Smoking-associated Electrocardiographic Abnormalities Predict Cardiovascular Mortality: Insights from NHANES.

Background­: Smoking is associated with arrhythmia and sudden cardiac death, but the biological mechanisms remain unclear. Abnormal electrocardiogram (ECG) durations of ventricular repolarization (QT interval), atrial depolarization (P wave), and atrioventricular depolarization (PR interval and segment), predict cardiac arrhythmia and mortality. Objectives­: To elucidate how smoking affects cardiac excitation, we assessed in a nationally representative sample (NHANES III) associations between cotinine, abnormalities in P duration, PR interval, PR segment, rate-corrected QT (QTc), QRS duration, and JT interval, and long-term mortality. Methods­: We analyzed data from 5,633 adults using survey-weighted multinomial logistic regression to estimate associations between tobacco use (>15 ng/ml serum cotinine) and short (<5th percentile) or long (>95th percentile) ECG intervals, relative to reference (5 - 95th percentile). Results­: After adjustment for demographics, risk factors, and conduction-altering medications, smoking was associated with a higher odds of short PR interval, PR segment, and QRS, and long JT. Broader ECG effects of smoking were also assessed by survey-weighted linear regression of continuous cotinine and ECG intervals, which revealed cotinine inversely associated with PR segment and QTc. Over a 22-year follow-up, many ECG abnormalities predicted cardiovascular mortality in smokers, including long JT, QRS, and QTc, and short QRS. Conclusions­: Smoking increases likelihood for rapid atrioventricular conduction, rapid ventricular depolarization, and slow ventricular repolarization. The ventricular electrophysiologic abnormalities associated with smoking also predict cardiovascular mortality in smokers; however, traditional ECG measures of cardiac risk like QTc can overlook these ventricular defects and their independent predictive value in smokers.

Characterization of patients receiving surgical versus non-surgical treatment for infective endocarditis in West Virginia.

BACKGROUND: Infective endocarditis (IE) has increased in rural states such as West Virginia (WV) with high injection drug use. IE is medically managed with antimicrobial treatment alone or combined with surgical treatment. This study aimed to characterize the predictors associated with surgical treatment and rates of inpatient mortality and readmission among IE patients in WV's rural centers. METHODS: This retrospective review of electronic health records includes all adults hospitalized for IE at major rural tertiary cardiovascular centers in WV during 2014-2018. Descriptive statistics were presented on demographics, history of injection drug use, clinical characteristics, and hospital utilization by surgery status, and multivariable logistic regression examined the association of surgery with key predictor variables, generating odds ratios (OR). RESULTS: Of the 780 patients with IE, 38% had surgery, with a 26-fold increase in patients undergoing surgery between 2014-2018. Comparing surgery and non-surgery patients revealed significant differences. Surgery patients were significantly younger (median age 35.6 vs. 40.5 years; p<0.001); had higher rates of drug use history (80% vs. 65%; p<0.001), psychiatric disorders (57% vs. 31%; p<0.001), and readmissions (18% vs.12%; p = 0.015). Surgery patients had lower rates of discharge against medical advice (11% vs.17%; p = 0.028) and in-hospital mortality (5% vs.12%; p<0.001). In the multivariable logistic regression, surgery was associated with injection drug use (OR: 1.9; 95% CI:1.09-3. 3), indications for surgery (OR: 1.68; 95% CI:1.48-1.91), left-sided IE (OR: 2.14; 95%CI:1.43-3.19) and later years (OR:3.75; 95%CI:2.5-5.72). CONCLUSION: This study characterizes the predictors associated with surgical treatment and rates of inpatient mortality and readmission among IE patients across rural WV. The decision to perform cardiac surgery on IE patients is complex. Results with increased injection drug use-associated IE emphasize the importance of comprehensive care by a multidisciplinary team for optimal management of patients with IE.

Steep rise in drug use-associated infective endocarditis in West Virginia: Characteristics and healthcare utilization.

