WO2014091227A1

WO2014091227A1 - Electrocardiography apparatus and method

Info

Publication number: WO2014091227A1
Application number: PCT/GB2013/053257
Authority: WO
Inventors: Dr Velislav BATCHVAROV; Dr Elijah BEHR
Original assignee: St George's Hospital Medical School
Priority date: 2012-12-11
Filing date: 2013-12-11
Publication date: 2014-06-19
Also published as: GB201222262D0

Abstract

There is provided an electrocardiography apparatus and method based on using bipolar chest leads showing the difference in potential between a precordial electrode and a limb electrode of a standard 12-lead electrocardiography arrangement.

Description

ELECTROCARDIOGRAPHY APPARATUS AND METHOD

The present invention relates to an electrocardiography apparatus and method.

A standard 12-lead electrocardiogram (ECG) is well known in relevant technical field. It records differences between the electrical potentials of 9 electrodes attached to the skin. Six of these electrodes are attached to the chest in close proximity to the heart whereas the other three are positioned on the limbs. A tenth 'neutral' electrode is also applied to one of the limbs.

So-called ECG 'leads' represent the time- varying difference in electrical potential between electrodes. Each of the standard 12 leads represent the difference either between the potentials of two electrodes or between the potential of one electrode and the combined potential of several other electrodes. The positions of the electrodes and the way the leads are constructed (i.e. exactly which potential differences each of the leads represents) have been standardised in the 1930' s and 1940' s and have remained virtually unchanged since then. However, the reasons for this are historic rather than scientific. It has never been demonstrated that the current 12-lead ECG system provides the most medically useful information compared to other possible ECG systems (e.g. systems with different number of electrodes or on different positions, or linked into another system of leads). In fact, other ECG lead systems (using different number or other positions of the electrodes) also have been developed over the years and their usefulness in some clinical scenarios has been documented. However, the standard 12-lead system is by far the most popular and best established and has been thoroughly tested in medical practice (approximately a few hundred million ECGs are being recorded worldwide each year). As such, generations of cardiologists and other medical professionals have been trained to interpret ECGs recorded with this system.

The present invention identifies that the potentials of the 9 electrodes that are used to acquire the standard 12-lead ECG can be utilised to construct other ECG leads. These new leads can provide a different view of the electrical activity of the heart, thereby revealing details that would otherwise hardly be noticeable, or be invisible, in the 12 standard ECG leads.

Significantly, these new leads do not need to be recorded de novo; they can be derived from the originally recorded standard 12-lead ECG if it is available in a digital form using software programmes. Thus, the derived leads can be an important clinical tool that can be retrofitted to existing systems at low cost, making it very simple to upgrade existing equipment as well as produce new enhanced ECG systems. This invention for the first time demonstrates the clinical usefulness of deriving the new leads from the standard 12-lead ECG (if it available in a digital form) and shows that a software upgrade for their derivation can easily be fitted in modern ECG recorders thus increasing their clinical value. The following text provides a summary of methods for derivation of new ECG leads from the standard 12-lead ECG and presents evidence supporting their potential clinical usefulness.

According to the invention there is provided an electrocardiography apparatus comprising: a signal receiving unit for receiving signals from RA, LA, LL, VI, V2, V3, V4, V5 and V6 electrodes, and a signal processing unit configured to calculate at least one bipolar chest lead VnF as defined in Equation 1, and/or at least one bipolar chest lead VnL as defined in Equation 2, and/or at least one bipolar chest lead VnR as defined in Equation 3 :

Lead VnF = E_n - E_F; Equation 1

Lead VnL = E_n - E_L; and Equation 2

Lead VnR = E_n - E_R, Equation 3

where VnF, VnL and VnR are the bipolar chest leads based on differences in potential between the respective precordial electrode (Vn, for n= 1 to 6) and the left foot electrode (VF, for lead VnF), the left arm electrode (VL, for lead VnL) or the right arm electrode (VR, for lead VnR), and E_n (for n=l to 6), E_F, E_L and E_R are the potentials at the Vn, VF, VL and VR electrodes respectively.

According to this aspect, bipolar chest leads can be obtained which in many instances can give a clearer representation of the electrical activity of the heart, with less noise, than the conventional unipolar precordial leads of the 12-lead ECG. Further, although the bipolar chest leads are defined above with respect to the actual potentials recorded at the electrodes, the leads can be calculated (as discussed in more detail below) from the conventional 12 leads obtained from an ECG. That is, the leads do not need to be calculated from the definitions above: they can be calculated according to equivalent calculations (i.e. producing the same resulting leads) based on the conventional 12 leads rather than the raw potentials measured by the electrodes.

According to another aspect of the invention, there is provided an electrocardiography apparatus comprising: a signal receiving unit for receiving signals from VI, V2, V3, V4, V5 and V6 electrodes, and a signal processing unit configured to calculate at least one multipolar precordial lead from the received signals.

