Cardiac computed tomography in patients with symptomatic new-onset atrial fibrillation, rule-out acute coronary syndrome, but with intermediate pretest probability for coronary artery disease admitted to a chest pain unit.

BACKGROUND: Atrial fibrillation (AF) and coronary artery disease (CAD) may be encountered coincidently in a large portion of patients. However, data on coronary artery calcium burden in such patients are lacking. Thus, we sought to determine the value of cardiac computed tomography (CCT) in patients presenting with new-onset AF associated with an intermediate pretest probability for CAD admitted to a chest pain unit (CPU). METHODS: Calcium scores (CS) of 73 new-onset, symptomatic AF subjects without typical clinical, electrocardiographic, or laboratory signs of acute coronary syndrome (ACS) admitted to our CPU were analyzed. In addition, results from computed tomography angiography (CTA) were related to coronary angiography findings whenever available. RESULTS: Calcium scores of zero were found in 25%. Median Agatston score was 77 (interquartile range: 1-270) with gender- and territory-specific dispersal. CS scores above average were present in about 50%, high (> 400)-to-very high (> 1000) CS scores were found in 22%. Overall percentile ranking showed a relative accordance to the reference percentile distribution. Additional CTA was performed in 47%, revealing stenoses in 12%. Coronary angiography was performed in 22% and resulted in coronary intervention or surgical revascularization in 7%. On univariate analysis, CS > 50th percentile failed to serve as an independent determinant of significant stenosis during catheterization. CONCLUSIONS: Within a CPU setting, relevant CAD was excluded or confirmed in almost 50%, the latter with a high proportion of coronary angiographies and subsequent coronary interventions, underlining the diagnostic value of CCT in symptomatic, non-ACS, new-onset AF patients when admitted to a CPU.

Electrophysiological alterations in a murine model of chronic coxsackievirus B3 myocarditis.

INTRODUCTION: Coxsackievirus B3 (CVB3) is known to induce acute and chronic myocarditis. Most infections are clinically unapparent but some patients suffer from ventricular arrhythmias (VA) and sudden cardiac death (SCD). Studies showed that acute CVB3 infection may cause impaired function of cardiac ion channels, creating a proarrhythmic substrate. However, it is unknown whether low level CVB3+ expression in myocytes may cause altered cardiac electrophysiology leading to VA. METHODS: Cellular electrophysiology was used to analyze cellular action potentials (APs) and occurrence of afterdepolarizations from isolated cardiomyocytes of wildtype (WT) and transgenic CVB3ΔVP0 (CVB3+) mice. Further, we studied surface ECGs, monophasic APs, ventricular effective refractory period (VERP) and inducibility of VAs in Langendorff-perfused whole hearts. All used cardiomyocytes and whole hearts originated from male mice. RESULTS: Cellular action potential duration (APD) in WT and CVB3+ myocytes was unchanged. No difference in mean occurrence or amplitude of afterdepolarizations in WT and CVB3+ myocytes was found. Interestingly, resting membrane potential in CVB3+ myocytes was significantly hyperpolarized (WT: -90.0±2.2 mV, n = 7; CVB3+: -114.1±3.0 mV, n = 14; p<0.005). Consistently, in Langendorff-perfused hearts, APDs were also not different between WT and CVB3+ whole hearts. Within both groups, we found a heart rate dependent shortening of ADP90 with increasing heart rate in Langendorff-perfused hearts. VERP was significantly prolonged in CVB3+ hearts compared to WT (WT: 36.0±2.7 ms, n = 5; CVB3+: 47.0±2.0 ms, n = 7; p = 0.018). Resting heart rate (HR) in Langendorff-perfused hearts was not significantly different between both genotypes. Electrical pacing protocols induced no VA in WT and CVB3+ hearts. CONCLUSION: In CVB3+ mice, prolonged ventricular refractoriness and hyperpolarized resting membrane potentials in presence of unchanged APD were observed, suggesting that low level CVB3 expression does not promote VA by altered cardiac electrophysiology in this type of chronic myocarditis. These findings may suggest that other mechanisms such as chronic myocardial inflammation or fibrosis may account for arrhythmias observed in patients with chronic enteroviral myocarditis.

Increased sodium/calcium exchanger activity enhances beta-adrenergic-mediated increase in heart rate: Whole-heart study in a homozygous sodium/calcium exchanger overexpressor mouse model.

BACKGROUND: The cardiac sodium/calcium (Na+/Ca2+) exchanger (NCX) contributes to diastolic depolarization in cardiac pacemaker cells. Increased NCX activity has been found in heart failure and atrial fibrillation. The influence of increased NCX activity on resting heart rate, beta-adrenergic-mediated increase in heart rate, and cardiac conduction properties is unknown. OBJECTIVE: The purpose of this study was to investigate the influence of NCX overexpression in a homozygous transgenic whole-heart mouse model (NCX-OE) on sinus and AV nodal function. METHODS: Langendorff-perfused, beating whole hearts of NCX-OE and the corresponding wild-type (WT) were studied ± isoproterenol (ISO; 0.2 µM). Epicardial ECG, AV nodal Wenckebach cycle length (AVN-WCL), and retrograde AVN-WCL were obtained. RESULTS: At baseline, basal heart rate was unaltered between NCX-OE and WT (WT: cycle length [CL] 177.6 ± 40.0 ms, no. of hearts [n] = 20; NCX-OE: CL 185.9 ± 30.5 ms, n = 18; P = .21). In the presence of ISO, NCX-OE exhibited a significantly higher heart rate compared to WT (WT: CL 133.4 ± 13.4 ms, n = 20; NCX-OE: CL 117.7 ± 14.2 ms, n = 18; P <.001). ISO led to a significant shortening of the anterograde and retrograde AVN-WCL without differences between NCX-OE and WT. CONCLUSION: This study is the first to demonstrate that increased NCX activity enhances beta-adrenergic increase of heart rate. Mechanistically, increased NCX inward mode activity may promote acceleration of diastolic depolarization in sinus nodal pacemaker cells, thus enhancing chronotropy in NCX-OE. These findings suggest a novel potential therapeutic target for heart rate control in the presence of increased NCX activity, such as heart failure.

