These early defibrillators used the alternating current from a power socket, transformed from the 110–240 volts available in the line, up to between 300 and 1000 volts, to the exposed heart by way of "paddle" type electrodes.  The technique was often ineffective in reverting VF while morphological studies showed damage to the cells of the heart muscle post-mortem.  The nature of the AC machine with a large transformer also made these units very hard to transport, and they tended to be large units on wheels. [ citation needed ]


Until the early 1950s, defibrillation of the heart was possible only when the chest cavity was open during surgery. The technique used an alternating voltage from a 300 or greater  volt  source derived from standard AC power, delivered to the sides of the exposed heart by "paddle" electrodes where each electrode was a flat or slightly concave metal plate of about 40 mm diameter. The closed-chest defibrillator device which applied an alternating voltage of greater than 1000 volts, conducted by means of externally applied electrodes through the chest cage to the heart, was pioneered by Dr V. Eskin with assistance by A. Klimov in Frunze, USSR (today known as  Bishkek ,  Kyrgyzstan ) in the mid-1950s. [ 34 ]  The duration of AC shocks was typically in the range of 100–150 milliseconds. [ 35 ]


Early successful experiments of successful defibrillation by the discharge of a capacitor performed on animals were reported by  N. L. Gurvich  and G. S. Yunyev in 1939. [ 36 ]  In 1947 their works were reported in western medical journals. [ 37 ]  Serial production of Gurvich's pulse defibrillator started in 1952 at the electromechanical plant of the institute, and was designated model ИД-1-ВЭИ ( Импульсный Дефибриллятор 1, Всесоюзный Электротехнический Институт , or in English,  Pulse Defibrillator 1, All-Union Electrotechnical Institute ). It is described in detail in Gurvich's 1957 book,  Heart Fibrillation and Defibrillation . [ 38 ]


The first Czechoslovak  "universal defibrillator Prema" was manufactured in 1957 by the company Prema, designed by Dr. Bohumil Peleška. In 1958 his device was awarded Grand Prix at  Expo 58 . [ 39 ]


In 1958, US senator  Hubert H. Humphrey  visited  Nikita Khrushchev  and among other things he visited the Moscow Institute of Reanimatology, where, among others, he met with Gurvich. [ 40 ]   Humphrey immediately recognized importance of reanimation research and after that a number of American doctors visited Gurvich. At the same time, Humphrey worked on establishing a federal program in the  National Institute of Health   in physiology and medicine, telling Congress: "Let's compete with U.S.S.R. in research on reversibility of death". [ 41 ]


In 1959  Bernard Lown  commenced research in his animal laboratory in collaboration with engineer  Barouh Berkovits  into a technique which involved charging of a bank of  capacitors  to approximately 1000 volts with an  energy  content of 100–200  joules  then delivering the charge through an inductance such as to produce a heavily damped sinusoidal wave of finite duration (~5  milliseconds ) to the heart by way of paddle electrodes.  This team further developed an understanding of the optimal timing of shock delivery in the cardiac cycle, enabling the application of the device to  arrhythmias  such as  atrial fibrillation ,  atrial flutter , and supraventricular  tachycardias  in the technique known as " cardioversion ".


The Lown-Berkovits waveform, as it was known, was the standard for defibrillation until the late 1980s. Earlier in the 1980s, the "MU lab" at the University of Missouri had pioneered numerous studies introducing a new waveform called a biphasic truncated waveform (BTE). In this waveform an exponentially decaying DC voltage is reversed in polarity about halfway through the shock time, then continues to decay for some time after which the voltage is cut off, or truncated. The studies showed that the biphasic truncated waveform could be more efficacious while requiring the delivery of lower levels of energy to produce defibrillation. [ 35 ]  An added benefit was a significant reduction in weight of the machine. The BTE waveform, combined with automatic measurement of transthoracic impedance, is the basis for modern defibrillators. [ citation needed ]


A major breakthrough was the introduction of portable defibrillators used out of the hospital. Already Peleška's Prema defibrillator was designed to be more portable than original Gurvich's model. In Soviet Union, a portable version of Gurvich's defibrillator, model ДПА-3 (DPA-3), was reported in 1959. [ 42 ]   In the west this was pioneered in the early 1960s by Prof.  Frank Pantridge  in  Belfast .  Today portable defibrillators are among the many very important tools carried by ambulances.  They are the only proven way to resuscitate a person who has had a  cardiac arrest unwitnessed by Emergency Medical Services (EMS) who is still in  persistent ventricular fibrillation or ventricular  tachycardia  at the arrival of pre-hospital providers.


Gradual improvements in the design of defibrillators, partly based on the work developing implanted versions (see below), have led to the availability of Automated External Defibrillators. These devices can analyse the heart rhythm by themselves, diagnose the shockable rhythms, and charge to treat.  This means that no clinical skill is required in their use, allowing lay people to respond to emergencies effectively.


Until the mid 1990s, external defibrillators delivered a Lown type waveform (see  Bernard Lown ), a heavily damped  sinusoidal  impulse having a mainly uniphasic characteristic. Biphasic defibrillation alternates the direction of the pulses, completing one cycle in approximately 12 milliseconds. Biphasic defibrillation was originally developed and used for implantable cardioverter-defibrillators. When applied to external defibrillators, biphasic defibrillation significantly decreases the energy level necessary for successful defibrillation, decreasing the risk of burns and  myocardial  damage.


Ventricular fibrillation (VF) could be returned to  sinus rhythm  in 60% of cardiac arrest patients treated with a single shock from a monophasic defibrillator. Most biphasic defibrillators have a first shock success rate of greater than 90%. [ 43 ]


A further development in defibrillation came with the invention of the implantable device, known as an  implantable cardioverter-defibrillator  (or ICD).  This was pioneered at  Sinai Hospital  in  Baltimore  by a team that included Stephen Heilman, Alois Langer, Jack Lattuca,  Morton Mower ,  Michel Mirowski , and  Mir Imran , with the help of industrial collaborator Intec Systems of Pittsburgh. [ 44 ]  Mirowski teamed up with Mower and Staewen, and together they commenced their research in 1969. However, it was 11 years before they treated their first patient. Similar developmental work was carried out by Schuder and colleagues at the  University of Missouri .


The work was commenced, despite doubts amongst leading experts in the field of arrhythmias and sudden death. There was doubt that their ideas would ever become a clinical reality. In 1962  Bernard Lown  introduced the external  DC  defibrillator. This device applied a direct current from a discharging capacitor through the chest wall into the heart to stop heart  fibrillation . [ 45 ]  In 1972, Lown stated in the journal  Circulation  – "The very rare patient who has frequent bouts of ventricular fibrillation is best treated in a coronary care unit and is better served by an effective antiarrhythmic program or surgical correction of inadequate coronary blood flow or ventricular malfunction. In fact, the implanted defibrillator system represents an imperfect solution in search of a plausible and practical application." [ 46 ]


The problems to be overcome were the design of a system which would allow detection of ventricular fibrillation or ventricular tachycardia. Despite the lack of financial backing and grants, they persisted and the first device was implanted in February 1980 at  Johns Hopkins Hospital  by Dr.  Levi Watkins  Jr. assisted by  Vivien Thomas . Modern ICDs do not require a  thoracotomy  and possess  pacing , cardioversion, and defibrillation capabilities.


The invention of implantable units is invaluable to some people with regular heart problems, although they are generally only given to those people who have already had a cardiac episode.


People can live long normal lives with the devices.  Many patients have multiple implants.  A patient in Houston, Texas had an implant at the age of 18 in 1994 by the recent Dr. Antonio Pacifico. He was awarded "Youngest Patient with Defibrillator" in 1996. Today these devices are implanted into small babies shortly after birth.


As devices that can quickly produce dramatic improvements in patient health, defibrillators are often depicted in movies, television, video games and other fictional media. Their function, however, is often exaggerated with the defibrillator inducing a sudden, violent jerk or convulsion by the patient. The pad placement is also shown wrong, along with sudden rising of patient to large height when shock is given. In reality, while the muscles may contract, such dramatic patient presentation is rare. Similarly, medical providers are often depicted defibrillating patients with a "flat-line" ECG rhythm (also known as  asystole ). This is not normal medical practice, as the heart cannot be restarted by the defibrillator itself. Only the cardiac arrest rhythms  ventricular fibrillation  and pulseless  ventricular tachycardia  are normally defibrillated. The purpose of defibrillation is to depolarize the entire heart all at once so that it is synchronized, effectively inducing temporary asystole, in the hope that in the absence of the previous abnormal electrical activity, the heart will spontaneously resume beating normally. Someone who is already in asystole cannot be helped by electrical means, and usually needs urgent  CPR  and  intravenous  medication (and even these are rarely successful in cases of asystole). A useful analogy to remember is to think of defibrillators as power-cycling, rather than jump-starting, the heart. There are also several heart rhythms that can be "shocked" when the patient is not in cardiac arrest, such as  supraventricular tachycardia  and ventricular tachycardia that produces a  pulse ; this more-complicated procedure is known as  cardioversion , not defibrillation.


In  Australia  up until the 1990s it was relatively rare for ambulances to carry defibrillators. This changed in 1990 after Australian  media mogul   Kerry Packer  had a cardiac arrest due to a heart attack and, purely by chance, the ambulance that responded to the call carried a defibrillator. After recovering, Kerry Packer donated a large sum to the  Ambulance Service of New South Wales  in order that all ambulances in  New South Wales  should be fitted with a personal defibrillator, which is why defibrillators in Australia are sometimes  colloquially  called "Packer Whackers". [ 47 ]


Defibrillation threshold  indicates the minimum amount of energy needed to return normal rhythm to a heart that is beating in a  cardiac dysrhythmia . Typical examples are the minimum amount of energy, expressed in  joules , delivered by external defibrillator paddles or pads, required to break  atrial fibrillation  and restore normal  sinus rhythm . Other common scenarios are restoring normal rhythm from  atrial flutter ,  ventricular tachycardia  or  ventricular fibrillation . The defibrillation threshold ranking in these settings, from lowest to highest, would be, in order, ventricular tachycardia, atrial flutter, atrial fibrillation, ventricular fibrillation. The highest amount of energy that an  external defibrillator  can deliver at the present time is 360 joules biphasic. In clinical practice, the real threshold can be approximated but not exactly established, since the defibrillating shock can be delivered only once. Aside from that, energy isn't directly related to stimulus strength and efficiency, which is primarily determined by the delivered charge over time in  mC  and not power over time or energy, which are still used due to historical reasons. Charge based thresholds are more realistic parameters for shock efficacy. Usual values delivered by biphasic defibrillators lay between 50 and 300 mC. The amount of charge needed is influenced by certain medications, in particular  sotalol , tend to lower such threshold, while others, such as  amiodarone , may increase it. [ 1 ]


Defibrillation threshold is a concept also applicable to internal or  implantable cardiac defibrillators . [ 2 ]  The test needed to establish the defibrillation threshold is often referred to as DFT.


In  mammals , cardiac electrical activity originates from specialized  myocytes  of the  sinoatrial node  (SAN) which generate spontaneous and rhythmic  action potentials  (AP). The unique functional aspect of this type of myocyte is the absence of a stable  resting potential  during diastole.  Electrical discharge from this  cardiomyocyte  may be characterized by a slow smooth transition from the Maximum Diastolic Potential (MDP, -70 mV) to the threshold (-40 mV) for the initiation of a new AP event. The voltage region encompassed by this transition is commonly known as pacemaker phase, or slow diastolic depolarization or phase 4.