According to this aspect, a multipolar lead can be constructed from the precordial electrodes of a standard 12-lead ECG. This can reveal information that cannot be obtained from standard 'unipolar' precordial leads. Advantageously, the multipolar leads can be constructed from recorded unipolar leads - that is, it is not necessary to use the raw data from the electrodes (although that too is possible) and so the multipolar leads can be calculated after an ECG has already been taken. In one example, the signal processing unit is configured to calculate at least one quadripolar precordial lead, lead Vi-jk, according to the equation:

Lead Vi-jk= 2 Ei-Ej-Ek

where i,j,k are in the set n=l to 6, for precordial electrodes Vn (for n= 1 to 6) recording potentials En (for n=l-6) respectively.

Further , the electrocardiography apparatus can be further configured such that: the signal receiving unit is for receiving signals from RA, LA, LL, VI, V2, V3, V4, V5 and V6 electrodes, and the signal processing unit is further configured to calculate at least one bipolar chest lead VnF as defined in Equation 1, and/or at least one bipolar chest lead VnL as defined in Equation 2, and/or at least one bipolar chest lead VnR as defined in Equation 3 :

Lead VnF = En - EF; Equation 1

Lead VnL = En - EL; and Equation 2

Lead VnR = En - ER, Equation 3

where VnF, VnL and VnR are the bipolar chest leads based on differences in potential between the respective precordial electrode (Vn, for n= 1 to 6) and the left foot electrode (VF, for lead VnF), the left arm electrode (VL, for lead VnL) or the right arm electrode (VR, for lead VnR), and En (for n=l-6), EF, EL and ER are the potentials at the Vn, VF, VL and VR electrodes respectively. As such, the apparatuses of the first two aspects can be combined.

The apparatus of either of the first two aspects can further comprise a signal output for outputting at least one of the calculated bipolar chest leads. The output can comprise a display or graphing unit for receiving and visualising the at least one calculated bipolar chest lead. As such the leads can be observed by a clinician. The leads can be output together or individually or a sub-set of the leads can be output.

The apparatus can further comprise the RA, LA, RL, LL, VI, V2, V3, V4, V5 and V6 electrodes, wherein the electrodes are connected to the signal receiving unit.

The signal processing unit can be further configured to calculate a standard 12-lead electrocardiogram. Accordingly, the apparatus can provide both the conventional leads as well as the new leads of the invention, thereby providing a clinician with as many leads as possible to choose from, as required.

According to another aspect of the invention, there is provided an electrocardiography method comprising: receiving signals from at least some of RA, LA, RL, LL, VI, V2, V3, V4, V5 and V6 electrodes, and calculating at least one bipolar chest lead VnF as defined in Equation 1, and/or at least one bipolar chest lead VnL as defined in Equation 2, and/or at least one bipolar chest lead VnR as defined in Equation 3 :

Lead VnF = E_n - E_F; Equation 1 Lead VnL and Equation 2

Lead VnR Equation 3

where VnF, VnL and VnR are the bipolar chest leads based on differences in potential between the respective precordial electrode (Vn, for n= 1 to 6) and the left foot electrode (VF, for lead VnF), the left arm electrode (VL, for lead VnL) or the right arm electrode (VR, for lead VnR), and E_n (for n=l-6), E_F, E_L and E_R are the potentials at the Vn, VF, VL and VR electrodes respectively.

According to this aspect there is provided a method that provides new and advantageous ECG leads. It is not necessary to receive signals from all the electrodes of a standard 12-lead ECG if it is only desired to calculate specific individual leads - in that case, it is sufficient to receive signals from the electrodes relevant to the derivation of the desired leads.

According to another aspect, there is provided an electrocardiography method

comprising: receiving signals from at least some of VI, V2, V3, V4, V5 and V6 electrodes, and calculating at least one multipolar precordial lead from the received signals.

The calculating can comprise calculating at least one quadripolar precordial lead, lead Vi- jk, according to the equation:

Lead Vi-jk= 2 Ei-Ej-Ek

The method can coprise: receiving signals from RA, LA, LL, VI, V2, V3, V4, V5 and V6 electrodes, and calculating at least one bipolar chest lead VnF as defined in Equation 1, and/or at least one bipolar chest lead VnL as defined in Equation 2, and/or at least one bipolar chest lead VnR as defined in Equation 3 :

Lead VnF Equation 1

Lead VnL and Equation 2

Lead VnR Equation 3

Either method aspect can further comprise outputting at least one of the calculated bipolar chest leads, wherein said outputting comprises displaying or graphing the at least one calculated bipolar chest lead.

The methods can further comprising applying at least the relevant ones of the RA, LA, RL, LL, VI, V2, V3, V4, V5 and V6 electrodes to a patient.

The methods can further comprise calculating a standard 12-lead electrocardiogram. According to another aspect of the invention, there is provided a computer program capable of execution by an electrocardiography apparatus comprising a computer processor, the computer program comprising instructions such that, when executed by the processor, the electrocardiography apparatus performs the steps of either method aspect discussed above.

According to another aspect of the invention, there is provided a computer-readable storage medium storing the program of the previous aspect.

