Basal variability in CREB phosphorylation predicts trait-like differences in amygdala-dependent memory.

Much of what is known about the neurobiology of learning and memory comes from studies of the average behavior. In contrast, intersubject differences that emerge within groups are difficult to study systematically and are often excluded from scientific discussion. Nevertheless, population-wide variability is a virtually universal feature of both complex traits, such as intelligence, and hardwired responses, such as defensive behaviors. Here, we use outbred rats to investigate if cAMP response element-binding protein (CREB), a transcription factor that has long been known in experimental settings to be crucial for associative plasticity, participates in natural memory phenotypes. Using a combination of behavioral, biochemical, and viral techniques, we show that a subset of rats with trait-like deficits in aversive memory have basally reduced CREB activity in the lateral amygdala but can be induced to perform at average levels by directly or indirectly enhancing pretraining CREB phosphorylation. These data suggest that endogenous CREB activity in the amygdala may set a critical threshold for plasticity during memory formation.

The selectivity of aversive memory reconsolidation and extinction processes depends on the initial encoding of the Pavlovian association.

In reconsolidation studies, memories are typically retrieved by an exposure to a single conditioned stimulus (CS). We have previously demonstrated that reconsolidation processes are CS-selective, suggesting that memories retrieved by the CS exposure are discrete and reconsolidate separately. Here, using a compound stimulus in which two distinct CSs are concomitantly paired with the same aversive unconditioned stimulus (US), we show in rats that reexposure to one of the components of the compound CS triggers extinction or reconsolidation of the other component. This suggests that the original training conditions play a critical role in memory retrieval and reconsolidation.

Finger photoplethysmography during the Valsalva maneuver reflects left ventricular filling pressure.

It is often challenging to assess cardiac filling pressure clinically. An improved system for detecting or ruling out elevated cardiac filling pressure may help reduce hospitalizations for heart failure. The blood pressure response to the Valsalva maneuver reflects left heart filling pressure, but its underuse clinically may be due in part to lack of continuous blood pressure recording along with lack of standardization of expiratory effort. In this study, we tested whether Valsalva-induced changes in the pulse amplitude of finger photoplethysmography (PPG), a technology already widely available in medical settings, correlate with invasively measured left ventricular end-diastolic pressure (LVEDP). We tested 33 subjects before clinically scheduled cardiac catheterizations. A finger photoplethysmography waveform was recorded during a Valsalva effort of 20 mmHg expiratory pressure sustained for 10 s, an effort most patients can achieve. Pulse amplitude ratio (PAR) was calculated as the PPG waveform amplitude just before release of expiratory effort divided by the waveform amplitude at baseline. PAR was well correlated with LVEDP (r = 0.68; P < 0.0001). For identifying LVEDP > 15 mmHG, PAR > 0.4 was 85% sensitive [95% confidence interval (95CI): 54-97%] and 80% specific (95CI: 56-93%). In conclusion, finger PPG, a technology already ubiquitous in medical centers, may be useful for assessing clinically meaningful categories of left heart filling pressure, using simple analysis of the waveform after a Valsalva maneuver effort that most patients can achieve.

Diagnostic performance of coronary angiography by 64-row CT.

