Because of their relevance to generation of pacemaker activity and modulation of spontaneous frequency, f-channels are natural targets of drugs aimed to pharmacologically control heart rate. Several agents called "heart rate reducing agents" act by specifically inhibiting f-channel function. [ 3 ]   Ivabradine  is the most specific and selective I f  inhibitor and the only member of this family that is now marketed for pharmacological treatment of chronic stable angina in patients with normal sinus rhythm who have a contraindication or intolerance to beta-blockers. Recent studies have also indicated that funny channel inhibition can be used to reduce the incidence of coronary artery disease outcomes in a subgroup of patients with heart rate ≥70 bpm. [ 9 ]


Cardiovascular diseases represent a major cause of worldwide mortality, and the relevance of the genetic component in these diseases has recently become more apparent. Genetic alterations of HCN4 channels (the molecular correlate of sinoatrial f-channels) coupled to rhythm disturbances have been reported in humans. For example, an inherited mutation of a highly conserved residue in the CNBD of the HCN4 protein (S672R) is associated with inherited  sinus bradycardia . [ 10 ]   In vitro  studies indicate that the S672R mutation causes a hyperpolarizing shift of the HCN4 channel open probability curve of about 5 mV in heterozygosis, an effect similar to the hyperpolarizing shift caused by parasympathetic stimulation and able to explain a reduction of inward current during diastole and the resulting slower spontaneous rate. [ citation needed ]


Biological pacemakers, generally intended as cell substrates able to induce spontaneous activity in silent tissue, represent a potential tool to overcome the limitations of  electronic pacemakers . One of the strategies used to generate biological pacemakers involves the use of cells inherently expressing or engineered to express funny channels. Different types of stem cells can be used for this purpose. [ 8 ]


The  Heart Rhythm Society  is an international  non-profit organization  that promotes education and advocacy for cardiac arrhythmia professionals and patients. The society was founded in 1979 and counted over 7,500 members from over 90 countries as of January 2023. [ 1 ] [ third-party source needed ]  The official journal of the Heart Rhythm Society is  Heart   Rhythm , which provides readers scientific developments devoted to  arrhythmias , devices, and cardiovascular  electrophysiology . The Heart Rhythm Society is headquartered in  Washington, DC , US. [ 2 ]


The Heart Rhythm Society, through its efforts during Atrial Fibrillation Awareness Month in September and throughout the year, is working to increase public knowledge about atrial fibrillation, including its symptoms, warning signs, and treatments. [ 3 ] [ 4 ]


Sudden Cardiac Arrest Awareness Month represents an initiative by the Heart Rhythm Society to raise awareness and help the public become more familiar with sudden cardiac arrest, how it affects people, and what can be done to help save lives. [ 5 ]  The society's award-winning "Apples and Oranges" campaign uses a simple analogy to educate people about the difference between a heart attack and sudden cardiac arrest. The campaign targets heart attack survivors, who are at the highest risk for sudden cardiac arrest, and stresses the importance of maintaining a healthy heart lifestyle and learning critical risk markers, especially their ejection fraction, which is the percentage of blood pumped out of the left ventricle with each heartbeat. [ 6 ] [ 7 ]


In October 2012, the Heart Rhythm Society launched a multi-year, national awareness campaign, "Arrest the Risk", in an effort to elevate the issue of preventing sudden cardiac arrest, early intervention, and appropriate treatment among the African-American and Hispanic populations; increase awareness of disparities at the point of care; and reduce mortality and re-hospitalization rates from sudden cardiac arrest in the US. [ 8 ] [ 9 ]


The Heart Rhythm Society's government advocacy efforts center on operating as an intermediary between regulatory agencies and its members. The society promotes programs to take action regarding legislation, creates and endorses clinical guidelines, and helps its members find funding opportunities from government agencies such as the National Institutes of Health. [ citation needed ]


The society also provides several educational initiatives including courses held throughout the year, certification and  continuing medical education  programs and an annual conference, called Scientific Sessions. [ citation needed ]


Presidents of the Heart Rhythm Society from inception are listed below.  The leadership cycle is five years, with service as president being in the fourth year.  This allows the society to project presidents three years in advance.   Anne M. Gillis , whose election to the presidency for the 2012–13 term was revealed at the May 2009 meeting of the society, was the second non-American to serve in that capacity.  The first non-American president was Bernard S. Goldman in 1982; the second was Anne M. Gillis (both are Canadian). [ 10 ] [ 11 ]


An  implantable cardioverter-defibrillator  ( ICD ) or  automated implantable cardioverter defibrillator  ( AICD ) is a device  implantable  inside the body, able to perform  defibrillation , and depending on the type,  cardioversion  and  pacing  of the heart. The ICD is the first-line treatment and prophylactic therapy for patients at risk for  sudden cardiac death  due to  ventricular fibrillation  and  ventricular tachycardia . [ 1 ]


"AICD" was trademarked by the Boston Scientific corporation, so the more generic "ICD" is preferred terminology.


On average ICD  batteries  last about six to ten years. [ 2 ]  Advances in technology, such as batteries with more capacity or rechargeable batteries, [ 3 ]  may allow batteries to last over ten years. The leads (electrical cable wires connecting the device to the heart) have much longer average longevity, but can malfunction in various ways, specifically  insulation  failure or fracture of the  conductor ; thus, ICDs and leads generally require replacement after every 5 to 10 years. [ 4 ] [ 5 ]


The process of implantation of an ICD system is similar to implantation of an  artificial pacemaker . In fact, ICDs are composed of an ICD generator and of wires. The first component or generator contains a computer chip or circuitry with  RAM  (memory), programmable software, a  capacitor  and a battery; this is implanted typically under the skin in the left upper chest. The second part of the system is an  electrode  wire or wires that, similar to pacemakers, are connected to the generator and passed through a vein to the right chambers of the heart. The lead usually lodges in the apex or septum of the  right ventricle . [ 6 ]


Just like pacemakers, ICDs can have a single wire or lead in the heart (in the right ventricle, single chamber ICD), two leads (in the right atrium and right ventricle, dual chamber ICD) or three leads (biventricular ICD, one in the right atrium, one in the right ventricle and one on the outer wall of the  left ventricle ). The difference between pacemakers and ICDs is that pacemakers are also available as temporary units and are generally designed to correct slow heart rates, i.e.  bradycardia , while ICDs are often permanent safeguards against sudden life-threatening arrhythmias.


Recent developments include the  subcutaneous ICD  (S-ICD) which is placed entirely under the skin, leaving the vessels and heart untouched.  [ 7 ]  Implantation with an S-ICD is regarded as a procedure with even less risks, it is currently suggested for patients with previous history of infection or increased risk of infection. It is also recommended for very active patients, younger patients with will likely outlive their transvenous ICD (TV-ICD) leads and those with complicated anatomy/arterial access. S-ICDs are not able to be used in patients with  ventricular tachycardia  or  bradycardia .  [ 8 ]


People who have an implanted cardioverter-defibrillator can live full lives. Patients overall have either a sustained or improved quality of life after ICD implantation when compared to before ICD implantation. [ 9 ]  It may provide a strong degree of reassurance. As with a pacemaker, however, living with an ICD does impose some restrictions on the person's lifestyle.


Almost all forms of physical activities can be performed by patients with an ICD with moderation. [ 10 ]  All forms of sports that do not pose a risk of damaging the ICD or because of the underlying cardiomyopathy can be undertaken by the patient. Special care should be taken not to put excessive strain on the shoulder, arm and torso area where the ICD is implanted. Doing so may damage the ICD or the leads going from the ICD generator to the patient's heart. Particularly to be avoided are exercises that cause the  clavicle  to be pulled down towards the ribs, such as lifting weights with the arm, on the ICD site, while standing.


ICD patients in the United States are prohibited from professional or commercial driving per the Cardiovascular Advisory Panel Guidelines for the Medical Examination of Commercial Motor Vehicle Drivers. [ 11 ]  A driving abstinence for private drivers is recommended following ICD implantation, but the timeframe is variable depending on the country (between 3 and 6 months for secondary prevention and 1–4 weeks for primary prevention). Following an appropriate ICD-therapy, a driving ban is recommended for 3–6 months depending on the country. After inappropriate ICD-therapy delivered for non-ventricular arrhythmias or due to the device malfunction, driving restrictions usually apply until the cause of the inappropriate therapy has been eliminated. [ 12 ]


Equipment using magnets or generating magnetic fields, or any similar environment, must be avoided by patients with an ICD. As with other metallic objects, an ICD is normally a  contraindication  to the use of  magnetic resonance imaging  (MRI).  However, several ICD manufacturers [ who? ]  have recently [ when? ]  introduced  MR-Conditional  ICDs, which allow the use of MRI under specified safe operating conditions. [ citation needed ]


Implantable cardioverter defibrillators have demonstrated clear life-saving benefits, while concerns about patient acceptance and  psychological  adjustment to the ICD have been the focus of much research. [ 13 ]   Researchers, including those from the field of  cardiac psychology , have concluded that the quality of life (QoL) of ICD patients is at least equal to, or better than, that of those taking  anti-arrhythmic medications . [ 14 ]   The largest study of examined 2,521 patients with stable heart failure in the SCD-HeFT trial. [ 15 ]   Results indicated that there were no differences between ICD-treated and medication-treated groups at 30 months in patient-reported QoL. [ 16 ]  Psychological adjustment following ICD implantation has also been well studied. In rare cases, the ICD can become infected and is usually bacterial in origin but other organisms such as certain fungi have occasionally been implicated. [ 17 ]  This is more likely to occur in people with  diabetes ,  heart failure ,  kidney failure , or  a suppressed immune system . [ 17 ]


Anxiety  is a common psychological  side effect , with approximately 13–38% of ICD patients reporting clinically significant anxiety. [ 18 ] [ 19 ]  The primary etiological factors contributing to anxiety in ICD patients have not been determined, however.  Depressive  symptoms are also common, but the incidence of these problems has been shown to be similar to those observed in other cardiac patient groups, with approximately 24–41% of patients with ICDs experiencing depressive symptoms. [ 19 ]  Problems in psychosocial adjustment to ICDs, including the experience of anxiety, among spouses or other romantic partners are also prevalent. [ 20 ]  This phenomenon may be related, at least in part, to shared shock anxiety and avoidance of physical and sexual contact. [ 21 ]


Patients are generally required to follow up with their electrophysiologist cardiologist at regular intervals, mostly 3 to 6 months. At this time, many device manufactures have some form of home monitoring to allow for device data to be sent in electronically to the physician. [ 22 ]  Recent advances include app integration for home interrogation and remote care has been correlated with some mortality benefit.  [ 23 ]