INTRODUCTION: Life-threatening infections such as infective endocarditis (IE) are increasing simultaneously with the injection drug use epidemic in West Virginia (WV). We utilized a newly developed, statewide database to describe epidemiologic characteristics and healthcare utilization among patients with (DU-IE) and without (non-DU-IE) drug use-associated IE in WV over five years. MATERIALS AND METHODS: This retrospective, observational study, incorporating manual review of electronic medical records, included all patients aged 18-90 years who had their first admission for IE in any of the four university-affiliated referral hospitals in WV during 2014-2018. IE was identified using ICD-10-CM codes and confirmed by chart review. Demographics, clinical characteristics, and healthcare utilization were compared between patients with DU-IE and non-DU-IE using Chi-square/Fisher's exact test or Wilcoxon rank sum test. Multivariable logistic regression analysis was conducted with discharge against medical advice/in-hospital mortality vs. discharge alive as the outcome variable and drug use as the predictor variable. RESULTS: Overall 780 unique patients had confirmed first IE admission, with a six-fold increase during study period (p = .004). Most patients (70.9%) had used drugs before hospital admission, primarily by injection. Compared to patients with non-DU-IE, patients with DU-IE were significantly younger (median age: 33.9 vs. 64.1 years; p < .001); were hospitalized longer (median: 25.5 vs. 15 days; p < .001); had a higher proportion of methicillin-resistant Staphylococcus aureus (MRSA) isolates (42.7% vs. 29.9%; p < .001), psychiatric disorders (51.2% vs. 17.3%; p < .001), cardiac surgeries (42.9% vs. 26.6%; p < .001), and discharges against medical advice (19.9% vs. 1.4%; p < .001). Multivariable regression analysis showed drug use was an independent predictor of the combined outcome of discharge against medical advice/in-hospital mortality (OR: 2.99; 95% CI: 1.67-5.64). DISCUSSION AND CONCLUSION: This multisite study reveals a 681% increase in IE admissions in WV over five years primarily attributable to injection drug use, underscoring the urgent need for both prevention efforts and specialized strategies to improve outcomes.

Sex Differences in Characteristics of Patients with Infective Endocarditis: A Multicenter Study.

Infectious diseases like infective endocarditis (IE) may manifest or progress differently between sexes. This study sought to identify the differences in demographic and clinical characteristics among male and female patients with IE. Data were obtained from a newly developed registry comprising all adult patients with first IE admission at the four major tertiary cardiovascular centers in West Virginia, USA during 2014−2018. Patient characteristics were compared between males and females using Chi-square test, Fisher's exact test, and Wilcoxon rank-sum test. A secondary analysis was restricted to IE patients with drug use only. Among 780 unique patients (390 males, 390 females), significantly more women (a) were younger than males (median age 34.9 vs. 41.4, p < 0.001); (b) reported drug use (77.7% vs. 64.1%, p < 0.001); (c) had tricuspid valve endocarditis (46.4% vs. 30.8%, p < 0.001); and (d) were discharged against medical advice (20% vs. 9.5%, p < 0.001). These differences persisted even within the subgroup of patients with drug use-associated IE. In a state with one of the highest incidences of drug use and overdose deaths, the significantly higher incident IE cases in younger women and higher proportion of women leaving treatment against medical advice are striking. Differential characteristics between male and female patients are important to inform strategies for specialized treatment and care.

Smoking Accelerates Atrioventricular Conduction in Humans Concordant with Increased Dopamine Release.