BACKGROUND: The accuracy of multidetector computed tomographic (CT) angiography involving 64 detectors has not been well established. METHODS: We conducted a multicenter study to examine the accuracy of 64-row, 0.5-mm multidetector CT angiography as compared with conventional coronary angiography in patients with suspected coronary artery disease. Nine centers enrolled patients who underwent calcium scoring and multidetector CT angiography before conventional coronary angiography. In 291 patients with calcium scores of 600 or less, segments 1.5 mm or more in diameter were analyzed by means of CT and conventional angiography at independent core laboratories. Stenoses of 50% or more were considered obstructive. The area under the receiver-operating-characteristic curve (AUC) was used to evaluate diagnostic accuracy relative to that of conventional angiography and subsequent revascularization status, whereas disease severity was assessed with the use of the modified Duke Coronary Artery Disease Index. RESULTS: A total of 56% of patients had obstructive coronary artery disease. The patient-based diagnostic accuracy of quantitative CT angiography for detecting or ruling out stenoses of 50% or more according to conventional angiography revealed an AUC of 0.93 (95% confidence interval [CI], 0.90 to 0.96), with a sensitivity of 85% (95% CI, 79 to 90), a specificity of 90% (95% CI, 83 to 94), a positive predictive value of 91% (95% CI, 86 to 95), and a negative predictive value of 83% (95% CI, 75 to 89). CT angiography was similar to conventional angiography in its ability to identify patients who subsequently underwent revascularization: the AUC was 0.84 (95% CI, 0.79 to 0.88) for multidetector CT angiography and 0.82 (95% CI, 0.77 to 0.86) for conventional angiography. A per-vessel analysis of 866 vessels yielded an AUC of 0.91 (95% CI, 0.88 to 0.93). Disease severity ascertained by CT and conventional angiography was well correlated (r=0.81; 95% CI, 0.76 to 0.84). Two patients had important reactions to contrast medium after CT angiography. CONCLUSIONS: Multidetector CT angiography accurately identifies the presence and severity of obstructive coronary artery disease and subsequent revascularization in symptomatic patients. The negative and positive predictive values indicate that multidetector CT angiography cannot replace conventional coronary angiography at present. (ClinicalTrials.gov number, NCT00738218.)

Coronary artery stenoses: accuracy of 64-detector row CT angiography in segments with mild, moderate, or severe calcification--a subanalysis of the CORE-64 trial.

PURPOSE: To evaluate the influence of cross-sectional arc calcification on the diagnostic accuracy of computed tomography (CT) angiography compared with conventional coronary angiography for the detection of obstructive coronary artery disease (CAD). MATERIALS AND METHODS: Institutional Review Board approval and written informed consent were obtained from all centers and participants for this HIPAA-compliant study. Overall, 4511 segments from 371 symptomatic patients (279 men, 92 women; median age, 61 years [interquartile range, 53-67 years]) with clinical suspicion of CAD from the CORE-64 multicenter study were included in the analysis. Two independent blinded observers evaluated the percentage of diameter stenosis and the circumferential extent of calcium (arc calcium). The accuracy of quantitative multidetector CT angiography to depict substantial (≥ 50%) stenoses was assessed by using quantitative coronary angiography (QCA). Cross-sectional arc calcium was rated on a segment level as follows: noncalcified or mild (< 90°), moderate (90°-180°), or severe (> 180°) calcification. Univariable and multivariable logistic regression, receiver operation characteristic curve, and clustering methods were used for statistical analyses. RESULTS: A total of 1099 segments had mild calcification, 503 had moderate calcification, 338 had severe calcification, and 2571 segments were noncalcified. Calcified segments were highly associated (P < .001) with disagreement between CTA and QCA in multivariable analysis after controlling for sex, age, heart rate, and image quality. The prevalence of CAD was 5.4% in noncalcified segments, 15.0% in mildly calcified segments, 27.0% in moderately calcified segments, and 43.0% in severely calcified segments. A significant difference was found in area under the receiver operating characteristic curves (noncalcified: 0.86, mildly calcified: 0.85, moderately calcified: 0.82, severely calcified: 0.81; P < .05). CONCLUSION: In a symptomatic patient population, segment-based coronary artery calcification significantly decreased agreement between multidetector CT angiography and QCA to detect a coronary stenosis of at least 50%.

Noradrenergic enhancement of reconsolidation in the amygdala impairs extinction of conditioned fear in rats--a possible mechanism for the persistence of traumatic memories in PTSD.

BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with enhanced noradrenergic activity. Animal and human studies demonstrate that noradrenergic stimulation augments consolidation of fear learning. Retrieval of well-established memories by presenting a learned fear cue triggers reconsolidation processes during which memories may be updated, weakened, or strengthened. We previously reported that noradrenergic blockade in the rat amygdala impairs reconsolidation of fear memories. Here we investigated the effects of noradrenergic enhancement on reconsolidation of learned fear. METHODS: Using auditory fear conditioning in rats, we tested the effects of postretrieval intraamygdala infusion of the ß-adrenergic receptor agonist isoproterenol or the antagonist propranolol on conditioned fear in the amygdala. RESULTS: A single intraamygdala infusion of isoproterenol following a retrieval of a well-consolidated memory enhanced fear memory elicited by the learned fear stimulus and impaired extinction of this memory 48 hr later. Intraamygdala infusion of the ß-adrenergic receptor antagonist propranolol following a consecutive retrieval trial blocked the enhancing effects of isoproterenol on fear memory. CONCLUSIONS: Postretrieval ß-adrenergic stimulation in the amygdala enhances reconsolidation of fear memories, making them resistant to extinction. Noradrenergic augmentation during retrieval of fear memories may thus contribute to persistence and severity of traumatic memories. Reconsolidation may be a useful tool in understanding the pathology of PTSD and may thus help in developing new and in modifying existing treatments of traumatic memories.

Dissociable roles for the ventromedial prefrontal cortex and amygdala in fear extinction: NR2B contribution.

Fear extinction, which involves learning to suppress the expression of previously learned fear, requires N-methyl-D-aspartate receptors (NMDARs) and is mediated by the amygdala and ventromedial prefrontal cortex (vmPFC). Like other types of learning, extinction involves acquisition and consolidation phases. We recently demonstrated that NR2B-containing NMDARs (NR2Bs) in the lateral amygdala (LA) are required for extinction acquisition, but whether they are involved in consolidation is not known. Further, although it has been shown that NMDARs in the vmPFC are required for extinction consolidation, whether NR2Bs in vmPFC are involved in consolidation is not known. In this report, we investigated the possible role of LA and vmPFC NR2Bs in the consolidation of fear extinction using the NR2B-selective antagonist ifenprodil. We show that systemic treatment with ifenprodil immediately after extinction training disrupts extinction consolidation. Ifenprodil infusion into vmPFC, but not the LA, immediately after extinction training also disrupts extinction consolidation. In contrast, we also show pre-extinction training infusions into vmPFC has no effect. These results, together with our previous findings showing that LA NR2Bs are required during the acquisition phase in extinction, indicate a double dissociation for the phase-dependent role of NR2Bs in the LA (acquisition, not consolidation) and vmPFC (consolidation, not acquisition).

Coronary CT angiography using 64 detector rows: methods and design of the multi-centre trial CORE-64.

Multislice computed tomography (MSCT) for the noninvasive detection of coronary artery stenoses is a promising candidate for widespread clinical application because of its non-invasive nature and high sensitivity and negative predictive value as found in several previous studies using 16 to 64 simultaneous detector rows. A multi-centre study of CT coronary angiography using 16 simultaneous detector rows has shown that 16-slice CT is limited by a high number of nondiagnostic cases and a high false-positive rate. A recent meta-analysis indicated a significant interaction between the size of the study sample and the diagnostic odds ratios suggestive of small study bias, highlighting the importance of evaluating MSCT using 64 simultaneous detector rows in a multi-centre approach with a larger sample size. In this manuscript we detail the objectives and methods of the prospective "CORE-64" trial ("Coronary Evaluation Using Multidetector Spiral Computed Tomography Angiography using 64 Detectors"). This multi-centre trial was unique in that it assessed the diagnostic performance of 64-slice CT coronary angiography in nine centres worldwide in comparison to conventional coronary angiography. In conclusion, the multi-centre, multi-institutional and multi-continental trial CORE-64 has great potential to ultimately assess the per-patient diagnostic performance of coronary CT angiography using 64 simultaneous detector rows.

Effect of depression on late (8 years) mortality after myocardial infarction.