Implantation of ICD is meant to prevent  sudden cardiac death  and is indicated under various conditions. Two broad but distinct categories are primary and secondary prevention. Primary prevention refers to patients who have not suffered a life-threatening arrhythmia episode. Secondary prevention has the strongest evidence for benefit and it refers to survivors of cardiac arrest secondary to  ventricular fibrillation  (VF) or hemodynamically unstable sustained  ventricular tachycardia  (VT) after reversible causes are excluded. [ 24 ]


Similarly, ICD use in primary prevention is to prevent cardiac death in patients who are at risk for sustained ventricular tachycardia or ventricular fibrillation. This population accounts for the bulk of all ICD implants. There are a multitude of guideline indications for ICD use in primary preventions with varying degree of supporting evidence. Periodically, both the American College of Cardiology (ACC)/American Heart Association (AHA) and European Society of Cardiology provide an update to this guideline. Some of the Class I indications are as follows: [ 24 ]


A number of clinical trials have demonstrated the superiority of the ICD over AAD (antiarrhythmic drugs) in the prevention of death from malignant arrhythmias.
The SCD-HeFT trial (published in 2005) [ 25 ]  showed a significant all-cause mortality benefit for patients with ICD.  Congestive heart failure  patients that were implanted with an ICD had an all-cause death risk 23% lower than placebo and an absolute decrease in mortality of 7.2 percentage points after five years in the overall population. 1
Reporting in 1999, the  Antiarrhythmics Versus Implantable Defibrillators  (AVID) trial consisted of 1,016 patients, and deaths in those treated with AAD were more frequent ( n  = 122) compared with deaths in the ICD groups ( n  = 80,  p  < 0.001). [ 26 ]  In 2002 the  MADITII  trial showed benefit of ICD treatment in patients after myocardial infarction with reduced left ventricular function (EF<30).


Initially ICDs were implanted via thoracotomy with defibrillator patches applied to the  epicardium  or  pericardium . The device was attached via subcutaneous and transvenous leads to the device contained in a subcutaneous abdominal wall pocket. The device itself acts as an electrode. Most ICDs nowadays are implanted transvenously with the devices placed in the left pectoral region similar to pacemakers. Intravascular spring or coil electrodes are used to defibrillate.  The devices have become smaller and less invasive as the technology advances.  Current ICDs weigh only 70 grams and are about 12.9 mm thick.


A recent study by Birnie and colleagues at the University of Ottawa Heart Institute has demonstrated that ICDs are underused in both the United States and Canada. [ 27 ]  An accompanying editorial by Simpson of Queen's University explores some of the economic, geographic, social and political reasons for this. [ 28 ]


The development of the ICD was pioneered at  Sinai Hospital  in  Baltimore  by a team including  Michel Mirowski ,  Morton Mower ,  Alois Langer , William Staewen, and Joseph "Jack" Lattuca. Mirowski teamed up with Mower and Staewen and together they commenced their research in 1969 but it was 11 years before they treated their first patient. [ 29 ] [ 30 ]


The work was commenced against much skepticism even by leading experts in the field of arrhythmias and sudden death. There was doubt that their ideas would ever become a clinical reality. In 1972  Bernard Lown , the inventor of the external  defibrillator , and Paul Axelrod 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  anti-arrhythmic  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." [ 29 ] [ 31 ]


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. [ 29 ] [ 32 ]


The first devices required  the chest to be cut open  and a mesh electrode sewn onto the heart; the  pulse generator  was placed in the abdomen. [ 29 ]


ICDs constantly monitor the rate and rhythm of the heart and can deliver therapies, by way of an electrical shock, when the heart rate exceeds a preset number.  More modern devices have software designed to attempt a discrimination between  ventricular fibrillation  and  ventricular tachycardia  (VT), and may try to pace the heart faster than its intrinsic rate in the case of VT, to try to break the tachycardia before it progresses to ventricular fibrillation. This is known as overdrive pacing, or anti-tachycardia pacing (ATP).  ATP is only effective if the underlying rhythm is ventricular tachycardia, and is never effective if the rhythm is ventricular fibrillation.


Many modern ICDs use a combination of various methods to determine if a fast rhythm is normal,  supraventricular tachycardia , ventricular tachycardia, or ventricular fibrillation.


Rate discrimination  evaluates the rate of the lower chambers of the  heart  (the  ventricles ) and compares it to the rate in the upper chambers of the heart (the  atria ). If the rate in the atria is faster than or equal to the rate in the ventricles, then the rhythm is most likely not ventricular in origin, and is usually more benign. If this is the case, the ICD does not provide any therapy, or withholds it for a programmable length of time.


Rhythm discrimination  will see how regular a ventricular tachycardia is. Generally, ventricular tachycardia is regular. If the rhythm is irregular, it is usually due to conduction of an irregular rhythm that originates in the atria, such as  atrial fibrillation . In the picture, an example of  torsades de pointes  can be seen; this represents a form of irregular ventricular tachycardia. In this case, the ICD will rely on rate, not regularity, to make the correct diagnosis.


Morphology discrimination  checks the morphology of every ventricular beat and compares it to what the ICD knows is the morphology of normally conducted ventricular impulse for the patient.  This normal ventricular impulse is often an average of a multiple of normal beats of the patient acquired in the recent past and known as a template.


The integration of these various parameters is very complex, and clinically, the occurrence of inappropriate therapy is still occasionally seen and a challenge for future software advancements.


An  implantable loop recorder  ( ILR ), also known as an  insertable cardiac monitor  ( ICM ), is a small device that is implanted under the skin of the chest for  cardiac monitoring , to record the heart's electrical activity for an extended period. [ 1 ]


The ILR  monitors the electrical activity  of the heart, continuously storing information in its  circular memory  (hence the name "loop" recorder) as  electrocardiograms  (ECGs). Abnormal electrical activity -  arrhythmia  is recorded by "freezing" a segment of the memory for later review. Limited number of episodes of abnormal activity can be stored, [ 2 ]  with the most recent episode replacing the oldest. [ 3 ]


Recording can be activated in two ways. First, recording may be activated automatically according to  heart rate  ranges previously defined and set in the ILR by the physician. If the heart rate drops below, or rises above, the set rates, the ILR will record without the patient's knowledge.  The second way the ILR records is through a hand-held "patient activator" whereby the patient triggers a recording by pushing a button when they notice symptoms such as skipped beats, lightheadedness or dizziness. [ 4 ]  The ILR records by "freezing" the electrical information preceding, during and after the symptoms in the format of an electrocardiogram. [ 1 ]  The technician or physician can download and review the recorded events during an office visit using a special  programmer [ 4 ]  or via online data transmission. [ 5 ]


The ILR is a useful  diagnostic  tool to investigate patients who experience symptoms such as  syncope  (fainting),  seizures , recurrent  palpitations , lightheadedness, or dizziness not often enough to be captured by a 24-hour or 30-day external monitor. Because of the ILR's long battery life (up to 3 years), the heart can be monitored for an extended period.


New devices are able to store a total of 60 minutes of recordings on their memory. Thirty minutes is reserved for automatic storage of arrhythmias according to preprogrammed criteria. The remaining 30 minutes can be divided into a selectable number of slots for storage of manually triggered retrograde recordings as an answer to symptoms (fainting, palpitations etc.) which may be caused by an arrhythmia. [ 4 ]


Recent studies have underscored the diagnostic effectiveness and cost-efficiency of implantable loop recorders (ILRs) in specific patient populations. In patients with unexplained palpitations, especially those with infrequent symptoms, ILRs have shown a significantly higher diagnostic yield compared to conventional methods. One study reported a diagnosis in 73% of subjects using ILRs, against 21% with conventional strategies, while also proving to be more cost-effective despite higher initial costs. [ 6 ]  Another study focused on ILR use for detecting asymptomatic atrial fibrillation in individuals aged 70-90 years with additional stroke risk factors. This trial found that ILR screening led to a threefold increase in atrial fibrillation detection and anticoagulation initiation. However, it did not show a significant reduction in the risk of stroke or systemic arterial embolism, indicating that not all screen-detected atrial fibrillation might warrant anticoagulation treatment. [ 7 ]


The ILR is implanted by an  electrophysiologist  under  local anesthesia . A small incision (about 3–4 cm or 1.5 inches) is made just lateral to the sternum below the nipple line, usually on the patient's left side. [ 8 ]  A pocket is created under the skin, and the ILR is placed in the pocket. Patients can go home the day of the procedure with few restrictions on activities. [ 4 ]  Bruising and discomfort in the implant area may persist for several weeks.


Patients are instructed in use of the activator, and advised to schedule an appointment with their physician after using it so that information stored in the ILR can be retrieved for diagnosis.


In the  electrocardiogram , the  intrinsicoid deflection  is the downstroke of the  QRS complex , from its highest amplitude until it reaches the baseline or lower. [ 1 ]  Since the  ventricles  normally  depolarize  from inside to outside, this deflection reflects the depolarization vector from the  endocardium  to the  epicardium . The  time of the onset of the intrinsicoid deflection , also referred to as the  ventricular activation time  or  R wave peak time , is measured from the beginning of the QRS complex to the peak of the R wave. [ 1 ]


In the presence of bundle branch block or ventricular hypertrophy, the depolarization impulse takes a longer than normal period of time to reach the recording electrode. This delays the onset of the intrinsicoid deflection.
This prolongation or delay is an important criterion for diagnosing bundle branch block or ventricular hypertrophy. Time of onset of intrinsicoid deflection > 0.04 seconds (just over one small box) is used as a non-voltage related criterion to diagnose  left ventricular hypertrophy . [ 2 ]


Leonardo Krys  [1944-2009] was a travel agent whose 1991 heart attack aboard a  Lufthansa  flight prompted U.S.-based airlines to install  Automated External Defibrillators , or AED, on their planes.


On November 30, 1991, Krys boarded a Lufthansa 747 in Miami, headed to Frankfurt, Germany. About an hour out, he suffered the symptoms of a cardiac infarction. The crew did not make an unscheduled landing and landed in Germany after a 10 hours flight. Upon landing, the plane was met by an ambulance which transported Krys to a hospital. At the hospital, the doctors concluded that Krys had indeed suffered a heart attack.


Krys and his wife argued that Lufthansa's crew acted negligently in responding to the symptoms displayed by Mr. Krys and thus aggravated the damage to his heart. They won a lawsuit against Lufthansa in Miami federal court which the 11th Circuit Court of Appeals upheld. [ 1 ]  Later the  United States Supreme Court  refused to hear the airline's appeal arguing that the incident should have been classified as an accident, per the Warsaw Convention, capping his payout.


The result of this suit prompted the airlines to review their safety manuals, including portable defibrillators and training the crew on how to use them.


