InternationalJournal of CardiacImaging 7: 151-167,1991. © 1991KluwerAcademic Publishers. Printedin the Netherlands.

Clinical magnetocardiography 10 Years experience at the Catholic University, Riccardo R. Fenici, Guido Melillo & Mariella Masselli Clinical Physiology - Cardiovascular Biomagnetism Unit C.N.R., Catholic University of S. Heart, L.go A. Gemelli, Rome, Italy Accepted 1 October 1991

Key words: Ablation of cardiac arrhythmias, biomagnetism, localization of accessory pathways, magnetocardiography, ventricular tachycardia, Wolff-Parkinson-White Abstract

Since the introduction, in 1982, of a Biomagnetic facility in the clinical environment, efforts were concentrated to investigate whether magnetocardiogaphy could really provide new information of potential diagnostic use, even avoiding electromagnetic shielding to facilitate simultaneous biomagnetic and conventional cardiac investigations, including cardiac catheterization for invasive electrophysiological procedures. More than 350 patients have been magnetically investigated using a single-channel second-order gradiometer. Results of 281 MCG studies, whose data have been extensively analyzed with updated software programs, are reported. Magnetocardiographic (MCG) mapping during endocardial pacing was performed to quantify the accuracy of MCG localization of intracardiac dipolar sources. MCG classification of ventricular preexcitation has been attempted in 70 patients with overt preexcitation. MCG localization of the ventricular preexcited area was accurate and reproducible, provided that during mapping a sufficient degree of ventricular preexcitation was present. MCG mapping during orthodromic A-V re-entry tachycardia has been also employed to attempt the localization of retrograde atrial preexcitation as well as the site of origin of atrial and ventricular tachyarrhythmias. For validation, the results of catheter and epicardial mappings have been used. Other applications of clinical magnetocardiography are under evaluation. The use of the Relative smoothness index needs, in our opinion, a larger experience to define its reliability as a predictor of risk for sudden death. MCG follow-up study of patients with transplanted hearts seems to be a promising application, for early detection of acute graft rejection reaction. Our reported case strongly supports this potentiality. Present work is also addressed to develop an integrated system allowing easy MCG mapping during cardiac catheterization, as a new method to guide diagnostic and therapeutic procedures as close as possible to the arrhythmogenic substrate. Abbreviations: 3D - three-dimensional, A/D - analog to digital, APs - accessory pathways, A R V D arrhythmogenic right ventricular displasia, A-V R T - atrio-ventricular reciprocating tachycardia, CME current multipole expansion, ECD - equivalent current dipole, EPS - electrophysiologic study, MCG magnetocardiographic, MI - myocardial infarction, pT - pico Tesla, RC - recursive, RS Index - relative smoothness index, SQUID - Superconducting Quantum Interference Device, S/N - signal to noise, VT ventricular tachycardia

152 Introduction

Magnetocardiography is a new method to non invasively study cardiac electrogenesis, which can provide direct information about the intracellular action currents, without the typical constrains of electrocardiographic measurements. Notwithstanding until 10 years ago only a few clinical MCG investigations had been reported, mainly because of the need of complicate instrumentation usually confined in Physics laboratories, lack of immediate clearcut interpretation of MCG data and uncertain diagnostic applicability of the method [1]. In Italy, since 1980, in the framework of the Special Project on Biomedical and Clinical Engineering of the Italian National Research Council (C.N.R.), it was decided to introduce biomagnetometry in a hospital setting [2, 3] in order to investigate whether magnetocardiography could really provide new information of potential diagnostic use [3, 4]. A second fundamental decision was to use an instrumentation capable to record good quality MCGs without the need of electromagnetic shielding, to avoid the constrain of a shielded room which would have impaired the study of severely ill cardiac patients and, besides, to allow the combination between biomagnetic recordings with other conventional diagnostic methods, including cardiac catheterization for invasive etectrophysiological procedures. A single channel superconducting instrumentation, developed by the physicists of the Istituto di Elettronica dello Stato Solido of the C.N.R., featuring a specially designed second order gradiometer was the optimal solution to obtain sufficient sensitivity (5 × 10-14 Tesla) to perform magnetocardiographic recordings in our unshielded laboratory located in between the Institute and the wards of Internal Medicine [3]. After two years of preliminary measurements to optimize the system and to define the normality standard for the laboratory, the Cardiovascular Biomagnetism Unit of the Catholic University was instituted and clinical activity was started in 1982. A significant step forward toward the understanding of the electrogenesis of the MCG patterns was achieved in 1984, when the present laboratory configuration became availa-

ble, which allows MCG recording in combination with cardiac catheterization, invasive electrophysiology and cardiac pacing [6-2t] (Fig. 1). Magnetic mapping during reciprocating atrioventricular (A-V RT) and ventricular tachycardias (VTs) have been performed to evaluate the accuracy of MCG for localization of arrhythmogenic structures and for detection of patient at risk of sudden arrhythmic death. A magnetocardiographic mapping technique under cardiac pacing originally developed as an independent calibration method to quantify the accuracy and reliability of MCG functional localization of cardiac sources, has recently led to the refinement of a biomagnetically guided method for catheter ablation (Fenici/C.N.R., Patented) [8, 10, 12, 14, 16, 17, 20, 21]. In this paper 10 years of clinical experience in magnetocardiography will be synthetically outlined. A great extent of the reported work is at present mostly of historical interest. However it has been somehow propedeutical for the development of modern multichannel instrumentations and for the growing interest of clinicians for magnetocardiography as a new tool for both clinical research and diagnosis.