Coronary Artery Calcium as an Independent Surrogate Marker in the Risk Assessment of Patients With Atrial Fibrillation and an Intermediate Pretest Likelihood for Coronary Artery Disease Admitted to a German Chest Pain Unit.

BACKGROUND: About 10% of patients admitted to a chest pain unit (CPU) exhibit atrial fibrillation (AF). HYPOTHESIS: To determine whether calcium scores (CS) are superior over common risk scores for coronary artery disease (CAD) in patients presenting with atypical chest pain, newly diagnosed AF, and intermediate pretest probability for CAD within the CPU. METHODS: In 73 subjects, CS was related to the following risk scores: Global Registry of Acute Coronary Events (GRACE) score, including a new model of a frequency-normalized approach; Thrombolysis In Myocardial Infarction score; European Society of Cardiology Systematic Coronary Risk Evaluation (SCORE); Framingham risk score; and Prospective Cardiovascular Münster Study score. Revascularization rates during index stay were assessed. RESULTS: Median CS was 77 (interquartile range, 1-270), with higher values in men and the left anterior descending artery. Only the modified GRACE (ρ = 0.27; P = 0.02) and the SCORE (ρ = 0.39; P < 0.005) were significantly correlated with CS, whereas the GRACE (τ = 0.21; P = 0.04) and modified GRACE (τ = 0.23; P = 0.02) scores were significantly correlated with percentile groups. Only the CS significantly discriminated between those with and without stenosis (P < 0.01). CONCLUSIONS: Apart from modified GRACE score, overall correlations between risk scores and calcium burden, as well as revascularization rates during index stay, were low. By contrast, the determination of CS may be used as an additional surrogate marker in risk stratification in AF patients with intermediate pretest likelihood for CAD admitted to a CPU.

Memory consolidation by replay of stimulus-specific neural activity.

Memory consolidation transforms initially labile memory traces into more stable representations. One putative mechanism for consolidation is the reactivation of memory traces after their initial encoding during subsequent sleep or waking state. However, it is still unknown whether consolidation of individual memory contents relies on reactivation of stimulus-specific neural representations in humans. Investigating stimulus-specific representations in humans is particularly difficult, but potentially feasible using multivariate pattern classification analysis (MVPA). Here, we show in healthy human participants that stimulus-specific activation patterns can indeed be identified with MVPA, that these patterns reoccur spontaneously during postlearning resting periods and sleep, and that the frequency of reactivation predicts subsequent memory for individual items. We conducted a paired-associate learning task with items and spatial positions and extracted stimulus-specific activity patterns by MVPA in a simultaneous electroencephalography and functional magnetic resonance imaging (fMRI) study. As a first step, we investigated the amount of fMRI volumes during rest that resembled either one of the items shown before or one of the items shown as a control after the resting period. Reactivations during both awake resting state and sleep predicted subsequent memory. These data are first evidence that spontaneous reactivation of stimulus-specific activity patterns during resting state can be investigated using MVPA. They show that reactivation occurs in humans and is behaviorally relevant for stabilizing memory traces against interference. They move beyond previous studies because replay was investigated on the level of individual stimuli and because reactivations were not evoked by sensory cues but occurred spontaneously.

Monitoring the mind: the neurocognitive correlates of metamemory.

Memory performance in everyday life is often far from perfect and therefore needs to be monitored and controlled by metamemory evaluations, such as judgments of learning (JOLs). JOLs support monitoring for goal-directed modification of learning. Behavioral studies suggested retrieval processes as providing a basis for JOLs. Previous functional imaging research on JOLs found a dissociation between processes underlying memory prediction, located in the medial prefrontal cortex (mPFC), and actual encoding success, located in the medial temporal lobe. However, JOL-specific neural correlates could not be identified unequivocally, since JOLs were given simultaneously with encoding. Here, we aimed to identify the neurocognitive basis of JOLs, i.e., the cognitive processes and neural correlates of JOL, separate from initial encoding. Using functional magnetic resonance imaging (fMRI), we implemented a face-name paired associative design. In general, we found that actual memory success was associated with increased brain activation of the hippocampi bilaterally, whereas predicted memory success was accompanied by increased activation in mPFC, orbital frontal and anterior cingulate cortices. Masking brain activation during predicted memory success with activation during retrieval success revealed BOLD increases of the mPFC. Our findings indicate that JOLs actually incorporate retrieval processes.