Leo (as he was known by his friend and family) was born in Argentina, and moved with his family to  Miami, USA  in the late 1970s, due to the local economical and political situation.


He owned a travel agency at the time of the heart attack, but the health crisis spurred a midlife career switch to acting. He acted in  Telemundo   telenovelas , local theater, an episode of  America's Most Wanted  (as an Israeli searching for his son's killer), several independent films and in Latin pop star  La India 's video, Traicion, as a priest.


One of Krys' son,  Sebastian , is a four-time American  Grammy  winner and eight-time  Latin Grammy Awards  producer and mixer (as of 2011)


Leonardo Krys died of a heart attack in Miami, on March 14, 2009.


3BJ4 ,  3HFC ,  3HFE ,  4UMO ,  4V0C


ENSG00000282076 ENSG00000053918


NM_181798 NM_000218 NM_181797


NP_000209 NP_861463


K v 7.1  ( KvLQT1 ) is a  potassium   channel   protein  whose primary subunit in humans is encoded by the  KCNQ1   gene . [ 5 ]   It's mutation causes  Long QT syndrome , K v 7.1 is a voltage and  lipid-gated  potassium channel present in the  cell membranes  of cardiac tissue and in inner ear  neurons  among other tissues.  In the cardiac  cells , K v 7.1 mediates the I Ks  (or slow delayed rectifying K + ) current that contributes to the  repolarization  of the cell, terminating the cardiac  action potential  and thereby the heart's  contraction . It is a member of the  KCNQ family  of potassium channels.


KvLQT1 is made of six membrane-spanning domains S1-S6, two intracellular domains, and a pore loop. [ 6 ]   The KvLQT1 channel is made of four KCNQ1 subunits, which form the actual ion channel.


This gene encodes a protein for a voltage-gated potassium channel required for the repolarization phase of the cardiac action potential. The gene product can form heteromultimers with two other potassium channel proteins,  KCNE1  and  KCNE3 . The gene is located in a region of  chromosome 11  that contains a large number of contiguous genes that are abnormally imprinted in cancer and the  Beckwith-Wiedemann syndrome . Two alternative transcripts encoding distinct isoforms have been described. [ 7 ]


Mutations  in the gene can lead to a defective protein and several forms of inherited arrhythmias as  Long QT syndrome [ 8 ]  which is a prolongation of the  QT interval  of heart repolarization,  Short QT syndrome , [ 8 ]  and Familial  Atrial Fibrillation .  KvLQT1 are also expressed in the pancreas, and KvLQT1 Long QT syndrome patients has been shown to have hyperinsulinemic hypoglycaemia following an oral glucose load. [ 9 ]  Currents arising from K v 7.1 in over-expression systems have never been recapitulated in native tissues - K v 7.1 is always found in native tissues with a modulatory subunit.  In cardiac tissue, these subunits comprise KCNE1 and yotiao.  Though  physiologically  irrelevant,  homotetrameric  K v 7.1 channels also display a unique form of C-type inactivation that reaches equilibrium quickly, allowing KvLQT1 currents to plateau.  This is different from the inactivation seen in A-type currents, which causes rapid current decay.


KvLQT1 has been shown to  interact  with  PRKACA , [ 11 ]   PPP1CA [ 11 ]  and  AKAP9 . [ 11 ]


KvLQT1 can also associate with any of the five members of the KCNE family of proteins, but interactions with  KCNE1 ,  KCNE2 ,  KCNE3  are the only interactions within this protein family that affect the human heart. KCNE2,  KCNE4 , and  KCNE5  have been shown to have an inhibitory effect on the functionality of KvLQT1, while KCNE1 and KCNE3 are activators of KvLQT1. [ 6 ]   KvLQT1 can associate with KCNE1 and KCNE4 with the activation effects of KCNE1 overriding the inhibitory effects of KCNE4 on the KvLQT1 channel, and KvLQT1 will commonly associate with anywhere from two to four different KCNE proteins in order to be functional. [ 6 ]   However, KvLQT1 most commonly associates with KCNE1 and forms the KvLQT1/KCNE1 complex since it has only been seen to function in vivo when associated with another protein. [ 6 ]   KCNQ1 will form a  heteromer  with KCNE1 in order to slow its activation and enhance the current density at the plasma membrane of the neuron. [ 6 ] [ 12 ]   In addition to associating with KCNE proteins, the  N-terminal  juxtamembranous domain of KvLQT1 can also associate with  SGK1 , which stimulates the slow delayed potassium rectifier current.  Since SGK1 requires structural integrity to stimulate KvLQT1/KCNE1, any mutations present in the KvLQT1 protein can result in reduced stimulation of this channel by SGK1. [ 13 ]   General mutations in KvLQT1 have been known to cause a decrease in this slow delayed potassium rectifier current, longer cardiac action potentials, and a tendency to have tachyarrhythmias. [ 12 ]


KCNE1  (minK), can assemble with KvLQT1 to form a slow delayed potassium rectifier channel.  KCNE1 slows the inactivation of KvLQT1 when the two proteins form a heteromeric complex, and the current amplitude is greatly increased compared to WT-KvLQT1  homotetrameric  channels.  KCNE1 associates with the pore region of KvLQT1, and its  transmembrane  domain contributes to the selectivity filter of this heteromeric channel complex. [ 12 ]  The  alpha helix  of the KCNE1 protein interacts with the pore domain S5/S6 and with the S4 domain of the KvLQT1 channel.  This results in structural modifications of the voltage sensor and the selectivity filter of the KvLQT1 channel. [ 14 ]   Mutations in either the alpha subunit of this complex, KvLQT1 or the beta subunit, KCNE1, can lead to  Long QT Syndrome  or other cardiac rhythmic deformities. [ 13 ]   When associated with KCNE1, the KvLQT1 channel activates much more slowly and at a more positive  membrane potential .  It is believed that two KCNE1 proteins interact with a  tetrameric  KvLQT1 channel, since experimental data suggests that there are 4 alpha subunits and 2 beta subunits in this complex. [ 14 ]
KVLQT1/KCNE1 channels are taken up from the plasma membrane through a  RAB5  dependent mechanism, but inserted into the membrane by  RAB11 , a  GTPase . [ 15 ]


51°03′55″N   114°08′06″W  /  51.0654°N 114.135°W  /  51.0654; -114.135


The  Libin Cardiovascular Institute  is an entity of  Alberta Health Services  and the  University of Calgary .  It connects all cardiovascular research, education and patient care in Southern Alberta, serving a population of about two million. Its more than 1,500 members include physicians, clinicians and other health professionals, researchers and trainees.


The Libin Cardiovascular Institute was made possible through the donation of founding donors Mona and  Alvin Libin .


On March 6, 2003, the Alvin and Mona Libin Foundation presented $15 million to Alberta Health Services and the University of Calgary to form the Libin Cardiovascular Institute. It was then the largest one-time donation to the organizations. The institute was formally created on January 27, 2004.


The Foundation renewed their commitment to the Institute in May 2022 with a  $7.5 million donation .


Research within the Libin Cardiovascular Institute extends from basic biomedical and clinical research to health outcomes and care delivery research.  Notable successes include:


Programs under the jurisdiction of the Libin Cardiovascular Institute include  Cardiology  and  Cardiovascular Surgery , in addition to contributions to other medical programs as well as graduate studies in the sciences. [ citation needed ]


The LCI also offers fellowships and/or advanced training in  interventional cardiology ,  electrophysiology , amyloidosis, heart function and  cardiac MRI . [ citation needed ]


The Libin Cardiovascular Institute is a wide-ranging program of cardiovascular integration which houses a growing list of scientists, clinicians, and researchers from various sites working together to advance the cardiovascular health of Albertans.


The Alberta Heritage Foundation for Medical Research (AHFMR) Prize for Excellence in Cardiovascular Research was established in honour of Mr. Alvin Libin for his many contributions to the AHFMR (now  Alberta Innovates ).


This $25,000 prize is awarded to an outstanding international researcher whose work has had a major impact on the understanding, prevention, recognition, or treatment of cardiovascular disease.


Past winners include:


Lifepak  (stylized  LIFEPAK ) is a series of vital signs monitors and external cardiac  defibrillators  produced by medical technology company  Physio-Control . [ 1 ] [ 2 ] [ 3 ] [ 4 ]


Lifepak defibrillators are manufactured and distributed from the company headquarters in  Redmond, Washington .


Physio-Control publicly demonstrated its first Lifepak branded defibrillator, Lifepak 33, in November 1968 and began commercial sale of the unit the next year in 1969. [ 5 ] [ 6 ]  The Lifepak 33 was the lightest defibrillator available at launch, weighing 34 pounds. The defibrillator was referred to by media as a "90-day wonder" due to the entirety of its development occurring within a 90-day period. Despite being the companies first "LIFEPAK" branded defibrillator, it was named the Lifepak 33 due to the companies target weight of 33 pounds for the defibrillator. [ 7 ]


In 1971, the Lifepak 911 was released with 12-lead ECG monitoring capability, with the Lifepak 2 being released the following year. The Lifepak 2 was designed specifically for rapid-response vehicles in emergency services, and was the first to allow transmission of ECGs via telephone to hospitals for prehospital assessment by cardiologists. In 1973, the Lifepak 3 was released with a "non-fade" display and the ability to "freeze" the cardioscope. The Lifepak 1 was released the same year and was marketed as a more basic, but more compact model, lacking a cardiograph for ECG monitoring. In 1974, the Lifepak 4 was released with an integrated ECG recorder, and was followed by the Physio 260 (for home use) and Physio 1440 cardiac care system defibrillators were released to the public. [ 7 ]


In 1976, the Lifepak 5 was released weighing only 5 pounds and 19 ounces, with a modified Lifepak 5 accompanying the 65-member American Medical Expedition to  Mount Everest  in 1981 and the China-Everest Expedition in 1982. The Lifepak 6 featured a modular design with removable paddles holder and ECG printer, the Lifepak 8 featured the ability to perform transchest  external pacing , and the Lifepak 100 and 200 automatic advisor defibrillators were released with an Incorporated Shock Advisory System able to recognise shockable arrhythmias. in 1989, the Lifepak 9 and 10 both integrated a "Code Summary" record for documentation, featuring the ability to record times medication was administered, when shocks were delivered and how many shocks were delivered. [ 7 ]


In 1994, the Lifepak 11 was released, which set standards in prehospital 12-lead acquisition and transmission. In 1997, the Lifepak 500 was released as a  public access defibrillator , and brought AEDs to the mainstream public. The following year, the Lifepak 12 was released, with improved monitoring and diagnostic capabilities, as well as a standardised button layout. Some ambulance services still use the Lifepak 12 due to its reliability and advanced capabilities. [ 7 ]


