Helicobacter pylori and Pro-Inflammatory Protein Biomarkers in Myocardial Infarction with and without Obstructive Coronary Artery Disease.

Myocardial infarction (MI) with obstructive coronary artery disease (MI-CAD) and MI in the absence of obstructive coronary artery disease (MINOCA) affect different populations and may have separate pathophysiological mechanisms, with greater inflammatory activity in MINOCA compared to MI-CAD. Helicobacter pylori (Hp) can cause systemic inflammation and has been associated with cardiovascular disease (CVD). We aimed to investigate whether Hp infection is associated with concentrations of protein biomarkers of inflammation and CVD. In a case-control study, patients with MINOCA (n = 99) in Sweden were included, complemented by matched subjects with MI-CAD (n = 99) and controls (n = 100). Protein biomarkers were measured with a proximity extension assay in plasma samples collected 3 months after MI. The seroprevalence of Hp and cytotoxin-associated gene A (CagA) was determined using ELISA. The associations between protein levels and Hp status were studied with linear regression. The prevalence of Hp was 20.2%, 19.2%, and 16.0% for MINOCA, MI-CAD, and controls, respectively (p = 0.73). Seven proteins were associated with Hp in an adjusted model: tissue plasminogen activator (tPA), interleukin-6 (IL-6), myeloperoxidase (MPO), TNF-related activation-induced cytokine (TRANCE), pappalysin-1 (PAPPA), soluble urokinase plasminogen activator receptor (suPAR), and P-selectin glycoprotein ligand 1 (PSGL-1). Hp infection was present in one in five patients with MI, irrespective of the presence of obstructive CAD. Inflammatory proteins were elevated in Hp-positive subjects, thus not ruling out that Hp may promote an inflammatory response and potentially contribute to the development of CVD.

Mortality and ventricular arrhythmias in patients on d,l-sotalol for rhythm control of atrial fibrillation: A nationwide cohort study.

BACKGROUND: Use of d,l-sotalol for rhythm control in patients with atrial fibrillation (AF) has raised safety concerns. Previous randomized studies are few and not designed for mortality outcome. OBJECTIVE: The purpose of this study was to compare the incidences of mortality and ventricular arrhythmias in AF patients treated with d,l-sotalol for rhythm control vs matched control patients treated with cardioselective beta-blockers. METHODS: This population-based cohort study included AF patients from the Swedish National Patient Registry (2006-2017) who underwent rhythm control after a second cardioversion. Incidence rates (IRs) and adjusted hazard ratios (aHRs) for mortality and a composite endpoint of cardiac arrest/death and ventricular arrhythmias were calculated for the overall cohort and a 1:1 propensity score matched cohort of d,l-sotalol vs beta-blocker treatment. RESULTS: Among patient treated with d,l-sotalol (n = 4987) and beta-blocker (n = 27,078) (mean follow-up 458 days), all-cause mortality was lower in patients treated with d,l-sotalol: IR 1.21; 95% confidence interval 0.95-1.52 vs 2.42 (2.26-2.60) deaths per 100 patient-years; aHR 0.66 (0.52-0.83). The difference in mortality persisted in the propensity score matched comparison (n = 4953 in each group): aHR 0.63 (0.48-0.86). No differences were observed in the composite outcome: IR in propensity cohorts 2.13 (1.78-2.52) vs 2.07 (1.73-2.53) events per 100 years; aHR 1.01 (0.78-1.29). CONCLUSION: There was no excess mortality with d,l-sotalol compared with cardioselective beta-blockers in patients undergoing rhythm control treatment for AF after a second cardioversion. Our results indicate that the risk associated with d,l-sotalol treatment for AF can be mitigated by careful patient selection and strict adherence to follow-up protocols.

Recent-onset atrial fibrillation: a study exploring the elements of Virchow's triad after cardioversion.

