Higher burden of supraventricular ectopic complexes early after catheter ablation for atrial fibrillation is associated with increased risk of recurrent atrial fibrillation.

Aims: Early identification of patients who could benefit from early re-intervention after catheter ablation is highly warranted. Our aim was to investigate the association between post-procedural burden of supraventricular ectopic complexes (SVEC) and the risk of long-term atrial fibrillation (AF) recurrence. Methods and results: A total of 125 patients undergoing catheter ablation for AF were included. Patients underwent 7-day Holter recordings immediately post-procedural. The number of SVEC in post-procedural Holter recordings was categorized into quartiles: 0-72, 73-212, 213-782 and ≥ 783 SVEC/day. Long-term AF recurrence was defined as a combined endpoint of AF ≥ 1 min during follow-up Holter recordings, cardioversion or hospitalization for AF after a 3-month blanking period and within 24 months of follow-up. High post-procedural supraventricular ectopy burden was associated with an increased risk of long-term AF recurrence in a dose-dependent manner (≥ 783 SVEC: HR 4.6 [1.9-11.5], P < 0.001) irrespective of AF recurrence during the blanking period or other risk factors. In patients with early AF recurrence < 90 days after catheter ablation ectopy burden was also highly predictive of long-term AF recurrence (SVEC ≥ 213: HR 3.0 [1.3-6.7], P = 0.007). Correspondingly, patients with early AF recurrence but low ectopy burden remained at low risk of long-term AF recurrence after the blanking period. Conclusion: Our results indicate that post-procedural ectopy burden is highly associated with long-term AF recurrence and could be a potent risk marker for selection of patients for early re-ablation. Development of future ablation risk stratification and strategies should include focus on post-procedural ectopy burden.

Layer-specific global longitudinal strain reveals impaired cardiac function in patients with reversible ischemia.

AIMS: Two-dimensional speckle tracking echocardiography (2DSTE) detects early signs of left ventricular dysfunction; however, it is unknown whether layer-specific global longitudinal strain (GLS) has incremental value in diagnosis of patients with reversible ischemia assessed by single photon emission computed tomography (SPECT). METHODS AND RESULTS: Eighty patients with stable angina pectoris (SAP), normal left ventricular ejection fraction (LVEF), and no history of ischemic heart disease were retrospectively identified to have been examined by 2DSTE, SPECT, and coronary angiography (CAG). Patients with a normal SPECT constituted the control group, and patients with a positive SPECT were divided into patients with or without (true- or false- positive SPECT) significant stenosis assessed by CAG. GLS was measured for two myocardial layers (endocardial and epicardial) and as well as mid-myocardial GLS. Patients with reversible ischemia had significantly lower GLS compared to the control group (GLSEndocardial : -19.0 ± 4.4% vs -21.4 ± 3.7%, P = .011; GLSEpicardial : -14.3 ± 2.9% vs -16.3 ± 2.9%, P = .004); GLSMid-myocardial : -16.5 ± 3.6% vs -18.6 ± 3.2%, P = .006. This difference was even more evident in patients with a true-positive SPECT (GLSEndocardial : -18.0 ± 4.4% vs -21.4 ± 3.7%, P < .001; GLSEpicardial : -13.6 ± 3.0% vs -16.3 ± 2.9%, P < .001); GLSMid-myocardial : -15.6 ± 3.6% vs -18.6 ± 3.2%, P < .001. Notably, no significant differences existed in patients with a false-positive SPECT. GLSEpicardial was the only independent predictor of coronary artery disease. IN CONCLUSION: In patients with SAP and preserved LVEF, layer-specific GLS at rest identifies patients with reversible ischemia. This seems to be evident only in patients with a true-positive SPECT, thus, 2DSTE at rest might improve the diagnostic accuracy of a positive SPECT.

Effect of exercise combined with glucagon-like peptide-1 receptor agonist treatment on cardiac function: A randomized double-blind placebo-controlled clinical trial.

