In 2013, several firms announced devices that could be inserted via a leg catheter rather than invasive surgery. The devices are roughly the size and shape of a pill, much smaller than the size of a traditional pacemaker. Once implanted, the device's prongs contact the muscle and stabilize heartbeats. Development of this type of device was continuing. [ 92 ]  In November 2014, Bill Pike of  Fairbanks, Alaska , received a  Medtronic  Micra pacemaker in Providence St Vincent Hospital in  Portland, Oregon . D. Randolph Jones was the EP doctor. Also in 2014,  St. Jude Medical Inc.  announced the first enrollments in the company's leadless Pacemaker Observational Study evaluating the Nanostim leadless pacing technology. The Nanostim pacemaker received European  CE marking  in 2013. Post-approval implant trials were carried out in Europe. [ 93 ]  The European study was stopped after reports of six perforations that led to two patient deaths. After investigations, St Jude Medical restarted the study. [ 94 ]  In the United States, this therapy had not been approved by the FDA as of 2014 [update] . [ 95 ]  While the St Jude Nanostim and the Medtronic Micra are single-chamber pacemakers, it was anticipated that leadless dual-chamber pacing for patients with atrioventricular block would become possible with further development. [ 96 ]


Worldwide each year, in a simple procedure to avoid explosions, thousands of pacemakers are removed from bodies to be cremated. Pacemakers with significant remaining battery life are potentially life-saving devices for people in low- and middle-income countries (LMICs). [ 97 ]  The  Institute of Medicine , a US  non-governmental organization , has reported that inadequate access to advanced cardiovascular technologies is a major contributor to cardiovascular disease morbidity and mortality in LMICs. Ever since the 1970s, multiple studies worldwide have reported on the safety and efficacy of pacemaker reuse. As of 2016 [update] , widely acceptable standards for safe pacemaker and ICD reuse had not been developed, and there continued to be legal and regulatory barriers to widespread adoption of medical device reuse. [ 98 ]


Current and prior manufacturers of implantable pacemakers


A  pacemaker action potential  is the kind of  action potential  that provides a reference rhythm for the network. The pacemaker potential is the slow depolarization because of sodium influx, and once threshold has been reached the continued depolarization due to calcium influx. [ 1 ]  Repolarization follows, which is due to the efflux of potassium, which allows for the membrane potential to return to its negative voltage. Additionally, the longer the action potential duration the slower the heart rate will be. [ 2 ]  This means that it takes longer for the threshold to be reached because of the slow influx of sodium and the calcium and potassium channels opening at a later time. This contrasts with  pacemaker potential  or current which drives rhythmic modulation of firing rate.


Some pacemaker action generate rhythms for the heart beat ( sino-atrial node ) or the  circadian rhythm  in the  suprachiasmatic nucleus .


In the  pacemaking cells  of the  heart  (e.g., the  sinoatrial node ), the  pacemaker potential  (also called the  pacemaker current ) is the slow, positive increase in voltage across the  cell 's membrane, that occurs between the end of one  action potential  and the beginning of the next. It is responsible for the self-generated rhythmic firing ( automaticity ) of pacemaker cells.


The  cardiac pacemaker  is the  heart 's natural rhythm generator. It employs pacemaker  cells  that generate electrical impulses, known as  cardiac action potentials . These potentials cause the  cardiac muscle  to contract, and the rate of which these muscles contract determines the  heart rate .


As with any other cells, pacemaker cells have an electrical charge on their membranes. This electrical charge is called the  membrane potential . After the firing of an action potential, the pacemaking cell's membrane  repolarizes  (decreases in voltage) to its  resting potential  of -60 mV. From here, the membrane gradually  depolarizes  (increases in voltage) to the  threshold potential  of -40 mV, [ 1 ]  upon which the cell would go on to fire the next action potential. The rate of depolarization is the slope: the faster voltage increases, the steeper the slopes are in graphs. The slope determines the time taken to reach the threshold potential, and thus the timing of the next action potential. [ 2 ]


In a healthy sinoatrial node (SAN, a complex tissue within the right atrium containing pacemaker cells that normally determine the intrinsic firing rate for the entire heart [ 3 ] [ 4 ] ), the pacemaker potential is the main determinant of the heart rate. Because the pacemaker potential represents the non-contracting time between heart beats ( diastole ), it is also called the  diastolic depolarization .
The amount of net inward current required to move the cell membrane potential during the pacemaker phase is extremely small, in the order of few pAs, but this net flux arises from time to time changing contribution of several currents that flow with different voltage and time dependence. Evidence in support of the active presence of K + , Ca 2+ , Na +  channels and Na + /K +  exchanger during the pacemaker phase have been variously reported in the literature, but several indications point to the “funny”(I f ) current as one of the most important. [ 5 ] (see  funny current ). There is now substantial evidence that also sarcoplasmic reticulum (SR) Ca 2+ -transients participate to the generation of the diastolic depolarization via a process involving the Na–Ca exchanger.


The rhythmic activity of some  neurons  like the  pre-Bötzinger complex  is modulated by neurotransmitters and neuropeptides, and such modulatory connectivity gives to the neurons the necessary plasticity to generating distinctive, state-dependent rhythmic patterns that depend on pacemaker potentials. [ 6 ]


The heart has several pacemakers, each which fires at its own intrinsic rate:


The potentials will normally travel in order
SA node → Atrioventricular node → Purkinje fibres


Normally, all the foci will end up firing at the SA node rate, not their intrinsic rate in a phenomenon known as overdrive-suppression. Thus, in the normal, healthy heart, only the SA node intrinsic rate is observable.


However, in pathological conditions, the intrinsic rate becomes apparent. Consider a heart attack which damages the region of the heart between the SA node and the AV node.


SA node → |block| AV node → Purkinje fibres


The other foci will not see the SA node firing; however, they will see the atrial foci. The heart will now beat at the intrinsic rate of the AV node.


The firing of the pacemaker cells is induced electrically by reaching the threshold potential of the cell membrane. The  threshold potential  is the potential an excitable cell membrane, such as a  myocyte , must reach in order to induce an action potential. [ 7 ]  This  depolarization  is caused by very small net inward currents of calcium ions across the cell membrane, which gives rise to the action potential. [ 8 ] [ 9 ]


Bio-pacemakers are the outcome of a rapidly emerging field of research into a replacement for the  electronic pacemaker . The bio-pacemaker turns quiescent myocardial cells (e.g. atrial cells) into pacemaker cells. This is achieved by making the cells express a gene which creates a pacemaker current. [ 10 ]


The  Pan–Tompkins algorithm [ 1 ]  is commonly used to detect  QRS complexes  in electrocardiographic signals ( ECG ). The QRS complex represents the ventricular  depolarization  and the main spike visible in an ECG  signal  (see figure). This feature makes it particularly suitable for measuring  heart rate , the first way to assess the heart health state. In the first derivation of  Einthoven  of a physiological heart, the QRS complex is composed by a downward deflection (Q wave), a high upward deflection (R wave) and a final downward deflection (S wave).


The Pan–Tompkins algorithm applies a series of filters to highlight the frequency content of this rapid heart depolarization and removes the background  noise . Then, it squares the signal to amplify the QRS contribution, which makes identifying the QRS complex more straightforward. Finally, it applies adaptive thresholds to detect the peaks of the filtered signal. The algorithm was proposed by  Jiapu Pan  and  Willis J. Tompkins  in 1985, in the journal IEEE Transactions on Biomedical Engineering. [ 1 ]  The performance of the method was tested on an annotated arrhythmia database ( MIT/BIH [ 2 ] [ 3 ] ) and evaluated also in presence of noise. Pan and Tompkins reported that the 99.3 percent of QRS complexes was correctly detected. [ 1 ]


As a first step, a  band-pass filter  is applied to increase the  signal-to-noise ratio . A filter bandwidth of 5-15  Hz  is suggested to maximize the QRS contribute and reduce muscle noise, baseline wander, powerline interference and the  P wave / T wave  frequency content. [ 1 ]  In the original algorithm proposed in 1985, the band-pass filter was obtained with a  low-pass filter  and a  high-pass filter  in cascade to reduce the computational cost and allow a real-time detection, while ensuring a 3  dB  passband in the 5–12 Hz frequency range, reasonably close to the design goal.


For a signal sampled at a frequency of 200 Hz, Pan and Tompkins suggested the filters with the following  transfer functions

 H
 (
 z
 )

 {\displaystyle H(z)}

  in an updated version of their article: [ 4 ]


As a third step, a derivative filter is applied to provide information about the slope of the QRS. For a signal sampled at 200 Hz, Pan and Tompkins suggested the following  transfer function : [ 4 ]


H
 (
 z
 )
 =
 0.1
 (
 −

 z

 −
 2

 −
 2

 z

 −
 1

 +
 2

 z

 1

 +

 z

 2

 )

 {\displaystyle H(z)=0.1(-z^{-2}-2z^{-1}+2z^{1}+z^{2})}

 for a 5-point derivative filter with gain of 0.1 and a processing delay of 2 samples.


The filtered signal is squared to enhance the dominant peaks (QRSs) and reduce the possibility of erroneously recognizing a T wave as an R peak. Then, a moving average filter is applied to provide information about the duration of the QRS complex. The number of samples to average is chosen in order to average on windows of 150 ms. [ 1 ]  The signal so obtained is called integrated signal.


In order to detect a QRS complex, the local peaks of the integrated signal are found. A peak is defined as the point in which the signal changes direction (from an increasing direction to a decreasing direction). After each peak, no peak can be detected in the next 200 ms (i.e. the lockout time). This is a physiological constraint due to the  refractory period  during which ventricular depolarization cannot occur even in the presence of a stimulus. [ 1 ]


Each fiducial mark is considered as a potential QRS. To reduce the possibility of wrongly selecting a noise peak as a QRS, each peak amplitude is compared to a threshold  ( Threshold I ) that takes into account the available information about already detected QRS and the noise level:


T
 h
 r
 e
 s
 h
 o
 l

 d

 I

 =
 N
 o
 i
 s
 e
 L
 e
 v
 e

 l

 I

 +
 0.25
 (
 S
 i
 g
 n
 a
 l
 L
 e
 v
 e

 l

 I

 −
 N
 o
 i
 s
 e
 L
 e
 v
 e

 l

 I

 )

 {\displaystyle Threshold_{I}=NoiseLevel_{I}+0.25(SignalLevel_{I}-NoiseLevel_{I})}


where  NoiseLevel I  is the running estimate of the noise level in the integrated signal and  SignalLevel I  is the running estimate of the signal level in the integrated signal.


The threshold is automatically updated after detecting a new peak, based on its classification as signal or noise peak:


S
 i
 g
 n
 a
 l
 L
 e
 v
 e

 l

 I

 =
 0.125
 P
 E
 A

 K

 I

 +
 0.875
 S
 i
 g
 n
 a
 l
 L
 e
 v
 e

 l

 I

 {\displaystyle SignalLevel_{I}=0.125PEAK_{I}+0.875SignalLevel_{I}}

 (if  PEAK I  is a signal peak)


N
 o
 i
 s
 e
 L
 e
 v
 e

 l

 I

 =
 0.125
 P
 E
 A

 K

 I

 +
 0.875
 N
 o
 i
 s
 e
 L
 e
 v
 e

 l

 I

 {\displaystyle NoiseLevel_{I}=0.125PEAK_{I}+0.875NoiseLevel_{I}}

 (if  PEAK I  is a noise peak)


where  PEAK I  is the new peak found in the integrated signal.


