The number of computed tomographic (CT) studies performed is increasing rapidly. Because CT scans involve much higher doses of radiation than plain films, we are seeing a marked increase in radiation exposure in the general population. Epidemiologic studies indicate that the radiation dose from even two or three CT scans results in a detectable increase in the risk of cancer, especially in children. This article summarizes the facts about this form of radiation exposure and the implications for public health.

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Computed Tomography — An Increasing Source of Radiation Exposure

Jeffrey L. Anderson, MD, FACC, FAHA, Chair 

Jonathan L. Halperin, MD, FACC, FAHA, Chair-Elect 

Nancy M. Albert, PhD, RN, FAHA

Biykem Bozkurt, MD, PhD, FACC, FAHA

Ralph G. Brindis, MD, MPH, MACC

Mark A. Creager, MD, FACC, FAHA[#][1]

Lesley H. Curtis, PhD, FAHA

David DeMets, PhD[#][1]

Robert A

/pdf/2014-aha-acc-hrs-guideline-for-the-management-of-patients-1v8ficsqox.pdf

2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society

Components of heart rate variability have attracted considerable attention in psychology and medicine and have become important dependent measures in psychophysiology and behavioral medicine. Quantification and interpretation of heart rate variability, however, remain complex issues and are fraught with pitfalls. The present report (a) examines the physiological origins and mechanisms of heart rate variability, (b) considers quantitative approaches to measurement, and (c) highlights important caveats in the interpretation of heart rate variability. Summary guidelines for research in this area are outlined, and suggestions and prospects for future developments are considered.

https://www.onlinelibrary.wiley.com/doi/epdf/10.1111/j.1469-8986.1997.tb02140.x

Heart rate variability: Origins, methods, and interpretive caveats

Sidney C. Smith, Jr, MD, FACC, FAHA, FESC, Chair; Alice K. Jacobs, MD, FACC, FAHA, Vice-Chair; Cynthia D. Adams, MSN, APRN-BC, FAHA; Jeffery L. Anderson, MD, FACC, FAHA; Elliott M. Antman, MD, FACC, FAHA[‡][1]; Jonathan L. Halperin, MD, FACC, FAHA; Sharon Ann Hunt, MD, FACC, FAHA; Rick Nishimura,

/pdf/acc-aha-esc-2006-guidelines-for-the-management-of-patients-5fc8py53ut.pdf

ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society

It is important that the medical profession plays a significant role in critically evaluating the use of diagnostic procedures and therapies as they are introduced and tested in the detection, management, or prevention of disease states. Rigorous and expert analysis of the available data documenting absolute and relative benefits and risks of those procedures and therapies can produce helpful guidelines that improve the effectiveness of care, optimize patient outcomes, and favorably affect the overall cost of care by focusing resources on the most effective strategies.

The American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) have jointly engaged in the production of such guidelines in the area of cardiovascular disease since 1980. The ACC/AHA Task Force on Practice Guidelines, whose charge is to develop, update, or revise practice guidelines for important cardiovascular diseases and procedures, directs this effort. The Task Force is pleased to have this guideline developed in conjunction with the European Society of Cardiology (ESC). Writing committees are charged with the task of performing an assessment of the evidence and acting as an independent group of authors to develop or update written recommendations for clinical practice.

Experts in the subject under consideration have been selected from all 3 organizations to examine subject-specific data and write guidelines. The process includes additional representatives from other medical practitioner and specialty groups when appropriate. Writing committees are specifically charged to perform a formal literature review, weigh the strength of evidence for or against a particular treatment or procedure, and include estimates of expected health outcomes where data exist. Patient-specific modifiers, comorbidities, and issues of patient preference that might influence the choice of particular tests or therapies are considered as well as frequency of follow-up and cost effectiveness. When available, information from studies on cost will be considered; however, review …