In 1999, biphasic defibrillation waveforms were made available for the Lifepak 12 and 500 defibrillators and the 'ADAPTIV' biphasic waveform would become the standard waveform used in future models. [ 8 ]


In 2002, the Lifepak 20 defibrillator/monitor was introduced to replace the 9 in the hospital market, while the Lifepak CR Plus was introduced for the public market. [ 8 ]


In 2006, the Lifepak 1000 was introduced to replace the Lifepak 500 in the professional AED market. [ 8 ]


In 2008, the Lifepak 15 was introduced to replace the Lifepak 12 in the prehospital and hospital settings and featured a more refined design, color LCD display, CPR metronome and  Bluetooth  connectivity for wireless transmission of ECGs. The 15 was also the first model to support  Masimo   RainbowSET  pulse oximetry. [ 9 ]


The newest model, Lifepak 35, was introduced in 2024 and features a complete redesign from earlier models including omitting most of the hard button controls and instead using a touchscreen to control most functions of the device. The 35 also features a diagnostic quality LCD display, cprINSIGHT and STJInsight technologies, pediatric AED protocols, and live 12 or 15 lead ECGs. [ 10 ]


Advanced models include the Lifepak 12, 15, 20, and 35 for use by healthcare professionals such as  emergency medical technicians  and  paramedics .  Automatic  units include the Lifepak 500, Lifepak 1000, Lifepak CR Plus and the Lifepak CR2 for use by members of the public who have been trained to operate them. [ 11 ]


Most Lifepak defibrillators are capable of performing more than only defibrillation. Many models allow for  cardiac monitoring  (including heart rate monitoring and 12-Lead  ECG  acquisition and interpretation) and alert the users to sudden changes. The Lifepak 15, 20/20e, 35 and CR2 include a CPR metronome that is also capable of verbally aiding rescuers in providing ventilations. Advanced Lifepak monitor/defibrillators also include options for  synchronized cardioversion ,  external pacing , oxygen saturation monitoring,  End tidal CO2 , and both non-invasive and invasive blood pressure. [ 12 ]  The Lifepak CR2 and 35 include CPRInsight analysis technology which allows for chest compression during analysis of the patient's  ECG . [ 13 ]


In the 1975 film  Three Days of the Condor , several Lifepak 911 monitors are used in an  ICU . One of them sounds an alarm when a patient is murdered.


Macroshock  is a medical term for the effects of body exposed to electrical current, which can lead to severe injury or death by  electrocution . It is used most often in the medical field, but is also commonly used in the fields of electrophysiology and bioengineering. [ 1 ] [ better source needed ]  Definitions of the term are inconsistent; there are three most commonly accepted definitions. Depending upon the medical text used, a macroshock is either:


Possible sources of macroshock include: poorly designed or malfunctioning  electrophysiology  equipment,  lightning , damaged power cords or other electrical hazards around the household, downed power lines, high-voltage electrical equipment such as transformer stations and other industrial electrical equipment, and malfunctioning electrical or electricity-using mechanical equipment capable of delivering a strong current, or which operates at a high voltage.


Microshock  refers to the risk that patients undergoing medical procedures involving externally protruding intracardiac  electrical conductors , such as external  pacemaker   electrodes , or  saline  filled  catheters , could suffer an electric shock causing ventricular fibrillation (VF) due to currents entering the body via these parts. [ 1 ]


It is important to note that microshock (or micro-shock) are not IEV [ 2 ]  defined terms and are not used in any international standard.


"Micro-shock" is an otherwise imperceptible electric current applied directly, or in very close proximity, to the heart muscle of sufficient strength, frequency, and duration to cause disruption of normal cardiac function.


Note: It can be safely assumed (and it usually is) that micro-shock is only possible during certain medical procedures as the electric current needs to be focused directly into the heart by some conductor inserted by invasive means for some desired medical outcome (for example Cardiac Catheterisation).


Micro-shock, if it occurs, is not always lethal. “ Micro-electrocution ” is the term that should be used whenever a micro-shock causes death.


“ Macro-shock ” is when a much larger current is passed through the body, usually via a skin to skin pathway, but more generally the current is not applied directly through the heart muscle. The current in macro-shock events can vary widely from being imperceptible to being extremely destructive of tissue. (see  Macroshock )


“ Electric Shock ” is usually referring to macro-shock. (see  Electric Shock )


“ Electrocution ” is usually referring to a macro-shock that has caused prolonged or severe disruption of normal cardiac function - ultimately leading to death. (see  Electrocution )


Microschock requires direct electrical connection to the heart muscle and is normally illustrated using a diagram such as Figure 1 (from TGE).


(an image is to be uploaded here shortly)


In this scenario the patient has inadvertently contacted both a source of current (it does not have to be AC, as shown) as well as a common return pathway during an invasive cardiac medical procedure. If the current flowing is below the threshold of perception, or the patient is sedated, or anaesthetized, there may be no pain or reflex response of either arm. If the current flow continues for sufficient time, at sufficient strength, the patient may die. Because of the low current and lack of patient response, this death may be unexpected, and without any obvious cause. In practice, however, this has never been proven to have happened. [ 3 ]


To a novice, however, this scenario looks incredibly dangerous, and it is therefore worth examining in some detail.


Firstly, let's follow the path of the electric current. There is a generic source of current. This source can be either large or small, as only a small voltage is required to drive the low current for micro-shock. Such sources might be, a wall socket, a faulty item of equipment, an inappropriate item of equipment, a poorly designed item of equipment, or an item of equipment designed to deliver current into the body. Our patient has unfortunately been contacted to one such electrical source and current is dispersing through their right arm and upper torso, to eventually converge on a catheter (as labelled – but it could be a lead or wire) that is placed into their heart. This concentration of current flow at the heart muscle is the danger from micro-shock.  If the catheter is conductive (from end to end) insulated in its passage through the body, the current may follow the catheter, emerging through the skin into some other energized item of equipment. For the circuit as shown to be complete, the loop needs to also be connected to the same ground/low-potential as the equipment. Finally, the hazardous circuit is complete – current can flow and if it continues the patient is in mortal danger. Again, while this is theoretically possible this has never been proven to have actually happened. [ 3 ]  Proving this type of event after the fact is difficult in autopsy, as the cause of the fatal  ventricular fibrillation  would be unknown and the death appears to be idiopathic.


So, why has this situation not arisen? Generally, electrically conductive connections made in or around a patient's heart will be those of medical-grade electrical equipment. In countries that have a regulatory environment (example: such as much of Europe and North America) micro-shock is contemplated and the surgical equipment is regulated to prevent micro-shock. These medical-grade products are generally constructed to strict standards that limit the allowable currents flowing via such connections (applied parts). This decreases the risk to the patient and increases the margin of safety.


There has never been a documented case of microshock. A U.S. Senate inquiry in the early 1970s, sparked by exaggerated reports of thousands of U.S. hospital patients dying of microshock, heard expert testimony about the effect. A review of the evidence in the early 2000s found that not a single case had been reported in the 30 years since the Senate inquiry. [ 4 ]  Regular checks of the FDA's MAUDE database also show no evidence of this risk being manifest, before or since the review.


Based on studies with dogs by Prof Leslie Geddes in the middle of last century, it is theorised that a current as low as 10 μA ( microampere ) directly through the  heart , may send a human patient directly into  ventricular fibrillation . Of course, the exact outcome is dependent on the duration of the current, the exact position of contact, the frequency of current oscillation, and the timing of the shock with the heart's rhythm e.g. R on T phenomenon. It is feared that such a small current may be introduced unwittingly, and unobserved, creating a very perilous situation for the patient. To guard against this slim theoretical possibility then, modern medical devices include a range of protective measures to limit current in cardiac-connected circuits to the assumed safe levels of below 10 μA ( microampere ). These measures include isolated patient connections, high impedance connections and current limiting circuits. Despite the in-built protections, and lack of observed incidents, microshock continues to be a concern to many practitioners of the fields of Biomedical and Clinical Engineering.


Despite the evidence of decades of absence of reports, in any condition where electrical conductors are run into the body in proximity of the heart (i.e. cardiac catheterizations) precautions are still taken to ensure hazardous current is not introduced through these conductors and it is still regarded as a high-risk activity.


Microvasculature remodeling  refers to the alterations in a blood vessel network resulting from  arteriogenesis  and  angiogenesis .  Briefly, arteriogenesis is an increase in arterial diameter while angiogenesis is an increase in the number of capillaries either by sprouting from or splitting existing capillaries.  External events stimulate these two types of vessel growth through a combination of mechanical and chemical pathways (Prior et al., 2004).


The  mini-maze procedures  are  cardiac surgery  procedures intended to cure  atrial fibrillation  (AF), a common disturbance of heart rhythm.  They are procedures derived from the original maze procedure developed by  James Cox, MD .


James Cox, MD , and associates developed the "maze" or "Cox maze" procedure, an "open-heart"  cardiac surgery  procedure intended to eliminate  atrial fibrillation , and performed the first one in 1987. [ 1 ]  "Maze" refers to the series of incisions arranged in a maze-like pattern in the  atria . The intention was to eliminate AF by using incisional scars to block abnormal electrical circuits (atrial macroreentry) that AF requires. This required an extensive series of  endocardial  (from the inside of the heart) incisions through both atria, a median sternotomy (vertical incision through the breastbone) and  cardiopulmonary bypass  (heart-lung machine;  extracorporeal circulation ). A series of improvements were made, culminating in 1992 in the Cox maze III procedure, originally a cut-and-sew procedure, but later performed with cryosurgical lesions. [ 2 ]  In 2002 Maze IV was first used combining  bipolar radiofrequency  clamps with linear cryoprobes. [ 2 ]  Cox-Maze IV is now considered to be the "gold standard" for effective surgical cure of AF, but the results are institution dependent. [ 3 ]   It was quite successful in eliminating AF, but had drawbacks as well. [ 4 ]  The Cox maze III is sometimes referred to as the "Traditional maze", the "cut and sew maze", or simply the "maze". [ citation needed ]


Efforts have since been made to equal the success of the Cox maze III while reducing surgical complexity and likelihood of complications. During the late 1990s, operations similar to the Cox maze, but with fewer  atrial  incisions, led to the use of the terms "minimaze", "mini maze" and "mini-maze", [ 5 ]  although these were still major operations.