Smoking is associated with cardiac arrhythmia, stroke, heart failure, and sudden cardiac arrest, all of which may derive from increased sympathetic influence on cardiac conduction system and altered ventricular repolarization. However, knowledge of the effects of smoking on supraventricular conduction, and the role of the sympathetic nervous system in them, remains incomplete. Participants with intermediate-high cardiovascular disease risk were measured for urinary catecholamines and cotinine, and 12-lead electrocardiograms (ECGs) were measured for atrial and atrioventricular conduction times, including P duration, PR interval, and PR segment (lead II), which were analyzed for associations with cotinine by generalized linear models. Statistical mediation analyses were then used to test whether any significant associations between cotinine and atrioventricular conduction were mediated by catecholamines. ECG endpoints and urinary metabolites were included from a total of 136 participants in sinus rhythm. Atrial and atrioventricular conduction did not significantly differ between smokers (n = 53) and non-smokers (n = 83). Unadjusted and model-adjusted linear regressions revealed cotinine significantly and inversely associated with PR interval and PR segment, but not P duration. Dopamine, norepinephrine, and epinephrine all inversely associated with PR interval, whereas only dopamine was also inversely associated with PR segment (p < 0.05). Dopamine and norepinephrine (but not epinephrine) also associated positively with cotinine. Dopamine mediated the relationship between cotinine and PR interval, as well as the relationship between cotinine and PR segment. Smoking is associated with accelerated atrioventricular conduction and elevated urinary dopamine and norepinephrine. Smoking may accelerate atrioventricular nodal conduction via increased dopamine production.

Clinical Determinants of Myocardial Injury, Detectable and Serial Troponin Levels among Patients with Hypertensive Crisis.

Introduction There is a high prevalence of hypertensive crisis with myocardial injury, as evidenced by elevation in cardiac troponin levels. The risk factors predisposing patients to developing a myocardial injury, detectable troponin, and increase in serial troponin in this population are not known. Methods A retrospective study was designed to include all patients, presenting to the emergency room, diagnosed with hypertensive crisis, using International Classification of Diseases, 10th revision, Clinical Modification (ICD-10-CM) codes between 2016-2018 (n=467). Logistic regression was used to determine the important predictors of myocardial injury evidenced by troponin elevation >99th percentile of upper reference level (URL), detectable troponin (> 0.015 ng/ml), and increase in serial troponin levels. Results The 99th percentile of the initial troponin level among all patients was 0.433 ng/ml. A total of 15% had a myocardial injury, and the significant risk factors associated with it were body mass index (BMI) < 30 kg/m2 (odds ratio [OR] 0.50, confidence interval [CI] 0.28-0.89), congestive heart failure (CHF; OR 4.28, CI 2.21-8.25) and prior use of aspirin (OR 1.98, CI 1.08-3.63). About 35% had detectable troponin, and BMI < 30 kg/m2 (OR 0.62, CI 0.40-0.97), CHF (OR 3.49, CI 2.06-5.9), elevated creatinine (OR 1.17, CI 1.02-1.34) and age <61 years (OR 0.59, CI 0.38-0.94) were associated with it. The factors associated with an increase in serial troponin were BMI < 30 Kg/m2 (OR 0.56, CI 0.36-0.87), CHF (OR 1.78, CI 1.06-3.0), coronary artery disease (CAD; OR 2.08, CI 1.28-3.36) and non-Caucasian race (OR 0.52, CI 0.29-0.93). Conclusion About one-third of patients with the hypertensive crisis have detectable troponin. Still, among these, less than half have troponin levels >99th percentile URL, and the majority of these patients have minimal changes in serial troponin. Low BMI was associated with higher initial and serial troponin levels, and this obesity paradox was stronger among females and older patients.

Association between serum cotinine levels and electrocardiographic left atrial abnormality.