According to another aspect of the invention, there is provided a method of diagnosing a heart condition, comprising the method the previous aspect and further comprising identifying an anomaly in the at least one calculated bipolar chest lead.

According to another aspect of the invention, there is provided a method of diagnosing arrhythmogenic right ventricular cardiomyopathy/dysplasia, the method comprising: calculating at least one bipolar chest lead V_nF as defined in Equation 1, and/or at least one bipolar chest lead V_nL as defined in Equation 2:

Lead VnF = E_n - E_F; Equation 1

Lead VnL = E_n - E_L; and Equation 2

where VnF and VnL are the bipolar chest leads based on differences in potential between the respective precordial electrode (Vn, for n= 1 to 6) and the left foot electrode (VF, for lead VnF), the left arm electrode (VL, for lead VnL), and En (for n=l-6), E_F, and E_L are the potentials at the Vn, VF and VL electrodes respectively. Leads VnF and VnL have proved to be particularly useful in assisting the diagnosis of arrhythmogenic right ventricular

cardiomyopathy/dysplasia.

According to another aspect, there is provided a method of identifying the onset of ventricular tachycardia, the method comprising: receiving signals from at least some of VI, V2, V3, V4, V5 and V6 electrodes, and calculating at least one multipolar precordial lead from the received signals.

The invention is described below, by way of non-limiting example only, with reference to the accompanying figures, in which:

Fig. 1 is a diagram that illustrates an example electrocardiograph (ECG) system;

Fig. 2 is a diagram that illustrates leads and placement of electrodes for standard ECG measurements;

Fig. 3 is an example ECG trace;

Fig. 4 is an excerpt from an ambulatory ECG (Holter) recording; Fig. 5 is another excerpt from the same Holter recording presented in Fig. 4;

Fig. 6 is a resting 12-lead ECG of a 22 year-old woman with ARVC;

Fig. 7 is an Example of standard unipolar precordial leads (left column) and bipolar chest leads referenced against the left foot electrode (right column) in a healthy 26-year-old woman; and

Fig. 8 is an excerpt from a continuous 15-lead electrocardiogram (12.5 mm/s, 1 mV/cm) acquired during a negative diagnostic ajmaline test for Brugada syndrome in a 43 -year-old man with congenital long QT syndrome carrying the SCN5A - E1784K mutation. In the Figures, Fig. 1 depicts a schematic view of an ECG system 100, in which electrodes 1 10 are attached to a patient 190. Only six electrodes 1 10 are shown, for simplicity, although in practice there would be 9 'active' electrodes. Signals from the electrodes 1 10 are transmitted via wires 1 1 land received by an ECG recorder unit 120. The number and positioning of the electrodes 1 10 is discussed in more detail below.

The ECG recorder unit comprises a signal input 121 for receiving the signals from the electrodes 1 10, which can be any suitable form of connection/reception device (such as a jack or jacks for plugging in wires 1 1 1). Signals are transmitted from the input 121 to a signal processing unit 122 for processing the signals received by the input unit 121 and calculating the leads (discussed below). The signals can be passed directly or indirectly (i.e. via another component) to the processing unit 122. The signals received at the input can also be passed to a memory or storage 123, to record the raw signals received from the electrodes 1 10. The memory 123 can be any suitable form of memory, preferably a digital memory, such as a hard disc or solid state drive.

The leads calculated by the signal processing unit 122 are output to a lead output unit 124. The output unit 124 can comprise a visual display, such as a screen or a graphing unit, and may also comprise a memory or a connection to a memory (such as memory 123) so that the leads can be recorded.

Although the ECG recorder 120 is depicted in Fig. 1 as a single device, the various functions of the recorder 120 may be spread across physically separate (but connected) devices. For example, it is envisioned that the present invention could be applied to existing devices by retrofitting them, either with additional hardware or through a software/firmware upgrade. As such, the processing unit 122 may be embodied by a separate device connected to the existing device, for example. Also, the output unit 124 may be a separate display or graphing unit. Fig. 2 depicts the placement of the electrodes in a standard 12-lead ECG. For reference, a patient 290 is indicted by a drawing with a mid-clavicular line 291, an anterior axillary line 292 and a mid- axillary line 293.

Electrodes for so-called bipolar peripheral leads are placed at the upper right arm (RA) 210a, the upper left arm (LA) 210b and the left leg or foot (LL or sometimes LF) 210c. A neutral electrode may also be placed on the right leg or foot (RL), but is not shown in Fig. 2. These same electrodes are also used for the construction of unipolar leads, as described below. Precordial electrodes for further unipolar leads are placed at six locations on the chest indicated by VI 210d, V2 210e, V3 21 Of, V4 210g on mid-clavicular line 291 , V5 21 Oh on anterior axillary line 292 and V6 21 Oi on the mid-axillary line 293.