PURPOSE: Atrial fibrillation (AF) imposes an inherent risk for stroke and silent cerebral emboli, partly related to left atrial (LA) remodeling and activation of inflammatory and coagulation systems. The aim was to explore the effects of cardioversion (CV) and short-lasting AF on left atrial hemodynamics, inflammatory, coagulative and cardiac biomarkers, and the association between LA functional recovery and the presence of a prior history of AF. METHODS: Patients referred for CV within 48 h after AF onset were prospectively included. Echocardiography and blood sampling were performed immediately prior, 1-3 h after, and at 7-10 days after CV. The presence of chronic white matter hyperintensities (WMH) on magnetic resonance imaging was related to biomarker levels. RESULTS: Forty-three patients (84% males), aged 55±9.6 years, with median CHA2DS2-VASc score 1 (IQR 0-1) were included. The LA emptying fraction (LAEF), LA peak longitudinal strain during reservoir, conduit, and contractile phases improved significantly after CV. Only LAEF normalized within 10 days. Interleukin-6, high-sensitivity cardiac-troponin-T (hs-cTNT), N-terminal-pro-brain-natriuretic peptide, prothrombin-fragment 1+2 (PTf1+2), and fibrinogen decreased significantly after CV. There was a trend towards higher C-reactive protein, hs-cTNT, and PTf1+2 levels in patients with WMH (n=21) compared to those without (n=22). At 7-10 days, the LAEF was significantly lower in patients with a prior history of AF versus those without. CONCLUSION: Although LA stunning resolved within 10 days, LAEF remained significantly lower in patients with a prior history of AF versus those without. Inflammatory and coagulative biomarkers were higher before CV, but subsided after 7-10 days, which altogether might suggest an enhanced thrombogenicity, even in these low-risk patients.

Antiphospholipid antibodies in patients with myocardial infarction with and without obstructive coronary arteries.

BACKGROUND: Recent studies demonstrate that prothrombotic antiphospholipid antibodies (aPL) are overrepresented in patients with myocardial infarction (MI) due to coronary artery disease (MICAD). However, it is not known whether aPL differ between the two subsets of MI: MICAD and MI with nonobstructive coronary arteries (MINOCA). OBJECTIVES: To determine whether aPL are associated with MINOCA or MICAD, or with hypercoagulability as assessed by activated protein C-protein C inhibitor (APC-PCI) complex. METHODS: Well-characterized patients with MINOCA (n = 98), age- and gender-matched patients with MICAD (n = 99), and healthy controls (n = 100) were included in a cross-sectional case-control study. Autoantibodies (IgA/G/M) targeting cardiolipin and ß2 glycoprotein-I and specific nuclear antigens were analyzed by multiplexed bead technology. The concentration of APC-PCI was determined as a measure of hypercoagulability by an immunofluorometric sandwich assay. RESULTS: Both prevalence and titers of aPL of the IgG isotype (anti-cardiolipin and/or anti-ß2 glycoprotein-I) were higher in patients with MINOCA and MICAD than in controls. aPL IgG positivity was twice as frequent among patients with MICAD than MINOCA (11% vs. 6%, nonsignificant). We observed no group differences regarding aPL IgA/M or antibodies targeting specific nuclear antigens. Levels of APC-PCI were elevated in aPL IgG-positive compared to aPL IgG-negative MICAD patients. CONCLUSIONS: aPL IgG, but not IgA/M, are enriched particularly in patients with MICAD but also in patients with MINOCA, as compared to controls. Interestingly, signs of hypercoagulability-measured by increased levels of the APC-PCI complex-were present in aPL IgG-positive MICAD patients, indicating an association with functional disturbances of the coagulation system.

Diurnal QT analysis in patients with sotalol after cardioversion of atrial fibrillation.

BACKGROUND: The risk of ventricular arrhythmias in patients on QT prolonging drugs is indicated to be increased early after cardioversion (CV) of atrial fibrillation (AF) to sinus rhythm (SR). Sotalol, used to prevent AF relapse, prolongs cardiac repolarization and corrected QT interval (QTc). A pronounced QTc prolongation is an established marker of pro-arrhythmias. Our objective was to use novel technique to quantify and evaluate the diurnal variation of the QTc interval after elective CV to SR in patients on sotalol or metoprolol. METHODS: Fifty patients underwent twelve-lead Holter recording for 24 hr after elective CV for persistent AF. All patients had the highest tolerable stable dose of sotalol (n = 27) or metoprolol (n = 23). Measurements of QT and RR intervals were performed on all valid beats. RESULTS: A clear diurnal variation of both HR and QTc was seen in both groups, more pronounced in patients on sotalol, where a high percentage of heartbeats with QTc >500 ms was observed, especially at night. Six patients (22%) on sotalol but none on metoprolol had >20% of all heart beats within the 24-hour recording with QTc >500 ms. CONCLUSION: Twenty-four-hour Holter recordings with QT-measurement immediately after CV demonstrated that one in five patients on sotalol had >20% of all heart beats with prolonged QTc >500 ms, especially during night-time. The QTc diurnal variation was retained in patients on ß-blockade or a potent class III anti-arrhythmic drug with ß-blocking properties.