A primary goal has been to perform a curative, "maze-like" procedure  epicardially  (from the outside of the heart), so that it could be performed on a normally beating heart, without cardiopulmonary bypass. Until recently this was not thought possible; as recently as 2004, Dr. Cox defined the mini-maze as requiring an  endocardial  approach: [ citation needed ]


"In summary, it would appear that placing the following lesions can cure most patients with  atrial fibrillation  of either type:  pulmonary vein  encircling incision, left atrial isthmus lesion with its attendant coronary sinus lesion, and the right  atrial  isthmus lesion. We call this pattern of  atrial  lesions the "mini-maze Procedure" ... None of the present energy sources—including cryotherapy, unipolar radiofrequency, irrigated radiofrequency, bipolar radiofrequency, microwave, and laser energy—are capable of creating the left atrial isthmus lesion from the epicardial surface, because of the necessity of penetrating through the circumflex  coronary artery  to reach the left atrial wall near the posterior  mitral  annulus. Therefore, the mini-maze procedure cannot be performed epicardially by means of any presently available energy source." [ 6 ]


Although Dr. Cox's 2004 definition specifically excludes an epicardial approach to eliminate AF, he and others pursued this important goal, and the meaning of the term changed as successful epicardial procedures were developed. In 2002 Saltman performed a completely  endoscopic  surgical  ablation  of AF [ 7 ]  and subsequently published their results in 14 patients. [ 8 ]  These were performed epicardially, on the beating heart,  without cardiopulmonary bypass or median sternotomy . Their method came to be known as the minimaze or microwave minimaze procedure, because  microwave energy  was used to make the lesions that had previously been performed by the surgeon's scalpel.


Shortly thereafter,  Randall K. Wolf , MD and others developed a procedure using  radiofrequency  energy rather than microwave, and different, slightly larger incisions. In 2005, he published his results in the first 27 patients. [ 9 ]   This came to be known as the Wolf minimaze procedure. [ citation needed ]


Today, the terms "minimaze", "mini-maze", and "mini maze" are still sometimes used to describe open heart procedures requiring cardiopulmonary bypass and median sternotomy, but more commonly they refer to minimally invasive, epicardial procedures not requiring cardiopulmonary bypass, such as those developed by Saltman, Wolf, and others. These procedures are characterized by:


Completely Endoscopic Microwave Ablation of Atrial Fibrillation on the Beating Heart Using Bilateral Thoracoscopy:  The microwave minimaze requires three 5 mm to 1 cm incisions on each side of the chest for the surgical tools and the  endoscope . The  pericardium  is entered, and two sterile rubber tubes are threaded behind the heart, in the transverse and oblique sinuses.  These tubes are joined, then used to guide the flexible  microwave  antenna energy source through the sinuses behind the heart, to position it for  ablation . Energy is delivered and the  atrial  tissue heated and destroyed in a series of steps as the  microwave  antenna is withdrawn behind the heart. The lesions form a "box-like" pattern around all four  pulmonary veins  behind the heart. The left atrial appendage is usually removed. [ 7 ] [ 8 ]


Video-assisted Bilateral Epicardial Bipolar Radiofrequency Pulmonary Vein Isolation and Left Atrial Appendage Excision:  The Wolf minimaze requires one 5 cm and two 1 cm incisions on each side of the chest. These incisions allow the surgeon to maneuver the tools, view areas through an  endoscope , and to see the heart directly. The right side of the left  atrium  is exposed first. A clamp-like tool is positioned on the left  atrium  near the right  pulmonary veins , and the  atrial  tissue is heated between the jaws of the clamp, cauterizing the area. The clamp is removed. The  autonomic  nerves ( ganglionated plexi ) that may cause AF [ 10 ]  may be eliminated as well. Subsequently, the left side of the chest is entered. The ligament of Marshall (a vestigial structure with marked  autonomic  activity) is removed. The clamp is subsequently positioned on the left  atrium  near the left  pulmonary veins  for  ablation . Direct testing to demonstrate complete electrical isolation of the  pulmonary veins , and that the ganglionated plexi are no longer active, may be performed. [ 9 ]


Surgical ablation of atrial fibrillation with off-pump, epicardial,  high-intensity focused ultrasound :  Although the HIFU minimaze is performed epicardially, on the normally beating heart, it is also usually performed in conjunction with other  cardiac surgery , and so would not be minimally invasive in those cases. An  ultrasonic  device is positioned epicardially, on the left  atrium , around the  pulmonary veins , and intense acoustic energy is directed at the  atrium  to destroy tissue in the appropriate regions near the  pulmonary veins . [ 11 ]


The mechanism by which AF is eliminated by curative procedures such as the maze, minimaze, or  catheter ablation  is controversial.  All successful methods destroy tissue in the areas of the left  atrium  near the junction of the  pulmonary veins , hence these regions are thought to be important.  A concept gaining support is that paroxysmal AF is mediated in part by the  autonomic nervous system [ 10 ]  and that the intrinsic cardiac nervous system, which is located in these regions, plays an important role. [ 12 ]  Supporting this is the finding that targeting these autonomic sites improves the likelihood of successful elimination of AF by  catheter ablation . [ 13 ] [ 14 ]


The minimaze procedures are alternatives to  catheter ablation  of AF, and the patient selection criteria are similar.  Patients are considered for minimaze procedures if they have moderate or severe symptoms and have failed medical therapy; asymptomatic patients are generally not considered.  Those most likely to have a good outcome have paroxysmal (intermittent) AF, and have a heart that is relatively normal. Those with severely enlarged  atria , [ 15 ]  marked  cardiomyopathy , or severely leaking  heart valves  are less likely to have a successful result; these procedures are generally not recommended for such patients. Previous  cardiac surgery  provides technical challenges due to scarring on the outside of the heart, but does not always preclude minimaze surgery. [ citation needed ]


A 2013 review found the results of the minimally-invasive mini-maze procedure to be intermediate between the standard maze procedure and catheter ablation. [ 16 ]


Long-term success of the minimaze procedures awaits a consensus. Attaining a consensus is hindered by several problems; perhaps the most important of these is incomplete or inconsistent post-procedure follow-up to determine if  atrial fibrillation  has recurred, although many reasons have been considered. [ 17 ]  It has been clearly demonstrated that longer or more intensive follow-up identifies much more recurrent  atrial fibrillation , [ 18 ]  hence a procedure with more careful follow-up will appear to be less successful. In addition, procedures continue to evolve rapidly, so long follow-up data do not accurately reflect current procedural methods. For more recent minimaze procedures, only relatively small and preliminary reports are available. With those caveats in mind, it can be said that reported short-term freedom from  atrial fibrillation  following the radiofrequency ("Wolf") procedure ranges from 67% to 91%  [ 8 ] [ 9 ] [ 11 ]  with longer-term results in a similar range, but limited primarily to patients with paroxysmal  atrial fibrillation . [ 19 ] [ 20 ]


The  monodomain model  is a reduction of the  bidomain model  of the electrical propagation in myocardial tissue.
The reduction comes from assuming that the intra- and extracellular domains have equal anisotropy ratios.
Although not as physiologically accurate as the  bidomain model , it is still adequate in some cases, and has reduced complexity. [ 1 ]


Being

 T

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 {\displaystyle {\frac {\lambda }{1+\lambda }}\nabla \cdot \left(\mathbf {\Sigma } _{i}\nabla v\right)=\chi \left(C_{m}{\frac {\partial v}{\partial t}}+I_{\text{ion}}\right)\quad \quad {\text{in }}\mathbb {T} \times (0,T),}


where

 Σ

 i

 {\displaystyle \mathbf {\Sigma } _{i}}

  is the intracellular conductivity tensor,

 v

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 I

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  is the transmembrane ionic current per unit area,

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  is the membrane capacitance per unit area,

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  is the intra- to extracellular conductivity ratio, and

 χ

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  is the membrane surface area per unit volume (of tissue). [ 1 ]


The monodomain model can be easily derived from the  bidomain model . This last one can be written as [ 1 ]

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 {\displaystyle {\begin{aligned}\nabla \cdot \left(\mathbf {\Sigma } _{i}\nabla v\right)+\nabla \cdot \left(\mathbf {\Sigma } _{i}\nabla v_{e}\right)&=\chi \left(C_{m}{\frac {\partial v}{\partial t}}+I_{\text{ion}}\right)\\\nabla \cdot \left(\mathbf {\Sigma } _{i}\nabla v\right)+\nabla \cdot \left(\left(\mathbf {\Sigma } _{i}+\mathbf {\Sigma } _{e}\right)\nabla v_{e}\right)&=0\end{aligned}}}


Assuming equal anisotropy ratios, i.e.

 Σ

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 {\displaystyle \nabla \cdot \left(\mathbf {\Sigma } _{i}\nabla v_{e}\right)=-{\frac {1}{1+\lambda }}\nabla \cdot \left(\mathbf {\Sigma } _{i}\nabla v\right).}


Then, inserting this into the first bidomain equation gives the unique equation of the monodomain model [ 1 ]

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 {\displaystyle {\frac {\lambda }{1+\lambda }}\nabla \cdot \left(\mathbf {\Sigma } _{i}\nabla v\right)=\chi \left(C_{m}{\frac {\partial v}{\partial t}}+I_{\text{ion}}\right).}


Differently from the bidomain model, the monodomain model is usually equipped with an isolated boundary condition, which means that it is assumed that there is not current that can flow from or to the domain (usually the heart). [ 3 ] [ 4 ]  Mathematically, this is done imposing a zero transmembrane potential flux (homogeneous  Neumann boundary condition ),  i.e. : [ 4 ]


where

 n

 {\displaystyle \mathbf {n} }

  is the unit outward normal of the domain and

 ∂

 T

 {\displaystyle \partial \mathbb {T} }

  is the domain boundary.


This  applied mathematics –related article is a  stub . You can help Wikipedia by  expanding it .


In  cardiology , the  P wave  on an  electrocardiogram  (ECG) represents  atrial depolarization , which results in atrial contraction, or  atrial systole .


The P wave is a summation wave generated by the depolarization front as it transits the atria. Normally the right atrium depolarizes slightly earlier than left atrium since the depolarization wave originates in the  sinoatrial node , in the high right atrium and then travels to and through the left atrium. The depolarization front is carried through the atria along semi-specialized conduction pathways including  Bachmann's bundle  resulting in uniform shaped waves. Depolarization originating elsewhere in the atria (atrial ectopics) result in P waves with a different morphology from normal.


