CHARACTERISATION OF INTRAVENTRICULAR CONDUCTION

Abstract: There is described a method of characterisation of cardiac electrophysiological behaviour for identifying patients at risk of sudden death from arhythmias, for example associated with hypertrophic cardiomyopathy (HCM). Paced ventricular electrograms are analysed, and latency values of transitions of the electrograms are used to construct conduction curves. Parameters of the curves such as the point of onset of a predetermined increase in latency and the increase in electrogram width in a predetermined interval during the pacing sequence are used to identify and/or characterise physiologically significant features of myocardial disarray.

Description: Characterisation of Intraventricular Conduction The invention relates to a method of characterisation of intraventricular conduction, and in particular to the detection and characterisation of electrophysiological effects of myocardial disarray on intraventricular conduction. Hypertrophic cardiomyopathy (HCM) is a common cause of sudden death other than by accident amongst people under 35 years old. One of the features of HCM in patients who are at risk is myofibrillar disarray, i.e. changes in the normal structure of the heart muscle, which is often accompanied by variation in cell diameter. This gives rise to scar tissue which causes thickening of the ventricle wall. These changes cause changes in intraventricular conduction behaviour, creating a number of different potential conduction paths between a paced and a recorded site within the ventricle. Conduction may then be dispersed which can indirectly give rise to uncoordinated contraction of the heart muscles in ventricular fibrillation. Such abnor¬ mal rhythms, or ventricular arrhythmias, are thought to be one factor involved in sudden death from HCM. However, a large number of patients with HCM are not at risk of sudden death. It is therefore desirable to be able to identify those patients who are at risk. Myofibrillar disarray may be expected to cause slow conduction between a paced and a recorded site within the ventricle due to an increase in the number of potential conduction paths between the sites, and vary¬ ing utilisation of the respective paths. Accordingly the demonstration of slow conduction may be useful in indicating patients at risk of sudden death. According to the invention there is provided a method of characterisation of cardiac electrophysio- logical behaviour by analysis of paced ve tricular elec¬ trograms, in which method latency values of transitions of the electrograms are used to construct conduction curves, selected parameters of the curves being used to identify and/or characterise physiologically-significant features of myocardial disarray. The pacing electrode may be located at one of the right ventricular apex, the right ventricular outflow tract (RVOT), the right ventricular inferior wall and the right ventricular septum. Electrograms may be recorded at each of the other sites. The pacing sequence may be computer generated. Preferably there is used a decremental sequence, which may consist of a 480 millisecond drive chain with an extrastimulus applied every third beat, followed by immediate continuation of the drive chain. The extra¬ stimulus coupling interval may be reduced in successive 1 ms steps from 479 ms until the ventricular effective refractory period (VERP) is reached. The selected parameters preferably include the point of onset of a predetermined increase in latency. The parameters preferably further include the value of the increase in electrogram width in a predetermined interval during the pacing sequence. Preferably the upper limit of the interval coincides with the ventricular effective refractory period (VERP). The results may be analysed by linear discriminant analysis. The invention will be further described, for the purposes of illustratation only, with reference to the following example and the accompanying drawings, in which:- Fig. 1 is a conduction curve obtained from a control patient; Fig. 2 is a conduction curve obtained from a patient with ventricular fibrillation; and Fig. 3 is a scatter diagram of change in electrogram duration against the extrastimulus coupling interval at which latency starts to increase. Example The patient is given suitable pre-medication and sedation. Multi-electrode pacing catheters are intro¬ duced, for example by way of the right femoral vein, to the right ventricular apex, the right ventricular out¬ flow tract, the right ventricular inferior wall and the right ventricular septum. During the subsequent experi¬ mental procedure, pacing is carried out at one of these electrodes, and, where necessary in certain patients, simultaneous pacing takes place at an electrode at the high right atrium to prevent fusion beats. Whilst pacing is carried out at one electrode, recordings are made from the remaining electrodes. The pacing sequence is a computer generated decre- mental sequence. The sequence comprises a continuous drive train of beats at constant 480 ms intervals, with an extrastimulus applied after every third beat, with immediate continuation of the drive chain. The extra- stimulus coupling interval is successively reduced by 1 ms on each occasion to give increasing extrastimulus prematurity, from an initial coupling interval of 479 ms until the ventricular effective refractory period (VERP) is reached. In each run, three sets of recordings are obtained, one from each non-paced electrode. Each set contains responses to between 200 and 300 extrastimuli . The run is repeated with each ventricular site in turn being paced. Electrograms recorded from patients with ventricular fibrillation show increasing fragmentation, or fractionation, of the electrogram with increasing stimulus prematurity, i.e. a splitting of the electrogram peaks and an increase in the width of the electrogram. There is also a variation in latency (the time interval from the stimulus to the particular transition) of the peaks. The electrograms are passed through a digital high pass filter, using conventional techniques, in order to emphasise the various transitions. Compensation is also made for noise, and only the transitions exceeding the calculated noise amplitude are used. The latency of each component of the electrogram is calculated, and conduction curves are constructed of latency values as a function of extrastimulus coupling interval. The conduction curves of patients at risk show clearly different patterns from control patients or patients with no family history of sudden death. In particular, control patients typically show short duration, non-fractionated electrograms as shown in Fig. 1. Patients with ventricular fibrillation by comparison show changes in the number of transitions, an increase in electrogram width and an early increase in latency (Fig. 2). Each conduction curve is characterised by an automated method which determines two parameters. Firstly, the extrastimulus coupling interval at which latency shows a predetermined increase is identified. Secondly, there is determined the increase in the width of the electrogram between a given extrastimulus coupling interval, in this case 350 ms, and at the ventricular effective refractory pariod. These parameters are used to construct a scatter diagram of change in electrogram duration (width) against onset of increase in latency, see Fig. 3. The data are subjected to linear discriminant analysis to distinguish various sub-groups of the patients studied. Electrograms from patients with ventricular fibrillation lie in a group with a marked increase in electrogram width and early increase in latency. By contrast, the controlled and low risk patients lie in a group with a late increase in latency and a small increase in electrogram width. An intermediate group comprises the patients with a family history of sudden death and with non-sustained ventricular tachycardia. The method therefore provides a means of analysing electrograms to obtain information about the rate and pathways of conduction between the pacing site and the recording site. This information can be used to identify patients who may be at risk of sudden death so that appropriate action may be taken preferentially in those cases. Although the method has been described with reference to ventricular fibrillation in hypertrophic cardiomyopathy, it will be appreciated that the invention is not limited to use in patients with HCM. Other conditions, such as left ventricular hypertrophy associated with hypertension, may also give rise to physical changes which are capable of investigation in a similar manner. It will be appreciated that modifications may be made within the scope of the invention. The pacing sequence and the arrangement of pacing and recording electrodes may be different from that described. The conduction curves may be analysised in a different manner within the scope of the invention. Whilst endeavouring in the foregoing Specification to draw attention to those features of the invention believed to be of particular importance it should be understood that the Applicant claims protection in respect of any patentable feature or combination of features hereinbefore referred to and/or shown in the drawings whether or not particular emphasis has been placed thereon.