Is rheumatoid arthritis a risk factor for acute coronary syndrome also among individuals at elevated risk, such as individuals presenting with acute chest pain?

BACKGROUND: Patients with rheumatoid arthritis (RA) are, on average, at increased risk of acute coronary syndrome (ACS) compared to the general population, but it remains unknown whether RA remains an ACS risk factor also in settings where the ACS risk is already high elevated, such as among individuals presenting to the emergency department (ED) with chest pain. METHODS AND RESULTS: We included 49 283 individuals (514 (1.0%) had RA) presenting with chest pain at the four hospital EDs in Stockholm, Sweden, 2013-2016 in a cohort study. Information on exposure (RA), outcome (ACS) and comorbidities was provided through national registers. The association between RA and ACS was assessed, overall and by levels of high-sensitivity cardiac troponin T (hs-cTnT) and number of ACS risk factors, using logistic regression models adjusted for age, sex, hospital, calendar year and cardiovascular risk factors. ACS was more common in patients with (8.2%) than without (4.6%) RA, adjusted OR =1.4, 95% CI 1.0 to 2.0. This association was particularly strong in individuals with initial hs-cTnT levels between 5 and 14 ng/L, or no additional ACS risk factors (adjusted ORs above 2), but no longer detectable in those with hs-cTnT >14 ng/L or with three or more additional ACS risk factors. CONCLUSION: RA is a risk factor for ACS also among patients at the ED with chest pain. This association is not explained by traditional ACS risk factors, and most pronounced in patients with normal hs-cTnT and few other ACS risk factors, prompting particular ACS vigilance in this RA patient group.

Serial Magnetic Resonance Imaging after Electrical Cardioversion of Recent Onset Atrial Fibrillation in Anticoagulant-Naïve Patients - A Prospective Study Exploring Clinically Silent Cerebral Lesions.

BACKGROUND: Patients with atrial fibrillation (AF) have a high incidence of cognitive impairment, which may be related to clinically silent microembolism causing cerebral infarctions. OBJECTIVE: To explore the occurrence and timing of silent brain lesions following electrical cardioversion (CV) of recent onset AF in anticoagulant-naïve patients and to study related effects on cognitive function and biomarkers of cerebral damage, S100b. METHODS: Patients with AF duration > 48 hours were prospectively included. Brain magnetic resonance imaging (MRI) and S100b, were obtained prior, after and 7-10 days following CV. Trail making tests (TMT-A and TMT-B) and their difference, ΔΤΜΤ, were assessed prior to CV, 7-10 days and 30 days after CV. RESULTS: Forty-three patients (84% males) with median CHA2DS2-VASc score 1 (interquartile range 0-1) were included. Sequential MRI, including diffusion weighted scans, showed no new brain lesions after CV. Chronic white matter hyperintensities were present at baseline in 21/43 (49%) patients. The S100b (µg/l) levels increased significantly from baseline, (mean ±SD) 0.0472±0.0182 to 0.0551±0.0185 after CV, p=0.001 and then decreased 7-10 days after CV to 0.0450±0.0186, p <.;0.001. Consecutive TMT scores improved successively after CV, being statistically and clinically significant for TMT-B (p<0.01) and ΔΤΜΤ (p=0.005) between 7-10 days and 30 days after CV (Reliable Change Index >1.96). CONCLUSIONS: New brain lesions could not be detected on MRI after CV, but the high incidence of white matter hyperintensities and the transient increase in S100b may indicate transient or minor brain damage undetectable by MRI thus heightening the need to reevaluate thromboembolic risk prior to CV even in low risk patients.

Family history of coronary artery disease is associated with acute coronary syndrome in 28,188 chest pain patients.

