Diagnostic accuracy for detecting atrial fibrillation using a novel machine learning algorithm in a blood pressure monitor.

BACKGROUND: Early detection of atrial fibrillation (AF) is key for preventing strokes. Blood pressure monitors (BPMs) with built-in AF screening features have the potential for early detection at home. Recently, 2 BPMs (HEM-7371T1-AZ and HEM-7372T1-AZAZ, Omron Healthcare Co., Ltd.) that share a novel AF screening feature have been developed. Their AF screening feature utilizes an algorithm that incorporates machine learning, with the potential to improve diagnostic accuracy. OBJECTIVE: The purpose of this study was to evaluate the performance of this AF screening feature in a multicenter, prospective clinical study at 5 sites in the United States. METHODS: A total of 559 subjects were enrolled for this study: 267 in AF cohort and 292 in the non-AF cohort. AF screening was performed in all subjects by the 2 Omron BPMs and by 1 Microlife BPM (BP 3MX1-3, WatchBP Home A, Microlife Corp.), and a simultaneous 12-lead electrocardiogram (ECG) was recorded for comparison. All 12-lead ECGs were interpreted by a board-certified cardiologist who was blinded to the BPM results. Sensitivity, specificity, and accuracy for the diagnosis of AF were calculated. RESULTS: Omron HEM-7371T1-AZ BPM had sensitivity of 95.1% (95% confidence interval [CI] 91.8%-97.4%), specificity 98.6% (95% CI 96.6%-99.7%), and accuracy of 97.0% (95% CI 95.2%-98.2%). Equivalent results were obtained with the Omron HEM-7371T1-AZAZ BPM. This compared favorably to the Microlife BPM (sensitivity 78.5%, 95% CI 73.1%-83.3%; specificity 97.6%, 95% CI 95.1%-99.0%; accuracy 88.4%, 95% CI 85.5%-91.0%). CONCLUSION: These data support both home and professional use of these novel Omron BPMs for the detection of AF.

Alirocumab treatment and neurocognitive function according to the CANTAB scale in patients at increased cardiovascular risk: A prospective, randomized, placebo-controlled study.

BACKGROUND AND AIMS: Trials of the fully human monoclonal antibody proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9) alirocumab in hypercholesterolemia demonstrated substantial low-density lipoprotein cholesterol (LDL-C) lowering, reduction in cardiovascular (CV) events and outcomes, and a generally acceptable safety and tolerability profile. The impact of maintaining low LDL-C levels on higher order brain function is unclear, with reports of neurocognitive disorders with other lipid-lowering therapies. METHODS: Patients (n = 2176) with heterozygous familial hypercholesterolemia (HeFH) or non-FH, at high or very-high CV risk despite maximally tolerated statin therapy, randomly received subcutaneous alirocumab 75/150 mg or placebo every 2 weeks in this double-blind, placebo-controlled trial. The primary outcome was prospectively evaluated every 24 weeks over 96 weeks by Cambridge Neuropsychological Test Automated Battery (CANTAB). RESULTS: Among 2086 patients with CANTAB cognitive domain Spatial Working Memory Strategy (SWMS) assessments, change from baseline to Week 96 in SWMS z-score (primary outcome) achieved noninferiority between alirocumab and placebo (least squares [LS] mean change at Week 96, -0.180 vs -0.200; LS mean difference vs placebo [95% confidence interval]: -0.020 [-0.094 to 0.055], p = 0.6055). Exploratory outcome measures, which further assessed neurocognitive function in the CANTAB domains, did not differ significantly over 96 weeks and achieved nominal noninferiority between treatment groups. Alirocumab resulted in nominally significant reductions in LDL-C and other lipid parameters, and was generally well tolerated. CONCLUSIONS: Confirming previous PCSK9 inhibitor data, alirocumab showed no effect on neurocognitive function over 96 weeks' treatment, substantially reduced LDL-C and was generally well tolerated in patients with HeFH or non-FH at high or very-high CV risk.

Use of ETC-1002 to treat hypercholesterolemia in patients with statin intolerance.