In patients with type 2 diabetes, both supervised exercise and treatment with the glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1RA) liraglutide may improve cardiac function. We evaluated cardiac function before and after 16 weeks of treatment with the GLP-1RA liraglutide or placebo, combined with supervised exercise, in 33 dysregulated patients with type 2 diabetes on diet and/or metformin. Early diastolic myocardial tissue velocity was improved by exercise in the placebo group (mean ± standard deviation [s.d.] -7.1 ± 1.6 to -7.7 ± 1.8 cm/s, P = .01), but not in the liraglutide group (-7.1 ± 1.4 to -7.0 ± 1.4 cm/s, P = .60; between groups, P = .02). Similarly, the mean ± s.d. ratio of early and atrial mitral annular tissue velocities improved in the placebo group (1.0 ± 0.4 to 1.2 ± 0.4, P = .003), but not in the liraglutide group (1.0 ± 0.3 to 1.0 ± 0.3, P = .87; between groups, P = .03). We found no significant differences in heart rate, left ventricular (LV) structure or function within or between the groups. In conclusion, the addition of liraglutide to exercise in sedentary patients with dysregulated type 2 diabetes may blunt the suggested beneficial effect of exercise on LV diastolic function.

Plasma neutrophil gelatinase-associated lipocalinin in the general population: association with inflammation and prognosis.

OBJECTIVE: Neutrophil gelatinase-associated lipocalin (NGAL) is a glycoprotein stored in granules of neutrophil leukocytes participating in inflammatory and atherosclerotic processes and possibly plaque rupture. Despite the putative role of NGAL in atherosclerosis and acute myocardial infarction, human studies of plasma NGAL are still limited. APPROACH AND RESULTS: We prospectively followed 5599 randomly selected men and women from the community in the fourth Copenhagen Heart Study. Plasma NGAL was measured at study entry. Participants were followed for 10 years. During follow-up, 20% died (n=1120) and 15% (n=884) developed a major adverse cardiovascular event. Plasma NGAL associated strongly with all inflammatory markers (high-sensitivity C-reactive protein, total leukocyte count, neutrophil count) and inversely with estimated glomerular filtration rate (all, P<0.001). Multivariate analysis identified neutrophil leukocyte count as the main determinant of plasma NGAL. During follow-up, participants with increasing NGAL had increased risk of all-cause mortality and major adverse cardiovascular event (both, P<0.001). Even after adjustment for confounding risk factors by Cox regression analysis, NGAL remained an independent predictor of both all-cause mortality and major adverse cardiovascular event. When added to the Framingham risk score, NGAL improved c-statistics and correctly reclassified ≈15% into more appropriate risk groups. In comparison with high-sensitivity C-reactive protein, when both markers were added to the Framingham risk score, NGAL conferred 3× to 4× the risk. CONCLUSIONS: Plasma NGAL is strongly associated with inflammation in the general population. NGAL independently associated with 10-year outcome, and when added to the Framingham risk score, NGAL both improves c-statistics and correctly reclassifies participants into more accurate risk categories.

Prevalence of systolic and diastolic dysfunction in patients with type 1 diabetes without known heart disease: the Thousand & 1 Study.

AIMS/HYPOTHESIS: Heart failure is one of the leading causes of mortality in type 1 diabetes. Early identification is vitally important. We sought to determine the prevalence and clinical characteristics associated with subclinical impaired systolic and diastolic function in type 1 diabetes patients without known heart disease. METHODS: In this cross-sectional examination of 1,093 type 1 diabetes patients without known heart disease, randomly selected from the Steno Diabetes Center, complete clinical and echocardiographic examinations were performed and analysed in uni- and multivariable regression models. RESULTS: The mean (SD) age was 49.6 (15) years, 53% of participants were men, and the mean duration of diabetes was 25.5 (15) years. Overall, 15.5% (n = 169) of participants had grossly abnormal systolic or diastolic function, including 1.7% with left ventricular ejection fraction (LVEF) < 45% and 14.4% with evidence of long-standing diastolic dysfunction. In univariable models, clinical characteristics associated with abnormal myocardial function were: age (per 10 years), OR (95% CI) 2.1 (1.8, 2.4); diabetes duration (per 10 years), 1.7 (1.4, 1.9); systolic BP ≥ 140 mmHg, 2.7 (1.9, 3.8); diastolic BP ≥ 90 mmHg, 1.8 (1.0, 3.1); estimated (e)GFR < 60 ml min(-1) 1.73 m(-2), 3.8 (2.5, 5.9); microalbuminuria, 2.0 (1.3, 3.0); macroalbuminuria, 5.9 (3.8, 9.3); proliferative retinopathy, 3.6 (2.3, 5.8); blindness, 10.1 (3.2, 31.6); and peripheral neuropathy, 3.8 (2.7, 5.3). In multivariable models only age (2.1 [1.7, 2.5]), female sex, (1.9 [1.2, 2.8]) and macroalbuminuria (5.2 [2.9, 10.3]) remained significantly associated with subclinical grossly abnormal myocardial function. CONCLUSIONS/INTERPRETATION: Subclinical myocardial dysfunction is a common finding in type 1 diabetes patients without known heart disease. Type 1 diabetes patients with albuminuria are at greatly increased risk of having subclinical abnormal myocardial function compared with patients without albuminuria. Echocardiography may be particularly warranted in patients with albuminuria.

