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Background and Objectives: Sexually transmitted infections (STIs) in Madagascar have primarily been monitored in selected groups of patients attending STI clinics in major cities as part of the HIV surveillance program in Madagascar.Goal Of the Study: The aim of the study was to provide complementary data related to STI prevalence in a general rural population.Study Design: STIs were investigated in 643 subjects aged 15 to 49 years as part of a cross-sectional morbidity study of urogenital schistosomiasis. Infection rates were reassessed 3 weeks and 6 months after systematic STI treatment at baseline.Results: Neisseria gonorrhoeae (Ng), Chlamydia trachomatis (Ct), Mycoplasma genitalium (Mg), Trichomonas vaginalis (Tv), and/or antibodies to Treponema pallidum (Tp) were diagnosed in 125 (37.5%) of 333 women and in 83 (26.8%) of 310 men. In addition, 49% of the women and 28% of the men were infected with herpes simplex virus-2. Six (0.9%) subjects were found HIV-antibody positive. Between the 3-week and 6-month follow-up surveys Ng, Ct, and/or Mg prevalence increased most prominently in women aged 15 to 24 years.Conclusion: Study findings suggest that rural areas in Madagascar should be as closely monitored and assisted in STI and HIV control as their urban counterparts. Following the current consensus, young adults should constitute a priority target group in the control programs. [ABSTRACT FROM AUTHOR]

Background: Gelsolin is an actin-scavenger controlling the tissue damage from actin in the blood. Gelsolin levels in circulation drops when tissue damage and corresponding actin release is pronounced due to catabolic conditions. The purpose of this study was to determine if low plasma gelsolin independently predicts a reduced chance of weaning from ventilator-demanding respiratory failure in critically ill patients within 28 days from admission., Results: This cohort study included 746 critically ill patients with ventilator-demanding respiratory failure from the randomized clinical trial, "Procalcitonin And Survival Study (PASS)." Primary end point was successful weaning from mechanical ventilation within 28 days. We used multivariable Cox regression adjusted for age, sepsis, PaO2/FiO2 ratio and other known and suspected predictors of persistent respiratory failure. Follow-up was complete.For medical patients, baseline-gelsolin below the 25th percentile independently predicted a 40% lower chance of successful weaning within 28 days (HR 0.60, 95% CI 0.46-0.79, P = 0.0002); among surgical patients this end point was not predicted. Low gelsolin levels predicted chance of being "alive and out of intensive care at day 14" for both medical and surgical patients (HR 0.69, 95% CI 0.54-0.89, P = 0.004). Gelsolin levels did not predict 28 day mortality for surgical or medical patients., Conclusions: Low levels of serum gelsolin independently predict a decreased chance of successful weaning from ventilator within 28 days among medical intensive care patients. This finding has implications for identifying patients who need individualized intervention early in intensive care course to prevent unfavorable lung prognosis in acute respiratory failure., Trial Registration: This is a substudy to the PASS, Clinicaltrials.gov ID: NCT00271752, first registered January 1, 2006.

Objectives: The reason why some individuals develop chronic symptoms, whiplash-associated disorder, following whiplash trauma is poorly understood. We explored whether precollision pain-related diagnoses, medically unexplained symptoms, and psychiatric diagnoses are related to whiplash-associated disorder., Materials and Methods: A cohort of 719 individuals exposed to whiplash trauma and subsequently experiencing symptoms within 72 hours (whiplash-exposed cohort) and 3595 matched controls were included in this observational prospective study. At 12 months postcollision, the whiplash-exposed cohort rated their neck pain using the Visual Analog Scale. Data on health were obtained from the Danish National Patient Register for the whiplash-exposed cohort and for the controls for a 5-year period before collision., Results: The whiplash-exposed cohort had significantly increased incidences of precollision pain-related diagnoses: χ(1)=17.42, P<0.001 and medically unexplained symptoms: χ(1)=22.2, P<0.001 but not psychiatric diagnoses: χ(1)=3.60, P>0.05 compared with controls in the 5-year period. Participants from the whiplash-exposed cohort with precollision pain-related diagnoses (odds ratio=2.46; 95% confidence interval, 1.39; 4.35) and medically unexplained symptoms (odds ratio, 1.72; 95% confidence interval, 1.04; 2.84) had significantly increased odds for neck pain at follow-up., Discussion: Precollision pain and medically unexplained symptoms predict chronic neck pain following whiplash trauma. This may indicate that a sensitization process was initiated before the collision or that individuals with precollision low threshold for contacting health care services maintain this behavior postcollision. The collision may trigger existing individual vulnerabilities that constitute to be a risk factor for chronic whiplash.