/pdf/acc-aha-esc-2006-guidelines-for-management-of-patients-with-5a3f1emfzy.pdf

ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death

A mathematical model of the cardiac ventricular action potential is presented. In our previous work, the membrane Na+ current and K+ currents were formulated. The present article focuses on processes that regulate intracellular Ca2+ and depend on its concentration. The model presented here for the mammalian ventricular action potential is based mostly on the guinea pig ventricular cell. However, it provides the framework for modeling other types of ventricular cells with appropriate modifications made to account for species differences. The following processes are formulated: Ca2+ current through the L-type channel (ICa), the Na(+)-Ca2+ exchanger, Ca2+ release and uptake by the sarcoplasmic reticulum (SR), buffering of Ca2+ in the SR and in the myoplasm, a Ca2+ pump in the sarcolemma, the Na(+)-K+ pump, and a nonspecific Ca(2+)-activated membrane current. Activation of ICa is an order of magnitude faster than in previous models. Inactivation of ICa depends on both the membrane voltage and [Ca2+]i. SR is divided into two subcompartments, a network SR (NSR) and a junctional SR (JSR). Functionally, Ca2+ enters the NSR and translocates to the JSR following a monoexponential function. Release of Ca2+ occurs at JSR and can be triggered by two different mechanisms, Ca(2+)-induced Ca2+ release and spontaneous release. The model provides the basis for the study of arrhythmogenic activity of the single myocyte including afterdepolarizations and triggered activity. It can simulate cellular responses under different degrees of Ca2+ overload. Such simulations are presented in our accompanying article in this issue of Circulation Research.

A dynamic model of the cardiac ventricular action potential. I. Simulations of ionic currents and concentration changes.

A mathematical model of the membrane action potential of the mammalian ventricular cell is introduced. The model is based, whenever possible, on recent single-cell and single-channel data and incorporates the possibility of changing extracellular potassium concentration [K]o. The fast sodium current, INa, is characterized by fast upstroke velocity (Vmax = 400 V/sec) and slow recovery from inactivation. The time-independent potassium current, IK1, includes a negative-slope phase and displays significant crossover phenomenon as [K]o is varied. The time-dependent potassium current, IK, shows only a minimal degree of crossover. A novel potassium current that activates at plateau potentials is included in the model. The simulated action potential duplicates the experimentally observed effects of changes in [K]o on action potential duration and rest potential. Physiological simulations focus on the interaction between depolarization and repolarization (i.e., premature stimulation). Results demonstrate the importance of the slow recovery of INa in determining the response of the cell. Simulated responses to periodic stimulation include monotonic Wenckebach patterns and alternans at normal [K]o, whereas at low [K]o nonmonotonic Wenckebach periodicities, aperiodic patterns, and enhanced supernormal excitability that results in unstable responses ("chaotic activity") are observed. The results are consistent with recent experimental observations, and the model simulations relate these phenomena to the underlying ionic channel kinetics.

A model of the ventricular cardiac action potential. Depolarization, repolarization, and their interaction.

Cellular electrophysiology experiments, important for understanding cardiac arrhythmia mechanisms, are usually performed with channels expressed in non myocytes, or with non-human myocytes. Differences between cell types and species affect results. Thus, an accurate model for the undiseased human ventricular action potential (AP) which reproduces a broad range of physiological behaviors is needed. Such a model requires extensive experimental data, but essential elements have been unavailable. Here, we develop a human ventricular AP model using new undiseased human ventricular data: Ca2+ versus voltage dependent inactivation of L-type Ca2+ current (ICaL); kinetics for the transient outward, rapid delayed rectifier (IKr), Na+/Ca2+ exchange (INaCa), and inward rectifier currents; AP recordings at all physiological cycle lengths; and rate dependence and restitution of AP duration (APD) with and without a variety of specific channel blockers. Simulated APs reproduced the experimental AP morphology, APD rate dependence, and restitution. Using undiseased human mRNA and protein data, models for different transmural cell types were developed. Experiments for rate dependence of Ca2+ (including peak and decay) and intracellular sodium ([Na+]i) in undiseased human myocytes were quantitatively reproduced by the model. Early afterdepolarizations were induced by IKr block during slow pacing, and AP and Ca2+ alternans appeared at rates >200 bpm, as observed in the nonfailing human ventricle. Ca2+/calmodulin-dependent protein kinase II (CaMK) modulated rate dependence of Ca2+ cycling. INaCa linked Ca2+ alternation to AP alternans. CaMK suppression or SERCA upregulation eliminated alternans. Steady state APD rate dependence was caused primarily by changes in [Na+]i, via its modulation of the electrogenic Na+/K+ ATPase current. At fast pacing rates, late Na+ current and ICaL were also contributors. APD shortening during restitution was primarily dependent on reduced late Na+ and ICaL currents due to inactivation at short diastolic intervals, with additional contribution from elevated IKr due to incomplete deactivation.