Claims: Claims : - 1. A method of characterisation of cardiac electro-physiological behaviour by analysis of paced ventricular electrograms, in which method latency values of transitions of the electrograms are used to construct conduction curves, selected parameters of the curves being used to identify and/or characterise physiologically-significant features of myocardial disarray. 2. A method according to Claim 1, in which the pacing electrode is located at one of the right ventricular apex, the right ventricular outflow tract (RVOT), the right ventricular inferior wall and the right ventricular septum, and electrograms are recorded at each of the other sites. 3. A method according to Claim 1 or Claim 2, in which the pacing sequence is computer generated. 4. A method according to any of the preceding Claims, in which the pacing sequence is decremental. 5. A method according to Claim 4, in which the sequence consists of a drive chain with an extrastimulus applied every third beat, followed by immediate continuation of the drive chain. 6. A method according to Claim 5, in which the extra- stimulus coupling interval is reduced in successive steps until the ventricular effective refractory period (VERP) is reached. 7. A method according to any of the preceding Claims, in which the selected parameters include the point of onset of a predetermined increase in latency. 8. A method according to any of the preceding Claims, in which the selected parameters include the value of the increase in electrogram width in a predetermined interval during the pacing sequence. 9. A method according to Claim 8, in which the upper limit of the interval coincides with the ventricular effective refractory period (VERP). 10. A method according to any of the preceding Claims, in which the results are analysed by linear discriminant analysis. 11. A method substantially as hereinbefore described with reference to the accompanying example and drawings. 12. Any novel subject matter or combination including novel subject matter disclosed, whether or not within the scope of or relating to the same invention as any of the preceding Claims.

Inventors: SAUMAREZ RICHARD CHARLES, SAUMAREZ, RICHARD, CHARLES
Applicants: CRYOGENIC TECHNOLOGY LTD, SAUMAREZ RICHARD CHARLES, CRYOGENIC TECHNOLOGY LIMITED
Application year: 1993
Main classification: A61N1
IPC codes: A61B5, A61N1