BACKGROUND: Once-daily, oral ETC-1002 reduces low-density lipoprotein cholesterol (LDL-C) and has beneficial effects on other cardiometabolic risk factors but has not been examined in statin intolerant patients. OBJECTIVES: To study the efficacy and safety of ETC-1002 (a novel LDL-C-lowering agent) in patients with hypercholesterolemia and a history of statin intolerance. METHODS: Patients intolerant to at least 1 statin were entered into this multicenter, double-blind, 8-week trial. Participants were required to have a history of muscle complaints that developed during statin treatment and resolved within 4 weeks of statin discontinuation. Patients (n = 56) were randomized in a 2:1 ratio to ETC-1002 60 mg daily or placebo. The ETC-1002 dose was increased at 2-week intervals to 120 mg, 180 mg, and 240 mg. The primary end point was the percentage change from baseline to week 8 in calculated LDL-C. RESULTS: ETC-1002 reduced LDL-C 28.7% more than placebo (95% confidence interval, -35.4 to -22.1; P < .0001). ETC-1002 significantly reduced non-high-density lipoprotein cholesterol, total cholesterol, apolipoprotein B, and high-sensitivity C-reactive protein. Triglycerides and high-density lipoprotein cholesterol did not change with ETC-1002 treatment. Sixty-two percent of patients receiving ETC-1002 and none in the placebo group achieved the 2004 National Cholesterol Education Program Adult Treatment Panel III LDL-C goal (P < .0001). Muscle-related adverse events occurred with similar frequency in the placebo and ETC-1002 treatment groups, causing no discontinuations in ETC-1002-treated patients. CONCLUSIONS: ETC-1002 appears to be effective at reducing LDL-C and was well tolerated in patients with statin-associated muscle complaints. Longer and larger studies are required to confirm the absence of muscle side effects.

Prognostic value of adenosine stress cardiovascular magnetic resonance and dobutamine stress echocardiography in patients with low-risk chest pain.

Excluding obstructive coronary artery disease (CAD) as the etiology of acute chest pain in patients without diagnostic electrocardiographic changes or elevated serum cardiac biomarkers is challenging. Stress testing is a valuable risk-stratifying technique reserved for the subset of these patients with low-risk chest pain who have an intermediate clinical probability of obstructive CAD. Given the risks of radiation inherent to nuclear and computed tomography imaging, both adenosine stress cardiovascular magnetic resonance (AS-CMR) imaging and dobutamine stress echocardiography (DSE) are attractive alternative stress modalities. An essential characteristic of stress modalities is their negative prognostic value; as one must exclude clinically-relevant CAD such that patients can be discharged safely. Therefore, the aim of this study was to validate a favorable negative prognostic value for both AS-CMR and DSE in patients presenting with low-risk acute chest pain. This retrospective study included 255 patients with low-risk acute chest pain and no prior history of CAD presenting to the emergency department at our institution, with 89 patients evaluated by AS-CMR and 166 by DSE. Median follow-up was 292 days, and consisted of medical record review. The primary end-point was the composite of cardiac death, nonfatal acute myocardial infarction, obstructive CAD on invasive coronary angiography (ICA) or recurrent chest pain requiring hospital admission. Test characteristics such as sensitivity and specificity could not be evaluated as patients were not routinely evaluated with ICA. All patients completed the stress protocol without adverse events during testing. 82/89 patients (92.1%) and 164/166 patients (98.8%) had negative AS-CMR and DSE studies, respectively. Both AS-CMR and DSE had excellent negative prognostic values for the primary endpoint, 100 and 99%, respectively. Both AS-CMR and DSE are effective stress modalities for excluding clinically significant coronary artery disease in patients presenting acute low-risk chest pain. Patients without findings to suggest ischemia have an excellent intermediate-term prognosis.

Clear cell acanthoma: a rare clinical diagnosis prior to biopsy.

BACKGROUND: Clear cell acanthoma is a rare, benign epidermal tumor with a clinical hybrid appearance and a distinct histological one. It is frequently mistaken for other clinical lesions. OBJECTIVE: To evaluate the frequency that clear cell acanthoma was listed in the clinical differential diagnosis of histologically confirmed specimens. METHODS: A regional dermatopathology lab database was evaluated from January 1998 through March 2008 for histologically diagnosed cases of clear cell acanthoma. Clinical data that was submitted with these cases including differential diagnoses was analyzed. RESULTS: During this time period of review, 411 histologically confirmed cases of clear cell acanthoma were identified. This entity was listed as a diagnostic possibility in 11 (2.7%) of the cases. CONCLUSION: Clear cell acanthoma was rarely listed amongst the differential diagnosis of biopsy proven specimens. This may be due to a variable clinical appearance with overlapping features of several other lesions making it difficult to distinguish, or an entity that is rare and not frequently suspected. Additional studies with dermatoscopy may help to further delineate the reasons for the low diagnostic sensitivity.