Low cardiac output as physiological phenomenon in hibernating, free-ranging Scandinavian brown bears (Ursus arctos) - an observational study.

BACKGROUND: Despite 5-7 months of physical inactivity during hibernation, brown bears (Ursus arctos) are able to cope with physiological conditions that would be detrimental to humans. During hibernation, the tissue metabolic demands fall to 25% of the active state. Our objective was to assess cardiac function associated with metabolic depression in the hibernating vs. active states in free-ranging Scandinavian brown bears. METHODS: We performed echocardiography on seven free-ranging brown bears in Dalarna, Sweden, anesthetized with medetomidine-zolazepam-tiletamine-ketamine during winter hibernation in February 2013 and with medetomidine-zolazepam-tiletamine during active state in June 2013. We measured cardiac output noninvasively using estimates of hemodynamics obtained by pulsed wave Doppler echocardiography and 2D imaging. Comparisons were made using paired T-tests. RESULTS: During hibernation, all hemodynamic indices were significantly decreased (hibernating vs. active state): mean heart rate was 26.0 (standard deviation (SD): 5.6) beats per min vs. 75.0 (SD: 17.1) per min (P=0.002), mean stroke volume 32.3 (SD: 5.2) ml vs. 47.1 (SD: 7.9) ml (P=0.008), mean cardiac output 0.86 (SD: 0.31) l/min vs. 3.54 (SD: 1.04) l/min (P=0.003), and mean cardiac index 0.63 (SD: 0.21) l/min/kg vs. 2.45 (SD: 0.52) l/min/ m2 (P<0.001). Spontaneous echo contrast was present in all cardiac chambers in all seven bears during hibernation, despite the absence of atrial arrhythmias and valvular disease. CONCLUSION: Free-ranging brown bears demonstrate hemodynamics comparable to humans during active state, whereas during hibernation, we documented extremely low-flow hemodynamics. Understanding these physiological changes in bears may help to gain insight into the mechanisms of cardiogenic shock and heart failure in humans.

Acute myocardial infarction is associated with endothelial glycocalyx and cell damage and a parallel increase in circulating catecholamines.

INTRODUCTION: Excessive sympathoadrenal activation in critical illness contributes directly to organ damage, and high concentrations of catecholamines damage the vascular endothelium. This study investigated associations between potential drivers of sympathoadrenal activation, circulating catecholamines and biomarkers of endothelial damage and outcome in ST segment elevation myocardial infarction (STEMI)-patients, hypothesizing that the catecholamine surge would reflect shock degree and correlate with biomarkers of endothelial damage. METHODS: This was a prospective study of 678 consecutive STEMI-patients admitted to a single high-volume invasive heart centre for primary percutaneous coronary intervention (pPCI) from September 2006 to July 2008. Blood samples were drawn immediately before pPCI. Plasma adrenaline, noradrenaline, syndecan-1 and thrombomodulin were measured retrospectively with complete data in 571 patients (84%). Median follow-up time was 28 (IQR 23 to 34) months. Follow-up was 99.7% complete. Outcomes were all-cause and cardiovascular mortality, re-myocardial infarction and admission due to heart failure. RESULTS: Circulating noradrenaline and adrenaline correlated weakly but independently with syndecan-1 (rho = 0.15 and rho = 0.13, both P <0.01) and thrombomodulin (rho = 0.11 and rho = 0.17, both P <0.01), biomarkers of glycocalyx and endothelial cell damage, respectively. Considering biomarkers, patients with shock pre-pPCI had higher adrenaline and syndecan-1 and patients admitted to ICU post-pPCI had higher syndecan-1 (all P <0.05), and in the patients with shock (n = 51) catecholamines correlated strongly with thrombomodulin and syndecan-1 (rho = 0.31 to 0.42, all P <0.05). During follow-up, 78 (14%) patients died (37 cardiovascular deaths) and 65 (11%) were admitted with heart failure. By multivariate Cox proportional hazards analyses, one quartile higher plasma adrenaline was weakly but independently associated with both 30-day and long term mortality and heart failure (30-day all-cause mortality hazard ratio (95% CI) 1.39 (1.01 to 1.92), P = 0.046; 30-day heart failure 1.65 (1.17 to 2.34), P = 0.005; and long-term cardiovascular mortality 1.49 (1.08 to 2.04), P = 0.014). Furthermore, one quartile higher syndecan-1 was also weakly but independently associated with long-term all cause mortality (1.26 (1.02 to 1.57), P = 0.034). CONCLUSIONS: In STEMI patients treated with pPCI, catecholamines correlated weakly with biomarkers of endothelial damage, with the strongest correlations and highest adrenaline and syndecan-1 levels in patients with shock. Furthermore, adrenaline and syndecan-1 were weakly but independently associated with mortality and heart failure. Acute myocardial infarction appears to cause significant endothelial cell and glycocalyx injury and a parallel increase in circulating catecholamines.