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Simulation of the Undiseased Human Cardiac Ventricular Action Potential: Model Formulation and Experimental Validation

Propagation of excitation in the heart involves action potential (AP) generation by cardiac cells and its propagation in the multicellular tissue. AP conduction is the outcome of complex interactions between cellular electrical activity, electrical cell-to-cell communication, and the cardiac tissue structure. As shown in this review, strong interactions occur among these determinants of electrical impulse propagation. A special form of conduction that underlies many cardiac arrhythmias involves circulating excitation. In this situation, the curvature of the propagating excitation wavefront and the interaction of the wavefront with the repolarization tail of the preceding wave are additional important determinants of impulse propagation. This review attempts to synthesize results from computer simulations and experimental preparations to define mechanisms and biophysical principles that govern normal and abnormal conduction in the heart.

Basic Mechanisms of Cardiac Impulse Propagation and Associated Arrhythmias

In cardiac tissue, reduced membrane excitability and reduced gap junction coupling both slow conduction velocity of the action potential. However, the ionic mechanisms of slow conduction for the two conditions are very different. We explored, using a multicellular theoretical fiber, the ionic mechanisms and functional role of the fast sodium current, INa, and the L-type calcium current, ICa(L), during conduction slowing for the two fiber conditions. A safety factor for conduction (SF) was formulated and computed for each condition. Reduced excitability caused a lower SF as conduction velocity decreased. In contrast, reduced gap junction coupling caused a paradoxical increase in SF as conduction velocity decreased. The opposite effect of the two conditions on SF was reflected in the minimum attainable conduction velocity before failure: decreased excitability could reduce velocity to only one third of control (from 54 to 17 cm/s) before failure occurred, whereas decreased coupling could reduce velocity to as low as 0.26 cm/s before block. Under normal conditions and conditions of reduced excitability, ICa(L) had a minimal effect on SF and on conduction. However, ICa(L) played a major role in sustaining conduction when intercellular coupling was reduced. This phenomenon demonstrates that structural, nonmembrane factors can cause a switch of intrinsic membrane processes that support conduction. High intracellular calcium concentration, [Ca]i, lowered propagation safety and caused earlier block when intercellular coupling was reduced. [Ca]i affected conduction via calcium-dependent inactivation of ICa(L). The increase of safety factor during reduced coupling suggests a major involvement of uncoupling in stable slow conduction in infarcted myocardium, making microreentry possible. Reliance on ICa(L) for this type of conduction suggests ICa(L) as a possible target for antiarrhythmic drug therapy.

Ionic Mechanisms of Propagation in Cardiac Tissue Roles of the Sodium and L-type Calcium Currents During Reduced Excitability and Decreased Gap Junction Coupling

Yoram Rudy

Papers

A dynamic model of the cardiac ventricular action potential. I. Simulations of ionic currents and concentration changes.

A model of the ventricular cardiac action potential. Depolarization, repolarization, and their interaction.

Simulation of the Undiseased Human Cardiac Ventricular Action Potential: Model Formulation and Experimental Validation

Basic Mechanisms of Cardiac Impulse Propagation and Associated Arrhythmias

Ionic Mechanisms of Propagation in Cardiac Tissue Roles of the Sodium and L-type Calcium Currents During Reduced Excitability and Decreased Gap Junction Coupling