Background: Influenza infection is a serious event for patients with heart failure (HF). Little knowledge exists about the association between influenza vaccination and outcome in patients with HF. This study sought to determine whether influenza vaccination is associated with improved long-term survival in patients with newly diagnosed HF., Methods: We performed a nationwide cohort study including all patients who were >18 years of age and diagnosed with HF in Denmark in the period of January 1, 2003, to June 1, 2015 (n=134 048). We collected linked data using nationwide registries. Vaccination status, number, and frequency during follow-up were treated as time-varying covariates in time-dependent Cox regression., Results: Follow-up was 99.8% with a median follow-up time of 3.7 years (interquartile range, 1.7-6.8 years). The vaccination coverage of the study cohort ranged from 16% to 54% during the study period. In unadjusted analysis, receiving ≥1 vaccinations during follow-up was associated with a higher risk of death. After adjustment for inclusion date, comorbidities, medications, household income, and education level, receiving ≥1 vaccinations was associated with an 18% reduced risk of death (all-cause: hazard ratio, 0.82; 95% CI, 0.81-0.84; P<0.001; cardiovascular causes: hazard ratio, 0.82; 95% CI, 0.81-0.84; P<0.001). Annual vaccination, vaccination early in the year (September to October), and greater cumulative number of vaccinations were associated with larger reductions in the risk of death compared with intermittent vaccination., Conclusions: In patients with HF, influenza vaccination was associated with a reduced risk of both all-cause and cardiovascular death after extensive adjustment for confounders. Frequent vaccination and vaccination earlier in the year were associated with larger reductions in the risk of death compared with intermittent and late vaccination.

Background: The optimal timing of invasive coronary angiography (ICA) and revascularization in patients with non-ST-segment elevation acute coronary syndrome is not well defined. We tested the hypothesis that a strategy of very early ICA and possible revascularization within 12 hours of diagnosis is superior to an invasive strategy performed within 48 to 72 hours in terms of clinical outcomes., Methods: Patients admitted with clinical suspicion of non-ST-segment elevation acute coronary syndrome in the Capital Region of Copenhagen, Denmark, were screened for inclusion in the VERDICT trial (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography) ( ClinicalTrials.gov NCT02061891). Patients with ECG changes indicating new ischemia or elevated troponin, in whom ICA was clinically indicated and deemed logistically feasible within 12 hours, were randomized 1:1 to ICA within 12 hours or standard invasive care within 48 to 72 hours. The primary end point was a combination of all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or hospital admission for heart failure., Results: A total of 2147 patients were randomized; 1075 patients allocated to very early invasive evaluation had ICA performed at a median of 4.7 hours after randomization, whereas 1072 patients assigned to standard invasive care had ICA performed 61.6 hours after randomization. Among patients with significant coronary artery disease identified by ICA, coronary revascularization was performed in 88.4% (very early ICA) and 83.1% (standard invasive care). Within a median follow-up time of 4.3 (interquartile range, 4.1-4.4) years, the primary end point occurred in 296 (27.5%) of participants in the very early ICA group and 316 (29.5%) in the standard care group (hazard ratio, 0.92; 95% CI, 0.78-1.08). Among patients with a GRACE risk score (Global Registry of Acute Coronary Events) >140, a very early invasive treatment strategy improved the primary outcome compared with the standard invasive treatment (hazard ratio, 0.81; 95% CI, 0.67-1.01; P value for interaction=0.023)., Conclusions: A strategy of very early invasive coronary evaluation does not improve overall long-term clinical outcome compared with an invasive strategy conducted within 2 to 3 days in patients with non-ST-segment elevation acute coronary syndrome. However, in patients with the highest risk, very early invasive therapy improves long-term outcomes., Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02061891.

Background: Cardiovascular death (CVD) is a leading cause of death and constitutes a major burden on society. Left ventricular mechanical dyssynchrony (LVMD), evaluated as SD of time to peak regional longitudinal strain, is a capable predictor of many cardiovascular outcomes related to CVD, including ventricular arrhythmias, but the prognostic utility of LVMD in the general population is unknown. Hence, this study sought to determine the prognostic value of LVMD in the general population in predicting CVD., Methods and Results: A total of 1138 participants underwent a general health examination and an echocardiographic examination including speckle tracking analysis with subsequent calculation of LVMD from time-to-peak regional strain. Primary end point was CVD, and secondary end point was noncardiovascular death. Follow-up was 100%. During a median follow-up of 11.1 years (interquartile range: 10.2-11.3 years), 62 participants suffered CVD (5.5%) while 131 participants experienced noncardiovascular death (11.5%). LVMD was an independent predictor of CVD (subdistribution hazard ratio, 1.04; 95% CI, 1.01-1.06; P=0.004, per 10-ms increase) in competing risk regression treating noncardiovascular death as a competing risk and retained prognostic capability after extensive multivariable adjustment. LVMD was not a significant predictor of noncardiovascular death. LVMD added incremental prognostic information in predicting CVD beyond the Systematic Coronary Risk Evaluation risk chart and a modified version of the American College of Cardiology/American Heart Association Pooled Cohort Equation., Conclusions: Left ventricular mechanical dyssynchrony adds incremental prognostic information in addition to established risk factors in prediction of CVD in individuals from the general population without atrial fibrillation and significant valvular disease.