The duration of this slow diastolic depolarization (pacemaker phase) thus governs the cardiac chronotropism. It is also important to point out that the modulation of the cardiac rate by the  autonomic nervous system  also acts on this phase. Sympathetic stimuli induce the acceleration of rate by increasing the slope of the pacemaker phase, while parasympathetic activation exerts the opposite action.


The amount of net inward current required to move the cell membrane potential during the pacemaker phase is extremely small, in the order of few pAs, but this net flux arises from the time to time changing contribution of several currents that flow with different voltage and time dependence. Evidence in support of the active presence of K + , Ca 2+  , Na +   channels and Na + /K +  exchanger during the pacemaker phase have been variously reported in the literature, but several indications point to the  funny current  (I f ) as one of the most important. [ 1 ] [ 2 ]  There is now substantial evidence that also sarcoplasmic reticulum (SR) Ca 2+  -transients participate in the generation of the diastolic depolarization via a process involving the Na–Ca exchanger.


In  electrocardiography , during a  cardiac cycle , once an action potential is initiated, there is a period of time that a new action potential cannot be initiated. This is termed the  effective refractory period  (ERP) of the tissue. This period is approximately equal to the  absolute refractory period  (ARP), it occurs because the fast  sodium channels  remain closed until the cell fully repolarizes. [ 1 ]
During this period, depolarization on adjacent cardiac muscles does not produce a new depolarization in the current cell as it has to refract back to phase 4 of the action potential before a new action potential can activate it. ERP acts as a protective mechanism and keeps the heart rate in check and prevents  arrhythmias , and it helps coordinates muscle contraction.  Anti-arrhythmic agents  used for arrhythmias usually prolong the ERP. For the treatment of  atrial fibrillation , it is a problem that the prolongation of the ERP by these agents also affects the ventricles, which can induce other types of arrhythmias. [ 2 ]


Einthoven's triangle  is an imaginary formation of three limb leads in a triangle used in the  electrocardiography , formed by the two shoulders and the pubis. [ 1 ]  The shape forms an inverted equilateral triangle with the heart at the center. It is named after  Willem Einthoven , who theorized its existence. [ 2 ]


Einthoven used these measuring points, by immersing the hands and feet in pails of salt water, as the contacts for his  string galvanometer , the first practical ECG machine. [ 3 ]


Electrodes may be placed  distally  or  proximally  on the limb without affecting the recording. [ 5 ]  The right leg electrode acts to reduce interference, and can be placed anywhere without an effect on the ECG results. [ 6 ]


Each lead measures the electric field created by the heart during the  depolarization  and  repolarization  of  myocytes . The electric field can be represented as a vector that changes continuously and can be measured by recording the voltage difference between electrodes. [ 7 ]


Einthoven's triangle can be helpful in the identification in incorrect placement of leads. Incorrect placement of leads can lead to error in the recording, which can ultimately lead to misdiagnosis.


If the arm electrodes are reversed, lead I changes polarity, causing lead II and lead III to switch. If the right arm electrode is reversed with the leg's electrode, lead II changes polarity, causing lead I to become lead III, and vice versa. Reversal of the left arm and leg causes a change in polarity of lead III and switching of leads I and II. [ 6 ]


Electroanatomic mapping  is a method of creating a three dimensional model of the  human heart  during  clinical cardiac electrophysiology  procedures.


The fundamental concept of electroanatomic mapping systems is to localize catheters within the heart in three dimensional space (a sort of " GPS " within the heart). Building a 3-D model of the heart with real-time visualization permits reduction in  fluoroscopy  use. In addition to 3-D structure, the voltage and timing of signals at each point of the heart is recorded to generate different maps to understand and treat different rhythm disturbances.


Each of the three systems utilizes different techniques to localize catheters:  [ 1 ]


There are three electroanatomic mapping systems commercially available.


Biosense-Webster, a subsidiary of  Johnson & Johnson , produces a cardiac electrophysiology system called CARTO. [ 2 ]  The system is designed to visualise the real-time calculated position and orientation of a specialised  RF ablation   catheter  within the patient's heart in order to minimise  radiation exposure  during  fluoroscopy , increase the accuracy of targeted RF ablation and reacquisition of  pacing  sites for re- ablation . [ 3 ]   Its navigation system calculates the position and orientation of the catheter tip, using three known magnetic sources as references. The system uses  static magnetic fields  that are calibrated and computer controlled. Due to the nature of magnetic fields, the orientation may also be calculated while the tip is stationary. By calculating the strength and orientation of the magnetic fields at a given location, the x,y,z position may be calculated along with the  roll, pitch, yaw  orientation. [ 2 ]


St. Jude Medical , now a part of  Abbott , manufactures EnSite family of cardiac mapping systems, the latest edition being EnSite Precision, which allows speedy heart mapping during catheter ablation with better accuracy to be able to treat cardiac rhythm disturbances.  [ 4 ]


Mapping system developed by  Boston Scientific .


Mapping systems generate three kinds of data:


Electrocardiography  is the process of producing an  electrocardiogram  ( ECG  or  EKG [ a ] ), a recording of the heart's electrical activity through repeated  cardiac cycles . [ 4 ]  It is an  electrogram  of the  heart  which is a graph of  voltage  versus time of the electrical activity of the heart [ 5 ]  using  electrodes  placed on the skin. These electrodes detect the small electrical changes that are a consequence of  cardiac muscle   depolarization  followed by  repolarization  during each  cardiac cycle  (heartbeat). Changes in the normal ECG pattern occur in numerous cardiac abnormalities, including:


Traditionally, "ECG" usually means a  12-lead ECG  taken while lying down as discussed below.
However, other devices can record the electrical activity of the heart such as a  Holter monitor  but also some models of  smartwatch  are capable of recording an ECG.
ECG signals can be recorded in other contexts with other devices.


In a conventional 12-lead ECG, ten electrodes are placed on the patient's limbs and on the surface of the chest. The overall  magnitude  of the heart's  electrical potential  is then measured from twelve different angles ("leads") and is recorded over a period of time (usually ten seconds). In this way, the overall magnitude and direction of the heart's electrical depolarization is captured at each moment throughout the  cardiac cycle . [ 11 ]


There are three main components to an ECG: [ 12 ]


During each heartbeat, a healthy heart has an orderly progression of depolarization that starts with  pacemaker cells  in the  sinoatrial node , spreads throughout the  atrium , and passes through the  atrioventricular node  down into the  bundle of His  and into the  Purkinje fibers , spreading down and to the left throughout the  ventricles . [ 12 ]  This orderly pattern of depolarization gives rise to the characteristic ECG tracing. To the trained  clinician , an ECG conveys a large amount of information about the structure of the heart and the function of its electrical conduction system. [ 13 ]  Among other things, an ECG can be used to measure the rate and rhythm of heartbeats, the size and position of the  heart chambers , the presence of any damage to the heart's muscle cells or conduction system, the effects of heart drugs, and the function of implanted  pacemakers . [ 14 ]


The overall goal of performing an ECG is to obtain information about the electrical functioning of the heart. Medical uses for this information are varied and often need to be combined with knowledge of the structure of the heart and physical examination signs to be interpreted. Some  indications  for performing an ECG include the following:


ECGs can be recorded as short intermittent tracings or  continuous  ECG monitoring. Continuous monitoring is used for critically ill patients, patients undergoing general anesthesia, [ 18 ] [ 17 ]  and patients who have an infrequently occurring cardiac arrhythmia that would unlikely be seen on a conventional ten-second ECG. Continuous monitoring can be conducted by using  Holter monitors , internal and external  defibrillators  and  pacemakers , and/or  biotelemetry . [ 19 ]


For adults, evidence does not support the use of ECGs among those without symptoms or at low risk of  cardiovascular disease  as an effort for prevention. [ 20 ] [ 21 ] [ 22 ]  This is because an ECG may falsely indicate the existence of a problem, leading to  misdiagnosis , the recommendation of invasive procedures, and  overtreatment . However, persons employed in certain critical occupations, such as aircraft pilots, [ 23 ]  may be required to have an ECG as part of their routine health evaluations.  Hypertrophic cardiomyopathy  screening may also be considered in adolescents as part of a  sports physical  out of concern for  sudden cardiac death . [ 24 ]


Electrocardiograms are recorded by machines that consist of a set of electrodes connected to a central unit. [ 25 ]  Early ECG machines were constructed with  analog electronics , where the signal drove a motor to print out the signal onto paper. Today, electrocardiographs use  analog-to-digital converters  to convert the electrical activity of the heart to a  digital signal . Many ECG machines are now portable and commonly include a screen, keyboard, and printer on a small wheeled cart. Recent advancements in electrocardiography include developing even smaller devices for inclusion in fitness trackers and  smart watches . [ 26 ]  These smaller devices often rely on only two electrodes to deliver a single lead I. [ 27 ]  Portable twelve-lead devices powered by batteries are also available.


Recording an ECG is a safe and painless procedure. [ 28 ]  The machines are powered by  mains power  but they are designed with several safety features including an earthed (ground) lead.
Other features include:


Most modern ECG machines include  automated interpretation   algorithms . This analysis calculates features such as the  PR interval ,  QT interval ,  corrected QT (QTc) interval , PR axis, QRS axis, rhythm and more. The results from these automated algorithms are considered "preliminary" until verified and/or modified by expert interpretation. Despite recent advances, computer misinterpretation remains a significant problem and can result in clinical mismanagement. [ 29 ]


Besides the standard electrocardiograph machine, there are other devices capable of recording ECG signals. Portable devices have existed since the  Holter monitor  was introduced in 1962.
Traditionally, these monitors have used electrodes with patches on the skin to record the ECG, but new devices can stick to the chest as a single patch without need for wires, developed by Zio (Zio XT), TZ Medical (Trident),  Philips  (BioTel) and BardyDx (CAM) among many others.
Implantable devices such as the  artificial cardiac pacemaker  and  implantable cardioverter-defibrillator  are capable of measuring a "far field" signal between the leads in the heart and the implanted battery/generator that resembles an ECG signal (technically, the signal recorded in the heart is called an  electrogram , which is interpreted differently).
Advancement of the Holter monitor became the  implantable loop recorder  that performs the same function but in an implantable device with batteries that last on the order of years.


Additionally, there are available various  Arduino  kits with ECG sensor modules and  smartwatch  devices that are capable of recording an ECG signal as well, such as with the 4th generation  Apple Watch ,  Samsung Galaxy Watch 4  and newer devices.