At the beginning of the QRS detection, a 2 seconds learning phase is needed to initialize  SignalLevel I  and  NoiseLevel I  as a percentage of the maximum and average amplitude of the integrated signal, respectively.


If a new  PEAK I  is under the  Threshold I , the noise level is updated. If  PEAK I  is above the  Threshold I , the algorithm implements a further check before confirming the peak as a true QRS, taking into consideration the information provided by the bandpass filtered signal.


In the filtered signal the peak corresponding to the one evaluated on the integrated signal is searched and compared with a threshold, calculated in a similar way to the previous step:


T
 h
 r
 e
 s
 h
 o
 l

 d

 F

 =
 N
 o
 i
 s
 e
 L
 e
 v
 e

 l

 F

 +
 0.25
 (
 S
 i
 g
 n
 a
 l
 L
 e
 v
 e

 l

 F

 −
 N
 o
 i
 s
 e
 L
 e
 v
 e

 l

 F

 )

 {\displaystyle Threshold_{F}=NoiseLevel_{F}+0.25(SignalLevel_{F}-NoiseLevel_{F})}


S
 i
 g
 n
 a
 l
 L
 e
 v
 e

 l

 F

 =
 0.125
 P
 E
 A

 K

 F

 +
 0.875
 S
 i
 g
 n
 a
 l
 L
 e
 v
 e

 l

 F

 {\displaystyle SignalLevel_{F}=0.125PEAK_{F}+0.875SignalLevel_{F}}

 (if  PEAK F  is a signal peak)


N
 o
 i
 s
 e
 L
 e
 v
 e

 l

 F

 =
 0.125
 P
 E
 A

 K

 F

 +
 0.875
 N
 o
 i
 s
 e
 L
 e
 v
 e

 l

 F

 {\displaystyle NoiseLevel_{F}=0.125PEAK_{F}+0.875NoiseLevel_{F}}

 (if  PEAK F  is a noise peak)


where the final F stands for filtered signal.


The algorithm takes into account the possibility of setting too high values of  ThresholdI I  and  ThresholdI F.  A check is performed to continuously assess the RR intervals (namely the temporal interval between two consecutively QRS peaks) to overcome this issue. The average RR is computed in two ways to consider both regular and irregular heart rhythm. In the first method  RRaverage1  is computed as the mean of the last RR intervals. In the second method  RRaverage2  is computed as the mean of the last RR intervals that fell between the limits specified as:


R
 R
 l
 o
 w
 =
 92
 %
 R
 R
 a
 v
 e
 r
 a
 g
 e
 2

 {\displaystyle RRlow=92\%RRaverage2}


R
 R
 h
 i
 g
 h
 =
 116
 %
 R
 R
 a
 v
 e
 r
 a
 g
 e
 2

 {\displaystyle RRhigh=116\%RRaverage2}


If no QRS is detected in a window of 166% of the average RR ( RRaverage1  or  RRaverage2 , if the heart rhythm is regular or irregular, respectively) ,  the algorithm adds the maximal peak in the window as a potential QRS and classify it considering half the values of the thresholds (both  ThresholdI I  and ThresholdI F ). This check is implemented because the temporal distance between two consecutive beats cannot physiologically change more quickly than this.


The algorithm takes particularly into consideration the possibility of a false detection of T waves. If a potential QRS falls up to a 160 ms window after the refractory period from the last correctly detected QRS complex, the algorithm evaluates if it could be a T wave with particular high amplitude. In this case, its slope is compared to that of the precedent QRS complex. If the slope is less than half the previous one, the current QRS is recognized as a T wave and discarded, and it also updates the  NoiseLevel  (both in the filtered signal and the integrated signal).


Once the QRS complex is successfully recognized, the heart rate is computed as a function of the distance in seconds between two consecutive QRS complexes (or R peaks):


H
 R

 (

 bpm

 )
 =

 60

 R
 R

 (

 s

 )

 {\displaystyle {\mathit {HR}}\ ({\text{bpm}})={60 \over {\mathit {RR}}\ ({\text{s}})}}


where bpm stands for beats per minute. The HR is often used to compute the  heart rate variability  (HRV) a measure of the variability of the time interval between heartbeats. HRV is often used in the clinical field [ 6 ]  to diagnose and monitor pathological conditions and their treatment, but also in the  affective computing  research to study new methods to assess the emotional state of people. [ 7 ]


In  electrocardiography , the  PR interval  is the period, measured in milliseconds, that extends from the beginning of the  P wave  (the onset of  atrial   depolarization ) until the beginning of the  QRS complex  (the onset of  ventricular  depolarization); it is normally between 120 and 200 ms in duration.
The PR interval is sometimes termed the  PQ interval .


Variations in the PQ interval can be associated with certain medical conditions:


A  Pro-arrhythmic agent  is a chemical, drug, or food that promotes  cardiac arrhythmias .


Omega 3 fatty acids . [ 1 ]


Chocolate ,  Coffee ,  Tea


Caffeine ,  cocaine ,  beta-adrenergic agonists


Encainide ,  Lorcainide


Pulsed field ablation  ( PFA ) is a non-thermal (not using extreme heat or cold) method of biological ablation (removal of structure or functionality) utilizing high-amplitude pulsed (microsecond duration)  electric fields  to create irreversible  electroporation  in tissues. [ 1 ]   [ 2 ]  It is used most widely to treat tumors ( cancer ) or  cardiac arrhythmias . [ 3 ]


Atrial fibrillation  frequently results from bursts of  tachycardia  that originate in muscle bundles extending from the  atrium  to the  pulmonary veins . [ 4 ]   Pulmonary vein isolation  ablation technology  has used thermal methods ( radiofrequency ablation  or, less often,  cryoablation ) to destroy pulmonary vein cells. [ 5 ]  As with thermal methods of ablation, in pulsed field ablation, a thin, flexible tube ( catheter ) is inserted into a blood vessel in the  groin  and threaded up into the heart to  ablate  the areas of the pulmonary vein causing excessively rapid electrical signals. [ 6 ]


A major reason for recurrence of atrial fibrillation after ablation has been the belief of electrical pulmonary vein reconnection, which has not been seen for PFA. [ 7 ]  In one study, atrial fibrillation recurrence in the thermal ablation group was 39% compared to 11% in the PFA group. [ 8 ]  PFA can achieve pulmonary vein isolation faster than other ablation methods. [ 1 ] [ 8 ]   Compared to radiofrequency ablation, PFA produces lesions of greater uniformity. [ 5 ]


Cell death following PFA is usually due to  apoptosis , which is a far less damaging and  inflammatory  form of cell death than  necrosis . [ 1 ] [ 3 ]  In contrast to thermal methods of ablation, PFA specifically kills  cardiomyocytes  (cardiac muscle cells) without injuring surrounding tissues. [ 1 ] [ 2 ]  Thermal ablation methods can damage the  esophagus ,  phrenic nerve , and   coronary vessels  (as high as 5%  [ 8 ] ), which are spared by PFA. [ 1 ]  One study showed an overall complication rate of 0.7% for PFA and no occurrence of phrenic nerve, esophageal, or pulmonary vein injury. [ 9 ]


Because PFA is a relatively newer ablation technique, there is a lack of uniformity in the parameters for its delivery. [ 8 ]  Better standardization could help reduce instances of coronary artery spasm and pulmonary artery hemorrhage, which can occur. [ 8 ]  The equipment cost and lack of specialized training have limited the widespread use of PFA, making it unavailable to many patients. [ 8 ]


Recent (2024) comparisons of PFA with thermal methods have shown reduced time spent in surgery, but no superiority in safety and no better reduction of atrial fibrillation. [ 10 ]  When used in areas other than the pulmonary vein, injuries have been seen. [ 10 ]


The  Purkinje fibers , named for  Jan Evangelista Purkyně , ( English:  / p ɜːr ˈ k ɪ n dʒ i /   pur- KIN -jee ; [ 1 ]   Czech:   [ˈpurkɪɲɛ]   ⓘ ;  Purkinje tissue  or  subendocardial branches ) are located in the inner  ventricular  walls of the  heart , [ 2 ]  just beneath the  endocardium  in a space called the subendocardium. The Purkinje fibers are specialized conducting fibers composed of  electrically excitable cells . [ 3 ]  They are larger than  cardiomyocytes  with fewer myofibrils and many  mitochondria . They conduct  cardiac action potentials  more quickly and efficiently than any of the other cells in the heart's  electrical conduction system . [ 4 ]  Purkinje fibers allow the heart's conduction system to create  synchronized contractions  of its ventricles, and are essential for maintaining a consistent  heart rhythm . [ 5 ]


Purkinje fibers are a unique  cardiac  end-organ. Further  histologic  examination reveals that these fibers are split in ventricles walls. The electrical origin of atrial Purkinje fibers arrives from the  sinoatrial node .


Given no aberrant channels, the Purkinje fibers are distinctly shielded from each other by  collagen  or the  cardiac skeleton .


The Purkinje fibers are further specialized to rapidly conduct impulses (having numerous fast  voltage-gated   sodium channels   and  mitochondria , and fewer  myofibrils , than the surrounding muscle tissue). Purkinje fibers take up stain differently from the surrounding muscle cells because of having relatively fewer myofibrils than other cardiac cells.  The presence of glycogen around the nucleus causes Purkinje fibers to appear, on a slide, lighter and larger than their neighbors, being arranged along the longitudinal direction (parallel to the cardiac vector). They are often  binucleated cells . [ 6 ]


Heart rate is governed by many influences from the  autonomic nervous system . The Purkinje fibers do not have any known role in setting heart rate unless the  SA node  is compromised (when they can act as  pacemaker  cells). [ 7 ]  They are influenced by  electrical discharge  from the sinoatrial node.


During the  ventricular contraction  portion of the  cardiac cycle , the Purkinje fibers carry the contraction impulse from both the left and right  bundle branch  to the  myocardium  of the ventricles. [ 5 ]  This causes the muscle tissue of the ventricles to contract. This generates  force  to eject  blood  out of the heart, either to the  pulmonary circulation  from the right ventricle, or to the  systemic circulation  from the left ventricle. [ 8 ]


Purkinje fibers also have the ability of firing at a rate of 20–40 beats per minute if upstream conduction or pacemaking ability is compromised. [ 9 ]  In contrast, the SA node in normal state can fire at 60-100 beats per minute. [ 9 ]  In short, they generate  action potentials , but at a slower rate than the  sinoatrial node . [ 9 ]  This capability is normally suppressed. Thus, they serve as the last resort when other pacemakers fail. When a Purkinje fiber does fire, it is called a  premature ventricular contraction  or PVC, or in other situations can be a  ventricular escape .


Purkinje fibers are named after the  Czech  scientist  Jan Evangelista Purkyně , who discovered them in 1839. [ 10 ]


The  QRS complex  is the combination of three of the graphical deflections seen on a typical  electrocardiogram (ECG or EKG) . It is usually the central and most visually obvious part of the tracing. It corresponds to the  depolarization  of the right and left  ventricles  of the heart and contraction of the large ventricular muscles.


In adults, the QRS complex normally lasts  80 to 100  ms ; in children it may be shorter. The Q, R, and S waves occur in rapid succession, do not all appear in all leads, and reflect a single event and thus are usually considered together. A  Q wave  is any downward deflection immediately following the  P wave . An  R wave  follows as an upward deflection, and the  S wave  is any downward deflection after the R wave. The  T wave  follows the S wave, and in some cases, an additional  U wave  follows the T wave.