The standard 12-lead ECG provides spatial information about the heart's electrical activity in 3 approximately orthogonal directions: patient right to left; patient head to toe (superior to inferior); and patient front to back (anterior to posterior). This information is gathered as so-called 'bipolar' and 'unipolar' leads. The term 'unipolar lead' is misleading because all ECG leads record potential variations between electrodes and in this sense are 'bipolar' . However, in the case of the so-called 'unipolar' lead, the potential of one of the electrode (the 'neutral' electrode, which is connected to the negative pole of the ECG recorder) is either practically zero, or is practically constant (i.e. varies very little in comparison to the potential of the other electrode - the 'exploring' electrode which is connected to the positive pole of the ECG recorder). Therefore, the unipolar lead practically records only the variations of one of the electrodes and hence it provides mainly localised information (i.e. information about the electrical processes in the regions of the heart muscle that is directly underneath or in close proximity to the 'exploring' electrode). In the case of the precordial unipolar leads, the role of the neutral electrode is taken by the so-called Wilson' s Central Terminal (WCT), which is formed by connecting the RA, LA and LL cables. Hence, WCT represents the sum (or the average) of the potentials of the left arm, right arm and left leg electrodes. The WCT remains relatively constant throughout the cardiac cycle, thus the 'unipolar' leads are conventionally considered to show exclusively variations in the potential at the precordial electrode.

The standard 12 leads are defined as follows.

Bipolar lead I records the difference between the potentials of electrode RA 210a and electrode LA 210b. Although all leads are sensitive to the propagation of electrical waves in any direction, an electrical wave parallel to the axis of a lead will have the highest amplitude in that lead. On the other hand, a wave perpendicular to the lead axis will have an amplitude of zero in that lead (i.e. no wave will be recorded). As a result, lead I primarily indicates the propagation 21 la of pulses from patient right to left. Bipolar lead II records the difference between electrode RA 210a and electrode LF 210c; and primarily indicates the propagation 21 lb of pulses from superior to inferior (with minor influence for right to left). Bipolar lead III is based on the difference between electrode LA 210b and electrode LL 210c; and primarily indicates the propagation 21 lc of pulses from superior to inferior (with minor influence for left to right). If the potentials at electrodes LA, RA and LL are designated as E_L, E_R, and E_F respectively, bipolar leads I, II and III can be calculated as follows:

Lead I = E_L-E_R

Lead II = E_F-E_R

Lead III = E_F-E_L

The so-called 'augmented unipolar' limb leads (frontal plane) are designated lead aVR, lead aVL and lead aVF; and, are based on average measurements at RA 210a, LA 210b and LF 210c. Lead aVR indicates the rightward propagation 21 Id of pulses perpendicular to lead III. They are termed 'unipolar' because a single positive electrode is referenced against a

combination of the other limb electrodes. Lead aVL indicates the leftward propagation 21 le of pulses perpendicular to lead II. Lead aVF indicates the inferior-ward propagation 211f of pulses perpendicular to lead I. If the potentials at electrodes LA, RA and LL are designated as E_L, E_R, and E_F respectively, leads aVR, aVL and aVF are calculated as follows:

Lead aVR = E_R-(E_F+E_L)/2

Lead aVL = E_L-(E_F+E_R)/2

Lead aVF = E_F-(E_L+E_R)/2;

The unipolar precordial leads indicate propagation from the heart approximately in a cross-sectional (horizontal) plane through the heart. Leads VI, V2, V3 from electrodes VI 210d, V2 210e, V3 21 Of, respectively, indicate propagation in the posterior to anterior direction (negative changes indicate the opposite direction). Leads V4, V5, V6 from electrodes V4 210g, V5 21 Oh, V6 210i, respectively, indicate propagation in the lateral right to left direction

(negative changes indicate the opposite direction). If the potentials at electrodes Vn (where n=l to 6) are designated as E_n, leads Vn (where n=l to 6) are calculated as follows:

Lead Vn = E„-(E_F+E_L+E_R)/3 = E_n-WCT

where WCT is the potential of Wilson's Central Terminal (which is equal to

(E_F+E_L+E_R)/3).

Actual measurements at the standard 12 lead configuration of electrodes vary from patient to patient, depending on the location and direction of the electrical pulses inside the patient, and the size and location and electrical properties of the tissues in the patient.

As should be apparent from the preceding discussion, it is potentially misleading to call any of the standard 12 leads 'unipolar' because each lead is calculated based on a difference in potentials. Further, it is theoretically possible to record a bipolar lead between any of the 6 precordial electrodes, although this is not part of the standard 12-lead configuration.

Fig. 3 shows an example ECG trace, indicating the peaks and troughs P, Q, R, S and T that are conventionally used to describe an ECG trace. In an ECG of a normal patient, heart beat (pulse rate) lies between 60 and 100 beats/minute. Rhythm is regular except for minor variations due mainly to respiration as well as other physiological factors. A P-R interval is the time required for completion of atrial depolarization, conduction through the atrial myocardium and the atrioventricular junction, and arrival at the ventricular myocardial cells. The normal P-R interval is 0.12 to 0.20 seconds. The QRS interval represents the time required for ventricular cells to depolarize. The normal duration is 0.06 to 0.10 seconds. The Q-T interval is the time required for depolarisation and repolarisation of the ventricles. The time required is proportional to the heart rate. The faster the heart rate, the faster the repolarisation, and therefore the shorter the Q-T interval. With slow heart rates, the Q-T interval is longer. At normal resting heart rates, the QT interval usually represents up to 50% of the total time between two QRS complexes (the so-called "R-R" interval). Many methods have been developed attempting to precisely characterise the relation between the duration of the QT interval and the heart rate.