Electrodes are the actual conductive pads attached to the body surface. [ 31 ]  Any pair of electrodes can measure the  electrical potential difference  between the two corresponding locations of attachment. Such a pair forms  a lead . However, "leads" can also be formed between a physical electrode and a  virtual electrode,  known as  Wilson's central terminal  ( WCT ), whose potential is defined as the average potential measured by three limb electrodes that are attached to the right arm, the left arm, and the left foot, respectively. [ citation needed ]


Commonly, 10 electrodes attached to the body are used to form 12 ECG leads, with each lead measuring a specific electrical potential difference (as listed in the table below). [ 32 ]


Leads are broken down into three types: limb; augmented limb; and precordial or chest. The 12-lead ECG has a total of three  limb leads  and three  augmented limb leads  arranged like spokes of a wheel in the  coronal plane  (vertical), and six  precordial leads  or  chest leads  that lie on the perpendicular  transverse plane  (horizontal). [ 33 ]


Leads should be placed in standard positions. Exceptions due to emergency or other issues should be recorded to avoid erroneous analysis. [ 34 ]


The 12 standard ECG leads are listed below. All leads are effectively bipolar, with one positive and one negative electrode; the term "unipolar" is not useful. [ 35 ]


Two types of electrodes in common use are a flat paper-thin sticker and a self-adhesive circular pad.
The former are typically used in a single ECG recording while the latter are for continuous recordings as they stick longer.
Each electrode consists of an  electrically conductive  electrolyte gel and a  silver/silver chloride  conductor. [ 36 ]
The gel typically contains  potassium chloride  – sometimes  silver chloride  as well – to permit  electron  conduction from the skin to the wire and to the electrocardiogram. [ 37 ]


The common virtual electrode, known as Wilson's central terminal (V W ), is produced by averaging the measurements from the electrodes RA, LA, and LL to give an average potential of the body:


In a 12-lead ECG, all leads except the limb leads are assumed to be unipolar (aVR, aVL, aVF, V 1 , V 2 , V 3 , V 4 , V 5 , and V 6 ).
The measurement of a voltage requires two contacts and so, electrically, the unipolar leads are measured from the common lead (negative) and the unipolar lead (positive).
This averaging for the common lead and the abstract unipolar lead concept makes for a more challenging understanding and is complicated by sloppy usage of "lead" and "electrode".
In fact, instead of being a constant reference, V W  has a value that fluctuates throughout the heart cycle. It also does not truly represent the center-of-heart potential due to the body parts the signals travel through. [ 38 ]   Because voltage is by definition a bipolar measurement between two points, describing an electrocardiographic lead as "unipolar" makes little sense electrically and should be avoided.  The American Heart Association states "All leads are effectively 'bipolar,' and the term 'unipolar' in description of the augmented limb leads and the precordial leads lacks precision." [ 39 ]


Leads I, II and III are called the  limb leads . The electrodes that form these signals are located on the limbs – one on each arm and one on the left leg. [ 40 ] [ 41 ]  The limb leads form the points of what is known as  Einthoven's triangle . [ 42 ]


Leads aVR, aVL, and aVF are the  augmented limb leads . They are derived from the same three electrodes as leads I, II, and III, but they use Goldberger's central terminal as their negative pole. Goldberger's central terminal is a combination of inputs from two limb electrodes, with a different combination for each augmented lead. It is referred to immediately below as "the negative pole".


Together with leads I, II, and III, augmented limb leads aVR, aVL, and aVF form the basis of the  hexaxial reference system , which is used to calculate the heart's electrical axis in the frontal plane. [ 43 ]


Older versions of the nodes (VR, VL, VF) use Wilson's central terminal as the negative pole, but the amplitude is too small for the thick lines of old ECG machines. The Goldberger terminals scale up (augments) the Wilson results by 50%, at the cost of sacrificing physical correctness by not having the same negative pole for all three. [ 44 ]


The  precordial leads  lie in the transverse (horizontal) plane, perpendicular to the other six leads. The six precordial electrodes act as the positive poles for the six corresponding precordial leads: (V 1 , V 2 , V 3 , V 4 , V 5 , and V 6 ). Wilson's central terminal is used as the negative pole. Recently, unipolar precordial leads have been used to create bipolar precordial leads that explore the right to left axis in the horizontal plane. [ 45 ]


Additional electrodes may rarely be placed to generate other leads for specific diagnostic purposes.  Right-sided  precordial leads may be used to better study pathology of the right ventricle or for  dextrocardia  (and are denoted with an R (e.g., V 5R ).  Posterior leads  (V 7  to V 9 ) may be used to demonstrate the presence of a posterior myocardial infarction. The  Lewis lead  or S5-lead (requiring an electrode at the right sternal border in the second intercostal space) can be used to better detect atrial activity in relation to that of the ventricles. [ 46 ]


An  esophageal lead  can be inserted to a part of the  esophagus  where the distance to the posterior wall of the  left atrium  is only approximately 5–6 mm (remaining constant in people of different age and weight). [ 47 ]  An esophageal lead avails for a more accurate differentiation between certain cardiac arrhythmias, particularly  atrial flutter ,  AV nodal reentrant tachycardia  and orthodromic  atrioventricular reentrant tachycardia . [ 48 ]  It can also evaluate the risk in people with  Wolff-Parkinson-White syndrome , as well as terminate  supraventricular tachycardia  caused by  re-entry . [ 48 ]


An intracardiac electrogram (ICEG) is essentially an ECG with some added  intracardiac leads  (that is, inside the heart). The standard ECG leads (external leads) are I, II, III, aVL, V 1 , and V 6 . Two to four intracardiac leads are added via cardiac catheterization. The word "electrogram" (EGM) without further specification usually means an intracardiac electrogram. [ 49 ]


A standard 12-lead ECG report (an electrocardiograph) shows a 2.5 second tracing of each of the twelve leads. The tracings are most commonly arranged in a grid of four columns and three rows. The first column is the limb leads (I, II, and III), the second column is the augmented limb leads (aVR, aVL, and aVF), and the last two columns are the precordial leads (V 1  to V 6 ).
Additionally, a rhythm strip may be included as a fourth or fifth row. [ 43 ]


The timing across the page is continuous and notes tracings of the 12 leads for the same time period.
In other words, if the output were traced by needles on paper, each row would switch which leads as the paper is pulled under the needle.
For example, the top row would first trace lead I, then switch to lead aVR, then switch to V 1 , and then switch to V 4 , and so none of these four tracings of the leads are from the same time period as they are traced in sequence through time. [ 50 ]


Each of the 12 ECG leads records the electrical activity of the heart from a different angle, and therefore align with different anatomical areas of the heart. Two leads that look at neighboring anatomical areas are said to be  contiguous . [ 43 ]


In addition, any two precordial leads next to one another are considered to be contiguous. For example, though V 4  is an anterior lead and V 5  is a lateral lead, they are contiguous because they are next to one another.


The study of the conduction system of the heart is called  cardiac electrophysiology  (EP). An EP study is performed via a right-sided  cardiac catheterization : a wire with an electrode at its tip is inserted into the right heart chambers from a peripheral vein, and placed in various positions in close proximity to the conduction system so that the electrical activity of that system can be recorded. [ citation needed ]


Standard catheter positions for an EP study include "high right atrium" or hRA near the  sinus node , a "His" across the septal wall of the tricuspid valve to measure  bundle of His , a "coronary sinus" into the  coronary sinus , and a "right ventricle" in the apex of the right ventricle. [ 51 ]


Interpretation of the ECG is fundamentally about understanding the  electrical conduction system of the heart .
Normal conduction starts and propagates in a predictable pattern, and deviation from this pattern can be a normal variation or be  pathological .
An ECG does not equate with mechanical pumping activity of the heart; for example,  pulseless electrical activity  produces an ECG that should pump blood but no pulses are felt (and constitutes a  medical emergency  and  CPR  should be performed).
 Ventricular fibrillation  produces an ECG but is too dysfunctional to produce a life-sustaining cardiac output. Certain rhythms are known to have good cardiac output and some are known to have bad cardiac output.
Ultimately, an  echocardiogram  or other anatomical imaging modality is useful in assessing the mechanical function of the heart. [ 52 ]


Like all medical tests, what constitutes "normal" is based on  population studies . The heartrate range of between 60 and 100 beats per minute (bpm) is considered normal since data shows this to be the usual resting heart rate. [ 53 ]


Interpretation of the ECG is ultimately that of pattern recognition.
In order to understand the patterns found, it is helpful to understand the theory of what ECGs represent.
The theory is rooted in  electromagnetics  and boils down to the four following points: [ 54 ]


Thus, the overall direction of depolarization and repolarization produces positive or negative deflection on each lead's trace.
For example, depolarizing from right to left would produce a positive deflection in lead I because the two vectors point in the same direction.
In contrast, that same depolarization would produce minimal deflection in V 1  and V 2  because the vectors are perpendicular, and this phenomenon is called isoelectric.


Normal rhythm produces four entities – a  P wave , a  QRS complex , a  T wave , and a  U wave  – that each have a fairly unique pattern.


Changes in the structure of the heart and its surroundings (including blood composition) change the patterns of these four entities.


The U wave is not typically seen and its absence is generally ignored. Atrial repolarization is typically hidden in the much more prominent QRS complex and normally cannot be seen without additional, specialized electrodes.


ECGs are normally printed on a grid.
The horizontal axis represents time and the vertical axis represents voltage.
The standard values on this grid are shown in the adjacent image at 25mm/sec: [ 55 ]


The "large" box is represented by a heavier  line weight  than the small boxes.


The standard printing speed in the United States is 25 mm per sec (5 big boxes per second), but in other countries it can be 50 mm per sec.
Faster speeds such as 100 and 200 mm per sec are used during electrophysiology studies.


Not all aspects of an ECG rely on precise recordings or having a known scaling of amplitude or time.
For example, determining if the tracing is a sinus rhythm only requires feature recognition and matching, and not measurement of amplitudes or times (i.e., the scale of the grids are irrelevant).
An example to the contrary, the voltage requirements of  left ventricular hypertrophy  require knowing the grid scale.


In a normal heart, the heart rate is the rate at which the  sinoatrial node  depolarizes since it is the source of depolarization of the heart.
Heart rate, like other  vital signs  such as blood pressure and respiratory rate, change with age.
In adults, a normal heart rate is between 60 and 100 bpm (normocardic), whereas it is higher in children. [ 56 ]
A heart rate below normal is called " bradycardia " (<60 in adults) and above normal is called " tachycardia " (>100 in adults).
A complication of this is when the atria and ventricles are not in synchrony and the "heart rate" must be specified as atrial or ventricular (e.g., the ventricular rate in  ventricular fibrillation  is 300–600 bpm, whereas the atrial rate can be normal [60–100] or faster [100–150]). [ citation needed ]


In normal resting hearts, the physiologic rhythm of the heart is  normal sinus rhythm  (NSR).
Normal sinus rhythm produces the prototypical pattern of P wave, QRS complex, and T wave.
Generally, deviation from normal sinus rhythm is considered a  cardiac arrhythmia .
Thus, the first question in interpreting an ECG is whether or not there is a sinus rhythm.
A criterion for sinus rhythm is that P waves and QRS complexes appear 1-to-1, thus implying that the P wave causes the QRS complex. [ 50 ]


Once sinus rhythm is established, or not, the second question is the rate.
For a sinus rhythm, this is either the rate of P waves or QRS complexes since they are 1-to-1.
If the rate is too fast, then it is  sinus tachycardia , and if it is too slow, then it is  sinus bradycardia .


If it is not a sinus rhythm, then determining the rhythm is necessary before proceeding with further interpretation.
Some arrhythmias with characteristic findings:


Determination of rate and rhythm is necessary in order to make sense of further interpretation.


The heart has several axes, but the most common by far is the axis of the QRS complex (references to "the axis" imply the QRS axis).
Each axis can be computationally determined to result in a number representing degrees of deviation from zero, or it can be categorized into a few types. [ 57 ]


The QRS axis is the general direction of the ventricular depolarization wavefront (or mean electrical vector) in the frontal plane.
It is often sufficient to classify the axis as one of three types: normal, left deviated, or right deviated.
Population data shows that a normal QRS axis is from −30° to 105°, with 0° being along lead I and positive being inferior and negative being superior (best understood graphically as the  hexaxial reference system ). [ 58 ]
Beyond +105° is  right axis deviation  and beyond −30° is  left axis deviation  (the third quadrant of −90° to −180° is very rare and is an indeterminate axis).
A shortcut for determining if the QRS axis is normal is if the QRS complex is mostly positive in lead I and lead II (or lead I and aVF if +90° is the upper limit of normal). [ 59 ]


The normal QRS axis is generally  down and to the left , following the anatomical orientation of the heart within the chest. An abnormal axis suggests a change in the physical shape and orientation of the heart or a defect in its conduction system that causes the ventricles to depolarize in an abnormal way. [ 50 ]


The extent of a normal axis can be +90° or 105° depending on the source.