Exenatide reduces reperfusion injury in patients with ST-segment elevation myocardial infarction.

AIMS: Exenatide, a glucagon-like-peptide-1 analogue, increases myocardial salvage in experimental settings with coronary occlusion and subsequent reperfusion. We evaluated the cardioprotective effect of exenatide at the time of reperfusion in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). METHODS AND RESULTS: A total of 172 patients with STEMI and Thrombolysis in Myocardial Infarction flow 0/1 were randomly assigned to exenatide or placebo (saline) intravenously. Study treatment was commenced 15 min before intervention and maintained for 6 h after the procedure. The primary endpoint was salvage index calculated from myocardial area at risk (AAR), measured in the acute phase, and final infarct size measured 90 ± 21 days after pPCI by cardiac magnetic resonance (CMR). In 105 patients evaluated with CMR, a significantly larger salvage index was found in the exenatide group than in the placebo group (0.71 ± 0.13 vs. 0.62 ± 0.16; P= 0.003). Infarct size in relation to AAR was also smaller in the exenatide group (0.30 ± 0.15 vs. 0.39 ± 0.15; P= 0.003). In a regression analysis, there was a significant correlation between the infarct size and the AAR for both treatment groups and an analysis of covariance showed that datapoints in the exenatide group lay significantly lower than for the placebo group (P= 0.011). There was a trend towards smaller absolute infarct size in the exenatide group (13 ± 9 vs. 17 ± 14 g; P= 0.11). No difference was observed in left ventricular function or 30-day clinical events. No adverse effects of exenatide were observed. CONCLUSION: In patients with STEMI undergoing pPCI, administration of exenatide at the time of reperfusion increases myocardial salvage.

Randomized comparison of final kissing balloon dilatation versus no final kissing balloon dilatation in patients with coronary bifurcation lesions treated with main vessel stenting: the Nordic-Baltic Bifurcation Study III.

BACKGROUND: It is unknown whether the preferred 1-stent bifurcation stenting approach with stenting of the main vessel (MV) and optional side branch stenting using drug-eluting stents should be finalized by a kissing balloon dilatation (FKBD). Therefore, we compared strategies of MV stenting with and without FKBD. METHODS AND RESULTS: We randomized 477 patients with a bifurcation lesion to FKBD (n=238) or no FKBD (n=239) after MV stenting. The primary end point was major adverse cardiac events: cardiac death, non-procedure-related index lesion myocardial infarction, target lesion revascularization, or stent thrombosis within 6 months. The 6-month major adverse cardiac event rates were 2.1% and 2.5% (P=1.00) in the FKBD and no-FKBD groups, respectively. Procedure and fluoroscopy times were longer and more contrast media was needed in the FKBD group than in the no-FKBD group. Three hundred twenty-six patients had a quantitative coronary assessment. At 8 months, the rate of binary (re)stenosis in the entire bifurcation lesion (MV and side branch) was 11.0% versus 17.3% (P=0.11), in the MV was 3.1% versus 2.5% (P=0.68), and in the side branch was 7.9% versus 15.4% (P=0.039) in the FKBD versus no-FKBD groups, respectively. In patients with true bifurcation lesions, the side branch restenosis rate was 7.6% versus 20.0% (P=0.024) in the FKBD and no-FKBD groups, respectively. CONCLUSIONS: MV stenting strategies with and without FKBD were associated with similar clinical outcomes. FKBD reduced angiographic side branch (re)stenosis, especially in patients with true bifurcation lesions. The simple no-FKBD procedures resulted in reduced use of contrast media and shorter procedure and fluoroscopy times. Long-term data on stent thrombosis are needed. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique identifier: NCT00914199.

Osteoprotegerin predicts long-term outcome in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention.

