharge in angiographic MVO patients (295 (183.50–389.25) pmol/l vs 322 (206–370) pmol/l, p=0.06), but not in patients with MR (p=0.56), with a trend for interaction between baseline and pre-discharge levels among the two groups (p=0.09).

Patients with MVO, but not those with myocardial reperfusion, have a sustained increase of NOX2 and 8-iso-PGF_2α. Therapies targeting NOX2 or high dosage antioxidants should be tested for MVO prevention and treatment.