Depression during hospitalization for myocardial infarction (MI) is associated with subsequent mortality, but whether this risk persisted long term is not well studied. This study was performed to determine whether depression during hospitalization for MI, which predicted mortality at 4 months, predicted mortality 8 years later. This was a prospective observational study of 284 hospitalized patients with MI. Major depression and dysthymia were assessed using structured interview for Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, and depressive symptoms, using the Beck Depression Inventory. Mortality was determined using the Social Security Death Index. Mean age during MI hospitalization was 64.8 years, 43.0% of patients were women, 66.7% had hypertension, and 35.7% had diabetes mellitus. Any depression (major depression, dysthymia, and/or Beck Depression Inventory score > or =10) was present in 76 patients (26.8%). The 8-year mortality rate was 47.9% (136 deaths). Any depression at the time of MI was not associated with mortality at 8 years in unadjusted (hazard ratio 1.25, 95% confidence interval 0.87 to 1.81, p = 0.22) or multivariate models (hazard ratio 0.76, 95% confidence interval 0.47 to 1.24, p = 0.27). In conclusion, depression after MI was associated with increased short-term mortality, but its relation with mortality over time appeared to wane, at least in a group of older patients who had multiple co-morbidities.

Acute selective serotonin reuptake inhibitors increase conditioned fear expression: blockade with a 5-HT(2C) receptor antagonist.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) effectively treat various anxiety disorders, although symptoms of anxiety are often exacerbated during early stages of treatment. We previously reported that acute treatment with the SSRI citalopram enhances the acquisition of auditory fear conditioning, which is consistent with the initial anxiogenic effects reported clinically. Here, we extend our findings by assessing the effects of acute SSRI treatment on the expression of previously acquired conditioned fear. METHODS: Rats underwent fear conditioning drug-free. Tone-evoked fear responses were tested after drug treatment the following day. This protocol more closely resembles the clinical setting than pre-conditioning treatment, because it evaluates effects of treatment on a pre-existing fear rather than on the formation of a new fear memory. RESULTS: A single pre-testing injection of the SSRIs citalopram or fluoxetine significantly increased fear expression. There was no effect of the antidepressant tianeptine or the norepinephrine reuptake inhibitor tomoxetine, indicating that this effect is specific to SSRIs. The SSRI-induced enhancement in fear expression was not blocked by tropisetron, a 5-HT(3) receptor antagonist, but was blocked by SB 242084, a specific 5-HT(2C) receptor antagonist. CONCLUSIONS: Enhanced activation of 5-HT(2C) receptors might be a mechanism for the anxiogenic effects of SSRIs observed initially during treatment.

Acquisition of fear extinction requires activation of NR2B-containing NMDA receptors in the lateral amygdala.

N-methyl-D-aspartate receptors (NMDARs) contribute to synaptic plasticity underlying learning in a variety of brain systems. Fear extinction, which involves learning to suppress the expression of previously learned fear, appears to require NMDAR activation in the amygdala. However, it is unclear whether amygdala NMDARs are required for the acquisition of extinction learning, and it is unknown whether NR2B-containing NMDARs are required in fear extinction. Here, we assessed the effects of selective NR2B blockade with ifenprodil on fear extinction learning, and found that both systemic and intra-amygdala ifenprodil treatment, given before extinction training, impaired the initial acquisition, and subsequent retrieval of fear extinction. These results confirm previous evidence showing that NMDARs in the amygdala are involved in fear extinction, and additionally show that NR2B-containing NMDARs are required. Contrary to the conclusion of previous studies, our findings demonstrate NMDARs are required for the initial acquisition, rather than only the retention, of fear extinction learning. Thus, our results support a previously not known role for NMDA-dependent plasticity in the lateral amygdala during the acquisition of fear extinction.

A robust automated method to analyze rodent motion during fear conditioning.

A central question in the study of LTP has been to determine what role it plays in memory formation and storage. One valuable form of learning for addressing this issue is associative fear conditioning. In this paradigm an animal learns to associate a tone and shock, such that subsequent presentation of a tone evokes a fear response (freezing behavior). Recent studies indicate that overlapping cellular processes underlie fear conditioning and LTP. The fear response has generally been scored manually which is both labor-intensive and subject to potential artifacts such as inconsistent or biased results. Here we describe a simple automated method that provides unbiased and rapid analysis of animal motion. We show that measured motion, in units termed significant motion pixels (SMPs), is both linear and robust over a wide range of animal speeds and detection thresholds and scores freezing in a quantitatively similar manner to trained human observers. By comparing the frequency distribution of motion during baseline periods and to the response to fox urine (which causes unconditioned fear), we suggest that freezing and non-freezing are distinct behaviors. Finally, we show how this algorithm can be applied to a fear conditioning paradigm yielding information on long and short-term associative memory as well as habituation. This automated analysis of fear conditioning will permit a more rapid and accurate assessment of the role of LTP in memory.