To measure the  QRS interval  start at the end of the PR  interval  (or beginning of the Q wave) to the end of the S wave. Normally this  interval  is 0.08 to 0.10 seconds. When the duration is longer it is considered a wide QRS complex.


Depolarization of the heart  ventricles  occurs almost simultaneously, via the  bundle of His  and  Purkinje fibers . If they are working efficiently, the QRS complex duration in adults is  80 to 110  ms . [ 1 ]


Any abnormality of conduction takes longer and causes "widened" QRS complexes. In  bundle branch block , there can be an abnormal second upward deflection within the QRS complex. In this case, such a second upward deflection is referred to as R′ (pronounced "R  prime "). This would be described as an RSR′ pattern.


Ventricles contain more muscle mass than the atria. Therefore, the QRS complex is considerably larger than the P wave. The QRS complex is often used to determine the  axis  of the electrocardiogram, although it is also possible to determine a separate P wave axis.


The duration, amplitude, and morphology of the QRS complex are useful in diagnosing  cardiac arrhythmias ,  conduction abnormalities ,  ventricular hypertrophy ,  myocardial infarction ,  electrolyte derangements , and other disease states.


High frequency analysis  of the QRS complex may be useful for detection of coronary artery disease during an  exercise stress test . [ 2 ]


Duration longer than 45 ms might indicate  left posterior fascicular block , LVH or  LBBB . [ 9 ]


Normal Q waves, when present, represent depolarization of the  interventricular septum . For this reason, they are referred to as septal Q waves and can be appreciated in the lateral leads I, aVL, V5 and V6.


Pathologic Q waves occur when the electrical signal passes through stunned or scarred  heart muscle ; as such, they are usually markers of previous  myocardial infarctions , with subsequent fibrosis. A pathologic Q wave is defined as having a deflection amplitude of 25% or more of the subsequent R wave, or being  > 0.04 s  (40 ms) in width and  > 2 mm  in amplitude. However, diagnosis requires the presence of this pattern in more than one corresponding lead.


Looking at the precordial leads, the R wave usually progresses from showing an rS-type complex in V 1  with an increasing R and a decreasing S wave when moving toward the left side. There is usually a qR-type of complex in V 5  and V 6,  with the R-wave amplitude usually taller in V 5  than in V 6 . It is normal to have a narrow QS and rSr' patterns in V 1 , and this is also the case for qRs and R patterns in V 5  and V 6 . The  transition zone  is where the QRS complex changes from predominantly negative to predominantly positive (R/S ratio becoming >1), and this usually occurs at V 3  or V 4 . It is normal to have the transition zone at V 2  (called "early transition") and at V 5  (called "delayed transition"). [ 11 ]  In biomedical engineering, the maximum amplitude in the R wave is usually called "R peak amplitude", or just "R peak". [ 12 ] [ 13 ]  Accurate R peak detection is essential in signal processing equipment for  heart rate  measurement and it is the main feature used for  arrhythmia  detection. [ 14 ] [ 15 ]


The definition of  poor R wave progression  (PRWP) varies in the literature. It may be defined, for example, as R wave of less than 2–4 mm in leads V 3  or V 4  and/or presence of a reversed R wave progression, which is defined as R in V 4  < R in V 3  or R in V 3  < R in V 2  or R in V 2  < R in V 1 , or any combination of these. [ 11 ]   Poor R wave progression  is commonly attributed to anterior  myocardial infarction , but it may also be caused by  left bundle branch block ,  Wolff–Parkinson–White syndrome , right and left  ventricular hypertrophy , or a faulty ECG recording technique. [ 11 ]


R wave peak time (RWPT) represents the time from the onset of QRS complex to the peak of R wave, which is usually measured in aVL and V5 or V6 leads. [ 16 ]


R-peak time for right ventricle is measured from leads V1 or V2, where upper range of normal is 35 ms. R wave peak time for left ventricle is measured from lead V5 or V6 and 45 ms is the upper range of normal. [ 7 ]   R wave peak time is considered to be prolonged if it's more than 45 ms.


The point where the QRS complex meets the  ST segment  is the J-point. The J-point is easy to identify when the ST segment is horizontal and forms a sharp angle with the last part of the QRS complex. However, when the ST segment is sloped or the QRS complex is wide, the two features do not form a sharp angle and the location of the J-point is less clear. There is no consensus on the precise location of the J-point in these circumstances. [ 17 ]  Two possible definitions are:


Not every QRS complex contains a Q wave, an R wave, and an S wave. By convention, any combination of these waves can be referred to as a QRS complex. However, correct interpretation of difficult ECGs requires exact labeling of the various waves. Some authors use lowercase and capital letters, depending on the relative size of each wave. For example, an Rs complex would be positively deflected, while an rS complex would be negatively deflected. If both complexes were labeled RS, it would be impossible to appreciate this distinction without viewing the actual ECG.


Monomorphic refers to all QRS waves in a single lead being similar in shape. Polymorphic means that the QRS change from complex to complex. [ 19 ]  These terms are used in the description of  ventricular tachycardia .


A common algorithm used for QRS complex detection is the  Pan-Tompkins [ 20 ]  algorithm (or method); another is based on the  Hilbert transform . [ 21 ] [ 22 ] [ 23 ] [ 24 ]  Numerous other algorithms have been proposed and investigated. [ 25 ]  In recent research, heart beat detection methods based on  visibility graphs  have been introduced, enabling fast and sample-precise R-peak annotation even in noisy ECG. [ 26 ] [ 27 ]


The  QT interval  is a measurement made on an  electrocardiogram  used to assess some of the electrical properties of the  heart .  It is calculated as the time from the start of the  Q wave  to the end of the  T wave , and approximates to the time taken from when the  cardiac ventricles  start to contract to when they finish relaxing. An abnormally long or abnormally short QT interval is associated with an increased risk of developing  abnormal heart rhythms  and  sudden cardiac death . Abnormalities in the QT interval can be caused by  genetic  conditions such as  long QT syndrome , by certain medications such as  sotalol  or  pitolisant , by disturbances in the concentrations of certain  salts  within the blood such as  hypokalaemia , or by  hormonal imbalances  such as  hypothyroidism .


The QT interval is most commonly measured in  lead  II for evaluation of serial ECGs, with leads I and V5 being comparable alternatives to lead II. Leads III, aVL and V1 are generally avoided for measurement of QT interval. [ 1 ]  The accurate measurement of the QT interval is subjective [ 2 ]  because the end of the T wave is not always clearly defined and usually merges gradually with the baseline. QT interval in an ECG complex can be measured manually by different methods, such as the threshold method, in which the end of the T wave is determined by the point at which the component of the T wave merges with the isoelectric baseline, or the tangent method, in which the end of the T wave is determined by the intersection of a tangent line extrapolated from the T wave at the point of maximum downslope to the isoelectric baseline. [ 3 ]


With the increased availability of digital ECGs with simultaneous 12-channel recording, QT measurement may also be done by the 'superimposed median beat' method. In the superimposed median beat method, a median ECG complex is constructed for each of the 12 leads. The 12 median beats are superimposed on each other and the QT interval is measured either from the earliest onset of the Q wave to the latest offset of the T wave or from the point of maximum convergence for the Q wave onset to the T wave offset. [ 4 ]


The QT interval changes in response to the  heart rate  - as heart rate increase the QT interval shortens.  These changes make it harder to compare QT intervals measured at different heart rates.  To account for this, and thereby improve the reliability of QT measurement, the QT interval can be corrected for heart rate (QTc) using  a variety of mathematical formulae, a process often performed automatically by modern ECG recorders.


The most commonly used QT correction formula is the  Bazett's formula , [ 5 ]  named after  physiologist   Henry Cuthbert Bazett  (1885–1950), [ 6 ]  calculating the heart rate-corrected QT interval (QTcB).


Bazett's formula is based on observations from a study in 1920.
Bazett's formula is often given in a form that returns QTc in dimensionally suspect units, square root of seconds. The dimensionally correct form of Bazett's formula is:


where QTc B  is the QT interval corrected for heart rate, and RR is the interval from the onset of one  QRS complex  to the onset of the next QRS complex. This dimensionally correct formula returns the QTc in the same units as QT, generally milliseconds. [ 7 ]


In some popular forms of this formula, it is assumed that QT is measured in milliseconds and that RR is measured in seconds, often derived from the heart rate (HR) as 60/HR. Therefore, the result will be given in seconds per square root of milliseconds. [ 8 ]  However, reporting QTc using this formula creates a "requirement regarding the units in which the original QT and RR are measured." [ 7 ]


In either form, Bazett's non-linear QT correction formula is generally not considered accurate, as it over-corrects at high heart rates and under-corrects at low heart rates. [ 8 ]  Bazett's correction formula is one of the most suitable QT correction formulae for neonates. [ 9 ]


Fridericia [ 10 ]  had proposed an alternative correction formula (QTcF) using the cube-root of RR.


The Framingham correction, also called as Sagie's formula based on the  Framingham Heart Study , which used long-term cohort data of over 5,000 subjects, is considered a better [ 11 ]  method. [ 12 ]


Again, here  QT  and  QTlc  are in milliseconds and  RR  is measured in seconds.


A  retrospective study  suggests that Fridericia's method and the Framingham method may produce results most useful for stratifying the 30-day and 1-year risks of mortality. [ 11 ]


Definitions of normal QTc vary from being equal to or less than 0.40 s (≤ 400 ms), [ 13 ]  0.41 s (≤ 410 ms), [ 15 ]  0.42 s (≤ 420 ms) [ 14 ]  or 0.44 s (≤ 440 ms). [ 16 ]  For risk of  sudden cardiac death , "borderline QTc" in males is 431–450 ms; and, in females, 451–470 ms. An "abnormal" QTc in males is a QTc above 450 ms; and, in females, above 470 ms. [ 17 ]


If there is not a very high or low heart rate, the upper limits of QT can roughly be estimated by taking QT = QTc at a heart rate of 60 beats per minute (bpm), and subtracting 0.02 s from QT for every 10 bpm increase in heart rate. For example, taking normal QTc ≤ 0.42 s, QT would be expected to be 0.42 s or less at a heart rate of 60 bpm. For a heart rate of 70 bpm, QT would roughly be expected to be equal to or below 0.40 s. Likewise, for 80 bpm, QT would roughly be expected to be equal to or below 0.38 s. [ 13 ]


Prolonged QTc causes premature action potentials during the late phases of depolarization. This increases the risk of developing ventricular arrhythmias, including fatal  ventricular fibrillation . [ 18 ]  Higher rates of prolonged QTc are seen in females, older patients, high systolic blood pressure or heart rate, and short stature. [ 19 ]  Prolonged QTc is also associated with ECG findings called  Torsades de Pointes , which are known to degenerate into ventricular fibrillation, associated with higher mortality rates. There are many causes of prolonged QT intervals, acquired causes being more common than genetic. [ 20 ]


An abnormally prolonged QT interval could be due to  long QT syndrome , whereas an abnormally shortened QT interval could be due to  short QT syndrome .


The QTc length is associated with variations in the  NOS1AP  gene. [ 21 ]  The  autosomal recessive  syndrome of Jervell and Lange-Nielsen is characterized by a prolonged QTc interval in conjunction with  sensorineural hearing loss .


