A unique population of effector memory lymphocytes identified by CD146 having a distinct immunophenotypic and genomic profile.

BACKGROUND: CD146 is a well described homotypic adhesion molecule found on endothelial cells and a limited number of other cell types. In cells from the peripheral circulation, CD146 has also been reported to be on activated lymphocytes in vitro and in vivo. The function associated with CD146 expression on lymphoid cells is unknown and very little information is available concerning the nature of CD146+ lymphocytes. In the current study, lymphocytes from healthy donors were characterized based upon the presence or absence of CD146 expression. RESULTS: CD146 was expressed on a low percentage of circulating T lymphocytes, B lymphocytes, and NK cells in healthy individuals. CD146 expression can be induced and upregulated in vitro on both B cells and T cells, but does not correlate with the expression of other markers of T cell activation. CD146 positive T cells do not represent clonal expansions as determined with the use of anti Vbeta reagents. Data suggest that CD146 positive cells have enhanced adherence to endothelial monolayers in vitro. Gene profiling and immunophenotyping studies between CD146+ and CD146- T cells revealed several striking genotypic distinctions such as the upregulation of IL-8 and phenotypic differences including the paucity of CCR7 and CD45RA among CD146 positive T cells, consistent with effector memory function. A number of genes involved in cell adhesion, signal transduction, and cell communication are dramatically upregulated in CD146+ T cells compared to CD146- T cells. CONCLUSION: CD146 appears to identify small, unique populations of T as well as B lymphocytes in the circulation. The T cells have immunophenotypic characteristics of effector memory lymphocytes. The characteristics of these CD146+ lymphocytes in the circulation, together with the known functions in cell adhesion of CD146 on endothelial cells, suggests that these lymphocytes may represent a small subpopulation of cells primed to adhere to the endothelium and possibly extravasate to sites of inflammation.

Decision to implant a cardioverter defibrillator after myocardial infarction: the role of ejection fraction v. other risk factor markers.

BACKGROUND: The Multicenter Automatic Defibrillator Implantation Trial showed that in post-myocardial infarction patients with a left ventricular ejection fraction (EF) 0.30, an implantable cardioverter defibrillator (ICD) resulted in a 31% relative reduction in the risk of death when compared with a conventional therapy group. Whether further refinement in risk estimation could be achieved with additional clinical testing to qualify patients for primary prevention with ICDs remains problematic. METHODS: The authors analyzed Cardiac Arrhythmia Suppression Trial registry data to estimate sensitivity and specificity of EF, ventricular premature frequency, and nonsustained ventricular tachycardia for predicting death. They combined the results with similar data from the literature and used summarizing receiver operating characteristic (meta-ROC) curves to estimate overall operational values for sensitivity and specificity for each clinical test. They estimated aggregate values for prior probability to project risks when tests were used singly and in combination. RESULTS: The authors used arrhythmia markers and heart rate variability to further stratify low-EF patients (prior risk = 20.3%); proportionately, 20.4% were predicted at high risk (>30%) and 40.5% at low risk (<10%). When heart rate variability is normal, those at high risk reduced proportionately to 9.2%, and those at low risk increased to 51.6%. CONCLUSIONS: The combined use of noninvasive markers for arrhythmia substrate and altered autonomic tone can improve risk stratification in low EF without optimal beta-block therapy, whereas for those with optimal beta-block therapy, markers for arrhythmia substrate alone work. Ancillary use of electrophysiologic stimulation can improve results.

Recommendations for the standardization and interpretation of the electrocardiogram. Part I: The electrocardiogram and its technology. A scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society.

This statement examines the relation of the resting ECG to its technology. Its purpose is to foster understanding of how the modern ECG is derived and displayed and to establish standards that will improve the accuracy and usefulness of the ECG in practice. Derivation of representative waveforms and measurements based on global intervals are described. Special emphasis is placed on digital signal acquisition and computer-based signal processing, which provide automated measurements that lead to computer-generated diagnostic statements. Lead placement, recording methods, and waveform presentation are reviewed. Throughout the statement, recommendations for ECG standards are placed in context of the clinical implications of evolving ECG technology.