BACKGROUND: Osteoprotegerin (OPG) is a glycoprotein with a regulatory role in immune, skeletal and vascular systems. Data suggest that high circulating OPG levels are associated with an increased risk of cardiovascular disease. We analyzed the association between OPG and long-term outcome in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). METHODS: We included 716 consecutive STEMI patients admitted to a single high-volume invasive heart center from September 2006 to December 2008. Endpoints were all-cause mortality, repeat myocardial infarction, admission due to heart failure and combinations thereof. Median follow-up lasted 27 months (interquartile range: 22-33). RESULTS: OPG levels exhibited a non-Gaussian distribution and were therefore divided into quartiles. High levels of OPG were significantly associated with a worse outcome. After adjustment for conventional risk factors (e.g. C-reactive protein, estimated glomerular filtration rate, symptom-to-balloon time and troponin I) using Cox regression, OPG remained a significantly independent predictor of death (HR per increase in OPG quartile: 1.28; CI: 1.03-1.59; p = 0.03), repeat myocardial infarction (HR: 1.30; CI: 1.00-1.68; p = 0.05) and admission with heart failure (HR: 1.50; CI: 1.18-1.90; p = 0.001). CONCLUSION: This study shows that OPG independently predicts long-term outcome in STEMI patients treated with pPCI. Eventually, this knowledge could improve risk stratification and overall outcome.

Intracoronary compared to intravenous bolus abciximab during primary percutaneous coronary intervention in ST-segment Elevation Myocardial Infarction (STEMI) patients reduces 30-day mortality and target vessel revascularization: a randomized trial.

BACKGROUND: Abciximab is beneficial in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). However, the optimal administration route of the initial bolus of abciximab, that is, intravenous (IV) versus intracoronary (IC), has been questioned. Preliminary studies suggest that IC-bolus is superior, probably due to high local concentration. In this study, we assess the short-term efficacy and safety of IC compared to IV bolus of abciximab in patients with STEMI during pPCI. METHODS: In 2006-2008, we randomized 355 STEMI patients who underwent pPCI and had indication for abciximab to either IV or IC bolus followed by a 12-hour IV infusion. Primary end-points at 30 days were target vessel revascularization (TVR), recurrent myocardial infarction (MI) or death, and the composite of the three. Secondary end-points were bleeding complications. RESULTS: The two groups (IV n = 170;IC n = 185) were similar with respect to baseline characteristics. Mortality at 30 days was 5.3% in the IV group compared to only 1.1% in the IC group (P = 0.02). TVR was performed in 9.4% in the IV group compared to 3.8% in the IC group (P = 0.03). No significant difference in MI rates was seen (IV 4.7% vs. IC 2.7%; P = 0.32). We found a significant reduction in the composite end-point (IV 19.4% vs. IC 7.6%; P = 0.001) in favor of IC use. Major bleeding complications were similar (IV 2.4% vs. IC 1.6%; P = 0.62). Neither difference was observed in minor bleedings (IV 14.1% vs. IC 9.7%; P = 0.20). CONCLUSION: IC administration of bolus abciximab in STEMI patients undergoing pPCI reduces 30-day mortality and TVR and tends to reduce MI, compared to IV-bolus.

Myocardial area at risk and salvage measured by T2-weighted cardiovascular magnetic resonance: reproducibility and comparison of two T2-weighted protocols.

BACKGROUND: Late gadolinium enhancement (LGE) and T2-weighted cardiovascular magnetic resonance (CMR) provides a means to measure myocardial area at risk (AAR) and salvage. Several T2-weighted CMR sequences are in use, but there is no consensus in terms of which sequence to be the preferred. Therefore, the aim of the present study was to: (1) Assess the reproducibility and (2) compare the two most frequently used T2-weighted CMR protocols for measuring AAR and salvage. METHODS: 91 patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention underwent a CMR scan 1-7 days after initial treatment. Two different T2-weighted protocols, varying in slice thickness and echo time (TE), were applied covering the entire left ventricle (LV) (protocol 1: TE 65 msec and slice thickness 15 mm; protocol 2: TE 100 msec and slice thickness of 8 mm). On a second scan performed 3 months later, infarct size was assessed with a standard LGE sequence. The two protocols were compared in terms of AAR and salvage index. Furthermore, intra- and interobserver reproducibility were assessed. RESULTS: Protocol 1 measures a larger AAR and salvage index than protocol 2 with a mean difference in AAR of 1±8%LV (p<0.01) and 6±12 g (p<0.01) and salvage index of 0.04±0.12 (p<0.01). Both protocols had a high intra- and interobserver reproducibility with acceptable limits of agreement (6-8%LV and 6-12 g in AAR and 0.06-0.08 in salvage index). CONCLUSIONS: We report acceptable reproducibility for AAR and salvage index measured by T2-weighted images. Thus CMR is a reliable tool for measuring AAR and salvage index. Protocol 2 (8 mm slice thickness and 100 msec TE) measures slightly smaller AAR than protocol 1 (15 mm slice thickness and 65 msec TE), but the present study does not allow for a clear recommendation of either of the protocols.