Prolongation of the QT interval may be due to an  adverse drug reaction . [ 22 ]


Antipsychotics  (especially first generation/"typical")


DMARDs and antimalarial drugs


Antibiotics


Other drugs


Some second-generation antihistamines, such as  astemizole , have this effect. The mechanism of action of certain antiarrhythmic drugs, like  amiodarone  or  sotalol , involve intentional pharmacological QT prolongation. In addition, high blood alcohol concentrations prolong the QT interval. [ 30 ]  A possible interaction between  selective serotonin reuptake inhibitors  and  thiazide  diuretics is associated with QT prolongation. [ 31 ]


Hypothyroidism , a condition of low function of the  thyroid  gland, can cause QT prolongation at the  electrocardiogram .  Acute hypocalcemia causes prolongation of the QT interval, which may lead to ventricular dysrhythmias.


A shortened QT can be associated with  hypercalcemia . [ 32 ]


Since 2005, the FDA and European regulators have required that nearly all new molecular entities be evaluated in a Thorough QT (TQT) or similar study to determine a drug's effect on the QT interval. [ 33 ]  The TQT study serves to assess the potential arrhythmia liability of a drug.  Traditionally, the QT interval had been evaluated by having an individual human reader measure approximately nine cardiac beats per clinical timepoint.  However, a substantial portion of drug approvals after 2010 have incorporated a partially automated approach, blending automated software algorithms with expert human readers reviewing a portion of the cardiac beats, to enable the assessment of significantly more beats in order to improve precision and reduce cost. [ 34 ]  In 2014, an industrywide consortium consisting of the FDA,  iCardiac Technologies  and other organizations released the results of a seminal study indicating how waivers from TQT studies can be obtained by the assessment of early phase data. [ 35 ]   As the pharmaceutical industry has gained experience in performing TQT studies, it has also become evident that traditional QT correction formulas such as QTcF, QTcB, and QTcLC may not always be suitable for evaluation of drugs impacting autonomic tone. [ 36 ]


Electrocardiography is a safe and noninvasive tool that can be used to identify those with a higher risk of mortality. In the general population, there has been no consistent evidence that prolonged QTc interval in isolation is associated with an increase in mortality from cardiovascular disease. [ 37 ]  However, several studies [ which? ]  have examined prolonged QT interval as a predictor of mortality for diseased subsets of the population.


Rheumatoid arthritis is the most common inflammatory arthritis. [ 38 ]  Studies have linked rheumatoid arthritis with increased death from cardiovascular disease. [ 38 ]
In a 2014 study, [ 18 ]  Panoulas et al. found a 50 ms increase in QTc interval increased the odds of all-cause mortality by 2.17 in patients with rheumatoid arthritis. Patients with the highest QTc interval (> 424 ms) had higher mortality than those with a lower QTc interval. The association was lost when calculations were adjusted for C-reactive protein levels. The researchers proposed that inflammation prolonged the QTc interval and created arrhythmias that were associated with higher mortality rates. However, the mechanism by which C-reactive protein is associated with the QTc interval is still not understood.


Compared to the general population, type 1 diabetes may increase the risk of mortality, due largely to an increased risk of cardiovascular disease. [ 19 ] [ 39 ]  Almost half of patients with type 1 diabetes have a prolonged QTc interval (> 440 ms). [ 19 ]  Diabetes with a prolonged QTc interval was associated with a 29% mortality over 10 years in comparison to 19% with a normal QTc interval. [ 19 ]  Anti-hypertensive drugs increased the QTc interval, but were not an independent predictor of mortality. [ 19 ]


QT interval dispersion (QTd) is the maximum QT interval minus the minimum QT interval, and is linked with ventricular repolarization. [ 40 ]  A QTd over 80 ms is considered abnormally prolonged. [ 41 ]  Increased QTd is associated with mortality in type 2 diabetes. [ 41 ]
QTd is a better predictor of cardiovascular death than QTc, which was unassociated with mortality in type 2 diabetes. [ 41 ]  QTd higher than 80 ms had a relative risk of 1.26 of dying from cardiovascular disease compared to a normal QTd.


QT interval variability  (QTV) refers to the physiological phenomenon of beat-to-beat fluctuations in  QT interval  of  electrocardiograms . Increased QTV appears to be a marker of arrhythmic and cardiovascular death; it may also play a role for noninvasive assessment of sympathetic nervous system activity. [ 1 ]


Other terms used include: "QT variability", "beat-to-beat variability of ventricular repolarization (BRV)"


Under normal resting conditions, beat-to-beat changes in QT interval are very small with a standard deviation typically below 5 ms. Digital high resolution ECG sampled at 300 Hz or higher and dedicated computer algorithms are required for QTV assessment. [ 2 ]  Template-based algorithms that use parts of, or the entire ECG waveform usually deliver good results; [ 3 ]  template stretching or warping techniques [ 4 ]  perform comparably well in the presence of noise.


A number of metrics have been proposed for QTV quantification. The QT variability index (QTVi) has been most frequently reported in the literature:

 Q
 T
 V
 i
 =
 log

 S
 D
 Q

 T

 2

 /

 (
 Q

 T

 m
 e
 a
 n

 )

 2

 S
 D
 H

 R

 2

 /

 (
 H

 R

 m
 e
 a
 n

 )

 2

 {\displaystyle QTVi=\log {\frac {SDQT^{2}/(QT_{mean})^{2}}{SDHR^{2}/(HR_{mean})^{2}}}}

 , where

 S
 D
 Q
 T

 {\displaystyle SDQT}

 ,

 S
 D
 H
 R

 {\displaystyle SDHR}

 ,

 Q

 T

 m
 e
 a
 n

 {\displaystyle QT_{mean}}

 , and

 H

 R

 m
 e
 a
 n

 {\displaystyle HR_{mean}}

  denote standard deviation and mean of QT interval and heart rate time series, respectively. [ 5 ]


More advanced approaches that take into account the relationship between QTV and  heart rate variability  include vector autoregressive process models [ 6 ]  and information domain approaches. [ 7 ]


Refractoriness  is the fundamental property of any object of  autowave  nature (especially  excitable medium ) not responding to stimuli, if the object stays in the specific  refractory state . In common sense,  refractory period  is the characteristic recovery time, a period that is associated with the motion of the image point on the left branch of the isocline

 u
 ˙

 =
 0

 {\displaystyle {\dot {u}}=0}

 [ B: 1 ]  (for more details, see also  Reaction–diffusion  and  Parabolic partial differential equation ).


In  physiology , [ B: 2 ]  a  refractory period  is a period of time during which an organ or cell is incapable of repeating a particular action, or (more precisely) the amount of time it takes for an  excitable membrane  to be ready for a second  stimulus once it returns to its resting state following an excitation. It most commonly refers to electrically excitable muscle cells or neurons.  Absolute refractory period  corresponds to depolarization and repolarization, whereas  relative refractory period  corresponds to hyperpolarization.


After initiation of an action potential, the refractory period is defined two ways:
The absolute refractory period coincides with nearly the entire duration of the action potential. In  neurons , it is caused by the  inactivation  of the  voltage-gated sodium channels  that originally opened to depolarize the membrane. These channels remain inactivated until the membrane hyperpolarizes. The channels then close, de-inactivate, and regain their ability to open in response to stimulus.


The relative refractory period immediately follows the absolute. As  voltage-gated potassium channels  open to terminate the action potential by repolarizing the membrane, the potassium conductance of the membrane increases dramatically.  K +  ions  moving out of the cell bring the membrane potential closer to the equilibrium potential for potassium. This causes brief hyperpolarization of the membrane, that is, the membrane potential becomes transiently more negative than the normal resting potential. Until the potassium conductance returns to the resting value, a greater stimulus will be required to reach the initiation threshold for a second depolarization. The return to the equilibrium resting potential marks the end of the relative refractory period.


The  refractory period  in cardiac physiology is related to the ion currents that, in  cardiac cells  as in nerve cells, flow into and out of the cell freely.  The flow of ions translates into a change in the voltage of the inside of the cell relative to the extracellular space.  As in nerve cells, this characteristic change in voltage is referred to as an action potential.  Unlike that in nerve cells, the cardiac action potential duration is closer to 100 ms (with variations depending on cell type, autonomic tone, etc.).  After an action potential initiates, the cardiac cell is unable to initiate another action potential for some duration of time (which is slightly shorter than the "true" action potential duration).  This period of time is referred to as the refractory period, which is 250ms in duration and helps to protect the heart.


In the classical sense, the cardiac refractory period is separated into an absolute refractory period and a relative refractory period.  During the absolute refractory period, a new action potential cannot be elicited.  During the relative refractory period, a new action potential can be elicited under the correct circumstances.


The cardiac refractory period can result in different forms of  re-entry , which are a cause of  tachycardia . [ 1 ] [ B: 3 ]  Vortices of excitation in the myocardium ( autowave vortices ) are a form of  re-entry . Such vortices can be a mechanism of life-threatening cardiac  arrhythmias . In particular, the  autowave reverberator , more commonly referred to as spiral waves or rotors, can be found within the  atria  and may be a cause of  atrial fibrillation .


The  refractory period in a  neuron  occurs after an  action potential  and generally lasts one millisecond. An action potential consists of three phases.


Phase one is depolarization. During depolarization, voltage-gated sodium ion channels open, increasing the neuron's membrane conductance for sodium ions and depolarizing the cell's membrane potential (from typically -70 mV toward a positive potential). In other words, the membrane is made less negative. After the potential reaches the activation threshold (-55 mV), the depolarization is actively driven by the neuron and overshoots the equilibrium potential of an activated membrane (+30 mV).


Phase two is repolarization. During repolarization, voltage-gated sodium ion channels inactivate (different from the closed state) due to the now-depolarized membrane, and voltage-gated potassium channels activate (open). Both the inactivation of the sodium ion channels and the opening of the potassium ion channels act to repolarize the cell's membrane potential back to its resting membrane potential.


When the cell's membrane voltage overshoots its resting membrane potential (near -60 mV), the cell enters a phase of hyperpolarization. This is due to a larger-than-resting potassium conductance across the cell membrane. This potassium conductance eventually drops and the cell returns to its resting membrane potential.


Recent research has shown that neuronal refractory periods can exceed 20 milliseconds. Furthermore, the relation between hyperpolarization and the neuronal refractory was questioned, as neuronal refractory periods were observed for neurons that do not exhibit hyperpolarization. [ 2 ] [ 3 ]  The neuronal refractory period was shown to be dependent on the origin of the input signal to the neuron, as well as the preceding spiking activity of the neuron. [ 3 ]


The refractory periods are due to the inactivation property of voltage-gated sodium channels and the lag of potassium channels in closing. Voltage-gated sodium channels have two gating mechanisms, the activation mechanism that opens the channel with depolarization and the inactivation mechanism that closes the channel with repolarization.  While the channel is in the inactive state, it will not open in response to depolarization. The period when the majority of sodium channels remain in the inactive state is the absolute refractory period.  After this period, there are enough voltage-activated sodium channels in the closed (active) state to respond to depolarization. However, voltage-gated potassium channels that opened in response to repolarization do not close as quickly as voltage-gated sodium channels; to return to the active closed state. During this time, the extra potassium conductance means that the membrane is at a higher threshold and will require a greater stimulus to cause action potentials to fire. In other words, because the membrane potential inside the axon becomes increasingly negative relative to the outside of the membrane, a stronger stimulus will be required to reach the threshold voltage, and thus, initiate another action potential. This period is the relative refractory period.