BACKGROUND: Although the harmful effect of tobacco exposure on cardiovascular disease (CVD) and its risk factors are well established, the constituents of cigarette-smoke and the pathophysiological mechanism involved are unknown. Recently, deep terminal negativity of P wave in V1 (DTNPV1) has emerged as a marker of left atrial abnormality that predicts atrial fibrillation, stroke, and death due to all-cause or CVD. Therefore, we examined the association between serum cotinine levels with abnormal DTNPV1 using the Third National Health and Nutrition Examination Survey. METHODS: This analysis included 4,507 participants (mean age 58 ± 13 years, 53% women, 49% non-Hispanic white) of NHANES III, without history of CVD or major electrocardiographic abnormalities and not on heart rate modifying medications. Multivariable logistic regression analysis was used to examine the association between serum cotinine and abnormal DTNPV1-defined from automatically processed electrocardiograms as values of the amplitude of the terminal negative phase of P wave in lead V1 exceeding 100 µV. RESULTS: Abnormal DTNPV1 was detected in 2.3% (n = 105) of the participants. In a model adjusted for demographics and CVD risk factors, each 10 ng/ml serum cotinine was associated with 2% increased odds of abnormal DTNPV1 (odds ratio 1.02, 95% confidence interval 1.01-1.03, p-value < 0.001). This association was consistent in subgroups stratified by age, sex, race, smoking status, hypertension, diabetes, dyslipidemia, and chronic obstructive pulmonary disease. CONCLUSION: Elevated serum cotinine levels are associated with an abnormal DTNPV1. This suggests that nicotine exposure can lead to left atrial abnormalities, a possible mechanism for increased risk of CVD.

Presence of multiple coronary angiographic characteristics for the diagnosis of acute coronary thrombus.

BACKGROUND: Coronary angiography is frequently employed to aid in the diagnosis of acute coronary thrombosis, but there is limited data to support its efficacy. The aim of the study was to evaluate sensitivity and specificity of five commonly used angiographic characteristics for diagnosis of acute coronary thrombosis: Ambrose complex lesion morphology; spherical, ovoid, or irregular filling defect; abrupt vessel cutoff; intraluminal staining; and any coronary filling defect. METHODS: Coronary angiography of 80 acute myocardial infarction or stable coronary artery disease subjects were assessed in blinded fashion, for the presence or absence of five angiographic characteristics. Only lesions of ≥ 10% stenosis were included in the analysis. Presence or absence of each angiographic characteristic was compared between lesions with or without the following study defined outcomes: 1) histologically confirmed thrombus, 2) highly probable thrombus, and 3) highly unlikely thrombus. RESULTS: A total of 323 lesions were evaluated. All studied angiographic characteristics were associated with histologically confirmed and highly probable thrombotic lesions vs. lesions not meeting criteria for these outcomes (p < 0.03), except for complex Ambrose morphology which was not associated with any of the study outcomes (p > 0.05). Specificity for identifying histologically confirmed or highly probable thrombotic lesion was high (92-100%), especially for spherical, ovoid, or irregular filling defect (99-100%) and intraluminal staining (99%). Sensitivity for identification of histologically confirmed or highly probable thrombotic lesions was low for all tested angiographic characteristics (17-60%). CONCLUSIONS: The presence of spherical, ovoid, or irregular filling defect or intraluminal staining was highly suggestive of coronary thrombus. However, none of the evaluated angiographic characteristics were useful for ruling out the presence of coronary thrombus. If confirmed in an independent cohort, these angiographic characteristic will be of significant value in confirming the diagnosis of acute coronary thrombosis.

Authors seldom report the most patient-important outcomes and absolute effect measures in systematic review abstracts.

OBJECTIVES: Explicit reporting of absolute measures is important to ensure treatment effects are correctly interpreted. We examined the extent to which authors report absolute effects for patient-important outcomes in abstracts of systematic review (SR). STUDY DESIGN AND SETTING: We searched OVID MEDLINE and Cochrane Database of Systematic Reviews to identify eligible SRs published in the year 2010. Citations were stratified into Cochrane and non-Cochrane reviews, with repeated random sampling in a 1:1 ratio. Paired reviewers screened articles and recorded abstract characteristics, including reporting of effect measures for the most patient-important outcomes of benefit and harm. RESULTS: We included 96 Cochrane and 94 non-Cochrane reviews. About 117 (77.5%) relative measures were reported in abstracts for outcomes of benefit, whereas only 34 (22.5%) absolute measures were reported. Similarly, for outcomes of harm, 41 (87.2%) relative measures were provided in abstracts, compared with only 6 (12.8%) absolute measures. Eighteen (9.5%) abstracts reported both absolute and relative measures for outcomes of benefit, whereas only two (1.1%) abstracts reported both measures for outcomes of harm. Results were similar between Cochrane and non-Cochrane reviews. CONCLUSION: SR abstracts seldom report measures of absolute effect. Journal editors should insist that authors report both relative and absolute effects for patient-important outcomes.