Epicardial adipose tissue volume and coronary artery calcium to predict myocardial ischemia on positron emission tomography-computed tomography studies.

BACKGROUND: There appears to be an association of epicardial adipose tissue (EAT) with coronary artery disease (CAD) and its risk factors. EAT is assumed to influence CAD development by altering vasomotor tone and via toxic paracrine effects. The relationship of EAT to myocardial perfusion has not been studied. METHODS: Quantification of EAT and CAC was performed on positron emission tomography/computed tomography (PET/CT) studies in 45 subjects (77% intermediate pre-test probability of CAD) with mild-moderate myocardial ischemia (5-14% perfusion defect, n = 23), severe ischemia (≥15% defect, n = 22) and a control group with no ischemia matched for CAD risk factors (n = 52). RESULTS: EAT volume showed a better correlation with myocardial ischemia than total CAC (r = .47 vs r = .28, P < .01). EAT volume increased significantly from the control group to subjects with mild-moderate and severe ischemia (96.9, 124.5, and 143.9 cm(3), P < .01 for both ischemia groups vs controls). Total mean CAC was significantly higher in the severe ischemia group (676.3) than in control group (229.4) (P < .01). Multivariable logistic regression analyses showed that EAT volume was, but CAC was not, a significant predictor of ischemia after adjustment for age, sex, body mass index, and each other. EAT volume was a better predictor of ischemia than total CAC [area under the curve (AUC): .764 vs .6291, P = .04]. The combination of EAT + CAC (AUC = .7694) did not improve over EAT volume alone (P = .57). CONCLUSIONS: In this study, EAT volume assessed by CT was an independent predictor of ischemia on PET, and outperformed CAC score in a CAD naïve population at intermediate pre-test probability of disease.

A rare coincidence of two coronary anomalies in an adult.

Anomalous right-sided left main coronary arteries and dual type IV left anterior descending arteries are rare coronary anomalies. In this case report, we present a 59 year old man with atypical chest pain and a combination of the above coronary anomalies as identified by selective coronary angiography and computed tomography angiography. To the best of our knowledge, the coincidence of these coronary anomalies has not been previously described.

Adenosine stress magnetic resonance imaging in women with low risk chest pain: the Emory University experience.

OBJECTIVES: The purpose of this study was to evaluate the accuracy of adenosine stress magnetic resonance imaging (ASMRI) for the evaluation of women with low-risk chest pain (CP). BACKGROUND: Coronary artery disease (CAD) can present differently among women than among men. There is increased interest in the use of ASMRI for lower risk patients in the emergency department to rule out CAD, and it would be valuable to assess its performance specifically in women. METHODS: This study included 82 women with low-risk CP who presented to the emergency department during a 2-year period at our institution and were evaluated by ASMRI. Clinical events were followed by review of medical records. RESULTS: The specificity of ASMRI for ischemia detection in this small cohort of patients was 100%. Sensitivity was 94.9%, negative predictive value 100%, and positive predictive value 42.9%. CONCLUSIONS: ASMRI may be used as the initial imaging modality for ruling out CAD in women with low-risk CP because of its very high sensitivity, specificity, and negative predictive value for the detection of ischemia. Further randomized controlled trials comparing ASMRI with established noninvasive nuclear and echocardiographic stress modalities are needed.

Epicardial adipose tissue and coronary artery plaque characteristics.