Digital 12-lead Ho Iter or ambulatory recorders are becoming increasingly popular in both research and clinical practice. A problem with all ambulatory ECG recordings during daily activities is the increased noise level which often renders long segments of the recordings virtually unreadable. In addition, the noise can often produce artefacts that can simulate arrhythmias or clinically important ST segment changes.

In the inventors' experience, during ambulatory 24-hour (or longer) 12-lead Ho Iter monitoring the noise in the precordial leads very often originates from the peripheral electrodes or cables. It is hypothesised that this is because they are longer and more exposed to mechanical effects during daily routines than the precordial ones. Such a noise can be equally transmitted to all precordial leads via WCT.

The so-called "unipolar" precordial leads introduced by Frank Wilson in the 1930's were believed to provide regional information about the electrical processes in the heart because they recorded exclusively the variations of the electrical potential of the positive ("exploring") precordial electrode while the potential of the negative electrode (the "central terminal", WCT, see above) remained practically constant throughout the cardiac cycle.

However, it is entirely possible to construct precordial leads which effectively use as a negative pole one of the three peripheral electrodes instead of the WCT. That is, the leads can be effectively constructed based on a difference in potential between a precordial/chest electrode (VI -V6) and a single electrode attached to a limb (RA, LA or LL). Such bipolar precordial leads can be referred to as "bipolar chest leads". In the following text this term is used to describe the bipolar leads with a positive pole being one of the six precordial electrodes and a negative pole being one of the electrodes on the left arm, right arm or left foot.

It has been identified that in some conditions bipolar chest leads can offer information which is not directly or not clearly visible in counterpart unipolar leads. In particular, bipolar chest leads derived in the following way have proved to be particularly useful:

Lead VnF = Vn - (II+III)/3 = Vn - 2 aVF/3 = E_n - E_F;

Lead VnL = Vn - (I-III)/3 = Vn - 2 aVL/3 = E_n - E_L; and

Lead VnR = Vn + (I+II)/3 = Vn - 2 aVR/3 = E_n - E_R,

where VnF, VnL and VnR are the leads between the respective precordial electrode (for n= 1 to 6) and the left foot electrode (leads V1F,V2F, ... ,V6F), the left arm electrode (leads V1L, V2L, ... , V6L) or the right arm electrode (leads V1R, V2R, ... , V6R).

It will readily be appreciated by the skilled reader that although alternative calculations are provided for calculating the bipolar chest leads, the definitions are equivalent and other equivalent calculations may be used to calculate the leads defined above. However, one advantage that is apparent from these alternative definitions is that the new leads can be calculated from the standard 12 leads if the raw data of the potentials E_n, E_F, E_L and E_R are not available (i.e. the original electrode data is not required; if only the recorded 12 lead data is available, the new leads can still be derived).

In the following examples, digital 12-lead resting ECGs were recorded at 500 samples/second, 5μν/Μΐ or digital 12-lead ambulatory (Holter) recordings (1000

samples/second, 5 μν/bit) were saved as XML files which were processed by a custom- developed Matlab based programme to obtain the new leads defined above. In the Figures, all ECGs are presented at 25 mm/s, 1 cm/mV.

The bipolar chest leads can be used to cancel or significantly reduce noise in the unipolar precordial leads that originates from one of the 3 peripheral cables or electrodes. This is shown, by way of example, in Figs. 4 and 5. In Fig. 4, the standard precordial leads (top panel) contain noise originating from the left leg cable or electrode. Therefore the bipolar chest leads with a negative electrode at the left arm (middle panel) and right arm (bottom panel) are noise free. In Fig. 5, even when the standard 12-lead traces are so noisy that the individual traces can not be discerned, the leads of the invention are clear. Even in Fig. 4, in which the standard leads can be individually discerned, the new leads still reveal detail which is obscured in the standard leads.

One advantage of the bipolar chest leads described above in comparison (for example) with bipolar leads constructed on the basis of signals from two precordial electrodes, is that the ECG complexes in the present bipolar chest leads are very similar to those in the respective unipolar leads and therefore can easily be used as their surrogates. In contrast, ECG complexes in bipolar precordial leads based on signals from two precordial electrodes often differ considerably from those in the standard unipolar precordial leads, and hence they may look unfamiliar to the general ECG readers. As such, the leads of the present invention provide an advantage of clarity whilst requiring minimal effort for experienced ECG readers to understand.