Systematic reviews experience major limitations in reporting absolute effects.

OBJECTIVES: Expressing treatment effects in relative terms yields larger numbers than expressions in absolute terms, affecting the judgment of the clinicians and patients regarding the treatment options. It is uncertain how authors of systematic reviews (SRs) absolute effect estimates are reported in. We therefore undertook a systematic survey to identify and describe the reporting and methods for calculating absolute effect estimates in SRs. STUDY DESIGN AND SETTING: Two reviewers independently screened title, abstract, and full text and extracted data from a sample of Cochrane and non-Cochrane SRs. We used regression analyses to examine the association between study characteristics and the reporting of absolute estimates for the most patient-important outcome. RESULTS: We included 202 SRs (98 Cochrane and 104 non-Cochrane), most of which (92.1%) included standard meta-analyses including relative estimates of effect. Of the 202 SRs, 73 (36.1%) reported absolute effect estimates for the most patient-important outcome. SRs with statistically significant effects were more likely to report absolute estimates (odds ratio, 2.26; 95% confidence interval: 1.08, 4.74). The most commonly reported absolute estimates were: for each intervention, risk of adverse outcomes expressed as a percentage (41.1%); number needed to treat (26.0%); and risk for each intervention expressed as natural units or natural frequencies (24.7%). In 12.3% of the SRs that reported absolute effect estimates for both benefit and harm outcomes, harm outcomes were reported exclusively as absolute estimates. Exclusively reporting of beneficial outcomes as absolute estimates occurred in 6.8% of the SRs. CONCLUSIONS: Most SRs do not report absolute effects. Those that do often report them inadequately, thus requiring users of SRs to generate their own estimates of absolute effects. For any apparently effective or harmful intervention, SR authors should report both absolute and relative estimates to optimize the interpretation of their findings.

Reporting, handling and assessing the risk of bias associated with missing participant data in systematic reviews: a methodological survey.

OBJECTIVES: To describe how systematic reviewers are reporting missing data for dichotomous outcomes, handling them in the analysis and assessing the risk of associated bias. METHODS: We searched MEDLINE and the Cochrane Database of Systematic Reviews for systematic reviews of randomised trials published in 2010, and reporting a meta-analysis of a dichotomous outcome. We randomly selected 98 Cochrane and 104 non-Cochrane systematic reviews. Teams of 2 reviewers selected eligible studies and abstracted data independently and in duplicate using standardised, piloted forms with accompanying instructions. We conducted regression analyses to explore factors associated with using complete case analysis and with judging the risk of bias associated with missing participant data. RESULTS: Of Cochrane and non-Cochrane reviews, 47% and 7% (p<0.0001), respectively, reported on the number of participants with missing data, and 41% and 9% reported a plan for handling missing categorical data. The 2 most reported approaches for handling missing data were complete case analysis (8.5%, out of the 202 reviews) and assuming no participants with missing data had the event (4%). The use of complete case analysis was associated only with Cochrane reviews (relative to non-Cochrane: OR=7.25; 95% CI 1.58 to 33.3, p=0.01). 65% of reviews assessed risk of bias associated with missing data; this was associated with Cochrane reviews (relative to non-Cochrane: OR=6.63; 95% CI 2.50 to 17.57, p=0.0001), and the use of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology (OR=5.02; 95% CI 1.02 to 24.75, p=0.047). CONCLUSIONS: Though Cochrane reviews are somewhat less problematic, most Cochrane and non-Cochrane systematic reviews fail to adequately report and handle missing data, potentially resulting in misleading judgements regarding risk of bias.

Cardiomyocyte injury induced by hemodynamic cardiac stress: Differential release of cardiac biomarkers.