All of the waves on an ECG tracing and the intervals between them have a predictable time duration, a range of acceptable amplitudes ( voltages ), and a typical morphology. Any deviation from the normal tracing is potentially pathological and therefore of clinical significance. [ 60 ]


For ease of measuring the amplitudes and intervals, an ECG is printed on graph paper at a standard scale: each 1 mm (one small box on the standard 25mm/s ECG paper) represents 40 milliseconds of time on the x-axis, and 0.1 millivolts on the y-axis. [ 61 ]


In electrocardiogram (ECG) signal processing, Time-Frequency Analysis (TFA) is an important technique used to reveal how the frequency characteristics of ECG signals change over time, especially in non-stationary signals such as arrhythmias or transient cardiac events.


Common Methods for Time-Frequency Analysis


Provides instantaneous frequency distribution.


Steps for Time-Frequency Analysis


Step1: Preprocessing


Step2: Select an Appropriate TFA Method


Step3: Compute the Time-Frequency Spectrum


Step4: Feature Extraction


Step5: Pattern Recognition or Diagnosis


Application Scenarios


Heart Rate Variability Analysis (HRV):


Atrial Fibrillation Detection:


Ventricular Fibrillation Analysis:


The animation shown to the right illustrates how the path of electrical conduction gives rise to the ECG waves in the limb leads.
What is green zone ?
Recall that a positive current (as created by depolarization of cardiac cells) traveling towards the positive electrode and away from the negative electrode creates a positive deflection on the ECG. Likewise, a positive current traveling away from the positive electrode and towards the negative electrode creates a negative deflection on the ECG. [ 64 ] [ 65 ]  The red arrow represents the overall direction of travel of the depolarization. The magnitude of the red arrow is proportional to the amount of tissue being depolarized at that instance. The red arrow is simultaneously shown on the axis of each of the 3 limb leads. Both the direction and the magnitude of the red arrow's projection onto the axis of each limb lead is shown with blue arrows. Then, the direction and magnitude of the blue arrows are what theoretically determine the deflections on the ECG. For example, as a blue arrow on the axis for Lead I moves from the negative electrode, to the right, towards the positive electrode, the ECG line rises, creating an upward wave. As the blue arrow on the axis for Lead I moves to the left, a downward wave is created. The greater the magnitude of the blue arrow, the greater the deflection on the ECG for that particular limb lead. [ 66 ]


Frames 1–3 depict the depolarization being generated in and spreading through the  sinoatrial node . The SA node is too small for its depolarization to be detected on most ECGs. Frames 4–10 depict the depolarization traveling through the atria, towards the  atrioventricular node . During frame 7, the depolarization is traveling through the largest amount of tissue in the atria, which creates the highest point in the P wave. Frames 11–12 depict the depolarization traveling through the AV node. Like the SA node, the AV node is too small for the depolarization of its tissue to be detected on most ECGs. This creates the flat PR segment. [ 67 ]


Frame 13 depicts an interesting phenomenon in an over-simplified fashion. It depicts the depolarization as it starts to travel down the interventricular septum, through the  bundle of His  and  bundle branches . After the Bundle of His, the conduction system splits into the left bundle branch and the right bundle branch. Both branches conduct action potentials at about 1 m/s. However, the action potential starts traveling down the left bundle branch about 5 milliseconds before it starts traveling down the right bundle branch, as depicted by frame 13. This causes the depolarization of the interventricular septum tissue to spread from left to right, as depicted by the red arrow in frame 14. In some cases, this gives rise to a negative deflection after the PR interval, creating a Q wave such as the one seen in lead I in the animation to the right. Depending on the mean electrical axis of the heart, this phenomenon can result in a Q wave in lead II as well. [ 68 ] [ 69 ]


Following depolarization of the interventricular septum, the depolarization travels towards the apex of the heart. This is depicted by frames 15–17 and results in a positive deflection on all three limb leads, which creates the R wave. Frames 18–21 then depict the depolarization as it travels throughout both ventricles from the apex of the heart, following the action potential in the  Purkinje fibers . This phenomenon creates a negative deflection in all three limb leads, forming the S wave on the ECG. Repolarization of the atria occurs at the same time as the generation of the QRS complex, but it is not detected by the ECG since the tissue mass of the ventricles is so much larger than that of the atria. Ventricular contraction occurs between ventricular depolarization and repolarization. During this time, there is no movement of charge, so no deflection is created on the ECG. This results in the flat ST segment after the S wave. [ 70 ]


Frames 24–28 in the animation depict repolarization of the ventricles. The epicardium is the first layer of the ventricles to repolarize, followed by the myocardium. The endocardium is the last layer to repolarize. The plateau phase of depolarization has been shown to last longer in endocardial cells than in epicardial cells. This causes repolarization to start from the apex of the heart and move upwards. Since repolarization is the spread of negative current as membrane potentials decrease back down to the resting membrane potential, the red arrow in the animation is pointing in the direction opposite of the repolarization. This therefore creates a positive deflection in the ECG, and creates the T wave. [ 71 ]


Ischemia or  non-ST elevation myocardial infarctions  (non-STEMIs) may manifest as  ST depression  or inversion of  T waves . It may also affect the  high frequency band of the QRS .


ST elevation myocardial infarctions  (STEMIs) have different characteristic ECG findings based on the amount of time elapsed since the MI first occurred. The earliest sign is  hyperacute T waves,  peaked T waves due to local  hyperkalemia  in ischemic myocardium. This then progresses over a period of minutes to elevations of the  ST segment  by at least 1 mm. Over a period of hours, a pathologic  Q wave  may appear and the T wave will invert. Over a period of days the ST elevation will resolve. Pathologic Q waves generally will remain permanently. [ 72 ]


The  coronary artery  that has been occluded can be identified in an STEMI based on the location of ST elevation. The  left anterior descending  (LAD) artery supplies the anterior wall of the heart, and therefore causes ST elevations in anterior leads (V 1  and V 2 ). The  LCx  supplies the lateral aspect of the heart and therefore causes ST elevations in lateral leads (I, aVL and V 6 ). The  right coronary artery  (RCA) usually supplies the inferior aspect of the heart, and therefore causes ST elevations in inferior leads (II, III and aVF). [ 73 ]


An ECG tracing is affected by patient motion. Some rhythmic motions (such as shivering or  tremors ) can create the illusion of cardiac arrhythmia. [ 74 ]  Artifacts are distorted signals caused by a secondary internal or external sources, such as muscle movement or interference from an electrical device. [ 75 ] [ 76 ]


Distortion poses significant challenges to healthcare providers, [ 75 ]  who employ various techniques [ 77 ]  and strategies to safely recognize [ 78 ]  these false signals. [ medical citation needed ]  Accurately separating the ECG artifact from the true ECG signal can have a significant impact on patient outcomes and  legal liabilities . [ 79 ] [ unreliable medical source? ]


Improper lead placement (for example, reversing two of the limb leads) has been estimated to occur in 0.4% to 4% of all ECG recordings, [ 80 ]  and has resulted in improper diagnosis and treatment including unnecessary use of  thrombolytic  therapy. [ 81 ] [ 82 ]


Whitbread, consultant nurse and paramedic, suggests ten rules of the normal ECG, deviation from which is likely to indicate pathology. [ 83 ]  These have been added to, creating the 15 rules for 12-lead (and 15- or 18-lead) interpretation. [ 84 ]


Rule 1: All waves in aVR are negative.


Rule 2: The ST segment (J point) starts on the isoelectric line (except in V1 & V2 where it may be elevated by not greater than 1 mm).


Rule 3: The PR interval should be 0.12–0.2 seconds long.


Rule 4: The QRS complex should not exceed 0.11–0.12 seconds.


Rule 5: The QRS and T waves tend to have the same general direction in the limb leads.


Rule 6: The R wave in the precordial (chest) leads grows from V1 to at least V4 where it may or may not decline again.


Rule 7: The QRS is mainly upright in I and II.


Rule 8: The P wave is upright in I II and V2 to V6.


Rule 9: There is no Q wave or only a small q (<0.04 seconds in width) in I, II and V2 to V6.


Rule 10: The T wave is upright in I II and V2 to V6. The end of the T wave should not drop below the isoelectric baseline.


Rule 11: Does the deepest S wave in V1 plus the tallest R wave in V5 or V6 equal >35 mm?


Rule 12: Is there an  Epsilon wave ?


Rule 13: Is there an J wave?


Rule 14: Is there a  Delta wave ?


Rule 15: Are there any patterns representing an  occlusive myocardial infarction  (OMI)?


Numerous diagnoses and findings can be made based upon electrocardiography, and many are discussed above. Overall, the diagnoses are made based on the patterns. For example, an "irregularly irregular" QRS complex without P waves is the hallmark of  atrial fibrillation ; however, other findings can be present as well, such as a  bundle branch block  that alters the shape of the QRS complexes. ECGs can be interpreted in isolation but should be applied – like all  diagnostic tests  – in the context of the patient. For example, an observation of peaked T waves is not sufficient to diagnose hyperkalemia; such a diagnosis should be verified by measuring the blood potassium level. Conversely, a discovery of hyperkalemia should be followed by an ECG for manifestations such as peaked T waves, widened QRS complexes, and loss of P waves. The following is an organized list of possible ECG-based diagnoses. [ 85 ]


Rhythm disturbances or arrhythmias: [ 86 ]


Heart block  and conduction problems:


Electrolytes disturbances and intoxication:


Ischemia and infarction:


Structural:


Other phenomena:


The word is derived from the  Greek   electro , meaning related to electrical activity;  kardia , meaning heart; and  graph , meaning "to write". [ 99 ]


Electrocardiography  in suspected  myocardial infarction  has the main purpose of detecting  ischemia  or acute coronary injury in  emergency department  populations coming for symptoms of myocardial infarction (MI). Also, it can distinguish clinically different types of myocardial infarction.