The Stanford Chronic Pain Self-Management Programme (CPSMP) consists of 6 2½-hour weekly workshops focusing on how to manage pain in daily life. The workshops are facilitated by 2 workshop leaders of whom at least 1 must suffer from a long-term pain condition. The program is highly structured and manualized. Only few controlled trials testing the effect of CPSMP exist. Enrolled in the study were 424 adults from 19 Danish municipalities, (72% women; age: 25-93 years) with pain of any etiology and great variation in pain history (0-50 yrs). Of these, 216 were randomized to a lay-led version of the CPSMP. The primary outcome was pain-related disability. Secondary outcomes were pain, pain catastrophizing, self-efficacy, emotional distress, physical symptoms, and illness worry. Outcomes were measured before randomization, immediately after the CPSMP (response rate: 94%), and at 3-month follow-up (response rate: 92%). National register data on health expenditure were obtained to examine effects on health care use. ClinicalTrials.gov Identifier: NCT01306747. The CPSMP had no effect on the primary outcome pain-related disability or on health expenditure during intervention and follow-up period. Small positive effects on emotional distress and illness worry 3 months after CPSMP were observed. Lay-led CPSMP is not recommended as treatment for chronic pain-related disability. This heterogeneous group of patients with pain did not benefit from the CPSMP except for a small, but clinically insignificant improvement in psychological well-being.

Background: Global longitudinal strain (GLS) is prognostic of adverse cardiovascular outcomes in various patient populations, but the prognostic utility of GLS for long-term cardiovascular morbidity and mortality in the general population is unknown., Methods and Results: A total of 1296 participants in a general population study underwent a health examination, including echocardiography measurement of GLS. The primary end point was the composite of incident heart failure, acute myocardial infarction, or cardiovascular death. During a median follow-up of 11 years, 149 (12%) participants were diagnosed with heart failure, acute myocardial infarction, or cardiovascular death. Lower GLS was associated with a higher risk of the composite end point (hazard ratio, 1.12; 95% confidence interval, 1.08-1.17; P <0.001 per 1% decrease), an association that persisted after multivariable adjustment for age, sex, heart rate, hypertension, systolic blood pressure, left ventricular ejection fraction, left ventricular mass index, left ventricular dimension, deceleration time, left atrium dimension, E / e ', and pro B-type natriuretic peptide (hazard ratio, 1.05; 95% confidence interval, 1.00-1.11; P =0.045 per 1% decrease). GLS provided incremental prognostic information beyond the Framingham Risk Score, the Systemic Coronary Evaluation risk chart, and the modified American College of Cardiology/American Heart Association Pooled Cohort Equation for the composite outcome and incident heart failure. Sex modified the relationship between GLS and outcome such that after multivariable adjustment, GLS was an independent predictor of outcomes in men but not in women (hazard ratio, 1.14; 95% confidence interval, 1.06-1.24; P =0.001, and hazard ratio, 0.99; 95% confidence interval, 0.92-1.07; P =0.81, respectively; P for interaction =0.032)., Conclusions: In the general population, GLS provides independent and incremental prognostic information regarding long-term risk of cardiovascular morbidity and mortality. GLS seems to be a stronger prognosticator in men than in women., (© 2017 American Heart Association, Inc.)