OBJECTIVE: Epicardial adipose tissue (EAT) has been implicated in the pathogenesis of coronary atherosclerosis. The association of EAT volume with type of coronary artery plaque on computed tomography angiography (CTA) is not known. METHODS: Coronary artery calcium (CAC) scoring and EAT volume measurement were performed on 214 consecutive patients (mean age 54+/-14 years) referred for coronary CTA. CAC was performed on non-contrast images, while EAT volume, the severity of luminal stenoses, and plaque characterization were assessed using contrast-enhanced CTA images. EAT volume was also indexed to body surface area (EAT-i). RESULTS: EAT volume correlated with age, height, body mass index (BMI), and CAC score. EAT volume increased significantly with the severity of luminal stenosis (p<0.001), and in patients with no plaques, calcified, mixed, and non-calcified plaques (62+/-33mL, 63+/-22mL, 98+/-47mL, and 99+/-36mL, respectively, p<0.001). The EAT volume was significantly larger in patients with mixed or non-calcified plaques compared to patients with calcified plaques or no plaques (all p<0.01 or smaller). The trend remained significant after adjustment for traditional risk factors for coronary artery disease. In adjusted models EAT was an independent predictor of CAC [exp(B)=3.916, p<0.05], atherosclerotic plaques of any type [exp(B)=4.532, p<0.01], non-calcified plaques [exp(B)=3.849, p<0.01], and obstructive CAD [exp(B)=3.824, p<0.05]. The above results were unchanged after replacing EAT with EAT-i. CONCLUSION: EAT volume was larger in the presence of obstructive CAD and non-calcified plaques. These data suggest that EAT is associated with the development of coronary atherosclerosis and potentially the most dangerous types of plaques.

Prognostic value of adenosine stress cardiovascular magnetic resonance in patients with low-risk chest pain.

BACKGROUND: Approximately 5% of patients with an acute coronary syndrome are discharged from the emergency room with an erroneous diagnosis of non-cardiac chest pain. Highly accurate non-invasive stress imaging is valuable for assessment of low-risk chest pain patients to prevent these errors. Adenosine stress cardiovascular magnetic resonance (AS-CMR) is an imaging modality with increasing application. The goal of this study was to evaluate the negative prognostic value of AS-CMR among low-risk acute chest pain patients. METHODS: We studied 103 patients, mean 56.7 + or - 12.3 years of age, with chest pain and no electrocardiographic evidence of ischemia and negative cardiac biomarkers of necrosis, who were admitted to the Cardiac Decision Unit of our institution. All patients underwent AS-CMR. A negative AS-CMR was defined as absence of all the following: regional wall motion abnormalities at rest; perfusion defects during stress (adenosine) and rest; and myocardial scar on late gadolinium enhancement images. The patients were followed for a mean of 277 (range 161-462) days. The primary end point was defined as the combination of cardiac death, nonfatal acute myocardial infarction, re-hospitalization for chest pain, obstructive coronary artery disease (>50% coronary stenosis on invasive angiography) and coronary revascularization. RESULTS: In 14 patients (13.6%), AS-CMR was positive. The remaining 89 patients (86.4%), who had negative AS-CMR, were discharged. No patient with negative AS-CMR reached the primary end-point during follow-up. The negative predictive value of AS-CMR was 100%. CONCLUSION: AS-CMR holds promise as a useful tool to rule out significant coronary artery disease in patients with low-risk chest pain. Patients with negative AS-CMR have an excellent short and mid-term prognosis.

Left ventricle: automated segmentation by using myocardial effusion threshold reduction and intravoxel computation at MR imaging.

UNLABELLED: This retrospective analysis of existing patient data had institutional review board approval and was performed in compliance with HIPAA. No informed consent was required. The purpose of the study was to develop and validate an algorithm for automated segmentation of the left ventricular (LV) cavity that accounts for papillary and/or trabecular muscles and partial voxels in cine magnetic resonance (MR) images, an algorithm called LV Myocardial Effusion Threshold Reduction with Intravoxel Computation (LV-METRIC). The algorithm was validated in biologic phantoms, and its results were compared with those of manual tracing, as well as those of a commercial automated segmentation software (MASS [MR Analytical Software System]), in 38 subjects. LV-METRIC accuracy in vitro was 98.7%. Among the 38 subjects studied, LV-METRIC and MASS ejection fraction estimations were highly correlated with manual tracing (R(2) = 0.97 and R(2) = 0.95, respectively). Ventricular volume estimations were smaller with LV-METRIC and larger with MASS than those calculated by using manual tracing, though all results were well correlated (R(2) = 0.99). LV-METRIC volume measurements without partial voxel interpolation were statistically equivalent to manual tracing results (P > .05). LV-METRIC had reduced intraobserver and interobserver variability compared with other methods. MASS required additional manual intervention in 58% of cases, whereas LV-METRIC required no additional corrections. LV-METRIC reliably and reproducibly measured LV volumes. SUPPLEMENTAL MATERIAL: http://radiology.rsnajnls.org/cgi/content/full/248/3/1004/DC1.