The standard 12 lead  electrocardiogram  (ECG) has several limitations. An ECG represents a brief sample in time. Because unstable ischemic syndromes have rapidly changing supply versus demand characteristics, a single ECG may not accurately represent the entire picture. [ 1 ]  It is therefore desirable to obtain  serial  12 lead ECGs, particularly if the first ECG is obtained during a pain-free episode. Alternatively, many  emergency departments  and  chest pain centers  use computers capable of continuous ST segment monitoring. [ 2 ]  The standard 12 lead ECG also does not directly examine the  right ventricle , and is relatively poor at examining the posterior basal and lateral walls of the  left ventricle . In particular, acute myocardial infarction in the distribution of the circumflex artery is likely to produce a nondiagnostic ECG. [ 1 ]  The use of additional ECG leads like right-sided leads V3R and V4R and posterior leads V7, V8, and V9 may improve sensitivity for right ventricular and posterior myocardial infarction. In spite of these limitations, the 12 lead ECG stands at the center of risk stratification for the patient with suspected acute myocardial infarction. Mistakes in interpretation are relatively common, and the failure to identify high risk features has a negative effect on the quality of patient care. [ 3 ]


The 12 lead ECG is used to classify MI patients into one of three groups: [ 4 ]


The 2018 European Society of Cardiology/American College of Cardiology Foundation/American Heart Association/World Health Federation Universal Definition of Myocardial Infarction for the ECG diagnosis of the ST segment elevation type of acute myocardial infarction require new ST elevation at J point of at least 1mm (0.1 mV) in two contiguous leads with the cut-points: ≥1 mm in all leads other than leads V2-V3. For leads V2-V3: ≥2 mm in men ≥40 years, ≥2.5 mm in men <40 years, or ≥1.5 mm in women regardless of age. This assumes usual calibration of 1mV/10mm. [ 5 ]  These elevations must be present in anatomically contiguous leads. [ 4 ]  (I, aVL, V5, V6 correspond to the lateral wall; V3-V4 correspond to the anterior wall ; V1-V2 correspond to the septal wall; II, III, aVF correspond to the inferior wall.) This criterion is problematic, however, as acute myocardial infarction is not the most common cause of ST segment elevation in  chest pain  patients. [ 6 ]  Over 90% of healthy men have at least 1 mm (0.1 mV) of ST segment elevation in at least one precordial lead. [ 7 ]  The clinician must therefore be well versed in recognizing the so-called ECG mimics of acute myocardial infarction, which include  left ventricular hypertrophy ,  left bundle branch block ,  paced rhythm ,  early repolarization ,  pericarditis ,  hyperkalemia , and  ventricular aneurysm . [ 7 ] [ 8 ] [ 9 ]


There are heavily researched clinical decision tools such as the TIMI Scores which help prognose and diagnose STEMI based on clinical data. For example, TIMI scores are frequently used to take advantage of EKG findings to prognose patients with MI symptoms. [ 10 ]  Based on symptoms and electrocardiographic findings, practitioners can differentiate between unstable angina, NSTEMI and STEMI, normally in the emergency room setting. [ 11 ]  Other calculators such as the GRACE [ 12 ]  and HEART  [ 13 ]  scores, assess other major cardiac events using electrocardiogram findings, both predicting mortality rates for 6 months and 6 weeks, respectively. [ citation needed ]


Sometimes the earliest presentation of acute myocardial infarction is the hyperacute T wave, which is treated the same as ST segment elevation. [ 14 ]  In practice this is rarely seen, because it only exists for 2–30 minutes after the onset of infarction. [ 15 ]  Hyperacute T waves need to be distinguished from the peaked T waves associated with  hyperkalemia . [ 16 ]


In the first few hours the ST segments usually begin to rise. [ 17 ]  Pathological  Q waves  may appear within hours or may take greater than 24 hr. [ 17 ]  The  T wave  will generally become inverted in the first 24 hours, as the ST elevation begins to resolve. [ 17 ]


Long term changes of ECG include persistent Q waves (in 90% of cases) and persistent inverted T waves. [ 17 ]  Persistent ST elevation is rare except in the presence of a  ventricular aneurysm . [ 17 ]


A  cardiac electrophysiology  study ( EP test  or  EP study ) is a  minimally invasive procedure  using  catheters  introduced through a  vein  or  artery  to record electrical activity from within the  heart . [ 1 ]  This electrical activity is recorded when the heart is in a normal rhythm ( sinus rhythm ) to assess the conduction system of the heart and to look for additional electrical connections ( accessory pathways ), and during any  abnormal heart rhythms  that can be induced. [ 2 ]  EP studies are used to investigate the cause, location of origin, and best treatment for various abnormal heart rhythms, and are often followed by a  catheter ablation  during the same procedure. [ 3 ]


It is important for patients not to eat or drink for up to 12 hours before the procedure. This is to prevent vomiting, which can result in aspiration, and also cause severe bleeding from the insertion site of the catheter. Failure to follow this simple preparation may result in dangerous consequences. In general, small amounts of water can be consumed up to 2 hours before the exam. Patients should try to schedule the exam at a time when they will be having symptoms and will not need to drive for 2 to 3 days.


An EP study is typically performed in an EP lab or  cath lab . These are specially equipped operating rooms that usually contain an X-ray machine capable of acquiring live X-ray video images (a  fluoroscope ), equipment to record electrical signals from the heart, a stimulator to electrically excite the heart and control the heart rate, and  ablation equipment  to destroy abnormal tissue. [ 3 ]  A 3D navigation system that tracks and records the catheter position and associated electrical signals may also be used. [ 3 ]


The procedure may be performed awake under  local anaesthetic , or under  general anaesthetic . Monitoring equipment is attached including an automated  blood pressure cuff  and a  pulse oximeter  to measure the oxygen saturation of the blood. A peripheral  venous cannula  is generally inserted to allow medication to be given such as  sedatives ,  anesthesia , or drugs. [ 3 ]


An access site that will allow catheters to be passed to the heart via an artery or vein is shaved and cleaned, usually in the  groin . The blood vessels used to reach the heart (the  femoral  or  subclavian veins , and sometimes the  femoral artery ) are punctured before a guidewire and plastic sheath are inserted into the vessel using the  Seldinger technique . [ 3 ]


Once the catheter is in and all preparations are complete elsewhere in the lab, the EP study begins. The X-ray machine will give the doctor a live view of the heart and the position of the electrodes. He will guide the (steerable) electrodes to the correct position inside the heart. The electrophysiologist begins by moving the electrodes along the conduction pathways and along the inner walls of the heart, measuring the electrical activity along the way.


The next step is pacing the heart, this means he/she will speed up or slow down the heart by placing the electrode at certain points along the conductive pathways of the heart and control the depolarization rate of the heart. The doctor will pace each chamber of the heart one by one, looking for any abnormalities. Then the electrophysiologist tries to provoke arrhythmias and reproduce any conditions that have resulted in the patient's placement in the study. This is done by injecting electric current into the conductive pathways and into the  endocardium  at various places. Last, the electrophysiologist may administer various drugs ( proarrhythmic agents ) to induce arrhythmia (inducibility of VT/VF [ 4 ] ). If the arrhythmia is reproduced by the drugs (inducible), the electrophysiologist will search out the source of the abnormal electrical activity. The entire procedure can take several hours.


If at any step during the EP study the electrophysiologist finds the source of the abnormal electrical activity, they may try to  ablate  the cells that are misfiring. This is done using high-energy  radio frequencies  (similar to  microwaves ) to effectively heat up the abnormal cells, to form scar tissue.
This can be painful with pain felt in the heart itself, the neck and shoulder areas. A more recent method of ablation is  cryoablation , which is considered less risky and less painful. [ 5 ]


When the necessary procedures are complete, the catheter is removed. Firm pressure is applied to the site to prevent bleeding. This may be done by hand or with a mechanical device. Other closure techniques include an internal suture and plug. If the femoral artery was used, the patient will probably be asked to lie flat for several hours (3 to 6) to prevent bleeding or the development of a  hematoma . Trying to sit up or even lift the head is strongly discouraged until an adequate  clot  has formed. The patient will be moved to a recovery area where he/she will be monitored.


For patients who had a catheterization at the femoral artery or vein (and even some of those with a radial insertion site), in general recovery is fairly quick, as the only damage is at the insertion site. The patient will probably feel fine within 8 to 12 hours after the procedure, but may feel a small pinch at the insertion site. After a short period of general rest, the patient may resume some minor activity such as gentle, short, slow walks after the first 24 hours. If stairs must be climbed, they should be taken one step at a time and very slowly. All vigorous activity must be postponed until approved by a physician.


It is also important to note that unless directed by a doctor, some patients should avoid taking blood thinners and foods that contain salicylates, such as cranberry-containing products until the clot has healed (1–2 weeks).


As with any surgical procedure, cardiac catheterizations come with a generic list of possible complications. One of the complications that are sometimes reported involves some temporary nerve involvement. Sometimes a small amount of swelling occurs that can put pressure on nerves in the area of the incision.  Venous thrombosis  is the most common complication with an incidence ranging between 0.5 and 2.5%. [ 6 ]  There have been reports of patients feeling like they have hot fluid like blood or urine running down their leg for up to a month or two after the incision has healed. This usually passes with time, but patients should tell their doctor if they have these symptoms and if they last.


More severe but relatively rare complications include: damage or trauma to a blood vessel, which could require repair; infection from the skin puncture or from the catheter itself; cardiac perforation, causing blood to leak into the sac around the heart and compromising the heart's pumping action, requiring removal using a needle under the breast bone (pericardiocentesis); hematoma at the site(s) of the puncture(s); induction of a dangerous cardiac rhythm requiring an external shock(s); a clot may be dislodged, which may travel to a distant organ and impede blood flow or cause a stroke; myocardial infarction; unanticipated reactions to the medications used during the procedure; damage to the conduction system, requiring a permanent pacemaker; death.


A  flatline  is an electrical time sequence measurement that shows no activity and therefore, when represented, shows a flat line instead of a moving one. It almost always refers to either a flatlined  electrocardiogram , where the heart shows no electrical activity [ 1 ]  ( asystole ), or to a flat  electroencephalogram , in which the  brain  shows no electrical activity ( brain death ). Both of these specific cases are involved in various definitions of  death .


A cardiac flatline is also called  asystole . It can possibly be generated by malfunction of the  electrocardiography  device, but it is recommended to first rule out true asystole because of the emergence of such condition.


Definition:


A cardiac flatline is referred to as asystole. It can be identified by using an ECG/EKG (electrocardiogram) test.  Asystole  occurs when the electrical and mechanical activities of the heart stop. [ 2 ]


Causes:


ECG/EKG flatline or asystole occurs when the heart's electrical and mechanical activities stop. It also results from other causes such as  hypoxia ,  acidosis ,  hypokalemia ,  hyperkalemia ,  hypovolemia , toxins,  pulmonary thrombosis , and  coronary thrombosis . Additional causes could also include  tension pneumothorax  and  cardiac tamponade . These conditions should be treated immediately when identified. [ 3 ] [ 2 ]


ECG flat line also occurs when the electrocardiographic (ECG/EKG) leads or recording electrodes are placed incorrectly. It can be caused by malfunction of the electrocardiogram (ECG/EKG) machine. [ 3 ]


Diagnosis:


ECG flatline or asystole is diagnosed when a person, who is in  cardiac arrest  (the heart stops beating), is experiencing the following conditions:


The eclectrocardiogram (ECG) test records the heart's electrical activity and will show a flat line if the heart stops beating. [ 2 ]


A neurological flatline is referred to as  brain death . It can be identified by using an EEG ( electroencephalogram ) test. Brain death is the loss of function of the brain, the  cerebrum , that is responsible for thinking and the deep brain or the  brain stem  that is responsible for the breathing and reflexes such as  pupillary light reflex  (the constriction of the pupil of the eye in response to light) and  gag reflex  or pharyngeal reflex (contraction of pharyngeal muscle). [ 4 ]


EEG flat line or brain death can result from a head injury that leads to brain damage and bleeding. Brain death also results from a lack of blood flow to the brain because the heart stops beating (cardiac arrest), which is when the ECG imaging shows a cardiac flat line (asystole). [ 4 ]


Brain death is diagnosed if a person is experiencing all of the following three conditions:


The electroencephalogram (EEG) records the brain's electrical activity and will show a flat line if the brain is dead. [ 4 ]


In a study published in the New England Journal of Medicine, 631 subjects' end of life was observed. Of the 631 subjects, 480 subjects were analyzed using a computer program that recorded each subject's vitals in order to monitor for return of pulse or heart activity after at least 1 minute of flatlining. The study found that 14% of subjects had a return of heart activity but none regained consciousness. [ 5 ]  Neuro flatline or brain death happens after cardiac arrest or cardiac flatline. It can take 2 to 20 seconds after cardiac flatline for the brain to show no activity. [ 6 ]


The definition of death has changed over time, but the loss of cardiac and neurological function have been the main criteria for centuries. The concept of flatlining begins to take form with the invention of technologies for death determination.