The muscle action potential lasts roughly 2–4 ms and the absolute refractory period is roughly 1–3 ms, shorter than other cells.


In a  biological membrane , the  reversal potential  is the  membrane potential  at which the direction of ionic current reverses. At the reversal potential, there is no net flow of ions from one side of the membrane to the other. For channels that are permeable to only a single type of ion, the reversal potential is identical to the  equilibrium potential  of the ion. [ 1 ] [ 2 ] [ 3 ]


The equilibrium potential for an ion is the  membrane potential  at which there is no net movement of the ion. [ 1 ] [ 2 ] [ 3 ]  The flow of any inorganic ion, such as  Na +  or  K + ,  through an  ion channel  (since membranes are normally impermeable to ions) is driven by the  electrochemical gradient  for that ion. [ 1 ] [ 2 ] [ 3 ] [ 4 ]  This gradient consists of two parts, the difference in the concentration of that ion across the membrane, and the voltage gradient. [ 4 ]  When these two influences balance each other, the electrochemical gradient for the ion is zero and there is no net flow of the ion through the channel; this also translates to no current across the membrane so long as only one ionic species is involved. [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ]  The voltage gradient at which this equilibrium is reached is the equilibrium potential for the ion and it can be calculated from the  Nernst equation . [ 1 ] [ 2 ] [ 3 ] [ 4 ]


We can consider as an example a positively charged ion, such as  K + , and a negatively charged membrane, as it is commonly the case in most organisms. [ 4 ] [ 5 ]  The membrane voltage opposes the flow of the potassium ions out of the cell and the ions can leave the interior of the cell only if they have sufficient thermal energy to overcome the energy barrier produced by the negative membrane voltage. [ 5 ]  However, this biasing effect can be overcome by an opposing concentration gradient if the interior concentration is high enough which favours the potassium ions leaving the cell. [ 5 ]


An important concept related to the equilibrium potential is the  driving force .  Driving force is simply defined as the difference between the actual membrane potential and an ion's equilibrium potential

 V

 m

 −

 E

 i

 {\displaystyle V_{\mathrm {m} }-E_{\mathrm {i} }\ }

 where

 E

 i

 {\displaystyle E_{\mathrm {i} }\ }

 refers to the equilibrium potential for a specific ion. [ 5 ]  Relatedly, the membrane current per unit area due to the type

 i

 {\displaystyle i}

  ion channel is given by the following equation:


where

 V

 m

 −

 E

 i

 {\displaystyle V_{\mathrm {m} }-E_{\mathrm {i} }\ }

  is the driving force and

 g

 i

 {\displaystyle g_{\mathrm {i} }}

  is the  specific conductance , or conductance per unit area. [ 5 ]  Note that the ionic current will be zero if the membrane is impermeable to that ion in question or if the membrane voltage is exactly equal to the equilibrium potential of that ion. [ 5 ]


When V m  is at the reversal potential for an event such as a synaptic potential ( V m  −  E rev  is equal to 0), the identity of the ions that flow during an EPC can be deduced by comparing the reversal potential of the EPC to the equilibrium potential for various ions. For instance several excitatory  ionotropic  ligand-gated  neurotransmitter   receptors  including  glutamate receptors  ( AMPA ,  NMDA , and  kainate ),  nicotinic   acetylcholine  (nACh), and  serotonin  (5-HT 3 ) receptors are nonselective cation channels that pass Na +  and K +  in nearly equal proportions, giving the reversal potential close to zero. The inhibitory ionotropic ligand-gated neurotransmitter receptors that carry  Cl − , such as  GABA A  and  glycine  receptors, have reversal potentials close to the resting potential (approximately –70 mV) in neurons. [ 2 ]


This line of reasoning led to the development of experiments (by Akira Takeuchi and Noriko Takeuchi in 1960) that demonstrated that acetylcholine-activated ion channels are approximately equally permeable to Na +  and K +  ions. The experiment was performed by lowering the external Na +  concentration, which lowers (makes more negative) the Na +  equilibrium potential and produces a negative shift in reversal potential. Conversely, increasing the external K +  concentration raises (makes more positive) the K +  equilibrium potential and produces a positive shift in reversal potential. [ 2 ]   A general expression for reversal potential of synaptic events, including for decreases in conductance, has been derived. [ 6 ]


Signal-averaged electrocardiography  (SAECG) is a special  electrocardiographic  technique, in which multiple electric signals from the  heart  are averaged to remove  interference  and reveal small variations in the  QRS complex , usually the so-called " late potentials ".  These may represent a predisposition towards potentially dangerous  ventricular tachyarrhythmias .


A resting  electrocardiogram  (ECG) is recorded in the  supine position  using an ECG machine equipped with SAECG software; this can be done by a  physician ,  nurse , or  medical technician .  Unlike standard basal ECG recording, which requires only a few seconds, SAECG recording requires a few minutes (usually about 7-10 minutes), as the machine must record multiple subsequent QRS potentials to remove interference due to  skeletal muscle  and to obtain a  statistically significant  average trace. For this reason, it is important for the patient to lie as still as possible during the recording.


SAECG recording yields a single, averaged QRS potential, usually printed in a much larger scale than standard ECGs, upon which the SAECG software performs calculations to reveal small variations (typically 1-25  uV ) in the final portion of the QRS complex (the so-called " late potentials , or more accurately, " late ventricular potentials "). These can be immediately interpreted by comparing results with cut-off values.


Late potentials are taken to represent delayed and fragmented  depolarisation  of the  ventricular   myocardium , which may be the substrate for a micro- re-entry  mechanism, implying a higher risk of potentially dangerous ventricular  tachyarrhythmias .  This has been used for the  risk stratification  of  sudden cardiac death  in people who have had a  myocardial infarction , as well as in people with known  coronary heart disease ,  cardiomyopathies , or unexplained  syncope .
Still, the real predictive value of these findings is questioned. Late potentials may be found in 0-10% of normal volunteers. When used as a prognostic factor for the development of  ventricular tachycardia , they have a  sensitivity  of 72% and a  specificity  of 75%, yielding a  positive predictive value  of 20% and a  negative predictive value  of 20%.


Sinoventricular conduction  is a rare form of  cardiac conduction  in which the sinoatrial node generates an impulse that is conducted to the  atrioventricular node  (AV node) in the absence of the right atrium contracting. This is the physiological proof for the presence of the internodal tracts, which have not been clearly demonstrated histologically. On electrocardiogram (ECG), there will be no P wave due to the inactivation of the atrial muscles. [ 1 ]


Hyperkalemia  can lead to sinoventricular conduction, as evidenced on  ECG  by the P waves becoming flatter and flatter and eventually disappearing. The impulse from the sinus node is still conducted via the internodal tracts to the AV node, and thus normal ventricular activation occurs. Sinoventricular conduction has also been demonstrated during acute myocardial ischemia. This has been further elucidated by the absence of P waves in any surface leads despite effective high right atrial pacing. [ 2 ]


Sinus arrhythmia  is a commonly encountered variation of  normal   sinus rhythm . Sinus arrhythmia characteristically presents with an irregular rate in which the variation in the R-R interval is more than 0.12 seconds (120 milliseconds). Additionally, P waves are typically mono-form and in a pattern consistent with atrial activation originating from the  sinus node . [ 1 ]


During respiration, the intermittent  vagus nerve  activation occurs, which results in beat to beat variations in the resting heart rate. During inspiration vagal tone is slowed down and the heart rate goes up (being maximal at the peak of inspiration), while during expiration vagal tone is increased and heart rate decreases, being slowest at end-expiration. [ 2 ] [ 1 ]


When present, respiratory sinus arrhythmia typically indicates good cardiovascular health and is more commonly seen in young healthy people, especially those with enhanced vagal tone or slower heart rates. [ 3 ] [ 1 ]


In  electrocardiography , the  ST segment  connects the  QRS complex  and the  T wave  and has a duration of 0.005 to 0.150 sec (5 to 150 ms).


It starts at the J point (junction between the QRS complex and ST segment) and ends at the beginning of the T wave. However, since it is usually difficult to determine exactly where the ST segment ends and the T wave begins, the relationship between the ST segment and T wave should be examined together. The typical ST segment duration is usually around 0.08 sec (80 ms). It should be essentially level with the PR and TP segments.


The ST segment represents the isoelectric period when the ventricles are in between depolarization and repolarization.


In  fetal electrocardiography , ST waveform analysis (sometimes abbreviated STAN) is used to get an indication of increasing levels of fetal  base deficit . [ 3 ]


In  electrocardiography , the  T wave  represents the  repolarization  of the  ventricles . The interval from the beginning of the  QRS complex  to the apex of the T wave is referred to as the  absolute  refractory period . The last half of the T wave is referred to as the  relative refractory period  or  vulnerable period . The T wave contains more information than the  QT interval . The T wave can be described by its symmetry, skewness, slope of ascending and descending limbs, amplitude and subintervals like the T peak –T end  interval. [ 1 ]


In most  leads , the T wave is positive. This is due to the repolarization of the membrane. During ventricle contraction (QRS complex), the heart depolarizes. Repolarization of the ventricle happens in the opposite direction of depolarization and is negative current, signifying the relaxation of the cardiac muscle of the ventricles. But this negative flow causes a positive T wave; although the cell becomes more negatively charged, the net effect is in the positive direction, and the ECG reports this as a positive spike. [ 2 ]  However, a negative T wave is normal in  lead aVR . Lead V1 generally have a negative T wave. In addition, it is not uncommon to have a negative T wave in lead III, aVL, or aVF. A periodic beat-to-beat variation in the amplitude or shape of the T wave may be termed  T wave alternans .


The  refractory period  of cardiac muscle is distinct from that of skeletal muscle. Nerves that innervate skeletal muscle have an extremely short refractory period after being subjected to an  action potential  (of the order of 1 ms). This can lead to sustained or  tetanic contraction . In the heart, contractions must be spaced to maintain a rhythm. Unlike in muscle, repolarization occurs at a slow rate (100 ms). This prevents the heart from undergoing sustained contractions because it forces the refractory period and  cardiac action potential  firing to be of the same length of time.


Repolarization depends on the charges of ions and their flow across membranes. In skeletal muscle cells, repolarization is simple. First,  sodium ions  flow into the cell to depolarize it and cause skeletal muscle contraction. Once the action potential is over,  potassium ions  flow out of the cell due to increased  cell membrane  permeability to those ions. This high permeability contributes to the rapid repolarization of the  membrane potential . This repolarization occurs quickly enough that another action potential can cause depolarization before the last action potential has dissipated. Cardiac muscle differs in that there are more calcium channels that counteract the potassium channels. While potassium quickly flows out of the cell, calcium slowly flows into the cell. This causes the repolarization to occur more slowly, making the refractory period as long as the action potential, preventing sustained contractions.