Individual differences in elevated plus-maze exploration predicted progressive-ratio cocaine self-administration break points in Wistar rats.

RATIONALE: There are considerable individual differences in vulnerability to drug addiction, but the mechanisms underlying such differences are poorly understood. Cocaine has potent reinforcing effects that support operant responding. However, cocaine also elicits aversive reactions and produces an approach-avoidance conflict in rats. We hypothesized that preexisting individual differences in open arm exploration on the elevated plus-maze, a well-known model for the study of clinically effective anxiolytic drugs, would predict individual differences in cocaine-motivated behavior. OBJECTIVES: To assess whether individual differences in sensitivity to anxiety-like behavior on the plus-maze predict motivation to self-administer intravenous (i.v.) cocaine. MATERIALS AND METHODS: Rats were assessed drug-free for individual differences in open arm exploration on the elevated plus-maze, and later trained to perform an operant response for i.v. cocaine (0, 0.1, 0.3, 0.6, 0.9, 1.2, and 1.5 mg kg(-1) infusion(-1)) on a progressive-ratio reinforcement schedule. Rats were split at the median into low and high open arm explorers based on time spent in the open arms of the plus-maze. Self-administration levels were compared across groups. RESULTS: Rats identified as high open arm explorers on the elevated plus-maze attained higher levels of operant responding for cocaine. Open arm times and break points were significantly correlated at the highest cocaine doses (1.2 and 1.5 mg kg(-1) infusion(-1)). CONCLUSIONS: These results indicate that individual differences in anxiety-like behavior on the elevated plus-maze predict motivation to self-administer cocaine, and suggest the possibility that reduced sensitivity to aversive stimuli may be associated with increased vulnerability to the rewarding properties of cocaine.

ß-Adrenergic Receptors Regulate the Acquisition and Consolidation Phases of Aversive Memory Formation Through Distinct, Temporally Regulated Signaling Pathways.

Memory formation requires the temporal coordination of molecular events and cellular processes following a learned event. During Pavlovian threat (fear) conditioning (PTC), sensory and neuromodulatory inputs converge on post-synaptic neurons within the lateral nucleus of the amygdala (LA). By activating an intracellular cascade of signaling molecules, these G-protein-coupled neuromodulatory receptors are capable of recruiting a diverse profile of plasticity-related proteins. Here we report that norepinephrine, through its actions on ß-adrenergic receptors (ßARs), modulates aversive memory formation following PTC through two molecularly and temporally distinct signaling mechanisms. Specifically, using behavioral pharmacology and biochemistry in adult rats, we determined that ßAR activity during, but not after PTC training initiates the activation of two plasticity-related targets: AMPA receptors (AMPARs) for memory acquisition and short-term memory and extracellular regulated kinase (ERK) for consolidating the learned association into a long-term memory. These findings reveal that ßAR activity during, but not following PTC sets in motion cascading molecular events for the acquisition (AMPARs) and subsequent consolidation (ERK) of learned associations.

Prevalence of depression in survivors of acute myocardial infarction.

OBJECTIVES: To assess the prevalence and persistence of depression in patients with acute myocardial infarction (AMI) and the relationship between assessment modality and prevalence. DATA SOURCES: MEDLINE, Cochrane, CINAHL, PsycINFO, and EMBASE. REVIEW METHODS: A comprehensive search was conducted in March 2004 to identify original research studies published since 1980 that used a standardized interview or validated questionnaire to assess depression. The search was augmented by hand searching of selected journals from October 2003 through April 2004 and references of identified articles and reviews. Studies were excluded if only an abstract was provided, if not in English, or if depression was not measured by a validated method. RESULTS: Major depression was identified in 19.8% (95% confidence interval [CI] 19.1% to 20.6%) of patients using structured interviews (N=10,785, 8 studies). The prevalence of significant depressive symptoms based on a Beck Depression Inventory score > or =10 was 31.1% (CI 29.2% to 33.0%; N=2,273, 6 studies), using a Hospital Anxiety and Depression Scale (HADS) score > or =8%, 15.5% (CI 13.2% to 18.0%; N=863, 4 studies), and with a HADS score > or =11%, 7.3% (CI 5.5% to 9.3%; N=830, 4 studies). Although a significant proportion of patients continued to be depressed in the year after discharge, the limited number of studies and variable follow-up times precluded specification of prevalence rates at given time points. CONCLUSIONS: Depression is common and persistent in AMI survivors. Prevalence varies depending on assessment method, likely reflecting treatment of somatic symptoms.