Interaction between leptin and leisure-time physical activity and development of hypertension.

OBJECTIVE. The mechanisms by which overweight and physical inactivity lead to hypertension are complex. Leptin, an adipocyte-derived hormone, has been linked with hypertension. We wanted to investigate the relationship between leptin, physical activity and new-onset hypertension. METHODS. The study was a prospective cohort study of 744 women and 367 men, who were normotensive in the third Copenhagen City Heart Study (CCHS) examination, performed 1991−94. Based on questionnaire items, the participants were divided into two groups with low (n = 674) and high (n = 437) levels of leisure-time physical activity, respectively. RESULTS. Between the third and the fourth CCHS examination, performed 2001?03, 304 had developed hypertension, defined as systolic blood pressure (SBP) ≥140 mmHg or diastolic blood pressure (DBP) ≥90 mmHg or use of antihypertensive medication. In a logistic regression model, including age, sex, body mass index, SBP, DBP, level of physical activity and leptin, we found a significant interaction between leptin and level of physical activity with new-onset hypertension as outcome variable (p = 0.012). When we entered the interaction variables, effect of leptin with low level of physical activity and with high level of physical activity, respectively, in the original model, leptin predicted new-onset hypertension in participants with low level of physical activity [odds ratio (95% confidence interval): 1.16 (1.01−1.33) for one unit increase in log-transformed leptin levels, p = 0.038], but not in participants with high level of physical activity [0.88 (0.74−1.05), p = 0.15]. CONCLUSION. We found that leptin predicted new-onset hypertension but only in participants with low level of physical activity.

Cardiac dysfunction assessed by echocardiographic tissue Doppler imaging is an independent predictor of mortality in the general population.

BACKGROUND: Tissue Doppler imaging (TDI) detects left ventricular dysfunction in patients with heart failure and normal ejection fraction, but the prognostic significance of left ventricular dysfunction by TDI in the general population is unknown. METHODS AND RESULTS: Within the Copenhagen City Heart Study, a large community-based population study, cardiac function was evaluated in 1036 participants by both conventional echocardiography and TDI. Averages of peak systolic (s'), early diastolic (e'), and late diastolic (a') velocities from 6 mitral annular sites were used. TDI was furthermore quantified by a combined index (eas index) of diastolic and systolic performance: e'/(a' x s'). During follow-up (median, 5.3 years), 90 participants died. Left ventricular dysfunction by TDI, in terms of low s' (hazard ratio, 1.23 per 1-cm/s decrease; P<0.05) and a' (hazard ratio, 1.20 per 1-cm/s decrease; P=0.001), were significant predictors of death in Cox proportional-hazards models adjusted for clinical variables (age, sex, body mass index, heart rate, hypertension, diabetes mellitus, and ischemic heart disease) and conventional echocardiography. The adjusted hazard ratio for death in the third tertile compared with the first tertile of the combined index of systolic and diastolic performance by TDI was 2.5 (P<0.005). CONCLUSIONS: In the general population, in which most are free of left ventricular systolic dysfunction and restrictive diastolic filling using conventional echocardiographic parameters, left ventricular dysfunction by TDI is a powerful and independent predictor of death, especially when systolic performance and diastolic performance are considered together, recognizing their interdependency and their complex relation to deteriorating cardiac function.

ST-Segment resolution and clinical outcome with ischemic postconditioning and comparison to magnetic resonance.