Peaked P waves (> 0.25 mV) suggest right atrial enlargement,  cor pulmonale , ( P pulmonale  rhythm), [ 1 ]  but have a low predictive value (~20%). [ 2 ]


A P wave with increased amplitude can indicate  hypokalemia . [ 3 ]  It can also indicate  right atrial enlargement . [ 4 ]


A P wave with decreased amplitude can indicate  hyperkalemia . [ 5 ]


Bifid P waves (known as  P mitrale ) indicate left-atrial abnormality - e.g. dilatation  [ 6 ]  or hypertrophy. [ 1 ]


If at least three different shaped P waves can be seen in a given ECG lead tracing, this implies that even if one of them arises from the SA node, at least two others are arising elsewhere. This is taken as evidence of multiple (i.e. at least two)  ectopic foci , and is called multifocal (or more correctly, multiform) atrial rhythm if the rate is ≤100) or  multifocal atrial tachycardia  if the rate is over 100. [ 7 ]  This appears particularly commonly in exacerbations of  chronic obstructive lung disease . [ 8 ]


If the baseline has a totally irregular form, this suggests fibrillatory waves of  atrial fibrillation  or possibly artefact; a saw tooth shaped baseline suggests the flutter waves of  atrial flutter . With either of these rhythms, if the ventricular rate is fast, the fibrillatory or flutter waves can easily be misinterpreted as P waves.


Absence of the  P wave  with a flat  baseline  may indicate:


If P waves are not clearly delineated in the surface ECG, a  Lewis lead  may be used to better visualize P waves.


This occurs a mean of 320 ms after the end of the P wave, with a duration of 2-3 times that of the P wave and a polarity always opposite to that of the P wave. It is represented on the surface ECG by a so-called Ta wave. The clinical relevance of this is that, although a normal phenomenon, the nadir of the Ta wave can occur just after the QRS complex and cause ST depression similar to (and easily mistaken with) that occurring with disease states such as cardiac ischaemia. [ 9 ]


An  artificial cardiac pacemaker , commonly referred to as simply a  pacemaker , is an  implanted   medical device  that generates  electrical pulses  delivered by  electrodes  to one or more of the  chambers of the heart . Each pulse causes the targeted chamber(s) to  contract  and pump blood, [ 3 ]  thus regulating the function of the  electrical conduction system of the heart .


The primary purpose of a pacemaker is to maintain an even  heart rate , either because the heart's natural  cardiac pacemaker  provides an inadequate or irregular heartbeat, or because there is a  block  in the heart's electrical conduction system. Modern pacemakers are externally programmable and allow a cardiologist to select the optimal pacing modes for individual patients. Most pacemakers are on demand, in which the stimulation of the heart is based on the dynamic demand of the  circulatory system . Others send out a fixed rate of impulses. [ 4 ]


A specific type of pacemaker, called an  implantable cardioverter-defibrillator , combines pacemaker and  defibrillator  functions in a single  implantable device . [ 5 ]  Others, called  biventricular pacemakers , have multiple electrodes stimulating different positions within the ventricles (the lower heart chambers) to improve their synchronization. [ 6 ]


Percussive pacing, also known as transthoracic mechanical pacing, is the use of the closed fist, usually on the left lower edge of the  sternum  over the  right ventricle  in the  vena cava , striking from a distance of 20 – 30 cm to induce a ventricular beat (the  British Journal of Anaesthesia  suggests this must be done to raise the ventricular pressure to 10–15 mmHg to induce electrical activity). This is an old procedure used only as a life-saving means until an electrical pacemaker is brought to the patient. [ 7 ]


Transcutaneous pacing (TCP), also called external pacing, is recommended for the initial stabilization of hemodynamically significant  bradycardias  of all types. The procedure is performed by placing two pacing pads on the patient's chest, either in the anterior/lateral position or the anterior/posterior position. The rescuer selects the pacing rate, and gradually increases the pacing current (measured in mA) until electrical capture (characterized by a wide  QRS complex  with a tall, broad  T wave  on the  ECG ) is achieved, with a corresponding pulse. Pacing artifact on the ECG and severe muscle twitching may make this determination difficult. External pacing should not be relied upon for an extended period of time. It is an emergency procedure that acts as a bridge until transvenous pacing or other therapies can be applied. [ 8 ]


Temporary epicardial pacing is used during open heart surgery should the surgical procedure create atrio-ventricular block. The electrodes are placed in contact with the outer wall of the ventricle (epicardium) to maintain satisfactory cardiac output until a temporary transvenous electrode has been inserted. [ 9 ]


Transvenous pacing, when used for temporary pacing, is an alternative to transcutaneous pacing. A pacemaker wire is placed into a vein, under sterile conditions, and then passed into either the right atrium or right ventricle. The pacing wire is then connected to an external pacemaker outside the body. Transvenous pacing is often used as a bridge to permanent pacemaker placement. It can be kept in place until a permanent pacemaker is implanted or until there is no longer a need for a pacemaker and then it is removed.


Permanent pacing with an implantable pacemaker involves transvenous placement of one or more pacing electrodes within a chamber, or chambers, of the heart, while the pacemaker is implanted under the skin below the clavicle. The procedure is performed by incision of a suitable vein into which the electrode  lead  is inserted and passed along the vein, through the valve of the heart, until positioned in the chamber. The procedure is facilitated by  fluoroscopy  which enables the physician to view the passage of the electrode lead. After satisfactory lodgement of the electrode is confirmed, the opposite end of the electrode lead is connected to the pacemaker generator.


There are three basic types of permanent pacemakers, classified according to the number of  chambers  involved and their basic operating mechanism: [ 10 ]


The pacemaker generator is a  hermetically sealed  device containing a power source, usually a  lithium battery , a sensing amplifier which processes the electrical manifestation of naturally occurring heart beats as sensed by the heart electrodes, the  computer  logic for the pacemaker and the output circuitry which delivers the pacing impulse to the electrodes.


Most commonly, the generator is placed below the subcutaneous fat of the chest wall, above the muscles and bones of the chest. However, the placement may vary on a case-by-case basis.


The outer casing of pacemakers is so designed that it will rarely be rejected by the body's  immune system . It is usually made of  titanium , which is inert in the body.


Leadless pacemakers are devices that are as small as a capsule and are small enough to allow the generator to be placed within the heart, therefore avoiding the need for pacing leads. [ 11 ]     As pacemaker leads can fail over time, a pacing system that avoids these components offers theoretical advantages.  Leadless pacemakers can be implanted into the heart using a steerable catheter fed into the  femoral vein  via an incision in the groin. [ 11 ]


Modern pacemakers usually have multiple functions. The most basic form monitors the heart's native electrical rhythm. When the pacemaker wire or "lead" does not detect heart electrical activity in the chamber – atrium or ventricle – within a normal beat-to-beat time period – most commonly one second – it will stimulate either the atrium or the ventricle with a short low voltage pulse. If it does sense electrical activity, it will hold off stimulating. This sensing and stimulating activity continues on a beat by beat basis and is called "demand pacing". In the case of a dual-chamber device, when the upper chambers have a spontaneous or stimulated activation, the device starts a countdown to ensure that in an acceptable – and programmable – interval, there is an activation of the ventricle, otherwise again an impulse will be delivered.


The more complex forms include the ability to sense and/or stimulate both the atrial and ventricular chambers.


From this the basic ventricular "on demand" pacing mode is VVI or with automatic rate adjustment for exercise VVIR – this mode is suitable when no synchronization with the atrial beat is required, as in atrial fibrillation. The equivalent atrial pacing mode is AAI or AAIR which is the mode of choice when atrioventricular conduction is intact but the  sinoatrial node  of the natural pacemaker is unreliable – sinus node disease (SND) or  sick sinus syndrome . Where the problem is  atrioventricular block  (AVB) the pacemaker is required to detect (sense) the atrial beat and after a normal delay (0.1–0.2 seconds) trigger a ventricular beat, unless it has already happened – this is VDD mode and can be achieved with a single pacing lead with electrodes in the right atrium (to sense) and ventricle (to sense and pace). These modes AAIR and VDD are unusual in the US but widely used in Latin America and Europe. [ 13 ] [ 14 ]  The DDDR mode is most commonly used as it covers all the options though the pacemakers require separate atrial and ventricular leads and are more complex, requiring careful programming of their functions for optimal results.


Automatic pacemakers are designed to be over-ridden by the heart's natural rate at any moment that it gets back to a non-pathologic  normal sinus rhythm  and can reinitiate influencing the electric activity in the heart when the pathologic event happens again. [ 15 ]  A " ventricular -demand pacemaker" produces a narrow vertical spike on the  ECG , just before a wide  QRS . The spike of an " atrial -demand pacemaker" appears just before the  P wave . [ 16 ]


Comparably, a  Triggered Pacemaker  is activated immediately after an electrical activity is commenced in the heart tissue by itself. A "ventricular triggered pacemaker" produces the impulse just after a pulse is created in the ventricular tissue and it appears as a simultaneous spike with QRS. An "atrial triggered pacemaker" is the mode in which an impulse is produced immediately after an electrical event in the atrium. It appears as a  discharge  following the p wave but prior to the QRS which is commonly widened. [ 17 ]


Cardiac resynchronization therapy (CRT) is used for people with  heart failure  in whom the left and right ventricles do not contract simultaneously ( ventricular dyssynchrony ), which occurs in approximately 25–50% of heart failure patients. To achieve CRT, a biventricular pacemaker (BVP) is used, which can pace both the  septal  and lateral walls of the  left ventricle . By pacing both sides of the left ventricle, the pacemaker can resynchronize the ventricular contractions.


CRT devices have at least two leads, one passing through the  vena cava  and the  right atrium  into the  right ventricle  to stimulate the  septum , and another passing through the  vena cava  and the right atrium and inserted through the  coronary sinus  to pace the epicardial wall of the left ventricle. Often, for patients in normal sinus rhythm, there is also a lead in the right atrium to facilitate synchrony with the atrial contraction. Thus, the timing between the atrial and ventricular contractions, as well as between the septal and lateral walls of the left ventricle can be adjusted to achieve optimal cardiac function.


CRT devices have been shown to reduce mortality and improve quality of life in patients with heart failure symptoms; a LV ejection fraction less than or equal to 35% and QRS duration on EKG of 120 ms or greater. [ 18 ] [ 19 ]


Biventricular pacing alone is referred to as CRT-P (for pacing). For selected patients at risk of arrhythmias, CRT can be combined with an  implantable cardioverter-defibrillator  (ICD): such devices, known as CRT-D (for defibrillation), also provide effective protection against life-threatening arrhythmias. [ 20 ]


Conventional placement of ventricular leads in or around the tip or  apex  of the right ventricle, or RV apical pacing, can have negative effects on heart function. It has been associated with increased risk of  atrial fibrillation ,  heart failure , weakening of the heart muscle and potentially shorter life expectancy.  His bundle pacing  (HBP) leads to a more natural or perfectly natural ventricular activation and has generated strong research and clinical interest. By stimulating the  His–Purkinje  fiber network directly with a special lead and placement technique, HBP causes a synchronized and therefore more effective ventricular activation and avoids long-term heart muscle disease. HBP in some cases can also correct  bundle branch block  patterns. [ 21 ] [ 22 ]


A major step forward in pacemaker function has been to attempt to mimic nature by utilizing various inputs to produce a rate-responsive pacemaker using parameters such as the  QT interval , pO 2  – pCO 2  (dissolved  oxygen  or  carbon dioxide  levels) in the arterial-venous system, physical activity as determined by an  accelerometer ,  body temperature ,  ATP  levels,  adrenaline , etc.
Instead of producing a static, predetermined heart rate, or intermittent control, such a pacemaker, a 'Dynamic Pacemaker', could compensate for both actual respiratory loading and potentially anticipated respiratory loading. The first dynamic pacemaker was invented by Anthony Rickards of the  National Heart Hospital , London, UK, in 1982. [ 23 ]


Dynamic pacemaking technology could also be applied to future  artificial hearts . Advances in transitional tissue welding would support this and other artificial organ/joint/tissue replacement efforts. Stem cells may be of interest in transitional tissue welding. [ citation needed ]


Many advancements have been made to improve the control of the pacemaker once implanted. Many of these have been made possible by the transition to  microprocessor  controlled pacemakers. Pacemakers that control not only the ventricles but the  atria  as well have become common. Pacemakers that control both the atria and ventricles are called dual-chamber pacemakers. Although these dual-chamber models are usually more expensive, timing the contractions of the atria to precede that of the ventricles improves the pumping efficiency of the heart and can be useful in congestive heart failure.


