A prospective survey of the characteristics, treatments and outcomes of patients with acute coronary syndromes in Europe and the Mediterranean basin; the Euro Heart Survey of Acute Coronary Syndromes (Euro Heart Survey ACS).

AIMS: To better delineate the characteristics, treatments, and outcomes of patients with acute coronary syndromes (ACS) in representative countries across Europe and the Mediterranean basin, and to examine adherence to current guidelines. METHODS AND RESULTS: We performed a prospective survey (103 hospitals, 25 countries) of 10484 patients with a discharge diagnosis of acute coronary syndromes. The initial diagnosis was ST elevation ACS in 42.3%, non-ST elevation ACS in 51.2%, and undetermined electrocardiogram ACS in 6.5%. The discharge diagnosis was Q wave myocardial infarction in 32.8%, non-Q wave myocardial infarction in 25.3%, and unstable angina in 41.9%. The use of aspirin, beta-blockers, angiotensin converting enzyme inhibitors, and heparins for patients with ST elevation ACS were 93.0%, 77.8%, 62.1%, and 86.8%, respectively, with corresponding rates of 88.5%, 76.6%, 55.8%, and 83.9% for non-ST elevation ACS patients. Coronary angiography, percutaneous coronary interventions, and coronary bypass surgery were performed in 56.3%, 40.4%, and 3.4% of ST elevation ACS patients, respectively, with corresponding rates of 52.0%, 25.4%, and 5.4% for non-ST elevation ACS patients. Among patients with ST elevation ACS, 55.8% received reperfusion treatment; 35.1% fibrinolytic therapy and 20.7% primary percutaneous coronary interventions. The in-hospital mortality of patients with ST elevation ACS was 7.0%, for non-ST elevation ACS 2.4%, and for undetermined electrocardiogram ACS 11.8%. At 30 days, mortality was 8.4%, 3.5%, and 13.3%, respectively. CONCLUSIONS: This survey demonstrates the discordance between existing guidelines for ACS and current practice across a broad region in Europe and the Mediterranean basin and more extensively reflects the outcomes of ACS in real practice in this region.     

Is multiple SNP testing in BRCA2 and BRCA1 female carriers ready for use in clinical practice? Results from a large Genetic Centre in the UK

BRCA1 and BRCA2 are major breast cancer susceptibility genes. Nineteen single nucleotide polymorphisms (SNPs) at 18 loci have been associated with breast cancer. We aimed to determine whether these predict breast cancer incidence in women with BRCA1/BRCA2 mutations. BRCA1/2 mutation carriers identified through the Manchester genetics centre between 1996 and 2011 were included. Using published odds ratios (OR) and risk allele frequencies, we calculated an overall breast cancer risk SNP score (OBRS) for each woman. The relationship between OBRS and age at breast cancer onset was investigated using the Cox proportional hazards model, and predictive ability assessed using Harrell's C concordance statistic. In BRCA1 mutation carriers we found no association between OBRS and age at breast cancer onset: OR for the lowest risk quintile compared to the highest was 1.20 (95% CI 0.82–1.75, Harrell's C = 0.54), but in BRCA2 mutation carriers the association was significant (OR for the lowest risk quintile relative to the highest was 0.47 (95% CI 0.33–0.69, Harrell's C = 0.59). The 18 validated breast cancer SNPs differentiate breast cancer risks between women with BRCA2 mutations, but not BRCA1. It may now be appropriate to use these SNPs to help women with BRCA2 mutations make maximally informed decisions about management options.     

Cardiac resynchronization therapy in patients with a narrow QRS complex.