It began in 1837 when Professor Manni at the University of Rome offered a cash prize to the doctor who could offer a true test of death. The winner, Dr.  Eugene Bouchut  used new technology– the stethoscope– to determine death when heart sounds were absent for over two minutes. In 1883 he updated his criteria to require five minutes without heart sounds to qualify cardiac death. [ 7 ]


Then, the standard for viewing cardiac activity changed in 1887 when Augustus Waller recorded the first ECG from the human heart with a mercury capillary electrometer. [ 8 ]  This sparked research into modern ECG technology, which was developed from the mercury capillary electrometer by Willem Einthoven. In 1901 to 1905, Einthoven developed the  string galvanometer , which could measure and record the heart's electrical activity. Electrodes were place on three points, the “Einthoven leads”, the right and left arms and on the left foot same as today and provided precise recordings of the heart. [ 9 ]  This led to Einthoven's Nobel Prize in 1924. [ 10 ] [ 8 ]  With the ECG, the characteristics of a dying heart were identified, creating the leading tool for diagnosing death– even to this day. [ 7 ]


However, in the mid 19th century with the invention of the defibrillator and cardioversion, it was realized that the flatline on the ECG did not always mean death. [ 7 ]  This instigated research into other ways to determine death, which eventually lead to the idea of brain death.


In 1924, a German physiologist and psychiatrist  Hans Berger  recorded the first EEG on a human brain. [ 11 ]  The machine consisted of steel electrodes that get mounted on the scalp with an EEG cap to visualize and interpret signals. [ 12 ]  He noted that the human brain has a specific pattern, called alpha oscillations, and went on to publish this in 1929. [ 13 ]   The presence of this technology along with resuscitation technology saw the use of the EEG to determine a time in which the person had reached total death. In 1959, this concept– brain death– was first coined as: "le coma dépassé by Mollaret and Goulon. [ 12 ]  They determined that a person reached this state when they were apneic, comatose, without brainstem reflexes, and showed no electroencephalographic (EEG) activity. [ 12 ]


When an individual experiences asystole or cardiac flatline, there is no electrical activity in their heart which is evidenced by the flatline recorded by an ECG. [ 2 ]  The lack of electrical activity also means that the individual's heart will stop pumping. Following a cardiac flatline a fast intervention is a priority and can affect individual outcomes and recovery.


Treatment [ 14 ]  for cardiac flatline or asystole can involve:


Treatment decisions will depend on where an individual is when they go into asystole. When an individual goes into cardiac arrest providers will start CPR immediately and then try to determine whether the rhythm is shockable. While defibrillation is often portrayed as a common treatment option in popular media, since asystole is an unshockable rhythm  defibrillation  is not a recommended course of treatment. Successful resuscitation is generally unlikely and is inversely related to the length of time spent attempting resuscitation.


Following a treatment intervention, the individuals who survive may still suffer long-term consequences of their cardiac flatline. [ 16 ]


An individual's cardiac flatline can progress to neurological flatline, which is also referred to as brain death. After an individual's heart stops beating, if providers are unable to successfully intervene within the window, the individual's brain cells will die from this lack of blood and oxygen and this damage is irreversible and permanent. The criteria to diagnose brain death has been outlined in the above sections of this article. While brain death cannot be treated, individuals and their families have several options  [ 4 ]  available to them:


The  forward problem of electrocardiology  is a computational and mathematical approach to study the  electrical activity  of the  heart  through the body surface. [ 1 ]  The principal aim of this study is to computationally reproduce an  electrocardiogram  (ECG), which has important clinical relevance to define  cardiac pathologies  such as  ischemia  and  infarction , or to test  pharmaceutical intervention . Given their important functionalities and the relative small invasiveness, the  electrocardiography  techniques are used quite often as clinical  diagnostic tests . Thus, it is natural to proceed to computationally reproduce an ECG, which means to mathematically model the cardiac behaviour inside the body. [ 1 ]


The three main parts of a forward model for the ECG are:


Thus, to obtain an ECG, a mathematical electrical cardiac model must be considered, coupled with a diffusive model in a  passive conductor  that describes the electrical propagation inside the  torso . [ 1 ]


The coupled model is usually a  three-dimensional model  expressed in terms of  partial differential equations . Such model is typically solved by means of  finite element method  for the solution's space evolution and  semi-implicit numerical schemes  involving  finite differences  for the solution's time evolution. However, the computational costs of such techniques, especially with three dimensional simulations, are quite high. Thus, simplified models are often considered, solving for example the heart electrical activity independently from the problem on the torso. To provide realistic results, three dimensional anatomically realistic models of the heart and the torso must be used. [ 1 ]


Another possible simplification is a  dynamical model  made of three  ordinary differential equations . [ 3 ]


The electrical activity of the heart is caused by the flow of  ions  across the  cell membrane , between the intracellular and extracellular spaces, which determines a wave of excitation along the  heart muscle  that coordinates the cardiac contraction and, thus, the pumping action of the heart that enables it to push  blood  through the  circulatory system . The modeling of cardiac electrical activity is thus related to the modelling of the flow of ions on a  microscopic  level, and on the propagation of the excitation wave along the muscle  fibers  on a  macroscopic  level. [ 1 ] [ 4 ]


Between the mathematical model on the macroscopic level,  Willem Einthoven  and  Augustus Waller  defined the ECG through the conceptual model of a dipole rotating around a fixed point, whose projection on the  lead  axis determined the lead recordings. Then, a  two-dimensional  reconstruction of the heart activity in the frontal plane was possible using the  Einthoven's limbs leads  I, II and III as theoretical basis. [ 5 ]
Later on, the rotating cardiac dipole was considered inadequate and was substituted by  multipolar  sources moving inside a bounded torso domain. The main shortcoming of the methods used to quantify these sources is their lack of details, which are however very relevant to realistically simulate cardiac phenomena. [ 4 ]


On the other hand, microscopic models try to represent the behaviour of single cells and to connect them considering their electrical properties. [ 6 ] [ 7 ] [ 8 ]  These models present some challenges related to the different scales that need to be captured, in particular considering that, especially for large scale phenomena such as re-entry or  body surface potential , the collective behaviour of the cells is more important than that of every single cell. [ 4 ]


The third option to model the electrical activity of the heart is to consider a so-called "middle-out approach", where the model incorporates both lower and higher level of details. This option considers the behaviour of a block of cells, called a continuum cell, thus avoiding scale and detail problems. The model obtained is called  bidomain model , which is often replaced by its simplification, the  monodomain model . [ 4 ]


The basic assumption of the bidomain model is that the heart tissue can be divided in two ohmic conducting continuous media, connected but separated through the cell membrane. This media are called intracellular and extracellular regions, the former representing the cellular tissues, and the latter representing the space between cells. [ 2 ] [ 1 ]


The standard formulation of the bidomain model, including a dynamical model for the ionic current, is the following [ 2 ]

 {

 ∇
 ⋅
 (

 σ

 i

 ∇

 V

 m

 )
 +
 ∇
 ⋅
 (

 σ

 i

 ∇

 u

 e

 )
 =

 A

 m

 (

 C

 m

 ∂

 V

 m

 ∂
 t

 +

 I

 ion

 (

 V

 m

 ,
 w
 )

 )

 +

 I

 app

 in

 Ω

 H

 ∇
 ⋅

 (

 (

 σ

 i

 +

 σ

 e

 )
 ∇

 u

 e

 )

 +
 ∇
 ⋅
 (

 σ

 i

 ∇

 V

 m

 )
 =
 0

 in

 Ω

 H

 ∂
 w

 ∂

 t

 +
 g
 (

 V

 m

 ,
 w
 )
 =
 0

 in

 Ω

 H

 {\displaystyle {\begin{cases}\nabla \cdot ({\boldsymbol {\sigma }}_{i}\nabla V_{m})+\nabla \cdot ({\boldsymbol {\sigma }}_{i}\nabla u_{e})=A_{m}\left(C_{m}{\dfrac {\partial V_{m}}{\partial t}}+I_{\text{ion}}(V_{m},w)\right)+I_{\text{app}}&{\text{in }}\Omega _{H}\\\nabla \cdot \left(({\boldsymbol {\sigma }}_{i}+{\boldsymbol {\sigma }}_{e})\nabla u_{e}\right)+\nabla \cdot ({\boldsymbol {\sigma }}_{i}\nabla V_{m})=0&{\text{in }}\Omega _{H}\\{\frac {\partial w}{\partial {t}}}+g(V_{m},w)=0&{\text{in }}\Omega _{H}\end{cases}}}

where

 V

 m

 {\displaystyle V_{m}}

  and

 u

 e

 {\displaystyle u_{e}}

  are the transmembrane and extracellular potentials respectively,

 I

 ion

 {\displaystyle I_{\text{ion}}}

  is the ionic current, which depends also from a so-called gating variable

 w

 {\displaystyle w}

  (accounting for cellular-level ionic behavior), and

 I

 app

 {\displaystyle I_{\text{app}}}

  is an external current applied to the domain. Moreover,

 σ

 i

 {\displaystyle {\boldsymbol {\sigma }}_{i}}

  and

 σ

 e

 {\displaystyle {\boldsymbol {\sigma }}_{e}}

  are the intracellular and extracellular conductivity tensors,

 A

 m

 {\displaystyle A_{m}}

  is the  surface to volume ratio of the cell membrane and

 C

 m

 {\displaystyle C_{m}}

  is the membrane capacitance per unit area. Here the domain

 Ω

 H

 {\displaystyle \Omega _{H}}

  represents the heart muscle. [ 2 ]


The boundary conditions for this version of the bidomain model are obtained through the assumption that there is no flow of intracellular potential outside of the heart, which means that

 σ

 i

 ∇

 V

 m

 ⋅

 n

 +

 σ

 i

 ∇

 u

 e

 ⋅

 n

 =
 0

 on

 Σ

 {\displaystyle {\boldsymbol {\sigma }}_{i}\nabla V_{m}\cdot \mathbf {n} +{\boldsymbol {\sigma }}_{i}\nabla u_{e}\cdot \mathbf {n} =0\quad \quad {\text{on }}\Sigma }

where

 Σ
 =
 ∂

 Ω

 H

 {\displaystyle \Sigma =\partial \Omega _{H}}

  denotes the boundary of the heart domain and

 n

 {\displaystyle \mathbf {n} }

  is the outward unit normal to

 Σ

 {\displaystyle \Sigma }

 . [ 2 ]


The monodomain model is a simplification of the bidomain model that, in spite of some unphysiological assumptions, is able to represent realistic electrophysiological phenomena at least for what concerns the transmembrane potential

 V

 m

 {\displaystyle V_{m}}

 . [ 2 ] [ 1 ]


The standard formulation is the following partial differential equation, whose only unknown

 V

 m

 {\displaystyle V_{m}}

  is the transmembrane potential:

 χ

 C

 m

 ∂

 V

 m

 ∂
 t

 −
 ∇
 ⋅

 (

 σ

 i

 λ

 1
 +
 λ

 ∇

 V

 m

 )

 +
 χ

 I

 ion

 =

 I

 app

 in

 Ω

 H

 {\displaystyle \chi C_{m}{\frac {\partial V_{m}}{\partial t}}-\nabla \cdot \left({\boldsymbol {\sigma }}_{i}{\frac {\lambda }{1+\lambda }}\nabla V_{m}\right)+\chi I_{\text{ion}}=I_{\text{app}}\quad \quad {\text{in }}\Omega _{H}}

where

 λ

 {\displaystyle \lambda }

  is a parameter that relates the intracellular and extracellular conductivity tensors. [ 2 ]


The boundary condition used for this model is [ 9 ]

 (

 σ

 i

 ∇

 V

 m

 )

 ⋅

 n

 =
 0

 on

 ∂

 Ω

 H

 .