The T wave is representative of the repolarization of the membrane. In an EKG reading, the T wave is notable because it must be present before the next depolarization. An absent or strangely shaped T wave may signify disruption in repolarization or another segment of the heartbeat. [ 3 ]


Normally, T waves are upright in all leads, except aVR and V1 leads. Highest amplitude of T wave is found at V2 and V3 leads. The shape of the T wave is usually asymmetrical with a rounded peak. T wave inversions from V2 to V4 leads are frequently found and normal in children. In normal adults, T wave inversions from V2 to V3 are less commonly found but can be normal. [ 4 ]  The depth of the T wave also becomes progressively shallow from one to the next lead. [ 5 ]  The height of the T wave should not exceed 5 mm in limb leads and more than 10 mm in precordial leads. [ 4 ]


Both the abnormalities of the  ST segment  and T wave represents the abnormalities of the ventricular repolarization or secondary to abnormalities in ventricular depolarisation. [ 5 ]


Inverted T wave is considered abnormal if inversion is deeper than 1.0 mm. Inverted T waves found in leads other than the V1 to V4 leads is associated with increased cardiac deaths. Inverted T waves associated with cardiac signs and symptoms ( chest pain  and  cardiac murmur ) are highly suggestive of  myocardial ischaemia . [ 4 ]  Other ECG changes associate with myocardial ischaemia are:  ST segment  depression with an upright T wave; ST segment depression with biphasic T wave or inverted T wave with negative  QRS complex ; [ 5 ]  T wave symmetrically inverted with a pointed apex, while the ST segment is either bowed upwards or horizontally depressed, or not deviated; and ST segment depression progressing to abnormal T wave during ischaemia free intervals. [ 4 ]  However, ST segment depression is not suggestive of ischaemic location of the heart. ST segment depression in eight or more leads, associated with ST segment elevation in aVR and V1 are associated with left main coronary artery disease or three-vessel disease (blockage of all three major branches of coronary arteries). ST segment depression most prominent from V1 to V3 is suggestive of posterior infarction. Furthermore, tall or wide QRS complex with an upright T wave is further suggestive of the posterior infarction. [ 5 ]


Wellens' syndrome  is caused by the injury or blockage of the  left anterior descending artery , therefore resulting in symmetrical T wave inversions from V2 to V4 with depth more than 5 mm in 75% of the cases. Meanwhile, the remaining 25% of the cases shows biphasic T wave morphology. ST segments remains neutral in this syndrome. Those who were treated without  angiography  will develop anterior wall myocardial infarction in a mean period of 9 days. [ 4 ]  An episode of chest pain in Wellens' syndrome is associated with ST elevation or depression and later progressed to T wave abnormality after chest pain subsided. T wave inversion less than 5 mm may still represents myocardial ischaemia, but is less severe than Wellens' syndrome. [ 5 ]


Hypertrophic cardiomyopathy  is the thickening of the  left ventricle , occasionally  right ventricle . It may be associated with left ventricular outflow tract obstruction or may not be associated with it in 75% of the cases. ECG would be abnormal in 75 to 95% of the patients. Characteristic ECG changes would be large  QRS complex  associated with giant T wave inversion [ 4 ]  in lateral leads I, aVL, V5, and V6, together with ST segment depression in left ventricular thickening. For right ventricular thickening, T waves are inverted from V2 to V3 leads. ST and T waves changes may not be apparent in hypertrophic cardiomyopathy, but if there is presence of ST and T waves changes indicates severe hypertrophy or ventricular systolic dysfunction. [ 5 ]  According to Sokolow-Lyon criterion, the height of R wave in V5 or V6 + the height of S wave in V1 more than 35 mm would be suggestive of left ventricular hypertrophy. [ 4 ]


Both right and left  bundle branch blocks  are associated with similar ST and T wave changes as in hypertrophic cardiomyopathy, but are opposite to the direction of the QRS complex. [ 5 ]


In  pulmonary embolism , T wave can be symmetrically inverted at V2 to V4 leads but  sinus tachycardia  is usually the more common finding. T wave inversion is only present in 19% of mild pulmonary embolism, but the T inversion can be present in 85% of the cases in severe pulmonary embolism. Besides, T inversion can also exists in leads III and aVF. [ 5 ]


Inversion of T waves in most of the ECG leads except aVR indicates many causes most commonly myocardial ischaemia and  intracranial haemorrhage . Others include: hypertrophic cardiomyopathy,  Takotsubo cardiomyopathy  (stress-induced cardiomyopathy),  cocaine  abuse,  pericarditis , pulmonary embolism, and advanced or complete atrioventricular block. [ 5 ]


Numbers from Lepeschkin E in  [ 6 ]


As the name suggests, Biphasic T waves move in opposite directions. The two main causes of these waves are myocardial ischemia and hypokalemia.


Wellens' Syndrome is a pattern of biphasic T waves in V2–3. It is generally present in patients with ischemic chest pain.


T wave is considered flat when the wave varies from -1.0 mm to + 1.0 mm in height.  Hypokalemia  or  digitalis  therapy can cause flattened T wave with a prominent  U wave . As hypokalemia progressively worsens, the T wave becomes more flattened while the U wave becomes more prominent, with progressively deeper ST segment depression. For digitalis toxicity, there will be a sagging QT interval, flattened T wave, and prominent U wave with a shortened QT interval. [ 5 ]


These T waves may be seen in patients displaying  Prinzmetal angina . Additionally, patients exhibiting the early stages of  STEMI  may display these broad and disproportional waves. [ 7 ]


The name of these T waves suggests the shape it exhibits (double peaks). Since these T wave abnormalities may arise from different events, i.e. hypothermia and severe brain damage, they have been deemed as nonspecific, making them much more difficult to interpret. [ 8 ]


High blood  potassium  levels ( hyperkalemia ) can cause "peaked t-waves." [ 9 ]


Transcutaneous pacing  ( TCP ), also called  external pacing , is a temporary means of pacing a patient's  heart  during a medical emergency. It should not be confused with  defibrillation  (used in more serious cases, in ventricular fibrillation and other shockable rhythms) using a manual or automatic defibrillator, though some newer defibrillators can do both, and pads and an electrical stimulus to the heart are used in transcutaneous pacing and defibrillation. Transcutaneous pacing is accomplished by delivering pulses of electric current through the patient's chest, which stimulates the  heart  to contract. [ citation needed ]


The most common  indication  for transcutaneous pacing is an abnormally slow  heart rate . By convention, a heart rate of fewer than 60 beats per minute in the adult patient is called  bradycardia . [ 1 ]  Not all instances of bradycardia require medical treatment. Normal heart rate varies substantially between individuals, and many athletes in particular have a relatively slow resting heart rate. [ 2 ]  In addition, the heart rate is known to naturally slow with age. It is only when bradycardia presents with signs and symptoms of  shock  that it requires  emergency treatment  with transcutaneous pacing.


Some common causes of  hemodynamically  significant bradycardia include  myocardial infarction ,  sinus node dysfunction  and  complete heart block . [ citation needed ]


Transcutaneous pacing is no longer indicated for the treatment of  asystole  ( cardiac arrest  associated with a "flat line" on the  ECG ), with the possible exception of witnessed asystole (as in the case of  bifascicular block  that progresses to  complete heart block  without an  escape rhythm ). [ 4 ]


During transcutaneous pacing, pads are placed on the patient's chest, either in the anterior/lateral position or the anterior/posterior position. The anterior/posterior position is preferred as it minimizes transthoracic  electrical impedance  by "sandwiching" the heart between the two pads [ citation needed ] . The pads are then attached to a monitor/defibrillator, a heart rate is selected, and current (measured in milliamps) is increased until electrical capture (characterized by a wide  QRS complex  with tall, broad T wave on the  ECG ) is obtained, with a corresponding pulse. Pacing artifact on the ECG and severe muscle twitching may make this determination difficult. It is therefore advisable to use another instrument (e.g. SpO2 monitor or bedside doppler) to confirm mechanical capture.


Transcutaneous pacing may be uncomfortable for the patient.  [ citation needed ]   Sedation  should therefore be considered. Before pacing the patient in a prehospital setting sedation is recommended by administering an analgesic or an anxiolytic. [ by whom? ]  Prolonged transcutaneous pacing may cause burns on the skin. According to the Zoll M Series Operator's Guide," Continuous pacing of neonates can cause skin burns. If it is necessary to pace for more than 30 minutes, periodic inspection of the underlying skin is strongly advised."  It is meant to stabilize the patient until a more permanent means of pacing is achieved.


Other forms of cardiac pacing are  transvenous pacing , epicardial pacing, [ 5 ]  and permanent pacing with an  implantable pacemaker .


In addition to synchronized transcutaneous pacing offered by newer cardiac monitor/defibrillators, there is also an option for asynchronous pacing. Sometimes in the prehospital setting a situation may arise where ECG electrodes are not available or something interferes with their adhesion to the patient's skin. In these rare situations where the patient must be paced and there are no other alternatives, asynchronous pacing may be used. Again, this setting should only be used as a last resort due to possible adverse cardiac effects it could cause.


Transvenous cardiac pacing  ( TVP ), [ 1 ]  also called  endocardial pacing , is a potentially life-saving intervention used primarily to correct profound  bradycardia . It can be used to treat symptomatic bradycardias that do not respond to  transcutaneous pacing  or to drug therapy.  Transvenous pacing is achieved by threading a pacing electrode through a vein into the  right atrium ,  right ventricle , or both.


This means of pacing the heart is not as popular as other means of pacing (like transcutaneous pacing,  implanted pacemaker ,  epicardial pacing ) because it is a temporary solution to pace the heart and yet involves a similar level of risk of bleeding as a more permanent solution like placing an implanted pacemaker.


For patients who present in an emergency setting with symptomatic bradycardias, usually drugs like  atropine  or  sympathomimetic  drugs ( epinephrine  or  dopamine ) can be used to increase the heart rate to an adequate level until the underlying cause of the bradycardia can be isolated and then, possibly, a permanent pacemaker can be placed.


For patients for whom transvenous pacing is chosen, the procedure is done at the bedside with a  local anesthetic  alone or in conjunction with  conscious sedation .  The pacing electrode is advanced through the vein under  fluoroscopic  and  electrocardiographic  guidance.  An  X-ray  after the procedure is always obtained to confirm placement of the pacing electrode.


The greater use of atropine and epinephrine or external pacing may make transvenous pacing unnecessary by stabilizing patients early in the process of caring for the patient.  Some debate exists over the efficacity and reliability of transvenous pacing, especially if the need for permanent pacing is anticipated.


The  U wave  is a wave on an  electrocardiogram  (ECG). It comes after the  T wave  of ventricular repolarization and may not always be observed as a result of its small size. 'U' waves are thought to represent repolarization of the  Purkinje fibers . [ 1 ] [ 2 ]
However, the exact source of the U wave remains unclear. The most common theories for the origin are:


According to V. Gorshkov-Cantacuzene:


"The U wave is the momentum carried by the blood in the coronary arteries and blood vessels". [ 4 ] [ 5 ] [ 6 ]


The  resistivity  of stationary blood is expressed as

 (

 Ht

 )

 =

 |

 Ht

 ⋅
 (
 1
 +
 α

 Ht

 )

 {\displaystyle \left({\text{Ht}}\right)=|{\text{Ht}}\cdot (1+\alpha {\text{Ht}})}

 , where

 α

 {\displaystyle \alpha }

  is a coefficient, and

 Ht

 {\displaystyle {\text{Ht}}}

  is the  hematocrit ; at that time, as during acceleration of the blood flow occurs a sharp decrease in the longitudinal resistance with small relaxation times.