Background: Although age-associated changes in left ventricular diastolic function are well recognized, limited data exist characterizing measures of diastolic function in older adults, including both reference ranges reflecting the older adult population and prognostically relevant values for incident heart failure (HF), as well as their associations with circulating biomarkers of HF risk., Methods: Among 5801 elderly participants in the ARIC study (Atherosclerosis Risk in Communities; age range, 67-90 years; mean age, 76±5 years; 42% male; 21% black), we determined the continuous association of diastolic measures (tissue Doppler imaging [TDI] e', E/e', and left atrial size) with concomitant N-terminal pro-brain natriuretic peptide and subsequent HF hospitalization or death. We also determined sex-specific 10th and 90th percentile limits for these measures using quantile regression in 401 participants free of prevalent cardiovascular disease and risk factors., Results: Each measure of diastolic function was robustly associated with N-terminal pro-brain natriuretic peptide and incident HF or death. ARIC-based reference limits for TDI e' (4.6 and 5.2 cm/s for septal and lateral TDI e', respectively) were substantially lower than guideline cut points (7 and 10 cm/s, respectively), whereas E/e' and left atrial size demonstrated good agreement with guideline cut points. TDI e' was nonlinearly associated with incident HF or death, with inflection points for risk supportive of ARIC-based limits. ARIC-based limits for diastolic function improved risk discrimination over guideline-based cut points based on the integrated discrimination improvement (P<0.001) and continuous net reclassification improvement (P<0.001), reclassifying 42% of the study population as having normal diastolic function. We replicate these findings in the Copenhagen City Heart Study. With these limits, 46% had normal diastolic function and were at low risk of HF hospitalization or death (1%/y over a mean 1.7-year follow-up), 49% had 1 or 2 abnormal measures and were at intermediate risk (2.4%/y), and all 3 diastolic measures were abnormal in 5% who were at high risk (7.5%/y)., Conclusions: Our findings suggest that left ventricular longitudinal relaxation velocity declines as a part of healthy aging and is largely prognostically benign. The use of age-based normative values when considering an elderly population improves the risk discrimination of diastolic measures for incident HF or death., Competing Interests: The other authors report no disclosures., (© 2016 American Heart Association, Inc.)

Background and Purpose: The DIAS-3 trial (Efficacy and Safety Study of Desmoteplase to Treat Acute Ischemic Stroke [phase 3]) did not demonstrate a significant clinical benefit of desmoteplase administered 3 to 9 hours after stroke in patients with major artery occlusion. We present the results of the prematurely terminated DIAS-4 trial together with a post hoc pooled analysis of the concomitant DIAS-3, DIAS-4, and DIAS-J (Japan) trials to better understand the potential risks and benefits of intravenous desmoteplase for the treatment of ischemic stroke in an extended time window., Methods: Ischemic stroke patients with occlusion/high-grade stenosis in major cerebral arteries were randomly assigned to intravenous treatment with desmoteplase (90 μg/kg) or placebo. The primary outcome was modified Rankin Scale (mRS) score of 0 to 2 at day 90. Safety assessments included mortality, symptomatic intracranial hemorrhage, and other serious adverse events., Results: In DIAS-4, 52 of 124 (41.9%) desmoteplase-treated and 46 of 128 (35.9%) placebo-treated patients achieved an mRS score of 0 to 2 (odds ratio, 1.45; 95% confidence interval, 0.79; 2.64; P=0.23) with equal mortality, frequency of symptomatic intracranial hemorrhage, and other serious adverse events in both the treatment arms. In the pooled analysis, mRS score of 0 to 2 was achieved by 184 of 376 (48.9%) desmoteplase-treated versus 171 of 381 (44.9%) placebo-treated patients (odds ratio, 1.33; 95% confidence interval, 0.95; 1.85; P=0.096). Treatment with desmoteplase was safe and increased the recanalization rate (107/217 [49.3%] versus 85/222 [38.3%]; odds ratio, 1.59; 95% confidence interval, 1.08-2.35; P=0.019). Recanalization was associated with favorable outcomes (mRS 0-2) at day 90 in both the treatment arms., Conclusions: Late treatment with intravenous 90 µg/kg desmoteplase is safe, increases arterial recanalization, but does not significantly improve functional outcome at 3 months., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00856661., (© 2016 American Heart Association, Inc.)

Patients with acute myocardial infarction are at increased risk of developing atrial fibrillation. We aimed to evaluate whether speckle tracking echocardiography improves risk stratification for atrial fibrillation in these patients.The study comprised of 373 patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention. Patients had an echocardiogram performed at a median of 2 days after their STEMI. The echocardiograms consisted of conventional measurements and myocardial strain analysis by speckle tracking from 3 apical projections. The endpoint was a composite of new-onset atrial fibrillation and ischemic stroke. At a median follow-up time of 5.5 years (interquartile range 4.9, 6.1 years), 44 patients developed the endpoint (atrial fibrillation: n = 24, ischemic stroke: n = 24, both: n = 4). Patients who reached the endpoint had significantly reduced systolic function by the left ventricular ejection fraction (LVEF) (43% vs 46%; P = 0.042) and global longitudinal strain (10.9% vs 12.6%; P = 0.004), both being univariable predictors. However, only global longitudinal strain remained a significantly independent predictor (hazard ratio 1.12, 95% confidence interval 1.00; 1.25, P = 0.042, per 1% decrease) after multivariable adjustment for baseline predictors (age, sex, diabetes, hypertension, diastolic dysfunction, and LVEF) using Cox regression. Furthermore, global longitudinal strain resulted in significantly higher c-statistics for prediction of outcome compared with LVEF <45% (0.63 vs 0.52; P = 0.026). When stratified into tertiles of global longitudinal strain, it became evident that patients in the lowest tertile mediated this signal with a 2-fold increased risk compared with the highest tertile (hazard ratio 2.10, 95% confidence interval 1.04; 4.25).Global longitudinal strain predicts atrial fibrillation after STEMI and may add valuable information which can help facilitate arrhythmia detection in these patients.