BACKGROUND: Ischemic postconditioning (IPost) during primary percutaneous coronary intervention (PPCI) is suggested to reduce myocardial damage. However, the association with ST-segment resolution (STR) and clinical outcome is not determined. The primary aim of this study was to evaluate the association of IPost with STR and clinical outcome. Secondly, we sought to determine the relationship between STR and cardiac magnetic resonance (CMR) parameters in these patients. METHODS: One hundred eighteen patients referred for PPCI were randomly assigned to either conventional PPCI or PPCI with IPost. In a single electrocardiographic lead, STR was determined. Treatment modalities were compared as regards STR, ST-segment elevation, and the number of patients achieving complete-STR (≥70%), incomplete-STR (30%-70%), and no-STR (<30%). Patients were evaluated for clinical outcome after 15 months. Furthermore, patients with and without complete-STR were compared as regards CMR parameters. RESULTS: There was a tendency toward a better outcome with IPost for the number of patients achieving complete-STR (55% vs 63%; P=.09), ST-segment elevation (1.41 vs 1.12 mm; P=.07), and New York Heart Association class (P=.06). No difference in other cardiac events was observed. Furthermore, data determine that patients with complete-STR have smaller infarct size (12.9% vs 21.1%; P<.01) and a better ejection fraction (55.7% vs 47.7%; P<.01). CONCLUSIONS: Patients treated with IPost are suggested to have improved STR and New York Heart Association classification. Infarct size and the functional CMR parameters were better in the patients with complete-STR; as to this, single-lead STR remains an important predictor for successful treatment in patients treated with IPost.

Tissue Doppler echocardiography in persons with hypertension, diabetes, or ischaemic heart disease: the Copenhagen City Heart Study.

AIMS: To test the hypothesis that echocardiographic tissue Doppler imaging (TDI) reveals reduced myocardial function in hypertension, diabetes, and ischaemic heart disease (IHD) in the general population. METHODS AND RESULTS: Within a large, community-based population study, cardiac function was evaluated in 1036 participants by both conventional echocardiography and colour TDI. Peak systolic (s') and early diastolic (e') velocities, longitudinal displacement (LD), and the ratio of mitral inflow E-wave to e' (E/e') were measured. TDI revealed significantly impaired parameters of systolic and diastolic cardiac function in hypertension [n = 345; LD 10.1 (+/-standard deviation, SD 2.0 mm), P < 0.001; E/e' 12.4 (x/SD 1.4), P < 0.001], diabetes [n = 65; LD 9.8 (+/-SD 2.2 mm), P < 0.001; E/e' 12.7 (x/SD 1.5), P < 0.001], and IHD [n = 93; LD 9.4 (+/-SD 2.5 mm), P < 0.001; E/e' 13.0 (x/SD 1.5), P < 0.001] compared with controls [n = 533; LD 11.4 (+/-SD 2.0 mm); E/e' 9.0 (x/SD 1.3)]. This pattern remained significant after adjusting for age, sex, body mass index, heart rate, and the results of conventional echocardiography. CONCLUSION: In the general population, persons with hypertension, diabetes, or IHD have impaired cardiac function by TDI independently of the result of conventional echocardiography.

The microbiology of alkaline-fermentation of indigenous seeds used as food condiments in Africa and Asia.

Alkaline-fermented food condiments play an important role in the diets of many people in developing and a few developed countries. The rise in pH during production of these foods is due to the ability of the dominant microorganisms, Bacillus spp., to hydrolyze proteins into amino acids and ammonia. Studies have been undertaken which have investigated a number of these products like dawadawa, ugba, bikalga, kinema, natto, and thua-nao. In this review, current knowledge about the principal microbiological activities and biochemical modifications which occur during the processing of the alkaline condiments including nutritional, antimicrobial, and probiotic aspects are discussed. The current use of molecular biology methods in microbiological research has allowed unambiguous and more reliable identification of microorganisms involved in these fermentations generating sufficient knowledge for the selection of potential starter cultures for controlled and better production procedures for alkaline-fermented seeds condiments.

Preclinical systolic and diastolic dysfunction assessed by tissue Doppler imaging is associated with elevated plasma pro-B-type natriuretic peptide concentrations.

BACKGROUND: Heart failure is a major public health problem. To improve its grave prognosis, early identification of cardiac dysfunction is mandatory. Conventional echocardiography is not suitable for this. Tissue Doppler imaging (TDI), however, could be so. METHODS AND RESULTS: Within a large community-based population-study (n = 1012), cardiac function was evaluated by conventional echocardiography (left ventricular hypertrophy, dilatation, systolic, and severe diastolic dysfunction), TDI, and plasma proBNP. Averages of peak systolic (s'), early diastolic (e'), and late diastolic (a') velocities from 6 mitral annular sites were used. TDI was furthermore quantified by a combined index (eas-index) of diastolic and systolic performance: e'/(a' x s'). Compared with controls, persons with elevated plasma proBNP concentrations (n = 100) displayed lower systolic and diastolic performance by TDI, in terms of lower s' (P = 0.017) and a' (P < .001), and higher e'/a' (P = .002) and eas-index (P < .001). This pattern remained significant after multivariable adjustment for age, sex, body mass index, heart rate, estimated glomerular filtration rate, hypertension, diabetes, ischemic heart disease, and conventional echocardiography. Furthermore, TDI provided incremental information over conventional echocardiography in predicting elevated plasma proBNP concentrations. CONCLUSIONS: Preclinical systolic and diastolic dysfunction by TDI is associated with elevated plasma proBNP levels, even when conventional echocardiography is normal.