Rate responsive pacing allows the device to sense the physical activity of the patient and respond appropriately by increasing or decreasing the base pacing rate via rate response algorithms.


The DAVID trials [ 24 ]  have shown that unnecessary pacing of the right ventricle can exacerbate  heart failure  and increases the incidence of atrial fibrillation. The newer dual-chamber devices can keep the amount of right ventricle pacing to a minimum and thus prevent worsening of the heart disease.


A pacemaker may be implanted whilst a person is awake using  local anesthetic  to numb the skin with or without  sedation , or asleep using a  general anesthetic . [ 25 ]  An antibiotic is usually given to reduce the risk of infection. [ 25 ]   Pacemakers are generally implanted in the front of the chest in the region of the left or right shoulder.  The skin is prepared by clipping or shaving any hair over the implant site before cleaning the skin with a disinfectant such as  chlorhexidine .  An incision is made below the collar bone and a space or pocket is created under the skin to house the pacemaker generator.  This pocket is usually created just above the  pectoralis major  muscle (prepectoral), but in some cases the device may be inserted beneath the muscle (submuscular). [ 26 ]  The  lead or leads  are fed into the heart through a large vein guided by X-ray imaging ( fluoroscopy ). The tips of the leads may be positioned within the  right ventricle , the  right atrium , or the coronary sinus, depending on the type of pacemaker required. [ 25 ]  Surgery is typically completed within 30 to 90 minutes.  Following implantation, the surgical wound should be kept clean and dry until it has healed.  Some movements of the shoulder within a few weeks of insertion carry a risk of dislodging the pacemaker leads. [ 25 ]


The batteries within a pacemaker generator typically last 5 to 10 years. When the batteries are nearing the end of life, the generator is replaced in a procedure that is usually simpler than a new implant. Replacement involves making an incision to remove the existing device, disconnecting the leads from the old device and reconnecting them to a new generator, reinserting the new device and closing the skin. [ 25 ]


Once the pacemaker is implanted, it is periodically checked to ensure the device is operational and performing appropriately; the device can be checked as often as is deemed necessary. Routine pacemaker checks are typically done in-office every six months, though will vary depending upon patient/device status and remote monitoring availability. Newer pacemaker models can also be interrogated remotely, with the patient transmitting their pacemaker data using a transmitter at home connected to a cellular telephone network.


During in-office follow-up, diagnostic tests may include:


A patient's lifestyle is usually not modified to any great degree after the insertion of a pacemaker. There are a few activities that are unwise, such as full-contact sports and exposure of the pacemaker to intense magnetic fields.


The pacemaker patient may find that some types of everyday actions need to be modified. For instance, the shoulder harness of a vehicle  seatbelt  may be uncomfortable if it falls across the pacemaker insertion site. Women will not be able to wear bras for a while after the operation, and later might have to wear bras with wide shoulder straps.


For some sports and physical activities, special pacemaker protection can be worn to prevent possible injuries, or damage to the pacemaker leads.


Pacemakers may be affected by  magnetic  or  electromagnetic fields , and  ionising  and  acoustic radiation . However, a 2013 study found that "The overall risk of clinically significant adverse events related to EMI (electromagnetic interference) in recipients of CIEDs (cardiovascular implantable electronic devices) is very low. Therefore, no special precautions are needed when household appliances are used. Environmental and industrial sources of EMI are relatively safe when the exposure time is limited and distance from the CIEDs is maximized. The risk of EMI-induced events is highest within the hospital environment." [ 27 ]  The study lists and tabulates many sources of interference, and many different potential effects: damage to circuitry, asynchronous pacing, etc. Some sources of hazard in older devices have been eliminated in newer ones.


Activities involving strong  magnetic fields  should be avoided. This includes activities such as  arc welding  with certain types of equipment, [ 28 ]  and maintaining heavy equipment that may generate strong magnetic fields. Some medical procedures, particularly  magnetic resonance imaging  (MRI), involve very strong magnetic fields or other conditions that may damage pacemakers.


However, many modern pacemakers are specified to be  MR conditional or MRI conditional , safe to use during MRI subject to certain conditions. [ 29 ]  The first to be so specified was the  Medtronic  Revo MRI SureScan, approved by the US FDA in February 2011, [ 30 ]  which was the first to be specified as MR conditional. [ 31 ] [ 32 ]  There are several conditions to use of MR Conditional pacemakers, including certain patients' qualifications and scan settings. An MRI conditional device has to have MRI settings enabled before a scan, and disabled afterwards. [ 33 ]


As of 2014 [update]  the five most commonly used cardiac pacing device manufacturers (covering more than 99% of the US market) made FDA-approved MR-conditional pacemakers. [ 34 ]  The use of MRI may be ruled out by the patient having an older, non-MRI Conditional pacemaker, or by having old pacing wires inside the heart, no longer connected to a pacemaker.


A 2008 US study found [ 35 ]  that the magnetic field created by some headphones used with portable music players or cellphones may cause interference if placed very close to some pacemakers.


In addition, according to the  American Heart Association , some home devices have the potential to occasionally inhibit a single beat. Cellphones do not seem to damage pulse generators or affect how the pacemaker works. [ 36 ]  It is recommended that objects containing magnets, or generating a significant magnetic field, should not be in close proximity to a pacemaker. Induction cooktops, in particular, can pose a risk. [ 37 ]


Before medical procedures, the patient should inform all medical personnel that they have a pacemaker. Having a pacemaker does not imply that a patient requires the use of  antibiotics  to be administered before procedures such as dental work. [ 38 ]


A panel of the  Heart Rhythm Society , a US specialist organization based in Washington, DC, deemed that it was legal and ethical to honor requests by patients, or by those with legal authority to make decisions for patients, to deactivate implanted cardiac devices. Lawyers say that the legal situation is similar to removing a feeding tube, though as of 2010 [update]  there was no legal precedent involving pacemakers in the United States. A patient in many jurisdictions (including the US) is deemed to have a right to refuse or discontinue treatment, including a pacemaker that keeps them alive. Physicians have a right to refuse to turn it off, but are advised by the HRS panel that they should refer the patient to a physician who will. [ 39 ] [ 40 ]  Some patients consider that hopeless, debilitating conditions, such as severe strokes or late-stage dementia, can cause so much suffering that they would prefer not to prolong their lives with supportive measures. [ 41 ]


Security and privacy concerns have been raised with pacemakers that allow wireless communication. Unauthorized third parties may be able to read patient records contained in the pacemaker, or reprogram the devices, as has been demonstrated by a team of researchers. [ 42 ]  The demonstration worked at short range; they did not attempt to develop a long range antenna. The proof of concept exploit helps demonstrate the need for better security and patient alerting measures in remotely accessible medical implants. [ 42 ]  In response to this threat, Purdue University and Princeton University researchers have developed a prototype firewall device, called MedMon, which is designed to protect wireless medical devices such as pacemakers and insulin pumps from attackers. [ 43 ]


Complications from having  surgery  to implant a  pacemaker  are uncommon (each 1-3% approximately), but could include: infection where the pacemaker is implanted or in the bloodstream;  allergic reaction  to the dye or  anesthesia  used during the procedure; swelling, bruising or bleeding at the generator site, or around the heart, especially if the patient is taking  blood thinners , elderly, of thin frame or otherwise on chronic  steroid  use. [ 45 ]


A possible complication of dual-chamber artificial pacemakers is 'pacemaker-mediated tachycardia' (PMT), a form of reentrant tachycardia. In PMT, the artificial pacemaker forms the anterograde (atrium to ventricle) limb of the circuit and the atrioventricular (AV) node forms the retrograde limb (ventricle to atrium) of the circuit. [ 46 ]  Treatment of PMT typically involves reprogramming the pacemaker. [ 46 ]


Another possible complication is "pacemaker-tracked tachycardia," where a  supraventricular tachycardia  such as  atrial fibrillation  or  atrial flutter  is tracked by the pacemaker and produces beats from a ventricular lead. [ 47 ]  This is becoming exceedingly rare as newer devices are often programmed to recognize supraventricular tachycardias and switch to non-tracking modes. [ 48 ]


It is important to consider leads as a potential nidus for  thromboembolic  events. The leads are small-diameter wires from the pacemaker to the implantation site in the heart muscle, and are usually placed intravenously through the  subclavian vein  in order to access the right atrium. Placing a foreign object within the venous system in such a manner may disrupt blood-flow and allow for thrombus formation. Therefore, patients with pacemakers may need to be placed on  anti-coagulation therapy to avoid potential life-threatening thrombosis or embolus. [ 49 ] [ 50 ]


These leads may also damage the  tricuspid valve leaflets , either during placement or through wear and tear over time. This can lead to  tricuspid regurgitation  and  right-sided heart failure , which may require  tricuspid valve replacement . [ 51 ]


Sometimes leads will need to be removed. The most common reason for lead removal is infection; however, over time, leads can degrade due to a number of reasons such as lead flexing. [ 52 ]  Changes to the programming of the pacemaker may overcome lead degradation to some extent. However, a patient who has several pacemaker replacements over a decade or two in which the leads were reused may require lead replacement surgery.


Lead replacement may be done in one of two ways. Insert a new set of leads without removing the current leads (not recommended as it provides additional obstruction to blood flow and heart valve function) or remove the current leads and then insert replacements. The lead removal technique will vary depending on the surgeon's estimation of the probability that simple traction will suffice to more complex procedures. Leads can normally be disconnected from the pacemaker easily, which is why device replacement usually entails simple surgery to access the device and replace it by simply unhooking the leads from the device to replace and hooking the leads to the new device. The possible complications, such as perforation of the heart wall, come from removing the lead{s} from the patient's body.