Several cardiac imaging modalities are able to visualize the left atrium (LA) and, therefore, allow for quantification of both structural and functional properties of this cardiac chamber. In echocardiography, only the maximal LA volume is included in the assessment of diastolic function at the current moment. Numerous studies, however, have shown that functional measures may be superior to the maximal LA volume in several aspects and to possess clinical value even in the absence of structural abnormalities. Such functional measures could prove particularly useful in the setting of predicting atrial fibrillation, which will be a point of focus in this review. Pivotal cardiac magnetic resonance imaging studies have revealed high correlation between LA fibrosis and risk of atrial fibrillation recurrence after catheter ablation, and subsequent multimodality imaging studies have uncovered an inverse relationship between LA reservoir function and degree of LA fibrosis. This has sparked an increased interest into the application of advanced imaging modalities, including both speckle tracking echocardiography and tissue tracking by cardiac magnetic resonance imaging. Even though increasing evidence has supported the use of functional measures and proven its superiority to the maximal LA volume, they have still not been adopted in clinical guidelines. The reason for this discrepancy may rely on the fact that there is little to no agreement on how to technically perform deformation analysis of the LA. Such technical considerations, limitations, and alternate imaging prospects will be addressed in this review., (© 2016 American Heart Association, Inc.)

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., (© 2014 American Heart Association, Inc.)

Background: Two-dimensional strain echocardiography detects early signs of left ventricular dysfunction; however, it is unknown whether myocardial strain analysis at rest in patients with suspected stable angina pectoris predicts the presence of coronary artery disease (CAD)., Methods and Results: In total, 296 consecutive patients with clinically suspected stable angina pectoris, no previous cardiac history, and normal left ventricular ejection fraction were included. All patients were examined by 2-dimensional strain echocardiography, exercise ECG, and coronary angiography. Two-dimensional strain echocardiography was performed in the 3 apical projections. Peak regional longitudinal systolic strain was measured in 18 myocardial sites and averaged to provide global longitudinal peak systolic strain. Duke score, including ST-segment depression, chest pain, and exercise capacity, was used as the outcome of the exercise test. Patients with an area stenosis≥70% in ≥1 epicardial coronary artery were categorized as having significant CAD (n=107). Global longitudinal peak systolic strain was significantly lower in patients with CAD compared with patients without (17.1±2.5% versus 18.8±2.6%; P<0.001) and remained an independent predictor of CAD after multivariable adjustment for baseline data, exercise test, and conventional echocardiography (odds ratio, 1.25 [P=0.016] per 1% decrease). Area under receiver operating characteristic curve for exercise test and global longitudinal peak systolic strain in combination was significantly higher than that for exercise test alone (0.84 versus 0.78; P=0.007). Furthermore, impaired regional longitudinal systolic strain identifies which coronary artery is stenotic., Conclusions: In patients with suspected stable angina pectoris, global longitudinal peak systolic strain assessed at rest is an independent predictor of significant CAD and significantly improves the diagnostic performance of exercise test. Furthermore, 2-dimensional strain echocardiography seems capable of identifying high-risk patients.

Background: Color tissue Doppler imaging M-mode through the mitral leaflet is an easy and precise method to estimate all cardiac time intervals from 1 cardiac cycle and thereby obtain the myocardial performance index (MPI). However, the prognostic value of the cardiac time intervals and the MPI assessed by color tissue Doppler imaging M-mode through the mitral leaflet in patients with ST-segment-elevation myocardial infarction (MI) is unknown., Methods and Results: In total, 391 patients were admitted with an ST-segment-elevation MI, treated with primary percutaneous coronary intervention, and examined by echocardiography a median of 2 days after the ST-segment-elevation MI. Outcome was assessed according to death (n=33), hospitalization with heart failure (n=53), or new MI (n=25). Follow-up time was a median of 25 months. The population was stratified according to tertiles of the MPI. The risk of new MI, being admitted with congestive heart failure or death, increased with increasing tertile of MPI, being ≈3 times as high for the third tertile compared with the first tertile (hazard ratio, 2.8; 95% confidence interval, 1.7-4.7; P<0.001). MPI provided independent prognostic information in a multivariable Cox regression model adjusted for age, sex, previous MI, peak troponin, and systolic and diastolic echocardiographic parameters, with a hazard ratio of 1.24 (P=0.005) for the combined end point per each 0.1 increase in MPI., Conclusions: MPI assessed by tissue Doppler imaging M-mode is a simple and reproducible measure that provides independent prognostic information, regardless of rhythm, incremental to conventional and novel echocardiographic parameters of systolic and diastolic function in patients with ST-segment-elevation MI treated with primary percutaneous coronary intervention.