In addition to removing or significantly reducing noise originating from a peripheral electrode or cable, the derived bipolar chest leads could also help in some cases the diagnosis of heart conditions. For example, arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a genetically determined cardiac disease characterised by fibro-fatty replacement of myocardial areas predominantly in the right ventricle and high incidence of malignant ventricular arrhythmias and sudden cardiac death. According to the currently accepted criteria, T wave inversions in leads VI to V3 or beyond in the absence of complete right bundle branch block (RBBB) (QRS >120 ms) represents a major diagnostic criterion, whereas T wave inversion in leads VI and V2 in the absence or in leads VI to V4 in the presence of complete RBBB is a minor diagnostic criterion.

The inventors have shown that bipolar chest leads with the same positive electrodes as the standard unipolar precordial leads VI to V6 and a negative electrode at either the left arm or the left foot can detect more sensitively the diagnostic T wave negativity (i.e. negative T waves satisfying the above criteria for a major or minor diagnostic criterion for ARVC) in patients with ARVC than the conventional unipolar precordial leads.

Resting 10-second 12-lead digital ECGs, acquired in 44 patients with documented ARVC (age mean±SD 43.5±14.9 years, 32 men, 72.7%) and 232 subjects with no apparent heart disease (negative personal and family medical history, normal physical examination, age 29.9±9.4 years, 106 men, 45.7%) using MACVU, MAC5000, MAC5500 or PC-based CardioSoft 6.1 ECG recorders of GE Healthcare (Milwaukee, Wisconsin, USA, 500 Hz, μν amplitude resolution), were analysed. None of the healthy subjects was involved in sport activity at professional level. All ECGs were acquired as part of ethically approved research projects.

The ECGs were uploaded into a commercially available program (CardioSoft 6.1, GE Healthcare) and from there were exported as XML files. The XML file of each ECG contained both the original 10-second raw signal as well as a lead-specific "median" P-QRS-T complex (i.e. one "representative" ECG complex for all ECG complexes within the 10-second recording). In the present examples, all analyses were performed on the median ECG complexes.

For T wave analysis, the bipolar chest leads VnF and VnL (with a positive pole at the respective precordial electrode (n=l,2,... ,6) and a negative pole at the left foot or left arm electrode, respectively) were derived from the standard precordial and peripheral leads using the above described formulae. Initial observations indicated that lead VnR (i.e. a bipolar chest lead with a negative electrode at the right arm) is not as useful as leads VnF and VnL for the diagnosis of ARVC.

In each patient or healthy control, the unipolar leads VI to V6, leads VIF to V6F and leads V1L to V6L were displayed on-screen with high magnification and the T waves were assessed and classified as positive, negative or flat (<0.05 mV).

After excluding one patient with permanent ventricular pacing, 43 patients with ARVC (age 43.0±14.7 years, 31 men, 72%) were analysed for the presence of diagnostic T wave negativity with the three different lead systems.

T wave inversion as a major criterion for ARVC was observed more commonly in the bipolar chest leads with a negative electrode at the left foot (60.5%) and left arm (48.8%) than in the standard unipolar precordial leads (44.2%). Examples of derived bipolar chest leads in a patient with ARVC and in a healthy subject are presented in Figs. 6 and 7 respectively (both figures showing median beats). Among healthy controls, negative T waves as a major sign of ARVC (i.e. beyond lead V2) were not observed in any subject with either the standard unipolar precordial leads or with the derived bipolar chest leads (100% specificity).

In Fig. 6, the T waves in VI and V2 are negative, which represents only a minor diagnostic criterion for ARVC (left column). However, the bipolar chest leads with a negative electrode at the left leg (right column) demonstrate negative T waves from VIF to V3F which is a major diagnostic criterion for ARVC. For comparison, Fig. 7 shows the precordial unipolar and bipolar (with a negative electrode at the left leg) leads of a healthy subject. The T waves with both lead systems are very similar; there is no negative T wave except in lead VI and VIF.

As a result, the derived bipolar chest leads (with a reference electrode at the left arm or left foot) can improve the ECG diagnosis of ARVC. They are more sensitive than the standard unipolar leads while maintaining practically the same high specificity.

Another development of the standard 12-lead ECG is to create 'multipolar precordial' leads. As will be clear from the preceding discussion, there is no reason why the number of electrodes used for lead derivation should be limited to two. For example, the standard so-called unipolar leads, which record potentials with reference to the WCT, are effectively derived from the reading at four electrodes (the precordial electrode of interest, and the three making up the WCT). However, it has been identified that multipolar leads using one of the precordial electrodes as a positive pole and the combined potential of several precordial electrodes as a negative electrode also can also be of clinical use. These are referred to herein as 'multipolar precordial leads' . Theoretically, a multipolar ECG lead detects electrical wavefronts from more directions (i.e. it is less dependent on the wavefront direction) than a bipolar lead. However, it also cancels the far-field electrical effects present in the so-called "unipolar" leads. For example, a "quadripolar" lead with a positive pole at V5 and a negative pole at V4 and V6 ( denoted lead V5-46) can be constructed using the formula:

Lead V₅-₄6 = Lead V5 2 - Lead V4 - Lead V6 = 2^χΕ₅-Ε₄-Ε₆

In general a quadripolar precordial lead can be defined as :

Lead Vi._jk= 2 Ei-E_rE_k

where i,j,k are members of the set n = 1 to 6, for precordial electrodes Vn, recording potentials En.