OBJECTIVE: We explored whether hemodynamic cardiac stress leads to a differential release of cardiomyocyte injury biomarkers, used in the diagnosis of acute myocardial infarction (AMI). METHODS: In an observational international multicenter study, we enrolled 831 unselected patients presenting with symptoms suggestive of AMI to the emergency department. The final diagnosis was adjudicated by two independent cardiologists. Hemodynamic cardiac stress was quantified by levels of B-type natriuretic peptide (BNP). Spearman's rho correlation was used to analyze the correlations between BNP and high-sensitivity cardiac troponin T (hs-cTnT), Siemens cTnI-Ultra (cTnI-ultra), CK-MB and Myoglobin. Patients were categorized according to the extent of hemodynamic cardiac stress as quantified by BNP tertiles. RESULTS: Among all patients, the positive pair-wise correlation with BNP was strongest with hs-cTnT and cTnI-ultra (r=0.58 and 0.50, respectively), moderate for Myoglobin (r=0.43), and weakest with CK-MB (r=0.25; p<0.001 for each). Similar pattern of correlations was also observed among AMI patients. Among patients diagnosed with non-cardiac cause of chest pain (n=385, 46%) and cardiac but non-coronary (n=109, 13%), BNP had significant positive correlations with hs-cTnT, cTnI-ultra and Myoglobin (p<0.05), but not with CK-MB (p=NS). A similar pattern of stronger correlation between BNP and hs-cTnT, cTnI-ultra and Myoglobin as compared to that with CK-MB was also observed within the higher BNP tertile range. There was no correlation between BNP and other biomarkers within the 1st BNP tertile group. CONCLUSION: Hemodynamic cardiac stress, as quantified by BNP, as a likely cause of cardiomyocyte injury, is more closely reflected by concentrations of hs-cTnT, cTnI-ultra and Myoglobin than CK-MB.

Right ventricular dysfunction as an echocardiographic prognostic factor in hemodynamically stable patients with acute pulmonary embolism: a meta-analysis.

BACKGROUND: We investigated whether right ventricular dysfunction (RVD) as assessed by echocardiogram can be used as a prognostic factor in hemodynamically stable patients with acute pulmonary embolism (PE). Short-term mortality has been investigated only in small studies and the results have been controversial. METHODS: A PubMed search was conducted using two keywords, "pulmonary embolism" and "echocardiogram", for articles published between January 1st 1998 and December 31st 2011. Out of 991 articles, after careful review, we found 12 articles that investigated the implications of RVD as assessed by echocardiogram in predicting short-term mortality for hemodynamically stable patients with acute PE. We conducted a meta-analysis of these data to identify whether the presence of RVD increased short-term mortality. RESULTS: Among 3283 hemodynamically stable patients with acute PE, 1223 patients (37.3%) had RVD, as assessed by echocardiogram, while 2060 patients (62.7%) had normal right ventricular function. Short-term mortality was reported in 167 (13.7%) out of 1223 patients with RVD and in 134 (6.5%) out of 2060 patients without RVD. Hemodynamically stable patients with acute PE who had RVD as assessed by echocardiogram had a 2.29-fold increase in short-term mortality (odds ratio 2.29, 95% confidence interval 1.61-3.26) compared with patients without RVD. CONCLUSIONS: In hemodynamically stable patients with acute PE, RVD as assessed by echocardiogram increases short-term mortality by 2.29 times. Consideration should be given to obtaining echocardiogram to identify high-risk patients even if they are hemodynamically stable.

Civilian craniocerebral gunshot injuries in a developing country: presentation, injury characteristics, prognostic indicators, and complications.