 {\displaystyle \left({\boldsymbol {\sigma }}_{i}\nabla V_{m}\right)\cdot \mathbf {n} =0\quad \quad {\text{on }}\partial \Omega _{H}.}


In the forward problem of electrocardiography, the torso is seen as a passive conductor and its model can be derived starting from the  Maxwell's equations  under quasi-static assumption. [ 1 ] [ 2 ]


The standard formulation consists of a partial differential equation with one unknown scalar field, the torso potential

 u

 T

 {\displaystyle u_{T}}

 . Basically, the torso model is the following generalized  Laplace equation

 ∇
 ⋅
 (

 σ

 T

 ∇

 u

 T

 )
 =
 0

 in

 Ω

 T

 ,

 {\displaystyle \nabla \cdot ({\boldsymbol {\sigma }}_{T}\nabla u_{T})=0\quad \quad {\text{in }}\Omega _{T},}

where

 σ

 T

 {\displaystyle {\boldsymbol {\sigma }}_{T}}

  is the conductivity tensor and

 Ω

 T

 {\displaystyle \Omega _{T}}

  is the domain surrounding the heart,  i.e.  the human torso. [ 2 ]


As for the bidomain model, the torso model can be derived from the Maxwell's equations and the  continuity equation  after some assumptions. First of all, since the electrical and magnetic activity inside the body is generated at low level, a quasi-static assumption can be considered. Thus, the body can be viewed as a passive conductor, which means that its capacitive, inductive and propagative effect can be ignored. [ 1 ]


Under quasi-static assumption, the Maxwell's equations are [ 1 ]

 {

 ∇
 ⋅

 E

 =

 ρ

 ϵ

 0

 ∇
 ×

 E

 =
 0

 ∇
 ⋅

 B

 =
 0

 ∇
 ×

 B

 =

 μ

 0

 J

 {\displaystyle {\begin{cases}\nabla \cdot \mathbf {E} &={\frac {\rho }{\epsilon _{0}}}\\\nabla \times \mathbf {E} &=0\\\nabla \cdot \mathbf {B} &=0\\\nabla \times \mathbf {B} &=\mu _{0}\mathbf {J} \end{cases}}}

and the continuity equation is [ 1 ]

 ∇
 ⋅

 J

 =
 0.

 {\displaystyle \nabla \cdot \mathbf {J} =0.}


Since its curl is zero, the electrical field can be represented by the gradient of a scalar potential field, the torso potential


where the negative sign means that the current flows from higher to lower potential regions. [ 1 ]


Then, the total current density can be expressed in terms of the conduction current and other different applied currents so that, from continuity equation, [ 1 ]


Then, substituting ( 1 ) in ( 2 )

 ∇
 ⋅
 (

 σ

 T

 ∇

 u

 T

 )
 =
 ∇
 ⋅

 J

 app

 =

 I

 v

 {\displaystyle \nabla \cdot ({\boldsymbol {\sigma }}_{T}\nabla u_{T})=\nabla \cdot \mathbf {J} _{\text{app}}=I_{v}}


in which

 I

 v

 {\displaystyle I_{v}}

  is the current per unit volume. [ 1 ]


Finally, since aside from the heart there is no current source inside the torso, the current per unit volume can be set to zero, giving the generalized Laplace equation, which represents the standard formulation of the diffusive problem inside the torso [ 1 ]

 ∇
 ⋅
 (

 σ

 T

 ∇

 u

 T

 )
 =
 0

 in

 Ω

 T

 .

 {\displaystyle \nabla \cdot ({\boldsymbol {\sigma }}_{T}\nabla u_{T})=0\quad \quad {\text{in }}\Omega _{T}.}


The boundary conditions accounts for the properties of the media surrounding the torso, i.e. of the air around the body. Generally, air has null conductivity which means that the current cannot flow outside the torso. This is translated in the following equation [ 1 ]

 σ

 T

 ∇

 u

 T

 ⋅

 n

 T

 =
 0

 on

 Γ

 T

 {\displaystyle {\boldsymbol {\sigma }}_{T}\nabla u_{T}\cdot \mathbf {n} _{T}=0\quad \quad {\text{on }}\Gamma _{T}}


where

 n

 T

 {\displaystyle \mathbf {n} _{T}}

  is the unit outward normal to the torso and

 Γ

 T

 {\displaystyle \Gamma _{T}}

  is the torso boundary, which means the torso surface. [ 1 ] [ 2 ]


Usually, the torso is considered to have isotropic conductivity, which means that the current flows in the same way in all directions. However, the torso is not an empty or homogeneous envelope, but contains different organs characterized by different conductivity coefficients, which can be experimentally obtained. A simple example of conductivity parameters in a torso that considers the bones and the lungs is reported in the following table. [ 2 ]


The coupling between the electrical activity model and the torso model is achieved by means of suitable boundary conditions at the epicardium, i.e. at the interface surface between the heart and the torso. [ 1 ] [ 2 ]


The heart-torso model can be fully coupled, if a perfect electrical transmission between the two domains is considered, or can be uncoupled, if the heart electrical model and the torso model are solved separately with a limited or imperfect exchange of information between them. [ 2 ]


The complete coupling between the heart and the torso is obtained imposing a perfect electrical transmission condition between the heart and the torso. This is done considering the following two equations, that establish a relationship between the extracellular potential and the torso potential [ 2 ]

 u

 e

 =

 u

 T

 on

 Σ

 (

 σ

 e

 ∇

 u

 e

 )
 ⋅

 n

 e

 =
 −
 (

 σ

 T

 ∇

 u

 T

 )
 ⋅

 n

 T

 on

 Σ
 .

 {\displaystyle {\begin{aligned}u_{e}&=u_{T}&{\text{on }}\Sigma \\({\boldsymbol {\sigma }}_{e}\nabla u_{e})\cdot \mathbf {n} _{e}&=-({\boldsymbol {\sigma }}_{T}\nabla u_{T})\cdot \mathbf {n} _{T}\quad &{\text{on }}\Sigma .\end{aligned}}}

This equations ensure the continuity of both the potential and the current across the epicardium. [ 2 ]


Using these boundary conditions, it is possible to obtain two different fully coupled heart-torso models, considering either the bidomain or the monodomain model for the heart electrical activity. From the numerical viewpoint, the two models are computationally very expensive and have similar computational costs. [ 2 ]


Boundary conditions that represent a perfect electrical coupling between the heart and the torso are the most used and the classical ones. However, between the heart and the torso there is the  pericardium , a sac with a double wall that contains a serous fluid which has a specific effect on the electrical transmission. Considering the  capacitance

 C

 p

 {\displaystyle C_{p}}

  and the  resistive

 R

 p

 {\displaystyle R_{p}}

  effect that the pericardium has, alternative boundary conditions that take into account this effect can be formulated as follows [ 10 ]

 R

 p

 σ

 e

 ∇

 u

 e

 ⋅

 n

 =

 R

 p

 C

 p

 ∂
 (

 u

 T

 −

 u

 e

 )

 ∂
 t

 +
 (

 u

 T

 −

 u

 e

 )

 on

 Σ

 σ

 e

 ∇

 u

 e

 ⋅

 n

 =

 σ

 T

 ∇

 u

 T

 ⋅

 n

 on

 Σ

 {\displaystyle {\begin{aligned}R_{p}{\boldsymbol {\sigma }}_{e}\nabla u_{e}\cdot \mathbf {n} &=R_{p}C_{p}{\frac {\partial (u_{T}-u_{e})}{\partial t}}+(u_{T}-u_{e})\quad \quad &{\text{on }}\Sigma \\{\boldsymbol {\sigma }}_{e}\nabla u_{e}\cdot \mathbf {n} &={\boldsymbol {\sigma }}_{T}\nabla u_{T}\cdot \mathbf {n} \quad \quad &{\text{on }}\Sigma \end{aligned}}}


The fully coupled heart-torso model, considering the  bidomain model  for the heart electrical activity, in its complete form is [ 2 ]

 {

 ∇
 ⋅
 (

 σ

 i

 ∇

 V

 m

 )
 +
 ∇
 ⋅
 (

 σ

 i

 ∇

 u

 e

 )
 =

 A

 m

 (

 C

 m

 ∂

 V

 m

 ∂
 t

 +

 I

 ion

 (

 V

 m

 ,
 w
 )

 )

 +

 I

 app

 in

 Ω

 H

 ∇
 ⋅

 (

 (

 σ

 i

 +

 σ

 e

 )
 ∇

 u

 e

 )

 +
 ∇
 ⋅
 (

 σ

 i

 ∇

 V

 m

 )
 =
 0

 in

 Ω

 H

 ∂
 w

 ∂

 t

 +
 g
 (

 V

 m

 ,
 w
 )
 =
 0

 in

 Ω

 H

 ∇
 ⋅
 (

 σ

 T

 ∇

 u

 T

 )
 =
 0

 in

 Ω

 T

 (

 σ

 i

 ∇

 V

 m

 )
 ⋅

 n

 +
 (

 σ

 i

 ∇

 u

 e

 )
 ⋅

 n

 =
 0

 on

 Σ

 u

 e

 =

 u

 T

 on

 Σ

 (

 σ

 e

 ∇

 u

 e

 )
 ⋅

 n

 =
 (

 σ

 T

 ∇

 u

 T

 )
 ⋅

 n

 on

 Σ

 (

 σ

 T

 ∇

 u

 T

 )
 ⋅

 n

 =
 0

 on

 Γ

 T

 {\displaystyle {\begin{cases}\nabla \cdot ({\boldsymbol {\sigma }}_{i}\nabla V_{m})+\nabla \cdot ({\boldsymbol {\sigma }}_{i}\nabla u_{e})=A_{m}\left(C_{m}{\dfrac {\partial V_{m}}{\partial t}}+I_{\text{ion}}(V_{m},w)\right)+I_{\text{app}}&{\text{in }}\Omega _{H}\\[1ex]\nabla \cdot \left(({\boldsymbol {\sigma }}_{i}+{\boldsymbol {\sigma }}_{e})\nabla u_{e}\right)+\nabla \cdot ({\boldsymbol {\sigma }}_{i}\nabla V_{m})=0&{\text{in }}\Omega _{H}\\[1ex]{\dfrac {\partial w}{\partial {t}}}+g(V_{m},w)=0&{\text{in }}\Omega _{H}\\[1ex]\nabla \cdot ({\boldsymbol {\sigma }}_{T}\nabla u_{T})=0&{\text{in }}\Omega _{T}\\[1ex]({\boldsymbol {\sigma }}_{i}\nabla V_{m})\cdot \mathbf {n} +({\boldsymbol {\sigma }}_{i}\nabla u_{e})\cdot \mathbf {n} =0&{\text{on }}\Sigma \\[1ex]u_{e}=u_{T}&{\text{on }}\Sigma \\[1ex]({\boldsymbol {\sigma }}_{e}\nabla u_{e})\cdot \mathbf {n} =({\boldsymbol {\sigma }}_{T}\nabla u_{T})\cdot \mathbf {n} &{\text{on }}\Sigma \\[1ex]({\boldsymbol {\sigma }}_{T}\nabla u_{T})\cdot \mathbf {n} =0&{\text{on }}\Gamma _{T}\end{cases}}}

where the first four equations are the  partial differential equations  representing the bidomain model, the ionic model and the torso model, while the remaining ones represent the boundary conditions for the bidomain and torso models and the coupling conditions between them. [ 2 ]


The fully coupled heart-torso model considering the  monodomain model  for the electrical activity of the heart is more complicated that the bidomain problem. Indeed, the coupling conditions relate the torso potential with the extracellular potential, which is not computed by the monodomain model. Thus, it is necessary to use also the second equation of the  bidomain model  (under the same assumptions under which the monodomain model is derived), yielding: [ 2 ]

 ∇
 ⋅

 (

 (

 σ

 i

 +

 σ

 e

 )
 ∇

 u

 e

 )

 +
 ∇
 ⋅
 (

 σ

 i

 ∇

 V

 m

 )
 =
 0

 in

 Ω

 H

 .