The free end of a pacemaker lead is actually implanted into the heart muscle with a miniature screw or anchored with small plastic hooks called tines. The longer the leads have been implanted (starting from a year or two), the more likely that they will have additional attachments to the patient's body at various places in the pathway from device to heart muscle, since the body tends to incorporate foreign devices into tissue. In some cases, for a lead that has been inserted for a short amount of time, removal may involve simple traction to pull the lead from the body. Removal in other cases is typically done with a laser or cutting device which threads like a cannula with a cutting edge over the lead and is moved down the lead to remove any organic attachments with tiny cutting lasers or similar device. [ 53 ] [ 54 ]


Pacemaker lead malposition in various locations has been described in the literature. Treatment varies, depending on the location of the pacer lead and symptoms. [ 55 ]


Another possible complication called  twiddler's syndrome  occurs when a patient manipulates the pacemaker and causes the leads to be removed from their intended location and causes possible stimulation of other nerves.


Overall life expectancy with pacemakers is excellent, and mostly depends upon underlying diseases, presence of atrial fibrillation, age and sex at the time of first implantation. [ 56 ]


Sometimes devices resembling pacemakers, called  implantable cardioverter-defibrillators  (ICDs) are implanted. These devices are often used in the treatment of patients at risk from sudden cardiac death. An ICD has the ability to treat many types of heart rhythm disturbances by means of pacing,  cardioversion , or  defibrillation . Some ICD devices can distinguish between ventricular fibrillation and  ventricular tachycardia  (VT), and may try to pace the heart faster than its intrinsic rate in the case of VT, to try to break the tachycardia before it progresses to ventricular fibrillation. This is known as  fast-pacing ,  overdrive pacing , or  anti-tachycardia pacing  (ATP). ATP is only effective if the underlying rhythm is ventricular tachycardia, and is never effective if the rhythm is ventricular fibrillation.


In 1889,  John Alexander MacWilliam  reported in the  British Medical Journal  (BMJ) of his experiments in which application of an electrical impulse to the human heart in  asystole  caused a  ventricular  contraction and that a heart rhythm of 60–70 beats per minute could be evoked by impulses applied at spacings equal to 60–70/minute. [ 58 ]


In 1926,  Mark C Lidwill  of the  Royal Prince Alfred Hospital  of Sydney, supported by physicist Edgar H. Booth of the  University of Sydney , devised a portable apparatus which "plugged into a lighting point" and in which "One pole was applied to a skin pad soaked in strong salt solution" while the other pole "consisted of a needle insulated except at its point, and was plunged into the appropriate cardiac chamber". "The pacemaker rate was variable from about 80 to 120 pulses per minute, and likewise the voltage variable from 1.5 to 120 volts". [ 59 ]  In 1928, the apparatus was used to revive a  stillborn  infant at  Crown Street Women's Hospital  in Sydney, whose heart continued "to beat on its own accord", "at the end of 10 minutes" of stimulation. [ 60 ] [ 61 ]


In 1932, American physiologist  Albert Hyman , with the help of his brother, described an electro-mechanical instrument of his own, powered by a spring-wound hand-cranked motor. Hyman himself referred to his invention as an "artificial pacemaker", the term continuing in use to this day. [ 62 ] [ 63 ]


An apparent  hiatus  in the publication of research conducted between the early 1930s and  World War II  may be attributed to the public perception of interfering with nature by "reviving the dead". [ 64 ]  For example, "Hyman did not publish data on the use of his pacemaker in humans because of adverse publicity, both among his fellow physicians, and due to newspaper reporting at the time. Lidwell may have been aware of this and did not proceed with his experiments in humans". [ 61 ]


In 1950, Canadian electrical engineer  John Hopps  designed and built the first external pacemaker based upon observations by cardio-thoracic surgeons  Wilfred Gordon Bigelow  and  John Callaghan  at  Toronto General Hospital . [ 65 ]  The device was first tested on a dog at the  University of Toronto 's Banting Institute. [ 66 ]  A substantial external device using  vacuum tube  technology to provide  transcutaneous pacing , it was somewhat crude and painful to the patient in use and, being powered from an AC wall socket, carried a potential hazard of  electrocution  of the patient and inducing  ventricular fibrillation . [ 67 ]


A number of innovators, including  Paul Zoll , made smaller but still bulky transcutaneous pacing devices from 1952 using a large rechargeable battery as the power supply. [ 68 ]


In 1957, William L. Weirich published the results of research performed at the  University of Minnesota . These studies demonstrated the restoration of heart rate, cardiac output and mean aortic pressures in animal subjects with complete  heart block  through the use of a  myocardial  electrode. [ 69 ]


In 1958 Colombian doctor Alberto Vejarano Laverde and Colombian electrical engineer  Jorge Reynolds Pombo  constructed an external pacemaker, similar to those of Hopps and Zoll, weighing 45 kg and powered by a 12 volt car  lead–acid battery , but connected to electrodes attached to the heart. This apparatus was successfully used to sustain a 70-year-old priest, Gerardo Florez. [ 70 ]


The development of the  silicon   transistor  and its first commercial availability in 1956 was the pivotal event that led to the rapid development of practical cardiac pacemaking. [ 71 ]


In 1958, engineer  Earl Bakken  of Minneapolis, Minnesota, produced the first wearable external pacemaker for a patient of  C. Walton Lillehei . This transistorized pacemaker, housed in a small plastic box, had controls to permit adjustment of pacing heart rate and output voltage and was connected to electrode  leads  which passed through the skin of the patient to terminate in electrodes attached to the surface of the  myocardium  of the heart.


In the UK in the 1960s, Lucas Engineering in  Birmingham  was asked by Mr Abrams of The  Queen Elizabeth Hospital  to produce a prototype for a transistorised replacement for the electro-mechanical product. The team was headed by Roger Nolan, an engineer with the Lucas Group Research Centre. Nolan designed and created the first blocking oscillator and transistor-powered pacemaker. This pacemaker was worn on a belt and powered by a rechargeable sealed battery, enabling users to live a more-normal life.


One of the earliest patients to receive this Lucas pacemaker device was a woman in her early 30s. The operation was carried out in 1964 by South African cardiac surgeon Alf Gunning, [ 72 ] [ 73 ]  a student of  Christiaan Barnard . This pioneering operation took place under the guidance of cardiac consultant  Peter Sleight  at the  Radcliffe Infirmary  in Oxford and his cardiac research team at St George's Hospital in London. [ 74 ] [ 75 ]


The first clinical implantation into a human of a fully implantable pacemaker was on October 8, 1958, [ 76 ]  at the  Karolinska Institute  in Solna,  Sweden , using a pacemaker designed by inventor  Rune Elmqvist  and surgeon  Åke Senning  (in collaboration with Elema-Schönander AB, later Siemens-Elema AB), connected to electrodes attached to the  myocardium  of the heart by  thoracotomy . The device failed after three hours. A second device was then implanted which lasted for two days. The world's first implantable pacemaker patient,  Arne Larsson , went on to receive 26 different pacemakers during his lifetime. He died in 2001, at the age of 86, outliving the inventor and the surgeon. [ 77 ]


In 1959, temporary  transvenous pacing  was first demonstrated by Seymour Furman and John Schwedel, whereby the  catheter  electrode was inserted via the patient's  basilic vein . [ 78 ]


In February 1960, an improved version of the Swedish Elmqvist design was implanted by Doctors  Orestes Fiandra  and Roberto Rubio in the Casmu 1 Hospital of  Montevideo , Uruguay. This pacemaker, the first implanted in the Americas, lasted until the patient died of other ailments, nine months later. The early Swedish-designed devices used batteries recharged by an induction coil from the outside.


Implantable pacemakers constructed by engineer  Wilson Greatbatch  entered use in humans from April 1960 following extensive  animal testing . The Greatbatch innovation varied from the earlier Swedish devices in using primary cells (a  mercury battery ) as the energy source. The first patient lived for a further 18 months.


The first use of  transvenous pacing  in conjunction with an implanted pacemaker was by  Parsonnet  in the United States, [ 79 ] [ 80 ] [ 81 ]  Lagergren in Sweden [ 82 ] [ 83 ]  and Jean-Jacques Welti in France [ 84 ]  in 1962–63.
The transvenous, or pervenous, procedure involved incision of a vein into which was inserted the  catheter  electrode lead under  fluoroscopic  guidance, until it was lodged within the  trabeculae  of the right ventricle. This became the method of choice by the mid-1960s.


Cardiothoracic surgeon  Leon Abrams  and medical engineer  Ray Lightwood  developed and implanted the first patient-controlled variable-rate heart pacemaker in 1960 at  the University of Birmingham . The first implant took place in March 1960, with two further implants the following month. These three patients made good recoveries and returned to a high quality of life. By 1966, 56 patients had undergone implantation with one surviving for over  5 + 1 ⁄ 2  years. [ 85 ] [ 86 ]


The preceding implantable devices all suffered from the unreliability and short lifetime of the available primary cell technology, mainly the  mercury battery . In the late 1960s, several companies, including  ARCO  in the US, developed  isotope-powered  pacemakers, but this development was overtaken by the development in 1971 of the  lithium iodide  cell by  Wilson Greatbatch . [ 88 ]  Lithium-iodide or lithium anode cells became the standard for pacemaker designs.


A further impediment to the reliability of the early devices was the diffusion of water vapor from body fluids through the  epoxy  resin encapsulation, affecting the electronic circuitry. This phenomenon was overcome by encasing the pacemaker generator in a hermetically sealed metal case, initially by  Telectronics  of Australia in 1969, followed by  Cardiac Pacemakers, Inc.  of  St. Paul, Minnesota  in 1972. This technology, using  titanium  as the encasing metal, became the standard by the mid-1970s.


On July 9, 1974,  Manuel A. Villafaña  and  Anthony Adducci , the founders of  Cardiac Pacemakers, Inc.  ( Guidant ), manufactured the world's first pacemaker with a lithium anode and a lithium-iodide electrolyte solid-state battery. Lithium-iodide or lithium anode cells increased the life of pacemakers from one year to as long as eleven years, and has become the standard for pacemaker designs. They began designing and testing their implantable cardiac pacemaker powered by a new longer-life lithium battery in 1971. The first patient to receive a CPI pacemaker emerged from surgery in June 1973. [ 87 ] [ 89 ]


Liza Morton was fitted with an implantable pacemaker at 11 days old in 1978, at Glasgow’s Yorkhill hospital, Scotland. She was the youngest baby at the time  [ 90 ]   [ 91 ]