BACKGROUND: The value of family history of coronary artery disease (CAD) in diagnosing acute coronary syndrome (ACS) in chest pain patients is uncertain, especially in relation to high-sensitivity assays for cardiac troponin T (hs-cTnT), which have improved ACS diagnostics. Our objective was to investigate the association between verified family history of CAD and ACS in chest pain patients, overall and in different strata of initial hs-cTnT. METHODS: Data on chest pain patients visiting four emergency departments in Sweden during 2013-2016 were cross-referenced with national registers of kinship, diseases and prescriptions. Family history of early CAD was defined as the occurrence of myocardial infarction or coronary revascularization before the age of 55 years in male and 65 years in female first-degree relatives. The outcome was combined including ACS and cardiovascular death within 30 days of presentation. RESULTS: Of 28,188 patients, 4.7% of patients had ACS. In total, 8.2% and 32.4% had a family history of early and ever-occurring CAD, respectively. Family history of CAD was positively associated with the outcome, independently of age, gender, cardiovascular risk factors and electrocardiogram findings. The strongest association was observed for family history of early CAD (odds ratio 1.62, 95% confidence interval 1.35-1.94). Stronger associations were observed in young patients (e.g. <65 years) and in patients with non-elevated initial hs-cTnT levels (p-value for interaction = 0.004 and 0.001, respectively). CONCLUSIONS: Family history of CAD is associated with ACS in chest pain patients, especially in patients of young age or with non-elevated initial hs-cTnT levels.

Increased Inflammatory Activity in Patients 3 Months after Myocardial Infarction with Nonobstructive Coronary Arteries.

BACKGROUND: Around 5%-10% of patients with myocardial infarction (MI) present with nonobstructive coronary arteries (MINOCA). We aimed to assess pathophysiological mechanisms in MINOCA by extensively evaluating cardiovascular biomarkers in the stable phase after an event, comparing MINOCA patients with cardiovascular healthy controls and MI patients with obstructive coronary artery disease (MI-CAD). METHODS: Ninety-one biomarkers were measured with a proximity extension assay 3 months after MI in 97 MINOCA patients, 97 age- and sex-matched MI-CAD patients, and 98 controls. Lasso analyses (penalized logistic regression models) and adjusted multiple linear regression models were used for statistical analyses. RESULTS: In the Lasso analysis (MINOCA vs MI-CAD), 8 biomarkers provided discriminatory value: P-selectin glycoprotein ligand 1, C-X-C motif chemokine 1, TNF-related activation-induced cytokine, and pappalysin-1 (PAPPA) with increasing probabilities of MINOCA, and tissue-type plasminogen activator, B-type natriuretic peptide, myeloperoxidase, and interleukin-1 receptor antagonist protein with increasing probabilities of MI-CAD. Comparing MINOCA vs controls, 7 biomarkers provided discriminatory value: N-terminal pro-B-type natriuretic peptide, renin, NF-κ-B essential modulator, PAPPA, interleukin-6, and soluble urokinase plasminogen activator surface receptor with increasing probabilities of MINOCA, and agouti-related protein with increasing probabilities of controls. Adjusted multiple linear regression analyses showed that group affiliation was associated with the concentrations of 7 of the 8 biomarkers in the comparison MINOCA vs MI-CAD and 5 of the 7 biomarkers in MINOCA vs controls. CONCLUSIONS: Three months after the MI, the biomarker concentrations indicated greater inflammatory activity in MINOCA patients than in both MI-CAD patients and healthy controls, and a varying degree of myocardial dysfunction among the 3 cohorts.

A Rule-Out Strategy Based on High-Sensitivity Troponin and HEART Score Reduces Hospital Admissions.

STUDY OBJECTIVE: We evaluate whether a combination of a 1-hour high-sensitivity cardiac troponin algorithm and History, ECG, Age, Risk Factors, and Troponin (HEART) score reduces admission rate (primary outcome) and affects time to discharge, health care-related costs, and 30-day outcome (secondary outcomes) in patients with symptoms suggestive of an acute coronary syndrome. METHODS: This prospective observational multicenter study was conducted before (2013 to 2014) and after (2015 to 2016) implementation of a strategy including level of high-sensitivity cardiac troponin T or I at 0 and 1 hour, combined with the HEART score. Patients with a nonelevated baseline high-sensitivity cardiac troponin level, a 1-hour change in high-sensitivity cardiac troponin T level less than 3 ng/L, or high-sensitivity cardiac troponin I level less than 6 ng/L and a HEART score less than or equal to 3 were considered to be ruled out of having acute coronary syndrome. A logistic regression analysis was performed to adjust for differences in baseline characteristics. RESULTS: A total of 1,233 patients were included at 6 centers. There were no differences in regard to median age (64 versus 63 years) and proportion of men (57% versus 54%) between the periods. After introduction of the new strategy, the admission rate decreased from 59% to 33% (risk ratio 0.55 [95% confidence interval {CI} 0.48 to 0.63]; odds ratio 0.33 [95% CI 0.26 to 0.42]; adjusted odds ratio 0.33 [95% CI 0.25 to 0.42]). The median hospital stay was reduced from 23.2 to 4.7 hours (95% CI of difference -20.4 to -11.4); median health care-related costs, from $1,748 to $1,079 (95% CI of difference -$953 to -$391). The number of clinical events was very low. CONCLUSION: In this before-after study, clinical implementation of a 1-hour high-sensitivity cardiac troponin algorithm combined with the HEART score was associated with a reduction in admission rate and health care burden, with very low rates of adverse clinical events.