OBJECTIVES: The purpose of this study was to evaluate the effects of cardiac resynchronization therapy (CRT) in heart failure patients with narrow QRS complex (<120 ms) and evidence of left ventricular (LV) dyssynchrony on tissue Doppler imaging (TDI). BACKGROUND: Cardiac resynchronization therapy is beneficial in selected heart failure patients with wide QRS complex (> or =120 ms). Patients with narrow QRS complex are currently not eligible for CRT, and the potential effects of CRT are not well studied. METHODS: Thirty-three consecutive patients with narrow QRS complex and 33 consecutive patients with wide QRS complex (control group) were prospectively included. All patients needed to have LV dyssynchrony > or =65 ms on TDI, New York Heart Association (NYHA) functional class III/IV heart failure, and LV ejection fraction < or =35%. RESULTS: Baseline characteristics, particularly LV dyssynchrony, were comparable between patients with narrow and wide QRS complex (110 +/- 8 ms vs. 175 +/- 22 ms; p = NS). No significant relationship was observed between baseline QRS duration and LV dyssynchrony (r = 0.21; p = NS). The improvement in clinical symptoms and LV reverse remodeling was comparable between patients with narrow and wide QRS complex (mean NYHA functional class reduction 0.9 +/- 0.6 vs. 1.1 +/- 0.6 [p = NS] and mean LV end-systolic volume reduction 39 +/- 34 ml vs. 44 +/- 46 ml [p = NS]). CONCLUSIONS: Cardiac resynchronization therapy appears to be beneficial in patients with narrow QRS complex and severe LV dyssynchrony on TDI, with similar improvement in symptoms and comparable LV reverse remodeling to patients with wide QRS complex. The current results need confirmation in larger patient cohorts.     

Does resting two-dimensional echocardiography identify patients with ischemic cardiomyopathy and low likelihood of functional recovery after coronary revascularization?

OBJECTIVE: To evaluate the potential of a simple and widely available technique as two-dimensional (2D) echocardiography to identify patients with ischemic cardiomyopathy and low likelihood of functional recovery after coronary revascularization. METHODS: Two-dimensional echocardiography and radionuclide ventriculography (RNV) were performed before coronary revascularization in 94 patients with ischemic cardiomyopathy. Left ventricular ejection fraction (LVEF) was measured by RNV. Regional wall motion abnormalities, wall motion score index, end-diastolic wall thickness (EDWT), left ventricular (LV) volumes and LV sphericity index were assessed in the echocardiographic images. RNV was repeated 9-12 months after revascularization to assess LVEF change; an improvement >or=5% was considered clinically significant. RESULTS: Nine hundred and ninety-nine segments were severely dysfunctional; 149 out of 999 (15%) had an EDWT or=100 ml/ml) and of the end-systolic volume index (>or=80 ml) was present in 32 (34%) and 21 (22%) patients, respectively. A spherical shape of the LV was observed in 35 (37%) patients. LVEF after revascularization increased in 30 out of 94 patients (32%) from 30+/-8% to 39+/-9% (P<0.0001). On multivariate analysis, the EDVI was the only predictor of no recovery in LVEF [odds ratio, 1.06, confidence interval (CI), 1.04-1.1, P<0.0001]. The cut-off value of EDVI >or=90 ml/ml accurately identified patients that virtually never recover. Post-operatively, LVEF increased in three out of 42 (7%, 95% CI 0-15%) patients with EDVI >or=90 ml/ml as compared to 27 out of 52 (52%) patients with EDVI<90 ml/ml (P<0.0001). CONCLUSIONS: In patients with ischemic cardiomyopathy and severe LV enlargement, improvement of LVEF after revascularization is unlikely to occur. Conversely, in patients with relatively preserved LV size, a higher likelihood of functional recovery may be anticipated.     