BACKGROUND: Civilian craniocerebral gunshot injuries (CGIs) are rare but increasing in incidence in the developing world and there is scare literature on presentation, injury characteristics, prognostic indicators, and complications of brain trauma due to projectiles. METHODS: A retrospective review of 51 civilian patients with CGI who presented to the Aga Khan University Hospital between 1998 and 2011 was carried out. Presentation, injury characteristics, and complications were analyzed with emphasis on outcomes and prognostic indicators. RESULTS: There were 43 male and 8 female patients with an average age of 28.92 (±12.33) years. Twenty-three patients had a Glasgow Coma Scale (GCS) score of 13-15, 6 patients had a GCS score of 9-12, and 22 patients had a GCS score of 3-8 on admission. The overall mortality rate was 22% (n = 11). The most common postoperative neurologic deficits were motor deficits (19 patients) followed by aphasias (11 patients). On univariate analysis, admission GCS score and bi- or multilobar injuries were found to be highly predictive of neurologic outcome. There was no difference in outcomes between penetrating and perforating injuries. We also failed to find a statistically significant correlation between ventricular injury and outcomes in our patients. CONCLUSION: Admission GCS and number of lobes involved are highly prognostic of outcome. Patients with a GCS score ≥9 and unilobar injury on computed tomographic scans may benefit the most from surgical management.

A methodological survey of the analysis, reporting and interpretation of Absolute Risk ReductiOn in systematic revieWs (ARROW): a study protocol.

BACKGROUND: Clinicians, providers and guideline panels use absolute effects to weigh the advantages and downsides of treatment alternatives. Relative measures have the potential to mislead readers. However, little is known about the reporting of absolute measures in systematic reviews. The objectives of our study are to determine the proportion of systematic reviews that report absolute measures of effect for the most important outcomes, and ascertain how they are analyzed, reported and interpreted. METHODS/DESIGN: We will conduct a methodological survey of systematic reviews published in 2010. We will conduct a 1:1 stratified random sampling of Cochrane vs. non-Cochrane systematic reviews. We will calculate the proportion of systematic reviews reporting at least one absolute estimate of effect for the most patient-important outcome for the comparison of interest. We will conduct multivariable logistic regression analyses with the reporting of an absolute estimate of effect as the dependent variable and pre-specified study characteristics as the independent variables. For systematic reviews reporting an absolute estimate of effect, we will document the methods used for the analysis, reporting and interpretation of the absolute estimate. DISCUSSION: Our methodological survey will inform current practices regarding reporting of absolute estimates in systematic reviews. Our findings may influence recommendations on reporting, conduct and interpretation of absolute estimates. Our results are likely to be of interest to systematic review authors, funding agencies, clinicians, guideline developers and journal editors.

Early diagnosis of myocardial infarction using absolute and relative changes in cardiac troponin concentrations.

BACKGROUND: Absolute changes in high-sensitivity cardiac troponin T (hs-cTnT) seem to have higher diagnostic accuracy in the early diagnosis of acute myocardial infarction compared with relative changes. It is unknown whether the same applies to high-sensitivity cardiac troponin I (hs-cTnI) assays and whether the combination of absolute and relative change might further increase accuracy. METHODS: In a prospective, international multicenter study, high-sensitivity cardiac troponin (hs-cTn) was measured with 3 novel assays (hs-cTnT, Roche Diagnostics Corp, Indianapolis, Ind; hs-cTnI, Beckman Coulter Inc, Brea, Calif; hs-cTnI, Siemens, Munich, Germany) in a blinded fashion at presentation and after 1 and 2 hours in a blinded fashion in 830 unselected patients with suspected acute myocardial infarction. The final diagnosis was adjudicated by 2 independent cardiologists. RESULTS: The area under the receiver operating characteristic curve for diagnosing acute myocardial infarction was significantly higher for 1- and 2-hour absolute versus relative hs-cTn changes for all 3 assays (P < .001). The area under the receiver operating characteristic curve of the combination of 2-hour absolute and relative change (hs-cTnT 0.98 [95% confidence interval {CI}, 0.97-0.99]; hs-cTnI, Beckman Coulter Inc, 0.97 [95% CI, 0.96-0.99]; hs-cTnI, Siemens, 0.96 [95% CI, 0.93-0.99]) were high and provided some benefit compared with the use of absolute change alone for hs-cTnT, but not for the hs-cTnI assays. Reclassification analysis confirmed the superiority of absolute changes versus relative changes. CONCLUSIONS: Absolute changes seem to be the preferred metrics for both hs-cTnT and hs-cTnI in the early diagnosis of acute myocardial infarction. The combination of absolute and relative changes provides a small added value for hs-cTnT, but not for hs-cTnI.