Sensitivity of undetectable level of high-sensitivity troponin T at presentation in a large non-ST-segment elevation myocardial infarction cohort of early presenters.

BACKGROUND: We aimed to evaluate the diagnostic sensitivity for myocardial infarction (MI) when using an undetectable level of high-sensitivity cardiac troponin T (hs-cTnT < 5 ng/L) at presentation combined with a non-ischemic electrocardiogram (ECG), to rule out MI in a non-ST-segment elevation MI (NSTEMI) cohort presenting ≤2 h from symptom onset. We also aimed to compare baseline characteristics and 30-day outcome in NSTEMI patients presenting with and without hs-cTnT < 5 ng/L. METHODS: All patients admitted to five centers in Sweden 2011-2015, after the introduction of hs-cTnT, who presented ≤2 h from symptom onset and received a final diagnosis of NSTEMI, were identified through the SWEDEHEART registry. These data and data of hs-cTnT levels were verified in the hospitals' medical records. The registry provided baseline and outcome data. RESULTS: Twenty-four (2.6%) of 911 NSTEMI patients presented with hs-cTnT < 5 ng/L. In patients presenting >1-≤2 h from symptom onset the sensitivity for MI when combining hs-cTnT and ECG was 99.4% (95% CI 98.4%-99.8%). In patients presenting ≤1 h, and in patients aged ≤65 years without prior MI, the sensitivity was insufficient. NSTEMI patients presenting with hs-cTnT < 5 ng/L were younger and had less often a prior MI. A total of 62.5 vs. 63.5% of the NSTEMI patients presenting with and without hs-cTnT < 5 ng/L underwent revascularization within 30 days and 4.5 and 3.2% died respectively. CONCLUSIONS: Hs-cTnT < 5 ng/L at presentation combined with a non-ischemic ECG may be used to rule out MI in patients presenting as early as >1 h from symptom onset with a sufficient sensitivity.

Personality Traits in Patients with Myocardial Infarction with Nonobstructive Coronary Arteries.

OBJECTIVE: The purpose of this study was to describe type A behavior pattern and trait anger in patients with myocardial infarction with nonobstructive coronary arteries (MINOCA) and compare them with patients with coronary heart disease and healthy controls. Type A behavior pattern and anger have been linked to coronary heart disease in previous studies. This is the first study to assess type A behavior pattern and trait anger in MINOCA patients. METHODS: One hundred MINOCA patients, consecutively recruited during 2007-2011 at 5 coronary care units in Stockholm, were matched for sex and age to 100 coronary heart disease patients and 100 healthy controls. All participants completed the Bortner Rating Scale to quantify type A behavior pattern and the Spielberger Trait Anger Scale to quantify anger 3 months after the acute event. RESULTS: MINOCA patients' Bortner Rating Scale score was 70.9 ± 10.8 (mean ± SD) and Spielberger Trait Anger Scale score was 14 (12-17) (median; interquartile range). Coronary heart disease patients' Bortner Rating Scale score was 70.5 ± 10.2 and Spielberger Trait Anger Scale score was 14 (12-17). Healthy controls' Bortner Rating Scale score was 71.9 ± 9.1 and Spielberger Trait Anger Scale score was 13 (11-16). CONCLUSION: We found no significant differences in Bortner Rating Scale score and Spielberger Trait Anger Scale score among MINOCA, coronary heart disease patients, and healthy controls, regardless of whether total scores, subscales, or cutoffs were used to classify type A behavior pattern and trait anger. However, we cannot exclude the existence of an occasional episode of anger or mental stress in relation to the coronary event. This is the first study to assess type A behavior pattern and trait anger in patients with MINOCA, and future studies need to confirm the current findings before any firm conclusions can be made.

Prevalence of Anxiety and Depression Symptoms in Patients with Myocardial Infarction with Non-Obstructive Coronary Arteries.