Effects of papillary muscles and trabeculae on left ventricular quantification: increased impact of methodological variability in patients with left ventricular hypertrophy.

BACKGROUND: Accurate quantification of left ventricular mass and ejection fraction is important for patients with left ventricular hypertrophy. Although cardiac magnetic resonance imaging has been proposed as a standard for these indices, prior studies have variably included papillary muscles and trabeculae in myocardial volume. This study investigated the contribution of papillary muscles and trabeculae to left ventricular quantification in relation to the presence and pattern of hypertrophy. METHODS: Cardiac magnetic resonance quantification was performed on patients with concentric or eccentric hypertrophy and normal controls (20 per group) using two established methods that included papillary muscles and trabeculae in myocardium (method 1) or intracavitary (method 2) volumes. RESULTS: Among all patients, papillary muscles and trabeculae accounted for 10.5% of ventricular mass, with greater contribution with left ventricular hypertrophy than normals (12.6 vs. 6.2%, P < 0.001). Papillary muscles and trabeculae mass correlated with ventricular wall mass (r = 0.53) and end-diastolic volume (r = 0.52; P < 0.001). Papillary muscles and trabeculae inclusion in myocardium (method 1) yielded smaller differences with a standard of mass quantification from linear ventricular measurements than did method 2 (P < 0.001). Method 1 in comparison with method 2 yielded differences in left ventricular mass, ejection fraction and volume in all groups, especially in patients with hypertrophy: the difference in ventricular mass index was three-fold to six-fold greater in hypertrophy than normal groups (P < 0.001). Difference in ejection fraction, greatest in concentric hypertrophy (P < 0.001), was independently related to papillary muscles and trabeculae mass, ventricular wall mass, and smaller ventricular volume (R = 0.56, P < 0.001). CONCLUSION: Established cardiac magnetic resonance methods yield differences in left ventricular quantification due to variable exclusion of papillary muscles and trabeculae from myocardium. The relative impact of papillary muscles and trabeculae exclusion on calculated mass and ejection fraction is increased among patients with hypertrophy-associated left ventricular remodeling.

Left ventricular papillary muscles and trabeculae are significant determinants of cardiac MRI volumetric measurements: effects on clinical standards in patients with advanced systolic dysfunction.

BACKGROUND: Left ventricular (LV) mass and ejection fraction are of diagnostic and therapeutic importance in patients with systolic dysfunction. Cardiac MRI (CMR) has been proposed as a standard for these indices. Prior studies have variably included papillary muscles and trabeculae in either intracavitary or myocardial volumes. Quantitative effects and clinical implications of this methodological difference in patients with systolic dysfunction are unknown. METHODS: Fifty consecutive patients with known systolic dysfunction (EF<40%) underwent CMR. LV volumes were determined using previously established methods: Method 1 included papillary muscles and trabeculae in cavity volume, method 2 included these in myocardial volume. Both methods were used for each patient with tracings superimposed to isolate papillary/trabecular volume and insure consistency of other endocardial contours. Readers applied methods in random order blinded to clinical findings and results of the other method. RESULTS: LV mass differed substantially by method (p<0.001) with absolute difference of 16.6%. Ejection fraction differed by 3 points (p<0.001) with absolute differences of > or =5 points in 16% of patients. Mean differences in LV mass and ejection fraction were produced by consistent methodological differences on a per-patient basis. Methodology used produced differences in patients meeting established criteria for LV hypertrophy (28% vs. 60%, p<0.001) and ICD implantation (64% vs. 48%, p<0.01). CONCLUSIONS: LV mass and ejection fraction differ significantly between commonly employed CMR methods. Alternative inclusion of papillary muscles and trabeculae in either cavity or myocardial volumes produces significant differences in clinical and therapeutic indices that can affect management of patients with advanced systolic dysfunction.