However, multiple factors affect blood resistivity.  Erythrocyte  aggregation occurs at low shear rates and implies that to all vessels (with the exception of large veins) the effect of aggregation is irrelevant. The interior of a blood vessel includes a near-wall layer of plasma (referred to as lubricant), the size of which strictly depends on Reynold's criterion and the  shear rate  of the flowing blood. Given that the thickness of this layer in all blood vessels (except  capillaries ) is less than 5 microns, and the resistivity of the plasma is two times less than in blood, then according to the scheme of parallel insertion, the contribution of this layer to the resistivity is negligible. By reducing the speed of blood flow profiles the dependence of Ht on the radius of the vessel becomes more elongated. However, at normal values of Ht, the effect is also insignificant. With high enough shear rates, the red blood cells become susceptible to deformation. The contribution of this phenomenon is difficult to assess because it is present in the background of all the above effects. However, even the sum of all these factors has little effect on blood resistivity.


It follows that at the time of ejection of blood from the left ventricle, part of the pulse is carried away, because there is no electrical resistivity of blood, which gradually increases high up in the  coronary arteries  and  blood vessels . The U wave is the momentum carried by the blood in the coronary arteries and blood vessels. It is possible to take this momentum back to Purkinje fibers along the vessels of the myocardium. This idea is also proved by the fact that  hypertrophy  of the left ventricle,  myocardial ischemia , coronary and insufficiency have momentum there is no possibility to move to the Purkinje fibers, therefore, the ECG recorded a negative U wave.


According to many studies [ which? ] , U waves often register in all leads except V6, most frequently in V2 and V3 when the heart rate is greater than 96 beats per minute. Its amplitude is often 0.1–0.33  mV.  Particularly difficult is the allocation of the boundaries of the U wave on the background of the T wave and  R wave , which may partial or complete (in the case of T wave) the merger. Higher values of heart rate or  hypocalcemia  U wave are superimposed on the  T wave  and in  tachycardia  — merges with the R-wave of the next cardiac cycle.


Prominent U waves (U waves are described as prominent if they are more than 1-2 mm or 25% of the height of the T wave.) are most often seen in  hypokalemia  but may be present in  hypercalcemia ,  thyrotoxicosis , or exposure to  digitalis ,  epinephrine  and Class 1A and 3  antiarrhythmics , as well as in congenital  long QT syndrome , and in the setting of  intracranial hemorrhage .


An inverted U wave may represent  myocardial ischemia  (and especially appears to have a high positive predictive accuracy for  left anterior descending coronary artery  disease [ 7 ]  ) or left ventricular  volume overload . [ 8 ]


A U-wave can sometimes be seen in normal younger, athletic individuals. [ 9 ]  The U-wave increases in adults that are older and less athletic. [ 10 ]


In  electrocardiography , the ventricular  cardiomyocyte   membrane potential  is about −90 mV at rest, [ 1 ]  which is close to the  potassium   reversal potential . When an  action potential  is generated, the membrane potential rises above this level in five distinct phases. [ 1 ]


The Na +  channel opening is followed by inactivation. Na +  inactivation comes with slowly activating Ca 2+  channels at the same time as a few fast K +  channels open. There is a balance between the outward flow of K +  and the inward flow of Ca 2+  causing a plateau of length in variables. The delayed opening of more Ca 2+ -activated K +  channels, which are activated by build-up of Ca 2+  in the sarcoplasm, while the Ca 2+  channels close, ends the plateau. This leads to repolarization.


The depolarization of the membrane allows  calcium  channels to open as well. As sodium channels close calcium provides current to maintain the potential around 20 mV. The plateau lasts on the order of 100 ms. At the time that calcium channels are getting activated, channels that mediate the transient outward potassium current open as well. This outward potassium current causes a small dip in membrane potential shortly after  depolarization . This current is observed in human and dog action potentials, but not in guinea pig action potentials.


Repolarization  is accomplished by channels that open slowly and are mostly activated at the end of the action potential ( slow delayed-rectifier channels ) and channels that open quickly but are inactivated until the end of the action potential ( rapid delayed rectifier channels ). Fast delayed rectifier channels open quickly but are shut by inactivation at high membrane potentials. As the membrane voltage begins to drop the channels recover from inactivation and carry current.


Clara Bonanad  is a clinical  cardiologist  at the University Clinical Hospital,  Valencia  in the department of  Cardiology . [ 1 ] [ 2 ]


Bonanada earned her PhD in Medicine at the  University of Valencia  in 2016 and her PhD thesis is “Prognostic impact of Geriatric Syndromes in Acute Coronary Syndromes”. [ 3 ] [ 4 ]


Her research on sex differences in the influence of frailty in senior outpatients with heart failure, as well as Bending Oxygen Saturation index (BOSI) and the Risk of Worsening Heart Failure Events in Chronic Heart Failure. [ 5 ]
 [ 6 ]


This is a list of people notable in the field of  cardiology . Presented along with their year of birth, death, nationality, notability, and reference(s).


Chen Haozhu  ( Chinese :  陈灏珠 ; 6 November 1924 – 30 October 2020) was a Chinese cardiologist.


Chen was born on 6 November 1924 and attended  National Zhongzheng Medical College  [ zh ] , where he completed a bachelor's degree in 1949. He was responsible for introducing the term " myocardial infarction " to Chinese medical professionals, and is credited with pioneering modern cardiology in China by using newer methods of treatment and diagnosis. Chen was the director of the Shanghai Institute of Cardiovascular Diseases and served as vice chair of the Chinese Society of Cardiology, as well as the Chinese Medical Association. [ 1 ]  He taught as a professor at  Zhongshan Hospital , affiliated to  Fudan University , and was elected a member of the  Chinese Academy of Engineering  in 1997. [ 2 ]


Chen died on 30 October 2020, aged 95. [ 1 ]


Bila M. Kapita  is a doctor from  Kinshasa ,  Democratic Republic of the Congo  who aided in initial research efforts investigating  HIV/AIDS  in Africa in the 1980s and 1990s. Kapita is credited as one of the first African scientists to independently identify that AIDS was prevalent in Central Africa. Research work in collaboration with  Project SIDA  helped identify and publicize the heterosexual sexual transmission of HIV. Following his research career, he continued caring for patients with HIV/AIDS and has more recently returned to practicing  cardiology .


Bila M. Kapita was raised in a Swedish mission in the  Bas-Congo  province of the former  Belgian Congo . [ 1 ]


Kapita received medical training in  Brussels, Belgium  at the  Cliniques Universitaires Saint-Luc , where he focused on  cardiology , publishing several research articles on the subject dating back to 1975. [ 2 ] [ 3 ] [ 4 ]


Upon return to Zaire, Kapita practiced cardiology and general medicine at the  Mama Yemo Hospital , becoming head of  internal medicine . [ 4 ] [ 5 ] [ 6 ]  Kapita was well established in Kinshasa and served as the head of the Kinshasa Medical Association. [ 4 ]


Kapita noted in retrospect that patients at his hospital displayed an increased amount of  Kaposi's sarcoma  beginning in the mid-1970s. Around the same time, patients were more frequently suffering from  Cryptococcal meningitis . [ 5 ]  Both diseases are  opportunistic infections  which were significant of decreased  immune system  response in patients.


Following the initial connection between these opportunistic infections in the United States in 1981, African scientists including Kapita recognized the similar clinical presentation. The prevalence of what would soon become known as  AIDS  in African countries caught the attention of European and American researchers. The United States’  Centers for Disease Control  and  National Institute of Allergy and Infectious Diseases  were alerted to the rising pandemic by former collaborators in Ebola research from Europe such as  Peter Piot . [ 4 ] [ 7 ]  A group of researchers from Belgium, the United States, and France were first introduced to the state of  Africa's AIDS pandemic  in the isolation wards of Kapita's hospital. [ 4 ] [ 5 ] [ 7 ]


Kapita was welcoming to the international researchers, allowing them to work from his hospital for long periods of time. Due to Kapita's notability in Kinshasa, he was able to protect these scientists from any government discontent involving outside research at the time. [ 4 ]  Peers described Kapita as being true to his ideals and well trained. [ 4 ] [ 6 ]


Patients in the wards of Mama Yemo were clearly affected by AIDS per the clinical definitions in place at that time. Almost all of the patients confirmed to have AIDS using laboratory based tests were already identified by Kapita without laboratory tests. [ 4 ] [ 7 ] [ 8 ]  Kapita is credited by his collaborators as being one of the first people in Africa to identify the presence of AIDS. [ 8 ]  The visiting researchers would soon realize the extent of AIDS in Africa and began research in Kinshasa. The resulting collaboration between African, American, and European scientists would become known as  Project SIDA . [ 1 ] [ 4 ] [ 5 ] [ 7 ]


Bila M. Kapita published his own book in 1988 titled  SIDA en Afrique. [ 9 ]


From 1984 to 1991 Kapita collaborated with Project SIDA at Mama Yemo, producing between 20 and 30 research articles on the transmission, history, and future of HIV/AIDS in Africa. Work was conducted in Kapita's hospital early on in the program to increase chances of approval from government authorities. [ 4 ]


Many of Kapita's articles focused on the rate of heterosexual transmission that was largely ignored by the United States in the early 1980s. [ 1 ] [ 10 ]


Kapita was present at the first  International AIDS Conference  in Atlanta, Georgia in 1985. [ 1 ]  Also in attendance were Project SIDA collaborators Peter Piot and  Nzila Nzilambi —as well as thousands of other scientists. [ 7 ]  During the second International AIDS Conference in  Paris , France, Kapita informed the community of his retrospective discovery of increased cases of Kaposi's sarcoma and  cytomegalovirus , indicators that HIV/AIDS likely existed in Kinshasa as far back as 1975. [ 7 ] [ 11 ]  Prior to public knowledge of HIV prevalence in Zaire at the time, Kapita faced the threat of becoming a political prisoner under  Mobutu Sese Seko ’s regime for acknowledging the issue on a global stage without permission from the government. [ 12 ] [ 5 ]


In 1990, as the civil war was beginning in Zaire, Kapita worked with Peter Piot in arranging an international AIDS conference in Kinshasa. The proceeds of the conference were returned to the region through donations to Mama Yemo Hospital and the establishment of a health clinic in Kapita's village. [ 1 ]


Kapita's work continued for a few years following the 1991 demise of Project SIDA. A notable collaboration featuring Kapita in 1992 was the  World Health Organization  publication:  AIDS in Africa: A Manual for Physicians. [ 13 ]


Following the end of Project SIDA due to civil war in Zaire, Kapita continued to appear on international research articles, the last being published in 1993. [ 14 ]  Kapita continued to work at Mama Yemo, until at least 1997, treating patients with HIV/AIDS. [ 15 ] [ 8 ]


A hallmark of Project SIDA was the training of Congolese researchers, resulting in many well-trained doctors such as Kapita existing in Kinshasa. American and European collaborators established traditional research procedure in Kinshasa, establishing an  institutional review board  led by Kapita. [ 4 ]


Kapita and the other Zairian collaborators of Project SIDA wished to return to research, but opportunities following the civil war were limited. [ 8 ]  Currently, Kapita practices cardiology at the Centre Medical De Kinshasa in  Gombe, Kinshasa . [ 16 ]


Sílvia Paula Valentim Lutucuta  (born 14 July 1968) is an Angolan politician and cardiologist, the incumbent Minister of Health.