BACKGROUND: Myocardial infarction with non-obstructive coronary arteries is a working diagnosis for several heart disorders. Previous studies on anxiety and depression in patients with myocardial infarction with non-obstructive coronary arteries are lacking. Our aim was to investigate the prevalence of anxiety and depression among patients with myocardial infarction with non-obstructive coronary arteries. METHODS: We included 99 patients with myocardial infarction with non-obstructive coronary arteries together with age- and sex-matched control groups who completed the Beck Depression Inventory and the Hospital Anxiety and Depression Scale (HADS) 3 months after the acute event. RESULTS: Using the Beck Depression Inventory, we found that the prevalence of depression in patients with myocardial infarction with non-obstructive coronary arteries (35%) was higher than in healthy controls (9%; P = .006) and similar to that of patients with coronary heart disease (30%; P = .954). Using the HADS anxiety subscale, we found that the prevalence of anxiety in patients with myocardial infarction with non-obstructive coronary arteries (27%) was higher than in healthy controls (9%; P = .002) and similar to that of patients with coronary heart disease (21%; P = .409). Using the HADS depression subscale, we found that the prevalence of depression in patients with myocardial infarction with non-obstructive coronary arteries (17%) was higher than in healthy controls (4%; P = .003) and similar to that of patients with coronary heart disease (13%; P = .466). Patients with myocardial infarction with non-obstructive coronary arteries and takotsubo syndrome scored higher on the HADS anxiety subscale than those without (P = .028). CONCLUSIONS: This is the first study on the mental health of patients with myocardial infarction with non-obstructive coronary arteries to show that prevalence rates of anxiety and depression are similar to those in patients with coronary heart disease.

Experiences of a One-hour Algorithm in Chest Pain Patients With a Nonelevated Troponin T at Presentation.

BACKGROUND: We aimed to evaluate the use of a 1-hour measurement of high-sensitivity cardiac troponin T (hs-cTnT) in an emergency department (ED) population of chest pain patients with a nonelevated baseline hs-cTnT and to examine the prevalence of early dynamic changes in hs-cTnT and the association with admission rate, diagnosis, and outcome. METHODS: All patients with a chief complaint of chest pain presenting to the ED of Karolinska University Hospital, Solna, Sweden, from December 2014 to September 2015 who had a baseline hs-cTnT of ≤14 ng/L and a second value obtained within >30 to ≤90 minutes were followed for 30 days regarding admission, readmission, myocardial infarction (MI), and death. RESULTS: A total of 1091 patients were included. Dynamic 1-hour changes in hs-cTnT defined as an increase or decrease of ≥3 ng/L occurred in 23 patients (2.1%). Fifteen patients (65.2%) in the dynamic group were admitted, compared with 148 patients (13.9%) in the nondynamic group (P < 0.001). Four of the admitted patients (26.7%) in the dynamic and 1 (0.7%) in the nondynamic group were diagnosed with an MI (P < 0.001). No death or MI occurred within 30 days among those discharged from the ED. CONCLUSIONS: Dynamic 1-hour changes in hs-cTnT were uncommon but associated with a higher rate of admission and of MI in an unselected population of chest pain patients with a nonelevated hs-cTnT at presentation. Lack of dynamic changes makes MI highly unlikely, and a 1-hour measurement may facilitate an early rule out of MI but should be used together with clinical assessment.

The value of predischarge exercise ECG testing in chest pain patients in the era of high-sensitivity troponins.

BACKGROUND: The aim of this study was to examine the value of predischarge exercise electrocardiogram (ECG) testing of chest pain patients in whom acute myocardial infarction (MI) had been ruled out by means of high-sensitivity troponins, ECG and history. METHODS: All patients hospitalised for chest pain who underwent exercise ECG testing before discharge from the Department of Cardiology, Södersjukhuset, Stockholm, Sweden from January 2011 to June 2012 were included. Endpoints were death, MI and post-discharge revascularisation within 90 and 365 days, respectively. The background one-year risk of death and MI for a corresponding age, gender and calendar time-matched Swedish population was also examined. RESULTS: A total of 951 patients were included. In 585 patients (61.5%) the exercise ECG test was negative, in 94 (9.9%) positive and in 272 (28.6%) inconclusive. There were no significant differences regarding death or MI between patients with a positive or a negative test, neither at 90 ( n=1 (1.1%) vs. n=1 (0.2%)) nor at 365 days ( n=2 (2.1%) vs. n=4 (0.7%)) of follow-up. In total there were nine (0.9%) deaths and 10 (1.1%) MIs within 365 days. The one-year rates of death (1.3%) and MI (0.5%) in a matched Swedish population were comparable. CONCLUSIONS: Predischarge exercise ECG testing after rule out of MI did not predict subsequent death or MI in a population of patients hospitalised for chest pain. Furthermore, the risks of death and MI in this population were comparable to a matched Swedish population. These findings suggest that patients could be discharged without this test.