Female sex: a protective role in suspected myocardial ischemia.

OBJECTIVE: Women are felt to have poor outcomes in coronary artery disease, largely on the basis of secondary observations in acute coronary syndrome trials. We sought to examine the neglected topic of sex differences in workup and outcomes in the general population presenting with chest pain. METHODS: We examined 439 consecutive patients admitted via the emergency department with ongoing chest pain. Cardiac testing was defined as any cardiac catheterization or stress test. Positive testing was defined as a 70% or greater stenosis in an epicardial coronary artery on catheterization, or a positive stress test result. Follow-up was obtained via telephone contact at 4 months following discharge. RESULTS: Further cardiac testing was deemed necessary in 68% (164/241) of women and 77% (153/198) of men (P=0.038). Among women undergoing further testing, only 21% (35/164) had positive tests, whereas 41% (62/153) of men had positive tests (P=0.002). At 4 months, women were less likely to have suffered the combined endpoint of subsequent myocardial infarction, revascularization, or death, than men (15 vs. 23%, P=0.027). Events were more likely to occur in patients who had further testing, and especially in those who had positive testing. CONCLUSIONS: These data suggest that women admitted with chest pain are less likely to have active coronary artery disease, and much less likely to have poor outcomes at 4 months than men. This apparent 'gender protection' effect warrants further study.

Insufficient treatment of hypercholesterolemia among patients hospitalized with chest pain.

BACKGROUND: Although morbidity and mortality from coronary artery disease can be improved with a variety of pharmacologic interventions, many patients remain undertreated. HYPOTHESIS: This study sought to assess whether hospitalization for possible coronary artery disease would prompt initiation of appropriate lipid-lowering therapy. METHODS: This prospective, observational study was conducted on consecutive patients with active chest pain admitted to the Emergency Department of the hospital for suspected myocardial ischemia. Elevated cholesterol, defined as low-density lipoprotein (LDL), was >100 mg/dl with a prior history or a new diagnosis of coronary artery disease, or an LDL >130 mg/dl without known coronary artery disease. Data were recorded at the time of admission, discharge, and at 4-month follow-up. RESULTS: Of the patients with hyperlipidemia, 65% men and 55% women were on medication at the time of admission (p = 0.30), while at discharge, 79% men and 60% women were on treatment (p = 0.002), with similar rates of treatment at 4-month follow-up (p = 0.030). At discharge, two variables were independently associated with patients receiving lipid-lowering therapy: age > or =65 years (odds ratio = 2.3; 95% confidence interval 1.2-4.5) and male gender (2.7; 15-5.0). CONCLUSIONS: In patients hospitalized with chest pain, particularly in women, the initiation of treatment of hyperlipidemia frequently does not happen. This oversight represents a lost opportunity for making an impact on the health of this population.

Can doctors and nurses recognize depression in patients hospitalized with an acute myocardial infarction in the absence of formal screening?