High resolution of heterogeneity among human neutrophil granules: physical, biochemical, and ultrastructural properties of isolated fractions

Previous studies on the fractionation of human neutrophil granules have identified two major populations: myeloperoxidase (MPO)-containing azurophil, or primary, granules and MPO-deficient specific, or secondary, granules. Peripheral blood neutrophils from individual donors were lysed in sucrose-free media by either hypotonic shock or nitrogen cavitation. Using a novel two-gradient Percoll density centrifugation system, the granule-rich postnuclear supernatant was rapidly (ten minutes) and reproducibly resolved into 13 granule fractions (L1 through L8 and H1 through H5). Granule flotation and recentrifugation experiments on both continuous, self-generated and multiple-step gradients using individual and mixed isolated fractions demonstrated that the banding patterns were isopycnic and nonartifactual. Isolated granules were intact based on the findings that biochemical latency of several granule enzymes was greater than 95%, and thin-sectioned electron micrographs demonstrated intact granule profiles. Biochemical analyses of the granule marker proteins MPO, beta-glucuronidase, lysozyme, and lactoferrin indicated that a number of the fractions were related to the major azurophil and specific granule populations. Lactoferrin was found in ten of 13 fractions (L1 through L8, H1 to H2), whereas MPO was found in every fraction. Consistent with these biochemical data, all fractions exhibited varying degrees of heterogeneity based on ultrastructural morphology and cytochemistry, including diaminobenzidine (DAB) reactivity for peroxidase and periodate-thiocarbohydrazide-silver proteinate (PA-TCH-SP) staining for complex glycoconjugates. A variable but significant percentage (23% to 70%) of the granules in fractions L1 through L8 and H1 and H2 showed DAB reactivity, while about 90% of the granules in fractions H3 through H5 were peroxidase positive. These results demonstrated that DAB-reactive granules spanned the entire range of granule size and density. Ultrastructural PA-TCH-SP staining of isolated granule fractions revealed patterns similar to those of granules in intact neutrophils at different stages of development. Granules from human acute promyelocytic leukemia cells (HL-60) exhibited a surprisingly low density compared with typical azurophil granules from normal, mature neutrophils. The data suggest that both functional and maturational differences contribute to granule heterogeneity, and provide a new practical and conceptual framework for further defining the phenomenon of neutrophil granule heterogeneity.     

Lipoprotein(a), interleukin-10, C-reactive protein, and 8-year outcome after percutaneous coronary intervention

Background:

This prospective study investigated the association between preprocedural biomarker levels and incident major adverse cardiac events (MACE) in complex patients undergoing percutaneous coronary intervention (PCI) with sirolimus‐eluting stenting.

Hypothesis:

Lipoprotein(a) (Lp[a]), interleukin‐10 (IL‐10), and high‐sensitivity C‐reactive protein (CRP) have long‐term prognostic value in patients undergoing PCI.

Methods:

Between April 2002 and February 2003, 161 patients were included in the study. Blood was drawn before the procedure, and biomarkers were measured. Patients were followed‐up for MACE (death, nonfatal myocardial infarction, and repeat revascularization). Cox proportional hazard models were used to determine risk of MACE for tertiles of biomarkers. Both 1‐year and long‐term follow‐up (median, 6 years; maximum, 8 years) were evaluated.

Results:

Mean age was 59 years, and 68% were men. During long‐term follow‐up, 72 MACE occurred (overall crude cumulative incidence: 45% [95% confidence interval (CI): 37%‐52%]). Lp(a) was associated with a higher 1‐year risk of MACE, with an adjusted hazard ratio (HR) of 3.1 (95% CI: 1.1‐8.6) for the highest vs the lowest tertile. This association weakened and lost significance with long‐term follow‐up. IL‐10 showed a tendency toward an association with MACE. The 1‐year HR was 2.1 (95% CI: 0.92‐5.0). Long‐term follow‐up rendered a similar result. The association of CRP with MACE did not reach statistical significance at 1‐year follow‐up. However, CRP was associated with long‐term risk of MACE, with an HR of 1.9 (95% CI: 1.0‐3.5).

Conclusions:

In this prospective study, preprocedural Lp(a) level was associated with short‐term prognosis after PCI. The preprocedural CRP level was associated with long‐term prognosis after PCI. Clin. Cardiol. 2012 DOI: 10.1002/clc.21988 The authors have no funding, financial relationships, or conflicts of interest to disclose.