It has been found that in some cases, derived multipolar precordial leads can detect changes immediately preceding the onset of ventricular tachycardias. These changes are hardly visible or invisible in the standard unipolar leads used for its derivation.

For example, Fig. 8 demonstrates an excerpt from a continuous 15-lead

electrocardiogram (12.5 mm/s, 1 mV/cm) acquired during a negative diagnostic ajmaline test for Brugada syndrome in a 43 -year-old man with congenital long QT syndrome carrying the SCN5A - E1784K mutation. Fifteen seconds after the end of ajmaline administration (1 mg/kg for 5 minutes), the patient developed ventricular bigeminy (top panel) which 1 minute and 30 seconds later degenerated into sustained polymorphic ventricular tachycardia (bottom panel). Leads V4, V5, V6 and a computed quadripolar lead consisting of lead V5 as a positive pole and the sum of V4 and V6 as a negative pole (lead V5-46) are displayed from top.

Lead V₅-₄₆was computed retrospectively from the digital recording using the formula: Lead V5-46 = V5><2 - (V4+V6). No visible changes are seen in leads V4 to V6 in the period immediately preceding the development of bigeminy. The quadripolar lead computed from the same leads, however, clearly shows QRS fractionation with increase in T wave amplitude starting 10 seconds before the arrhythmia (top panel, thick arrow). These changes are preceded by slight decrease in QRS amplitude for four beats (thin arrow).

Various bi-, quadri- or multipolar leads can be computed very easily (including in real time) from the standard 12-lead provided the latter is available in a digital form. In some cases, such as the one presented in Fig. 8, they can display clinically important information which is practically invisible in the standard leads used for their computation.

As it is anticipated that the present invention can be applied to existing systems, one aspect of the invention relates to computer programme that can be loaded into existing hardware to cause the hardware to implement the invention. The computer programme may be stored on a non-transitory computer-readable medium. The term computer-readable medium is used herein to refer to any medium that participates in providing information to a processor, including instructions for execution. Such a medium may take many forms, including, but not limited to, non-volatile media, volatile media and transmission media. Non-volatile media include, for example, optical or magnetic disks. Volatile media include, for example, dynamic memory.

Transmission media include, for example, coaxial cables, copper wire, fibre optic cables, and waves that travel through space without wires or cables, such as acoustic waves and

electromagnetic waves, including radio, optical and infrared waves.

Common forms of computer-readable media include, for example, a floppy disk, a flexible disk, a hard disk, a magnetic tape, or any other magnetic medium, a compact disk ROM

(CD-ROM), a digital video disk (DVD) or any other optical medium, punch cards, paper tape, or any other physical medium with patterns of holes, a RAM, a programmable ROM (PROM), an erasable PROM (EPROM), a FLASH-EPROM, or any other memory chip or cartridge, a carrier wave, or any other medium from which a computer can read.

In the foregoing specification, the invention has been described with reference to specific embodiments thereof. It will, however, be evident that various modifications and changes may be made by the skilled addressee. The specification and drawings are, accordingly, to be regarded in an illustrative rather than a restrictive sense.

Claims

An electrocardiography apparatus comprising:

a signal receiving unit for receiving signals from RA, LA, LL, VI, V2, V3, V4, V5 and V6 electrodes, and

a signal processing unit configured to calculate at least one bipolar chest lead VnF as defined in Equation 1, and/or at least one bipolar chest lead VnL as defined in Equation 2, and/or at least one bipolar chest lead VnR as defined in Equation 3 :

Lead VnF = E_n - E_F; Equation 1

Lead VnL = E_n - E_L; and Equation 2

Lead VnR = E_n - E_R, Equation 3 where VnF, VnL and VnR are the bipolar chest leads based on differences in potential between the respective precordial electrode (Vn, for n= 1 to 6) and the left foot electrode (VF, for lead VnF), the left arm electrode (VL, for lead VnL) or the right arm electrode (VR, for lead VnR), and E_n (for n=l-6), E_F, E_L and E_R are the potentials at the Vn, VF, VL and VR electrodes respectively.

An electrocardiography apparatus comprising:

a signal receiving unit for receiving signals from VI, V2, V3, V4, V5 and V6 electrodes, and

a signal processing unit configured to calculate at least one multipolar precordial lead from the received signals.