Background: Controversy persists regarding the correct strategy for bifurcation lesions. Therefore, we combined the patient-level data from 2 large trials with similar methodology: the NORDIC Bifurcation Study (NORDIC I) and the British Bifurcation Coronary Study (BBC ONE)., Methods and Results: Both randomized trials compared simple (provisional T-stenting) versus complex techniques, using drug-eluting stents. In the simple group (n=457), 129 patients had final kissing balloon dilatation in addition to main vessel stenting, and 16 had T-stenting. In the complex group (n=456), 272 underwent crush, 118 culotte, and 59 T-stenting techniques. A composite end point at 9 months of all-cause death, myocardial infarction, and target vessel revascularization occurred in 10.1% of the simple versus 17.3% of the complex group (hazard ratio 1.84 [95% confidence interval 1.28 to 2.66], P=0.001). Procedure duration, contrast, and x-ray dose favored the simple approach. Subgroup analysis revealed similar composite end point results for true bifurcations (n=657, simple 9.2% versus complex 17.3%; hazard ratio 1.90 [95% confidence interval 1.22 to 2.94], P=0.004), wide-angled bifurcations >60 to 70° (n=217, simple 9.6% versus complex 15.7%; hazard ratio 1.67 [ 95% confidence interval 0.78 to 3.62], P=0.186), large (≥2.75 mm) diameter side branches (n=281, simple 10.4% versus complex 20.7%; hazard ratio 2.42 [ 95% confidence interval 1.22 to 4.80], P=0.011), longer length (>5 mm) ostial side branch lesions (n=464, simple 12.1% versus complex 19.1%; hazard ratio 1.71 [95% confidence interval 1.05 to 2.77], P=0.029), or equivalent sized vessels (side branch <0.25 mm smaller than main vessel) (n=108, simple 12.0% versus complex 15.5%; hazard ratio 1.35 [95% confidence interval 0.48 to 3.70], P=0.57)., Conclusions: For bifurcation lesions, a provisional single-stent approach is superior to systematic dual stenting techniques in terms of safety and efficacy. A complex approach does not appear to be beneficial in more anatomically complicated lesions.

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.

Background: Postconditioning has been suggested to reduce myocardial damage during primary percutaneous coronary intervention (PPCI) in patients with ST-segment-elevation myocardial infarction. However, because clinical experience is limited, we examined the cardioprotective effects of postconditioning, using cardiac MRI in patients treated with PPCI., Methods and Results: One hundred eighteen patients with ST-segment-elevation myocardial infarction referred for PPCI were randomly assigned to have either conventional PPCI or PPCI with postconditioning. Postconditioning was performed immediately after obtained reperfusion with 4 balloon occlusions, each lasting 30 seconds, followed by 30 seconds of reperfusion. The primary end point was myocardial salvage after 3 months as judged by delayed enhancement cardiac MRI. We found a 19% relative reduction of infarct size in the postconditioning group (51+/-16% of total area at risk versus 63+/-17%, P<0.01), corresponding to a 31% increase in salvage ratio. The number of patients developing heart failure was significantly fewer in the postconditioning group (27% versus 46%, P=0.048). No significant evidence of interaction between the impact of postconditioning and the location of the culprit lesion or size of the myocardium at risk was detected (P=0.21 and P=0.71)., Conclusions: Mechanical postconditioning reduces infarct size in patients with ST-segment-elevation myocardial infarction treated with PPCI. The impact of mechanical postconditioning seems to be independent of the size of myocardium at risk., Clinical Trial Registration- Url: http://www.clinicaltrials.gov. Unique Identifier: NCT00507156.