Relationship Between Left Atrial Functional Measures and Incident Atrial Fibrillation in the General Population: The Copenhagen City Heart Study.

OBJECTIVES: This study sought to investigate whether left atrial (LA) functional measures predict atrial fibrillation (AF) in the general population. BACKGROUND: Increasing evidence suggests LA functional measures are predictors of AF in several patient groups. METHODS: In a community-based cohort study, approximately 2,000 individuals underwent a transthoracic echocardiogram. Conventional echocardiographic measures and extended LA measures, including the minimal and maximal LA volumes (LAVmin and LAVmax, respectively) and left atrial emptying fraction (LAEF), were performed. The endpoint was incident AF, and participants with known AF were excluded, which left 1,951 for inclusion. RESULTS: Over 11.0 years of follow-up, 184 (9.4%) developed AF. Those who developed AF had significantly larger LA volumes and lower LAEF than participants free of AF. These LA measures were univariable predictors of AF (LAVmax hazard ratio [HR]: 1.10 [95% confidence interval (CI): 1.08 to 1.12] per 1-ml increase, p < 0.001; LAVmin HR: 1.14 [95% CI: 1.12 to 1.16] per 1-ml increase, p < 0.001; LAEF HR: 1.03 [95% CI: 1.02 to 1.04] per percent decrease, p < 0.001). All LA measures remained predictors independent of clinical risk scores, with LAVmin providing the highest C-statistics when added to these risk scores (C-statistic for CHADS2 0.728 vs. CHADS2 + LAVmin 0.778; C-statistic for CHARGE-AF 0.815 vs. CHARGE-AF + LAVmin 0.830). However, hypertension modified the relationship between the measures of LA function (both LAVmin and LAEF) and risk of AF (p for interaction < 0.001), which was not the case for LAVmax (p = 0.22). The measures of LA function mainly provided prognostic information regarding risk of AF in participants without hypertension. Even when we restricted our analysis to individuals without hypertension and nondilated LA (LAVmax<34 ml/m2), the LAVmin and LAEF remained significantly independent predictors of AF after multivariable adjustments (LAVmin HR: 1.12 [95% CI: 1.01 to 1.24], p = 0.028, and LAEF HR: 1.03 [95% CI: 1.00 to 1.06], p = 0.021, respectively). CONCLUSIONS: LA functional measures predict AF in the general population and provide prognostic information incremental to clinical risk scores. In individuals without hypertension and nondilated LA, these measures indicate an increased risk of AF.

Prognostic importance of mechanical dyssynchrony in predicting heart failure development after ST-segment elevation myocardial infarction.

The aim of this study is to assess the prognostic value of mechanical dyssynchrony defined as the standard deviation of the time to peak longitudinal strain (SD T2P LS) in predicting the development of heart failure (HF) after an ST-segment elevation myocardial infarction (STEMI). Three hundred and seventy-three patients were admitted with STEMI and treated with primary percutaneous coronary intervention. Left ventricular (LV) mechanical dyssynchrony was examined through speckle tracking echocardiography and defined as SD T2P LS. The association with the outcome of HF hospitalization was assessed using Cox proportional hazard models. During a median follow-up of 5.12 years, 144 patients (38.6%) were admitted due to HF. Worse dyssynchrony was associated with the outcome in unadjusted and multivariable analysis (multivariable hazard ratio 1.05, 95% confidence interval 1.00-1.10, p-value 0.039, per 10 ms increase), but not after further adjustment for LV ejection fraction (LVEF), E/e' and global longitudinal strain (GLS) (hazard ratio 1.01, 95% confidence interval 1.00-1.07, p-value 0.71, per 10 ms increase), nor in a model only adjusting for GLS (hazard ratio 1.01, 95% confidence interval 1.00-1.06, p-value 0.61, per 10 ms increase). These findings were reproduced in a competing risk analysis treating all-cause mortality as a competing risk. LV mechanical dyssynchrony, as assessed by SD T2P LS is not an independent predictor of post-STEMI HF development and mechanical dyssynchrony does not provide independent prognostic information regarding HF when GLS is known.