Oxygen Therapy in Suspected Acute Myocardial Infarction.

BACKGROUND: The clinical effect of routine oxygen therapy in patients with suspected acute myocardial infarction who do not have hypoxemia at baseline is uncertain. METHODS: In this registry-based randomized clinical trial, we used nationwide Swedish registries for patient enrollment and data collection. Patients with suspected myocardial infarction and an oxygen saturation of 90% or higher were randomly assigned to receive either supplemental oxygen (6 liters per minute for 6 to 12 hours, delivered through an open face mask) or ambient air. RESULTS: A total of 6629 patients were enrolled. The median duration of oxygen therapy was 11.6 hours, and the median oxygen saturation at the end of the treatment period was 99% among patients assigned to oxygen and 97% among patients assigned to ambient air. Hypoxemia developed in 62 patients (1.9%) in the oxygen group, as compared with 254 patients (7.7%) in the ambient-air group. The median of the highest troponin level during hospitalization was 946.5 ng per liter in the oxygen group and 983.0 ng per liter in the ambient-air group. The primary end point of death from any cause within 1 year after randomization occurred in 5.0% of patients (166 of 3311) assigned to oxygen and in 5.1% of patients (168 of 3318) assigned to ambient air (hazard ratio, 0.97; 95% confidence interval [CI], 0.79 to 1.21; P=0.80). Rehospitalization with myocardial infarction within 1 year occurred in 126 patients (3.8%) assigned to oxygen and in 111 patients (3.3%) assigned to ambient air (hazard ratio, 1.13; 95% CI, 0.88 to 1.46; P=0.33). The results were consistent across all predefined subgroups. CONCLUSIONS: Routine use of supplemental oxygen in patients with suspected myocardial infarction who did not have hypoxemia was not found to reduce 1-year all-cause mortality. (Funded by the Swedish Heart-Lung Foundation and others; DETO2X-AMI ClinicalTrials.gov number, NCT01787110 .).

Effect of Myocardial Infarction With Nonobstructive Coronary Arteries on Physical Capacity and Quality-of-Life.

Patients with myocardial infarction with nonobstructive coronary arteries (MINOCA), including Takotsubo syndrome (TS), are considered to have a better survival compared with those with coronary heart disease (CHD). Studies of patients with MINOCA measuring physical and mental function including matched control groups are lacking. The aim of this study was to determine the physical capacity and quality of life in patients with MINOCA. One-hundred patients with MINOCA along with TS (25%) were investigated from 2007 to 2011. A bicycle exercise stress test was performed 6 weeks after hospitalization and QoL was investigated by the Short Form Survey 36 at 3 months' follow-up. Both a healthy and a CHD group that were age and gender matched were used as controls. The MINOCA group had a lower physical capacity (139 ± 42 W) compared with the healthy control group (167 ± 53 W, p <0.001) but better than the CHD control group (124 ± 39 W, p = 0.023). Patients with MINOCA had lower physical and mental component summary scores compared with the healthy controls (p <0.001) and lower mental component summary (p = 0.012), mental health (p = 0.016), and vitality (p = 0.008) scores compared with the CHD controls. In conclusion, the findings of this first study on exercise capacity and QoL in patients with MINOCA showed both physical and mental distress from 6 weeks to 3 months after the acute event similar to CHD controls and in some perspectives even lower scores especially in the mental component of QoL.

An algorithm for rule-in and rule-out of acute myocardial infarction using a novel troponin I assay.