OBJECTIVE: The objective of this study was to determine the ability of cardiovascular healthcare workers to assess the presence or absence of symptoms of depression in patients hospitalized with acute myocardial infarction (AMI) in the absence of formal screening. METHODS: Patients admitted with AMI underwent screening using the Beck Depression Inventory (BDI) administered by a research assistant. The cardiovascular nurse, medicine resident or intern, and attending cardiologist caring for the patient were then approached (blinded to the BDI results) and asked to assess, using a visual analog scale, whether the patient had symptoms that would warrant further evaluation for depression. RESULTS: BDI screening and at least one provider assessment were completed for 60 patients with AMI. A total of 18 of 60 patients (30.0%) had a BDI score of > or =10. Symptoms of depression were considered not present in 24 of 32 patient assessments when the BDI was > or =10 (75% false-negatives). The mean BDI score of patients assessed as depressed by at least one provider (6.7 +/- 6.3) was no different from the mean BDI score of patients assessed as not depressed (7.5 +/- 7.2, p = .67). Overall, there was little correlation between BDI scores and provider assessments, and this was not influenced by provider type or provider gender. CONCLUSIONS: Cardiovascular nurses and medicine residents and interns underrecognize depression in patients with AMI in the absence of formal screening. Formal screening for symptoms of depression should be considered part of routine AMI care.

Chest pain relief by nitroglycerin does not predict active coronary artery disease.

BACKGROUND: The belief that chest pain relief with nitroglycerin indicates the presence of active coronary artery disease is common. However, this hypothesis has not been tested. OBJECTIVE: To define the diagnostic and prognostic value of chest pain relief with nitroglycerin. DESIGN: Prospective observational cohort study. SETTING: Urban community teaching hospital. PATIENTS: 459 consecutive patients with chest pain admitted through the emergency department who received nitroglycerin from emergency services personnel or an emergency department nurse. Follow-up was obtained by telephone contact at 4 months. MEASUREMENTS: Chest pain relief was defined as a decrease of at least 50% in patients' self-reported pain within 5 minutes of the initial dose of sublingual or spray nitroglycerin. Active coronary artery disease was defined as any elevated serum enzyme levels, coronary angiography demonstrating a 70% or greater stenosis, or a positive exercise test result. RESULTS: Nitroglycerin relieved chest pain in 39% of patients (181 of 459). In patients with active coronary artery disease as the likely cause of their chest pain, 35% (49 of 141) had chest pain relief with nitroglycerin. In contrast, in patients without active coronary artery disease, 41% (113 of 275) had chest pain relief (P > 0.2). Four-month clinical outcomes were similar in patients with or without chest pain relief with nitroglycerin (P > 0.2). CONCLUSIONS: These data suggest that, in a general population admitted for chest pain, relief of pain after nitroglycerin treatment does not predict active coronary artery disease and should not be used to guide diagnosis.

Relation between achieved heart rate and outcomes in patients with atrial fibrillation (from the Atrial Fibrillation Follow-up Investigation of Rhythm Management [AFFIRM] Study).

Many patients with atrial fibrillation (AF) are treated with rate control and anticoagulation. However, the relation between the degree of heart rate (HR) control and clinical outcome is uncertain. We assessed whether lower achieved HR at rest and/or lower achieved exercise HR was associated with improved prognosis, quality of life (QoL), and functional status among patients in the AFFIRM study. Patients in the rate control arm and who were in AF at baseline and 2 months were included. Patients were grouped by quartile of achieved HR at rest (44 to 69, 70 to 78, 79 to 87, 88 to 148 beats/min) and achieved exercise HR following a 6-minute walk (53 to 82, 83 to 92, 93 to 106, 107 to 220 beats/min). QoL measurements and functional status were also analyzed. Complete data were available for 680 patients for achieved HR at rest, 349 patients for achieved exercise HR, and 118 patients for QoL. Survival free from cardiac hospitalization and overall survival were not significantly different among quartiles of achieved HR at rest (p = 0.19 and p = 0.8, respectively) or achieved exercise HR (p = 0.77 and p = 0.14, respectively). After controlling for covariates, there remained no significant relation between either achieved HR at rest or achieved exercise HR and event-free survival (hazard ratio 0.95, p = 0.35 and hazard ratio 0.98, p = 0.81) or overall survival (hazard ratio 1.03, p = 0.70 and hazard ratio 1.22, p = 0.13). Furthermore, there was no significant association between achieved HR and QoL measurements, New York Heart Association functional class, or 6-minute walking distance. After 2 months of drug titration, neither achieved HR at rest nor achieved exercise HR predicted survival free from cardiovascular hospitalization, overall survival, QoL, or functional status among patients with AF.