Recommendations for the standardization and interpretation of the electrocardiogram: part I: the electrocardiogram and its technology a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society endorsed by the International Society for Computerized Electrocardiology.

This statement examines the relation of the resting ECG to its technology. Its purpose is to foster understanding of how the modern ECG is derived and displayed and to establish standards that will improve the accuracy and usefulness of the ECG in practice. Derivation of representative waveforms and measurements based on global intervals are described. Special emphasis is placed on digital signal acquisition and computer-based signal processing, which provide automated measurements that lead to computer-generated diagnostic statements. Lead placement, recording methods, and waveform presentation are reviewed. Throughout the statement, recommendations for ECG standards are placed in context of the clinical implications of evolving ECG technology.

Recommendations for the standardization and interpretation of the electrocardiogram: part II: electrocardiography diagnostic statement list a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society Endorsed by the International Society for Computerized Electrocardiology.

This statement provides a concise list of diagnostic terms for ECG interpretation that can be shared by students, teachers, and readers of electrocardiography. This effort was motivated by the existence of multiple automated diagnostic code sets containing imprecise and overlapping terms. An intended outcome of this statement list is greater uniformity of ECG diagnosis and a resultant improvement in patient care. The lexicon includes primary diagnostic statements, secondary diagnostic statements, modifiers, and statements for the comparison of ECGs. This diagnostic lexicon should be reviewed and updated periodically.

Recommendations for the standardization and interpretation of the electrocardiogram: part II: Electrocardiography diagnostic statement list: a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society: endorsed by the International Society for Computerized Electrocardiology.

This statement provides a concise list of diagnostic terms for ECG interpretation that can be shared by students, teachers, and readers of electrocardiography. This effort was motivated by the existence of multiple automated diagnostic code sets containing imprecise and overlapping terms. An intended outcome of this statement list is greater uniformity of ECG diagnosis and a resultant improvement in patient care. The lexicon includes primary diagnostic statements, secondary diagnostic statements, modifiers, and statements for the comparison of ECGs. This diagnostic lexicon should be reviewed and updated periodically.

Recommendations for the standardization and interpretation of the electrocardiogram: part I: The electrocardiogram and its technology: a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society: endorsed by the International Society for Computerized Electrocardiology.

This statement examines the relation of the resting ECG to its technology. Its purpose is to foster understanding of how the modern ECG is derived and displayed and to establish standards that will improve the accuracy and usefulness of the ECG in practice. Derivation of representative waveforms and measurements based on global intervals are described. Special emphasis is placed on digital signal acquisition and computer-based signal processing, which provide automated measurements that lead to computer-generated diagnostic statements. Lead placement, recording methods, and waveform presentation are reviewed. Throughout the statement, recommendations for ECG standards are placed in context of the clinical implications of evolving ECG technology.

The triangular wave test for electrocardiographic devices: a historical perspective.

Baseline wander makes interpretation ECG recordings difficult, especially the assessment of ST deviation. Eliminating baseline wander without distorting the ST segment is a problem. The traditional high pass filter with a 0.5 Hz low frequency cutoff effectively suppresses baseline but introduces considerable distortion in the level of the ST segment. This distortion results from phase nonlinearities that occur when frequency content and wave amplitude change abruptly, as occurs where the end of the QRS complex meets the ST segment. Since the 1980s nonlinear, digital filters have been designed that can increase the low frequency cutoff without the introduction of phase distortion. The triangular wave test, first described in the 1990 AHA Recommendations, is an objective method for measuring the ability to suppress baseline wander without affecting the ST segment. This methodology was adopted in 3 American National Standards.

Risk stratification in diabetic patients with a previous myocardial infarction.