 {\displaystyle \nabla \cdot \left(({\boldsymbol {\sigma }}_{i}+{\boldsymbol {\sigma }}_{e})\nabla u_{e}\right)+\nabla \cdot ({\boldsymbol {\sigma }}_{i}\nabla V_{m})=0\quad \quad {\text{in }}\Omega _{H}.}


This way, the coupling conditions do not need to be changed, and the complete heart-torso model is composed of two different blocks: [ 2 ]


The fully coupled heart-torso models are very detailed models but they are also computationally expensive to solve. [ 2 ]  A possible simplification is provided by the so-called  uncoupled assumption  in which the heart is considered completely electrically isolated from the heart. [ 2 ]  Mathematically, this is done imposing that the current cannot flow across the epicardium, from the heart to the torso, namely [ 2 ]

 σ

 e

 ∇

 u

 e

 ⋅

 n

 =
 0

 on

 Σ
 .

 {\displaystyle {\boldsymbol {\sigma }}_{e}\nabla u_{e}\cdot \mathbf {n} =0\quad \quad {\text{on }}\Sigma .}


Applying this equation to the boundary conditions of the fully coupled models, it is possible to obtained two uncoupled heart-torso models, in which the electrical models can be solved separately from the torso model reducing the computational costs. [ 2 ]


The uncoupled version of the fully coupled heart-torso model that uses the bidomain to represent the electrical activity of the heart is composed of two separated parts: [ 2 ]


As in the case of the fully coupled heart-torso model which uses the monodomain model, also in the corresponding uncoupled model extracellular potential needs to be computed. In this case, three different and independent problems must be solved: [ 2 ]


Solving the fully coupled or the uncoupled heart-torso models allows to obtain the electrical potential generated by the heart in every point of the human torso, and in particular on the whole surface of the torso. Defining the electrodes positions on the torso, it is possible to find the time evolution of the potential on such points. Then, the  electrocardiograms  can be computed, for example according to the 12 standard leads, considering the following formulas [ 2 ]

 {

 I

 =

 u

 T

 (
 L
 )
 −

 u

 T

 (
 R
 )

 I
 I

 =

 u

 T

 (
 F
 )
 −

 u

 T

 (
 R
 )

 I
 I
 I

 =

 u

 T

 (
 F
 )
 −

 u

 T

 (
 L
 )

 a
 V
 R

 =

 3
 2

 (

 u

 T

 (
 R
 )
 −

 u

 w

 )

 a
 V
 L

 =

 3
 2

 (

 u

 T

 (
 L
 )
 −

 u

 w

 )

 a
 V
 F

 =

 3
 2

 (

 u

 T

 (
 F
 )
 −

 u

 w

 )

 V

 i

 =

 u

 T

 (

 V

 i

 )
 −

 u

 w

 i
 =
 1
 ,
 …
 ,
 6

 {\displaystyle {\begin{cases}\mathrm {I} &=u_{T}(L)-u_{T}(R)\\\mathrm {II} &=u_{T}(F)-u_{T}(R)\\\mathrm {III} &=u_{T}(F)-u_{T}(L)\\\mathrm {aVR} &={\frac {3}{2}}(u_{T}(R)-u_{w})\\\mathrm {aVL} &={\frac {3}{2}}(u_{T}(L)-u_{w})\\\mathrm {aVF} &={\frac {3}{2}}(u_{T}(F)-u_{w})\\\mathrm {V} _{i}&=u_{T}(V_{i})-u_{w}\quad i=1,\dots ,6\end{cases}}}

where

 u

 W

 =
 (

 u

 T

 (
 L
 )
 +

 u

 T

 (
 R
 )
 +

 u

 T

 (
 F
 )
 )

 /

 3

 {\displaystyle u_{W}=(u_{T}(L)+u_{T}(R)+u_{T}(F))/3}

  and

 L
 ,
 R
 ,
 F
 ,
 {

 V

 i

 }

 i
 =
 1

 6

 {\displaystyle L,R,F,\{V_{i}\}_{i=1}^{6}}

  are the standard locations of the electrodes. [ 2 ]


The heart-torso models are expressed in terms of  partial differential equations  whose unknowns are function of both space and time. They are in turn coupled with an ionic model which is usually expressed in terms of a system of  ordinary differential equations . A variety of numerical schemes can be used for the solution of those problems. Usually, the  finite element method  is applied for the space discretization and semi-implicit finite-difference schemes are used for the time discretization. [ 1 ] [ 2 ]


Uncoupled heart-torso model are the simplest to treat numerically because the heart electrical model can be solved separately from the torso one, so that classic numerical methods to solve each of them can be applied. This means that the bidomain and monodomain models can be solved for example with a  backward differentiation formula  for the time discretization, while the problems to compute the extracellular potential and torso potential can be easily solved by applying only the finite element method because they are time independent. [ 1 ] [ 2 ]


The fully coupled heart-torso models, instead, are more complex and need more sophisticated numerical models. For example, the fully heart-torso model that uses the bidomain model for the electrical simulation of the cardiac behaviour can be solved considering  domain decomposition  techniques, such as a Dirichlet-Neumann domain decomposition. [ 2 ] [ 11 ]


To simulate and  electrocardiogram  using the fully coupled or uncoupled models, a three-dimensional reconstruction of the human torso is needed. Today, diagnostic imaging techniques such as  MRI  and  CT  can provide a sufficiently accurate images that allow to reconstruct in detail anatomical human parts and, thus, obtain a suitable torso geometry.
For example, the Visible Human Data [ 13 ]  is a useful dataset to create a three-dimensional torso model detailed with internal organs including the skeletal structure and muscles. [ 1 ]


Even if the results are quite detailed, solving a three-dimensional model is usually quite expensive. A possible simplification is a dynamical model based on three coupled ordinary differential equations. [ 3 ]


The quasi-periodicity of the heart beat is reproduced by a three-dimensional trajectory around an attracting limit cycle in the

 (
 x
 ,
 y
 )

 {\displaystyle (x,y)}

  plane. The principal peaks of the ECG, which are the P,Q,R,S and T, are described at fixed angles

 θ

 P

 ,

 θ

 Q

 ,

 θ

 R

 ,

 θ

 S

  and

 θ

 T

 {\displaystyle \theta _{P},\theta _{Q},\theta _{R},\theta _{S}{\text{ and }}\theta _{T}}

 , which give the following three ODEs [ 3 ]


x
 ′

 =
 α
 z
 −
 ω
 y

 y
 ′

 =
 α
 y
 +
 ω
 x

 z
 ′

 =

 −

 ∑

 i
 ∈
 {
 P
 ,
 Q
 ,
 R
 ,
 S
 ,
 T
 }

 a

 i

 Δ

 θ

 i

 exp

 (

 −

 Δ

 θ

 i

 2

 /

 2

 b

 i

 2

 )

 −
 (
 z
 −

 z

 0

 )

 {\displaystyle {\begin{aligned}x'&=\alpha z-\omega y\\[1ex]y'&=\alpha y+\omega x\\[1ex]z'&=\textstyle -\sum _{i\in \{P,Q,R,S,T\}}a_{i}\Delta \theta _{i}{\text{exp}}\left(-{\Delta \theta _{i}^{2}}/{2b_{i}^{2}}\right)-(z-z_{0})\end{aligned}}}

with

 α
 =
 1
 −

 x

 2

 +

 y

 2

 {\textstyle \alpha =1-{\sqrt {x^{2}+y^{2}}}}

 ,

 Δ

 θ

 i

 =
 (
 θ
 −

 θ

 i

 )

 mod

 (

 2
 π
 )

 {\displaystyle \Delta \theta _{i}=(\theta -\theta _{i}){\bmod {(}}2\pi )}

 ,

 θ
 =

 atan

 2
 (
 y
 ,
 x
 )

 {\displaystyle \theta ={\text{atan}}2(y,x)}


The equations can be easily solved with classical numerical algorithms like  Runge-Kutta methods  for ODEs. [ 3 ]


The  pacemaker current  ( I f , or  I K f , also called  funny current ) is an  electric current  in the  heart  that flows through the  HCN channel  or pacemaker channel. Such channels are important parts of the  electrical conduction system of the heart  and form a component of the  natural pacemaker .


First described in the late 1970s in  Purkinje fibers  and  sinoatrial   myocytes , the cardiac pacemaker "funny" (I f ) current has been extensively characterized and its role in cardiac pacemaking has been investigated. [ 1 ] [ 2 ] [ 3 ]  Among the unusual features which justified the name "funny" are mixed Na +  and K +  permeability, activation on  hyperpolarization , and very slow kinetics. [ 1 ]


The funny current is highly expressed in spontaneously active cardiac regions, such as the  sinoatrial node  (SAN, the natural pacemaker region), the  atrioventricular node  (AVN) and the Purkinje fibres of conduction tissue. The funny current is a mixed sodium–potassium current that activates upon hyperpolarization at voltages in the diastolic range (normally from −60/−70 mV to −40 mV). When, at the end of a sinoatrial action potential, the membrane repolarizes below the I f  threshold (about −40/−50 mV), the funny current is activated and supplies inward current, which is responsible for starting the  diastolic depolarization  phase (DD); by this mechanism, the funny current controls the rate of spontaneous activity of sinoatrial myocytes, and thus the cardiac rate. The reversal potential of the funny current lies between -20 and -10 mV.  [ 4 ]


Another unusual feature of I f  is its dual activation by voltage and by cyclic nucleotides.  Cyclic adenosine monophosphate  (cAMP) molecules bind directly to f-channels and increase their open probability. [ 5 ]  cAMP dependence is a particularly relevant physiological property, since it underlies the I f -dependent autonomic regulation of heart rate. Sympathetic stimulation raises the level of cAMP-molecules which bind to f-channels and shift the I f  activation range to more positive voltages; this mechanism leads to an increase of the current at diastolic voltages and therefore to an increase of the steepness of DD and heart rate acceleration.


Parasympathetic stimulation (which acts to increase probability of potassium channels opening but decreases the probability of calcium channel opening) decreases the heart rate by the opposite action, that is by shifting the I f  activation curve towards more negative voltages. When vagally-released acetylcholine (ACh) binds to  muscarinic M2 receptors , this promotes dissociation of βγ subunit complexes, leading to direct opening of the G-protein–gated inwardly rectifying K+ channel (Girk/Kir)  IKACh. [ 6 ]


A similar current, termed I h  (hyperpolarization-activated), has also been described in different types of neurons, where it has a variety of functions, including the contribution to control of rhythmic firing, regulation of neuronal excitability, sensory transduction, synaptic plasticity and more. [ 7 ]


The molecular determinants of the pacemaker current belong to the  HCN channel  ( hyperpolarization -activated  cyclic nucleotide –gated channel), of which 4  isoforms  (HCN1 to HCN4) are known. Based on their sequence, HCN channels are classified as members of the superfamily of voltage-gated K +  (Kv) and CNG channels. [ 3 ] [ 8 ]