The value of history and goals of care with code status; even in an emergency setting.

This is a case report involving an elderly Jehovah's Witness woman with a history of chronic anaemia who suffers cardiac arrest and is resuscitated. This case illustrates, even in an emergency setting, (1) the value of obtaining relevant history, (2) addressing code status within the framework of achievable goals of care and (3) the need to revise both history and goals of care, as more information becomes available. We also propose aspects of this discussion that would benefit from future research.

Mid-regional pro-adrenomedullin in the early evaluation of acute chest pain patients.

BACKGROUND: The purpose of this study was to investigate the utility of mid-regional pro-adrenomedullin (MR-proADM) in the early diagnosis and risk stratification of patients with acute chest pain in comparison with established and novel biomarkers and risk scores. METHODS: In this prospective, observational, international, multi-center trial (APACE), MR-proADM was determined in 1179 unselected patients with acute chest pain. Patients were followed for 24 months. RESULTS: MR-proADM concentrations at presentation were higher in patients with AMI (median: 0.78 nmol/l, IQR 0.60-1.13) than in patients with other diagnoses (0.64 nmol/l, IQR 0.49-0.86 nmol/l; p<0.001). The diagnostic accuracy of MR-proADM for AMI as quantified by the area under the receiver operating characteristic curve (AUC) was 0.66. Adding MR-proADM to hs-cTnT could not improve its diagnostic accuracy for AMI (p=0.431). Seventy-six percent of all deaths occurred in the fourth quartile of MR-proADM (>0.90 nmol/l). Adding MR-proADM to the TIMI-score (AUC 0.87) predicted 1-year mortality more accurately than the TIMI-score alone (AUC 0.82; p<0.001). Net reclassification improvement (TIMI vs. additionally MR-proADM) amounted to 0.137 (p=0.012). MR-proADM had higher prognostic accuracy as compared to hs-cTnT in patients with AMI (p=0.015) and in those without AMI (p=0.003). MR-proADM at presentation was tantamount to GRACE score and BNP as to its prognostic accuracy for mortality. The AUC for the prediction of cardiovascular events amounted to 0.63. CONCLUSIONS: While MR-proADM does not have clinical utility in the early diagnosis of AMI or predicting cardiovascular events in patients with acute chest pain, it may provide prognostic value for all-cause mortality.

Pathophysiology of lower extremity edema in acute heart failure revisited.

BACKGROUND: The pathophysiology and key determinants of lower extremity edema in patients with acute heart failure are poorly investigated. METHODS: We prospectively enrolled 279 unselected patients presenting to the Emergency Department with acute heart failure. Lower extremity edema was quantified at predefined locations. Left ventricular ejection fraction, central venous pressure quantifying right ventricular failure, biomarkers to quantify hemodynamic cardiac stress (B-type natriuretic peptide), and the activity of the arginine-vasopressin system (copeptin) also were recorded. RESULTS: Lower extremity edema was present in 218 (78%) patients and limited to the ankle in 22%, reaching the lower leg in 40%, reaching the upper leg in 11%, and was generalized (anasarca) in 3% of patients. Patients in the 4 strata according to the presence and extent of lower leg edema had comparable systolic blood pressure, left ventricular ejection fraction, central venous pressure, and B-type natriuretic peptide levels, as well as copeptin and glomerular filtration rate (P=NS for all). The duration of dyspnea preceding the presentation was longer in patients with more extensive edema (P=.006), while serum sodium (P=.02) and serum albumin (P=.03) was lower. CONCLUSION: Central venous pressure, hemodynamic cardiac stress, left ventricular ejection fraction, and the activity of the arginine-vasopressin system do not seem to be key determinants of the presence or extent of lower extremity edema in acute heart failure.