Predictive value of microvolt T-wave alternans in patients with left ventricular dysfunction.

OBJECTIVES: The purpose of this study was to prospectively evaluate the utility of microvolt T-wave alternans (TWA) in predicting arrhythmia-free survival and total mortality in patients with left ventricular (LV) dysfunction. BACKGROUND: Microvolt TWA has been proposed as a useful tool in identifying patients unlikely to benefit from prophylaxis with implantable cardioverter-defibrillator (ICD) prophylaxis. METHODS: We evaluated 286 patients with an LV ejection fraction

Effect of bundle branch block on microvolt T-wave alternans and electrophysiologic testing in patients with ischemic cardiomyopathy.

BACKGROUND: T-wave alternans (TWA) and electrophysiology study (EPS) are used for risk stratification for sudden death. OBJECTIVE: The purpose of the study was to determine the effect of bundle branch block or intraventricular conduction delay on TWA and EPS. METHODS: 386 patients with coronary artery disease, nonsustained ventricular tachycardia, and left ventricular ejection fraction < or =40% underwent TWA and EPS, and were followed for 40 +/- 19 months. RESULTS: Patients with wide QRS were more likely than narrow QRS patients to have nonnegative TWA (77% vs 63%, P <.01) or positive EPS (60% vs 48%, P = .03). Nonnegative TWA predicted the combined endpoint of ventricular tachyarrhythmia or death in narrow QRS (HR = 1.64, P = .04) but not wide QRS patients (HR = 1.04, P = .91). Similarly, positive EPS predicted the combined endpoint in narrow QRS (HR = 2.28, P <.001) but not wide QRS patients (HR = 0.94, P = .84). In multivariate analysis, QRS width and TWA, as well as QRS width and EPS, were independent predictors of events. There was no TWA- or EPS-based difference in arrhythmia-free survival within any specific wide QRS morphology. CONCLUSION: TWA and EPS are more often abnormal in patients with a wide QRS than in those with a narrow QRS. In patients with narrow QRS, both TWA and EPS stratify patients according to their risk of ventricular tachyarrhythmia or death. However, among patients with a wide QRS, regardless of specific QRS morphology, the risk is high and comparable regardless of TWA or EPS results. Therefore, the only truly low-risk group consists of those patients with negative test results and a narrow QRS.

Effect of oral beta-blocker therapy on microvolt T-wave alternans and electrophysiology testing in patients with ischemic cardiomyopathy.

BACKGROUND: Prior investigation has shown that intravenous beta-blockers decrease T-wave alternans (TWA) positivity in patients undergoing electrophysiology study (EPS). The present study examined whether oral beta-blocker use within 24 hours of TWA influences yield and predictive value of TWA and EPS. METHODS: We prospectively evaluated 387 patients (312 [81%] men, mean age 67 +/- 11 years) with coronary artery disease, left ventricular ejection fraction < or = 40%, and nonsustained ventricular tachycardia who underwent EPS and were followed for a mean of 2.8 +/- 1.4 years. T-Wave alternans was performed using an atrial pacing protocol and interpreted using standard criteria. Beta-blocker status was determined based on oral beta-blocker use in the 24 hours preceding the test: beta-blocker (-) (n = 62), beta-blocker (+) (n = 325). Follow-up for ventricular tachycardia, ventricular fibrillation, and death was obtained from chart review, device interrogation, and the Social Security Death Index. Estimated sensitivity and specificity of TWA and EPS stratified by beta-blocker use were calculated based on event-free 2-year survival. RESULTS: There was no difference in EPS (31 [50%] inducible off beta-blockers vs 166 [51%] on beta-blockers [P = .89]) or TWA (26 [42%] positive, 17 [27%] indeterminate off beta-blockers vs 136 [42%] positive, 81 [25%] indeterminate on beta-blockers [P = .89]). Beta-blocker use within 24 hours of testing did not affect the predictive value of TWA or EPS for overall or 2-year event-free survival. CONCLUSIONS: Oral beta-blocker therapy appears to have no effect on yield or predictive value of EPS or TWA in patients with coronary artery disease, diminished left ventricular function, and a history of nonsustained ventricular tachycardia.