An electrocardiography apparatus according to clam 2, wherein:

the signal processing unit is configured to calculate at least one quadripolar precordial lead, lead Vi._jk, according to the equation:

Lead Vi._jk= 2 Ei-E_rE_k where i,j,k are in the set n=l to 6, for precordial electrodes Vn (for n= 1 to 6) recording potentials E_n (for n=l-6) respectively. An electrocardiography apparatus according to claim 2 or claim 3, wherein: the signal receiving unit is for receiving signals from RA, LA, LL, VI, V2, V3, V4, V5 and V6 electrodes, and

the signal processing unit is further configured to calculate at least one bipolar chest lead

VnF as defined in Equation 1, and/or at least one bipolar chest lead VnL as defined in

Equation 2, and/or at least one bipolar chest lead VnR as defined in Equation 3 :

Lead VnF = E_n - E_F; Equation 1

Lead VnL = E_n - E_L; and Equation 2

An apparatus according to any one of the preceding claims, further comprising a signal output for outputting at least one of the calculated bipolar chest leads.

An apparatus according to claim 5, wherein said output comprises a display or graphing unit for receiving and visualising the at least one calculated bipolar chest lead and/or multipolar precordial lead.

An apparatus according to any one of the preceding claims, further comprising the RA, LA, RL, LL, VI, V2, V3, V4, V5 and V6 electrodes, and wherein the electrodes are connected to the signal receiving unit.

An apparatus according to any one of the preceding claims, wherein the signal processing unit is further configured to calculate a standard 12-lead electrocardiogram.

An electrocardiography method comprising: receiving signals from at least some of RA, LA, RL, LL, VI, V2, V3, V4, V5 and V6 electrodes, and

calculating at least one bipolar chest lead VnF as defined in Equation 1, and/or at least one bipolar chest lead VnL as defined in Equation 2, and/or at least one bipolar chest lead VnR as defined in Equation 3 :

Lead VnF = E_n - E_F; Equation 1 Lead VnL = E_n - E_L; and Equation 2 Lead VnR = E_n - E_R, Equation 3

10. An electrocardiography method comprising:

receiving signals from at least some of VI, V2, V3, V4, V5 and V6 electrodes, and calculating at least one multipolar precordial lead from the received signals.

11. An electrocardiography method according to clam 10, wherein:

the calculating comprises calculating at least one quadripolar precordial lead, lead Vi._jk, according to the equation:

Lead Vi._jk= 2 Ei-E_rE_k where i,j,k are in the set n=l to 6, for precordial electrodes Vn (for n= 1 to 6) recording potentials E_n (for n=l-6) respectively.

12. An electrocardiography method according to claim 10 or claim 11, comprising:

receiving signals from RA, LA, LL, VI, V2, V3, V4, V5 and V6 electrodes, and calculating at least one bipolar chest lead VnF as defined in Equation 1, and/or at least one bipolar chest lead VnL as defined in Equation 2, and/or at least one bipolar chest lead VnR as defined in Equation 3 :

Lead VnF = E_n - E_F; Equation 1

Lead VnL = E_n - E_L; and Equation 2

13. A method according to any one of claims 9 to 12, further comprising outputting at least one of the calculated bipolar chest leads.

14. A method according to claim 13, wherein said outputting comprises displaying or graphing the at least one calculated bipolar chest lead.

15. A method according to any one of the preceding method claims, further comprising applying the RA, LA, RL, LL, VI, V2, V3, V4, V5 and V6 electrodes to a patient.

16. A method according to any one of the preceding method claims, further comprising calculate a standard 12-lead electrocardiogram.

17. A computer program capable of execution by an electrocardiography apparatus comprising a computer processor, the computer program comprising instructions such that, when executed by the processor, the electrocardiography apparatus performs the steps of:

receiving signals from at least some of RA, LA, RL, LL, VI, V2, V3, V4, V5 and V6 electrodes, and calculating at least one bipolar chest lead VnF as defined in Equation 1, and/or at least one bipolar chest lead VnL as defined in Equation 2, and/or at least one bipolar chest lead VnR as defined in Equation 3 :

18. A computer program capable of execution by an electrocardiography apparatus comprising a computer processor, the computer program comprising instructions such that, when executed by the processor, the electrocardiography apparatus performs the steps of:

19. A storage medium storing a computer program according to claim 17 and/or claim 18.

20. A method of diagnosing a heart condition, comprising the method of any one of the

preceding method claims and further comprising identifying an anomaly in the at least one calculated bipolar chest lead.

21. A method of diagnosing arrhythmogenic right ventricular cardiomyopathy/dysplasia, the method comprising:

calculating at least one bipolar chest lead V_nF as defined in Equation 1, and/or at least one bipolar chest lead V_nL as defined in Equation 2:

Lead VnF = E_n - E_F; Equation 1 Lead VnL = E_n - E_L; and Equation 2 where VnF and VnL are the bipolar chest leads based on differences in potential between the respective precordial electrode (Vn, for n= 1 to 6) and the left foot electrode (VF, for lead VnF), the left arm electrode (VL, for lead VnL), and En (for n=l-6), E_F, and E_L are the potentials at the Vn, VF and VL electrodes respectively.

22. A method of identifying the onset of ventricular tachycardia, the method comprising:

receiving signals from at least some of VI, V2, V3, V4, V5 and V6 electrodes, and

calculating at least one multipolar precordial lead from the received signals.