OBJECTIVE: To derive and validate a hybrid algorithm for rule-out and rule-in of acute myocardial infarction based on measurements at presentation and after 2 hours with a novel cardiac troponin I (cTnI) assay. METHODS: The algorithm was derived and validated in two cohorts (605 and 592 patients) from multicentre studies enrolling chest pain patients presenting to the emergency department (ED) with onset of last episode within 12 hours. The index diagnosis and cardiovascular events up to 30 days were adjudicated by independent reviewers. RESULTS: In the validation cohort, 32.6% of the patients were ruled out on ED presentation, 6.1% were ruled in and 61.3% remained undetermined. A further 22% could be ruled out and 9.8% ruled in, after 2 hours. In total, 54.6% of the patients were ruled out with a negative predictive value (NPV) of 99.4% (95% CI 97.8% to 99.9%) and a sensitivity of 97.7% (95% CI 91.9% to 99.7%); 15.8% were ruled in with a positive predictive value (PPV) of 74.5% (95% CI 64.8% to 82.2%) and a specificity of 95.2% (95% CI 93.0% to 96.9%); and 29.6% remained undetermined after 2 hours. No patient in the rule-out group died during the 30-day follow-up in the two cohorts. CONCLUSIONS: This novel two-step algorithm based on cTnI measurements enabled just over a third of the patients with acute chest pain to be ruled in or ruled out already at presentation and an additional third after 2 hours. This strategy maximises the speed of rule-out and rule-in while maintaining a high NPV and PPV, respectively.

Exenatide infusion decreases atrial natriuretic peptide levels by reducing cardiac filling pressures in type 2 diabetes patients with decompensated congestive heart failure.

BACKGROUND: The vascular effects exerted by GLP-1 are mediated by several synergistic mechanisms such as involvement of nitric oxide and natriuresis. Recently, it was demonstrated that atrial natriuretic peptide (ANP) is essential for the glucagon-like peptide-1 (GLP-1)-stimulated vascular smooth muscle relaxation that mediates anti-hypertensive action in rodents. Therefore a GLP-1-ANP axis has been suggested. The aim of this study was to investigate whether this effect can be demonstrated in patients with type 2 diabetes and congestive heart failure. METHODS: The study was a post hoc analysis of a randomized double-blinded, placebo-controlled trial. Twenty male patients with type 2 diabetes and congestive heart failure were randomized to receive a 6-h infusion of exenatide or placebo. Cardiac filling pressures were measured by right heart catheterization, and plasma levels of ANP, N-terminal pro-brain natriuretic peptide, and exenatide were measured at baseline and at the end of the exenatide infusion. RESULTS: Exenatide infusion resulted in a significant decrease of circulating ANP levels compared with placebo, concomitant with a decrease in pulmonary capillary wedge pressure (PCWP), pulmonary artery pressure (PAP) and right arterial pressure (RAP), and increased cardiac output. There was no correlation between plasma ANP levels and exenatide levels. A negative correlation between ANP levels and PCWP, PAP, and RAP, which remained significant after adjustment for plasma exenatide levels, was demonstrated during exenatide infusion. CONCLUSIONS: Exenatide infusion decreases cardiac filling pressure and ANP levels. The reduction of ANP levels was primarily because of the reduction in cardiac filling pressure, independent of exenatide levels. It seems unlikely that this was mediated via ANP. TRIAL REGISTRATION: http://www.isrctn.org/ISRCTN47533126.

Reduction over time of QTc prolongation in patients with sotalol after cardioversion of atrial fibrillation.

BACKGROUND: Sotalol is recommended to prevent relapse of atrial fibrillation after cardioversion (CV). Sotalol prolongs the action potential by blocking the rapid component of the delayed rectifier potassium current, which results in corrected QT (QTc) prolongation on the electrocardiogram. Pronounced QTc prolongation may lead to proarrhythmias and sudden death. OBJECTIVE: We investigated the dynamics of the QTc interval during the week after CV in patients treated with sotalol compared with patients treated with a ß-blocker. METHODS: Patients who underwent elective CV for persistent atrial fibrillation and maintained sinus rhythm for 1 week were included prospectively. All patients were on the highest tolerable stable dose of metoprolol or sotalol. Twelve-lead electrocardiograms were recorded 1 hour and 1 week after CV. RESULTS: A total of 104 patients on sotalol and 104 on metoprolol were included; clinical characteristics between groups were comparable. One hour after CV, the QTc interval was significantly longer in sotalol-treated patients than in metoprolol-treated patients (465 ± 25 ms vs 423 ± 30 ms; P ≤ .0001). After 1 week, the QTc interval was reduced by -20.3 ± 24 ms in sotalol-treated patients (P ≤ .001); no such effect was seen in metoprolol-treated patients (-2.5 ± 18 ms; P = 0.28). The heart rate was stable during the week in both groups. In multivariate analysis of sotalol-treated patients, factors contributing to pronounced reduction in the QTc interval were longer QTc interval after CV and renal function. CONCLUSION: The QTc interval is significantly reduced during the week after CV to sinus rhythm in sotalol-treated patients. This provides insight into the increased risk of proarrhythmias in the immediate time period after CV.