We used Kaplan-Meier 2-year survival analysis on CAST registry patients to estimate prognostic power of VPC frequency (> or =10/hr), presence of nonsustained ventricular tachycardia (NSVT), left ventricular ejection fraction, and presence of diabetes. We also used meta-analysis of reports in the literature to estimate prognostic power of signal-averaged electrocardiogram (SAECG) and electrophysiological tests (EPS) as well as VPCs, NSVT, and LVEF. Combined results from CAST analysis and literature meta-analysis yielded sensitivity and specificity for VPCs, NSVT, SAECG, LVEF, Diabetes, and EPS. The overall 2 year event rate for life-threatening arrhythmias or death was 7.88% for 51,144 cases in the combined CAST and literature data. After segmenting the population 21.3% were diabetic with a predicted 2 yr event rate of 13.5% and 78.7% were nondiabetic event rate of 6.4%. We defined low risk as <10% and high risk as > or =30%. Otherwise predicted event rate was classified as "unstratified." When all possible combination of noninvasive tests were applied, a prominent difference in the proportions of cases at risk between the diabetics and nondiabetics was revealed. When the unstratified cases were subsequently tested with EPS, the difference between the two groups was even more marked.

Simultaneous heart rate and blood pressure variability analysis. Insight into mechanisms underlying neurally mediated cardiac syncope in children.

OBJECTIVES: The purpose of our investigation was to examine serial changes in autonomic nervous system activity along with measurements of hemodynamics and cardiac contractility, in assessing the mechanism(s) that underlie neurally mediated cardiac syncope (NMCS) in children. BACKGROUND: Previous research that used heart rate variability analysis alone to understand changes in autonomic activity that result in NMCS has provided conflicting results. We performed simultaneous heart rate and blood pressure variability analyses to characterize dynamic alterations in sympathetic and vagal tone during tilt-table testing in 23 children with a history of syncope or frequent dizziness. METHODS: Power spectra of heart rate and blood pressure variability were analyzed using autoregressive modeling. Maximum dP/dT of systolic blood pressure and the electrical-mechanical activation time were used to assess cardiac contractility. RESULTS: Tilt-table testing was positive in 12 children and negative in 11. Syncope was associated with decreased heart rate, blood pressure and low-frequency (LF) power. Before episodes of syncope, systolic blood pressure dP/dT decreased, and the electrical-mechanical activation time was prolonged. The decrease in blood pressure LF power exceeded and occurred before the decrease in heart rate LF power. Despite similar early increases in LF power to the initial stress of upright tilting, no significant decline in LF power (heart rate or blood pressure) was observed during negative tilt-table tests. CONCLUSIONS: All of these changes considered in total provide evidence supporting the hypothesis of sympathetic withdrawal/failure, resulting in a decrease in peripheral vascular tone and cardiac contractility, which results in profound hypotension in children with NMCS.

Risk stratification applied to CAST registry data: combining 9 predictors. Cardiac Arrhythmia Suppression Trial.

Over 200,000 people in the United States die of sudden cardiac death (SCD) every year. Although many of these deaths occur in asymptomatic individuals, the vast majority of deaths occur in people who are under care for existing coronary heart disease. Implantable cardioverter/defibrillators (ICDs) have been shown in several randomized trials to be effective in prolonging lives of those at high risk for sudden cardiac death, but the criteria used in these trials and the ACC/AHA consensus guidelines would cover only a minority of patients. Developing methods to assign risk to individual patients without prior SCD events could promote the use of this life-saving therapy in those with especially high risk. Given sufficient physiologically relevant measurements from electrocardiogram analysis, clinical assessment, and demographic status, multivariate statistical methods for predicting survival can be used to combine many predictors of risk and calculate the risk for an individual patient. A survival analysis using Cox regression on data from the Cardiac Arrhythmia Suppression Trial (CAST) illustrates this concept. Patient age, sex, ejection fraction, smoking history, and prior myocardial infarction history, along with the frequency of premature beats and the presence of runs of ventricular tachycardia on Holter monitoring and the time from the index myocardial infarction to the baseline Holter and to recruitment into CAST were combined in a multivariate predictor derived from the Cox regression; this predictor significantly outperforms the individual predictors. A proposed test based on this predictor would identify as positive 7% of the CAST registry, with an average risk of death among the positives of 47%; 20% of those dead at 2 years would be positive. With improved component measurements, this approach has the potential for significantly improving risk stratification for the prevention of SCD.