Background: We sought to describe the long-term prognosis after routine primary percutaneous coronary intervention (pPCI) in a contemporary consecutive population of patients with presumed ST-segment elevation myocardial infarction, compare it with similar results from the landmark DANAMI-2 trial, and to identify a possible impact of time of presentation and referral pattern., Methods and Results: Long-term prognosis in 1019 presumed ST-segment elevation myocardial infarction patients, treated according to modern routine pPCI during the year 2004, was analyzed and compared with similar data from the DANAMI-2 trial. Furthermore, we analyzed the impact of patient presentation to the angioplasty center during "off hours" (4 pm to 8 am plus weekends and holidays) and the impact of being referred from noninvasive hospitals. At 3 years, 20.4% in the routinely treated population versus 19.6% in the DANAMI-2 trial reached the combined end point of death, reinfarction, or stroke (P=0.68), whereas the all-cause mortality was 13.0% and 13.7%, respectively (P=0.65). Patients admitted during off hours had the same risk of reaching the combined end point of death, reinfarction, or stroke compared with patients admitted during office hours (hazards ratio, 1.04; 95% CI, 0.8 to 1.5; P=0.81). Door-to-balloon times of less than 90 minutes were achieved in 60% among patients admitted directly to an invasive center but only in 40% among transferred patients (P<0.001). Despite this difference, no difference in unadjusted or adjusted long-term prognosis was found between the 2 groups., Conclusions: This study shows that ST-segment elevation myocardial infarction patients treated with contemporary routine pPCI achieve a similar long-term prognosis as patients in the landmark randomized pPCI trial (DANAMI-2). Furthermore, the long-term prognosis was the same regardless of whether the pPCI was performed during off hours or office hours. Thus, pPCI including transportation of patients from noninvasive centers can be applied successfully in a real-life population.

Background: In a number of coronary bifurcation lesions, both the main vessel and the side branch need stent coverage. Using sirolimus eluting stents, we compared 2 dedicated bifurcation stent techniques, the crush and the culotte techniques in a randomized trial with separate clinical and angiographic end-points., Methods and Results: A total of 424 patients with a bifurcation lesion were randomized to crush (n=209) and culotte (n=215) stenting. The primary end point was major adverse cardiac events; cardiac death, myocardial infarction, target vessel revascularization, or stent thrombosis after 6 months. At 6 months there were no significant differences in major adverse cardiac event rates between the groups; crush 4.3%, culotte 3.7% (P=0.87). Procedure and fluoroscopy times and contrast volumes were similar in the 2 groups. The rates of procedure-related increase in biomarkers of myocardial injury were 15.5% in crush versus 8.8% in culotte group (P=0.08). A total of 324 patients had a quantitative coronary assessment at the index procedure and after 8 months. The angiographic end-points of in-segment and in-stent restenosis of main vessel and/or side branch after 8 months were found in 12.1% versus 6.6% (P=0.10) and in 10.5% versus 4.5% (P=0.046) in the crush and culotte groups, respectively., Conclusions: Both the crush and the culotte bifurcation stenting techniques were associated with similar and excellent clinical and angiographic results. Angiographically, there was a trend toward less in-segment restenosis and significantly reduced in-stent restenosis following culotte stenting.

Objective: The increased risk of atherosclerosis associated with diabetes cannot be explained by conventional cardiovascular risk factors alone. We hypothesized that transvascular lipoprotein transport may be increased in patients with diabetes, possibly explaining increased intimal lipoprotein accumulation and, thus, atherosclerosis., Methods and Results: We developed an in vivo method for measurement of transvascular transport of low density lipoprotein (LDL) and applied it in 16 patients with maturity-onset diabetes (type 2) and 29 healthy control subjects. Autologous 131I-labeled LDL was reinjected intravenously in addition to 125I-labeled albumin, and the 1-hour fractional escape rates were taken as indices of transvascular transport. Both parameters were normally distributed, and they were tightly correlated (R2=0.69, P<0.0001). Transvascular LDL transport was 5.4+/-2.9%/h and 4.1+/-1.5%/h in patients with diabetes and control subjects, respectively (P<0.05); equivalent values for albumin were 6.5+/-2.5%/h and 5.3+/-1.6%/h (P<0.05). This difference most likely was not caused by altered hepatic LDL receptor expression, glycosylation of LDL, small LDL size, nephropathy, statin use, or different plasma insulin levels in diabetic patients., Conclusions: Transvascular LDL transport may be increased in patients with type 2 diabetes. This suggests that lipoprotein flux into the arterial wall is increased in people with diabetes, possibly explaining the accelerated development of atherosclerosis.