Lutucuta was born in  Huambo  in 1967. She trained in medicine and specialised in cardiology at the  Hospital de Santa Maria  in Lisbon, Portugal. [ 1 ]  In 2000 she moved to Houston in Texas where she undertook post-doctoral research at  Baylor College of Medicine . [ 2 ]


She joined the Angolan Society of Cardiovascular Diseases. [ 3 ]


She is a member of the Member of the MPLA Political Bureau. [ 1 ]  In 2017 she was nominated to be the Minister of Health in Angola. She has created thousands of new jobs, especially in rural layers. Under her leadership vaccines for COVID-19 were rolled out in her country and she organised the funding. [ 2 ]


This Angolan biographical article is a  stub . You can help Wikipedia by  expanding it .


Mrigendra Raj Pandey  is a Nepalese physician from Kathmandu. He is one of the most senior doctors in Nepal and probably the first cardiologist in the country. [ 1 ]  He is the Nepal first Member of the   Royal College of Physicians   and also the   FRCP  from Edinburgh.  He  was also the personal physician to the  King Mahendra . [ 2 ]  He was the founder chief-editor of the  Journal of Nepal Medical Association  from 1963 to 1964. [ 3 ]  He is the founder president of the Nepal Heart Foundation. [ 4 ]  He established the Mrigendra Samjhana Medical  Trust in year 1975. [ 5 ] [ 6 ] [ 7 ]  He is  Patron  of Cardiac Society of Nepal. [ 8 ]  He is involved in various research activities of medical field in Nepal since long time. [ 9 ]


Carlos Enrique Soto Menegazzo  (born August 26, 1951) is a  Guatemalan   cardiologist  and politician who served as  Minister of Public Health and Social Assistance  from 2017 to 2020 under the  government  of  Jimmy Morales . [ 1 ] [ 2 ]


On August 29, 2017 he was appointed to replace  Lucrecia Hernández Mack  as Minister of Public Health. [ 2 ]  Hernández had announced her resignation the sunday before, in protest over President  Jimmy Morales  ordering the expulsion of  United Nations  anti-corruption investigator  Iván Velásquez Gómez . [ 3 ]


Since February 2014, he had served as director of  Roosevelt Hospital  until that day. [ 4 ]


He is son of Carlos Armando Soto Gómez y Odilia Perina Menegazzo Vanfrette, his father was Minister of Health too from 1986 to 1990 and deputy of the Guatemalan National Constituent assembly of 1984. [ 5 ]


He married whit Beatriz Díaz in 1969 and they divorced in 1989. He married for the second time with Lucrecia Torcelli in 1989. [ 5 ]


This article about a Guatemalan politician is a  stub . You can help Wikipedia by  expanding it .


Abiomed, Inc.  is a  medical device  technology company that operates as a stand-alone business within  Johnson & Johnson's  MedTech Segment. [ 2 ]  Abiomed develops and manufactures temporary external and implantable mechanical circulatory support devices. The company is headquartered in  Danvers, Massachusetts  with additional offices in  Woburn ,  Baltimore ,  Berlin ,  Aachen , and  Tokyo .


Andrew Greenfield is President of the company, with Dr. Thorsten Siess as Executive Vice President and Chief Technology Officer and Dr. Chuck Simonton as Executive Vice President and Chief Medical Officer. [ 2 ]  According to Bloomberg, the company "engages in the research, development, and sale of medical devices to assist or replace the pumping function of the failing heart. It also provides continuum of care to heart failure patients". [ 3 ]


As of 2022, the company had secured five FDA approvals and 1,408 patents with 1,416 pending. [ 4 ]  For fiscal year 2022, Abiomed reported $1.032 billion in revenue and reported diluted earnings per share was $2.98 for the year. [ 1 ]


On December 22, 2022,  Johnson & Johnson  completed the acquisition of Abiomed. [ 5 ]


Abiomed was founded in  Danvers, Massachusetts  by  David M. Lederman  in 1981 as Applied Biomedical Corporation. [ 6 ]  That year, the company commenced the development of an  artificial heart . [ 7 ]  Funded by federal research grants, [ 8 ]  Lederman partnered with  The Texas Heart Institute  to develop the  AbioCor , a  grapefruit -sized electromagnetic device with an internal battery that completely replaces the heart without wires or tubes passing through the skin. [ 6 ]   In July 2001, AbioCor became the first artificial heart successfully implanted in a patient, where it pumped more than 20 million times. [ 9 ]  Fourteen of the AbioCor devices were implanted, during  clinical trials  from 2001 to 2004, with the longest-living recipient surviving 512 days. [ 6 ]  The AbioCor won  FDA approval  in 2006 for patients who are near death and do not qualify for a  heart transplant . [ 7 ]


In 2004, Michael R. Minogue became president and CEO of Abiomed. [ 10 ]  In 2005, Abiomed purchased  ventricular assist device  company Impella CardioSystems AG of  Aachen, Germany , [ 11 ]  maker of the  Impella  heart pump, developed by Thorsten Siess, [ 12 ]  who is now the  chief technology officer  at Abiomed. [ 13 ] [ self-published source ]  After Abiomed acquired Impella the company's focus shifted from heart replacement to heart recovery. [ 14 ]


In July 2014, Abiomed acquired German heart pump maker ECP in a deal worth up to $30 million. The deal included a nearly $2.8 million buyout of AIS GmbH Aachen Innovative Solutions, which owns some of the patents licensed to ECP. [ 15 ]


In May 2018, Abiomed was added to the  S&P 500 index . [ 16 ]  During the S&P's rise from 2000 to 3000, Abiomed was the index's top performing stock. [ 17 ]


In 2018, Abiomed built a $17 million Innovation Center to facilitate research and product development at its headquarters in Danvers. [ 18 ]  The 29,800-square-foot facility features laboratories for blood, optical, software, mechanical and electrical research, plus a production line. [ 19 ]


In 2019,  Barron's  ranked Abiomed the fourth best  stock  of the 2010s, with total return of 1,983%. [ 20 ]  while  Fortune  ranked Abiomed 19th on the magazine's list of 100 fastest-growing companies. [ 21 ]


In April 2020, Abiomed acquired medical device company Breethe, a startup that spun out of the University Of Maryland. [ 22 ]  The startup had developed a portable  extracorporeal membrane oxygenation (ECMO)  system that acts like an artificial lung, oxygenating and removing carbon dioxide from the blood of a patient in cardiogenic shock or respiratory failure. [ 23 ]  The technology, now known as the Abiomed Breethe OXY-1 System, received FDA 510(k) clearance later that year. [ 24 ]


In June 2020, Abiomed appointed Charles A. Simonton, MD, as vice president and Chief Medical Officer. [ 25 ]  Also in 2020, the FDA granted Emergency Use Authorization for the Impella heart pump to stabilize COVID-19 patients following the removal of pulmonary blood clots, as well as the use of the Impella in combination with the Breethe extracorporeal membrane oxygenation (ECMO) system, which pumps more oxygen into the bloodstream. [ 26 ]


In February and April 2021, Abiomed appointed neurosurgeon  Myron Rolle  and cardiologist  Paula Johnson  to the board of directors. [ 27 ]  Drs. Rolle and Johnson serve on the Governance and Nominating Committee and Regulatory and Compliance Committee of the board. [ 28 ] [ 29 ]


In June 2021, Abiomed acquired preCARDIA, a catheter developer whose system allows for a less-invasive option when treating  acute decompensated heart failure  (ADHF) patients. [ 30 ]


In November 2022, Abiomed announced that it would be acquired by Johnson & Johnson in a $16.6 billion deal. [ 31 ]  The deal closed on December 22. [ 32 ]  Following the acquisition, Abiomed continues to operate as a standalone business within Johnson & Johnson's MedTech segment. [ 2 ]


Impella is the world's smallest heart pump. [ 16 ]  It sits in the heart, spinning up to 50,000 revolutions per minute, sending blood throughout the body, allowing the heart to rest and recover. It is inserted through a minimally invasive procedure and guided through an artery to the heart. [ 14 ]  In 2007, the Impella 2.5 heart pump was among 35 healthcare products to receive a 2007 Medical Design Excellence Award. [ 33 ]  As of 2022, the Impella heart pump products include the Impella 2.5, Impella 5.0, Impella CP with SmartAssist, Impella 5.5 with SmartAssist, Impella RP with SmartAssist and Impella Connect, which gives providers 24/7 secure access to Impella status data in the cloud for Impella-supported patients. [ 34 ]


The Abiomed Breethe OXY-1 System is an  extracorporeal membrane oxygenation (ECMO)  system that pumps, oxygenates and removes carbon dioxide from blood of patients suffering from cardiogenic shock or respiratory failure due to ARDS, H1N1, SARS and COVID-19 among other causes. It can be used alone or in conjunction with the Impella heart pump. [ 24 ]


Since 2005 when Abiomed acquired the  Impella  technology, [ 35 ]  the heart devices have received a series of FDA approvals. [ 36 ]  Notably, in 2015, Abiomed received FDA approval to use the Impella 2.5 heart pump during elective and urgent high-risk percutaneous coronary intervention procedures. The FDA approval was based on the PROTECT II randomized controlled trial, which found high-risk percutaneous coronary intervention (PCI) patients who underwent PCI with Impella had fewer major adverse events at 90 days (although statistically non-significant), compared to patients who underwent PCI with the intra-aortic balloon pump (IABP). [ 37 ]  In 2016, the Impella RP system became the first percutaneous single-access heart pump designed for right-heart support to receive FDA approval. [ 38 ]


There is a lack of data from randomized controlled trials for Impella devices in cardiogenic shock, despite calls from the medical community. [ 39 ]  While early studies suggested short term benefits, propensity-matched analyses comparing the Impella device with intra-aortic balloon pump (IABP) showed no benefit for clinically relevant outcomes such as mortality. [ 40 ]  This may be partly due to increased risk of bleeding and peripheral vascular complications with the Impella device. [ 41 ]  Some studies have even suggested an increased risk of mortality with Impella devices, compared to the intra-aortic balloon pump (IABP), with an additional expense of >$50,000 at 30 days. [ 42 ]  There are currently no adequately powered randomized controlled trials of the Impella device for clinically relevant outcomes such as mortality.


In 2021, the FDA granted pre-market approval to the Impella RP with SmartAssist, a first single-access, dual-sensor technology device to provide temporary percutaneous ventricular support for patients with acute right heart failure or decompensation after implanting a left ventricular assist device, myocardial infarction, heart transplant or open-heart surgery. [ 43 ]  The FDA also granted breakthrough device designation for its smallest heart pump, the Impella ECP, which measures only 3mm in length. [ 44 ]


In April 2022, Abiomed's Impella Bridge-to-Recovery (BTR) minimally-invasive heart pump was successfully implanted in the first patient treated with the device as part of an early feasibility study. [ 45 ]  In August 2022, results from the Restore EF study were published in  The Journal of the Society of Cardiovascular Angiography and Interventions . The study demonstrated that Impella-supported high-risk percutaneous coronary intervention (PCI) led to significant improvements in left ventricular ejection fraction (LVEF), angina symptoms, and heart failure symptoms at the 90-day follow-up. [ 46 ]  In October 2022, the FDA granted pre-market approval to the Impella RP Flex with SmartAssist for treatment of acute right heart failure for up to 14 days. [ 47 ]


Andrew Greenfield is Abiomed's President since the company was acquired by Johnson & Johnson in December 2022. He succeeded Michael R. Minogue who retired after serving as chairman, President and CEO since 2004 when Abiomed's founder, David Lederman, had stepped down. [ 2 ] [ 7 ]