Background: Elevated urinary albumin excretion (UAE) predicts atherosclerotic cardiovascular disease. It is hypothesized that elevated UAE is associated with a generalized vascular dysfunction. This study tested this hypothesis for conduit arteries., Methods and Results: Clinically healthy subjects were selected: 19 with UAE >90th percentile in the background population (6.6 microgram/min

Cross-sectional studies suggest that an increased urinary albumin excretion rate is associated with cardiovascular disease, dyslipidemia, and hypertension. The purpose of this study was to analyze prospectively whether the urinary albumin-to -creatinine (A/C) ratio can independently predict ischemic heart disease (IHD) in a population-based cohort. In 1983, urinary albumin and creatinine levels were measured, along with the conventional atherosclerotic risk factors, in 2085 consecutive participants without IHD, renal disease, urinary tract infection, or diabetes mellitus. The participants were followed up until death, emigration, or December 31, 1993. IHD was defined as a hospital discharge diagnosis or cause of death including the diagnoses ICD-8 and 410 to 414. Seventy-nine individuals developed IHD during the 21 130 person-years of follow-up. They were characterized by a preponderance of males and higher age, body mass index, blood pressure, lipoproteins, and proportion of current smokers. Microalbuminuria was defined as an A/C ratio) >90 percentile (>0.65 mg/mmol). When adjusted for other risk factors, the relative risk of IHD associated with microalbuminuria was 2.3 (95% CI, 1.3 to 3.9, P=0.002), and the 10-year disease-free survival decreased from 97% to 91% (P<0.0001) when microalbuminuria was present. An interaction between microalbuminuria and smoking was observed, and the presence of microalbuminuria more than doubled the predictive effect of the conventional atherosclerotic risk factors for development of IHD. It is concluded that microalbuminuria is not only an independent predictor of IHD but also substantially increases the risk associated with other established risk factors.

Background: Preliminary studies have suggested that microalbuminuria--a slightly increased urinary excretion of albumin--is a risk factor for atherosclerosis. The aim of this study was to examine whether an association exists between urinary excretion of albumin and a history of acute myocardial infarction, in a major population sample., Methods: The study was performed as a part of the 3rd Copenhagen City Heart Study, Denmark, 1992-1994, and included 2,613 participants aged 30-70 years, and without diabetes mellitus, renal or urinary tract disease or haematuria. The study programme included measurement of urinary albumin excretion rate, acquisition of information regarding previous acute myocardial infarction (verified by the Danish Hospital Register) and tobacco and alcohol consumption, 12-lead resting electrocardiogram, and measurement of blood pressure, body mass index, waist:hip ratio, plasma concentrations of total cholesterol, HDL cholesterol and fibrinogen, serum albumin concentration and glomerular filtration rate., Results: Among the participants, 3.6% presented with a history of acute myocardial infarction. There was a positive association between urinary albumin excretion rate (logarithmically transformed) and acute myocardial infarction (odds ratio 1.35, 95% confidence interval 1.08 to 1.70, n = 2, 613; P = 0.01), which was independent of age, sex conventional atherosclerotic risk factors, and glomerular filtration rate. The odds ratio for acute myocardial infarction associated with microalbuminuria (urinary albumin excretion rate exceeding the upper decile in the entire study population) was 2.06 (95% confidence interval 1.20 to 3.55, n = 2,613; P = 0.009)., Conclusion: There exists a positive and independent association between urinary excretion of albumin and a history of acute myocardial infarction. Follow-up analyses should determine the time sequence of this association.

Microalbuminuria was recently proposed as a novel atherogenic risk factor. The pathophysiological link between microalbuminuria and atherosclerosis may be mediated through an increased generalized transvascular leakage of albumin. To investigate this hypothesis, urinary albumin excretion and clearance and systemic transvascular albumin leakage (TERalb) were measured in 23 patients with severe clinical atherosclerosis and 25 healthy controls. In addition, renal clearances of three other endogenous plasma proteins (IgG, IgG4, and beta 2-microglobulin) and of creatinine were measured. Measurements of urine and serum proteins were done by enzyme-linked immunosorbent assays. TERalb was measured by the fractional disappearance rate of 125I-albumin from the total intravascular compartment in 1 hour after intravenous injection. Glomerular filtration rate was estimated as creatinine clearance. Urinary albumin excretion (geometric means [95% confidence intervals], 10.5 [6.1 to 18.3] versus 5.7 [4.7 to 6.9] micrograms/min; P < .05), fractional urinary albumin clearance (2.8 [1.6 to 4.8] x 10(-6) versus 1.3 [1.0 to 1.6] x 10(-6); P < .05), and TERalb (6.0 [5.5 to 6.5] versus 5.1 [4.5 to 5.8] %/h; P < .05) were higher in patients than in control subjects. Glomerular charge selectivity (ratio of IgG clearance to IgG4 clearance) was lower in patients than in control subjects (1.5 [1.1 to 2.0] versus 2.3 [2.0 to 2.6]; P < .05). These alterations were independent of blood pressure, glomerular filtration rate, tubular function, and smoking status. It is concluded that atherosclerotic vascular disease is associated with renal and systemic transvascular leakiness for albumin. Theoretically, such leakiness may in addition allow for an increased lipid insudation into the large vessel wall, thereby linking microalbuminuria to atherogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)