Patients and methods

Since 1982 more than 350 patients (pts) have been magnetically investigated. Out of them 281 MCG studies, performed between January 1985 and June 1991, have been reprocessed with updated software programs and constitute the matter of this paper. All patients were studied after informed consent. The distribution of the underlying disease is outlined in Fig. 2. The reproducibility of the measurements was tested in more than 50% of the patients. MCG maps of 20 subjects with negative clinical history, physical examination, ECG and echocardiographic findings, were used as the laboratory normality standard. Magnetocardiographic Mapping was performed with the prototype of a commercial biomagnetic instrumentation (BIOMAG I, Elettronica S.p.A., Rome, Italy) which is based on a superconducting circuitry (RF SQUID: Superconduction QUantum

153

Fig. 1. Catheterization facilities in the BiomagneticLaboratoryof the Catholic Universityof Rome.

Interference Device) coupled to a detection coil (second order gradiometer) shaped in such a way as to be insensitive to fields generated by sources far and different from the patient's heart, in order to reduce the ambient noise. Two different symmetric second order gradiometers have been subsequently used in our laboratory, the diameter of the pick-up coil being respectively 3 or 1.5cm. In both gradiometers a baseline of 5 cm was adopted as the best compromise between optimal sensitivity to the investigated field and rejection of the environmental noise. The output of the SQUID was preamplified and coupled to a COMB filter to reject power line interferences (50 Hz) and harmonics. The final amplification and filtering before A/D conversion was provided by a custom signal conditioning unit, with RC high pass filter of the first order, intermediate adjustable gain amplifiers and final Bessel low pass filter of the 8th order (bandpass between 0.016 and 250 Hz). The signals were digitized with 12 bit resolution at 1000 Hz sampling rate. Computer processing after A/D conversion was performed with an HP A700 minicomputer which transfers a pre-processed patient's file to an HP Vectra 486/25 PC for interactive clinical analysis of

the MCG data. The software programs allow analysis of the recordings in the time domain at various level of resolution, dynamic imaging ('movie effect') of isofield contour maps with 1 msec time resolution and quick automatic source localization, using both the equivalent current dipole (ECD) and current multipole expansion (CME) models, with bidimensional displays of cardiac activation pathways within the patient's frontal and lateral heart silhouettes. A 'zoom' function can be interactively used to magnify the results of localization measurements (Fig. 7) [Burghoff et al., this workshop]. The patient's heart drawings were obtained by digital processing of fluoroscopic and echocardiographic images (Fig. 3). Fluoroscopic imaging of the heart was provided by a mobile X-ray unit with image intensifier and double digital TV memory (SIAS 9C1/U Bologna, Italy). Radiopaque references were placed on the chest surface as well as in the oesophagus both during cardiac catheterization and MCG recordings to define, in individual patients, the position and size of the heart as well as that of intracardiac catheters, with respect to the MCG recording grid. In all subjects MCG recordings were performed

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in supine position, mapping the signal sequentially from 36 positions over the anterior chest wall according to the standard grid proposed by Saarinen [22], which is normalized to the size of the subject's chest. However the recording grid was shifted to the left, or reduced to obtain a more appropriate window for the study of specific pathologies. Intraindividual reproducibility of MCG measurements was tested by repeating MCG mapping in different recording sessions, with the same and/or different gradiometer and with different extension of the recording grid (Fig. 3). Pharmacological Tests: when necessary, in patients with WPW syndrome, after a basal study MCG mapping was repeated during intravenous infusion of Verapamil or Ajmaline, to respectively favour or block the conduction along the accessory pathway. This provided additional information about the different and respective three-dimensional (3D) localization of normal and abnormal A-V activation pathways [15, 16] (Fig. 4). Electrophysiologic Studies: a programmable four channel MINGOGRAF 4 (Siemens-Etema AB, Sweden) was used for conventional intracardiac mapping and standard surface ECG recordings. Cardiac pacing was performed with a SAP 40 programmable stimulator (cb Bioelettronica S.p.A,, Firenze, Italy). When performing simultaneous

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Fig. 3. Typical localization images in the frontal and lateral planes. Valves and septal dimensions are proportional to the individual patient using parameters obtained by echocardiograms and digitally scaled to the fluoroscopic heart silhouettes. The intraindividual reproducibility of MCG localization of a right lateral accessory pathway (Kent-type) is also evident, by comparison of two MCG studies carried out eight months apart. The equivalent current dipole (ECD) localization is marked by the squares; black arrows indicate the onset of the calculated ECD sequence. Thin dots are one centimeter apart. Thick dots indicate the mapping points.

MCG and intracardiac recordings or MCG mapping under cardiac pacing, due to the presence of ferromagnetic material, commercial intracardiac electrocatheters induced rhythmic, rate-dependent artifacts which were increased when the sensor was moved closer to the catheter. This drawback, which obviously impeded good quality MCG recordings, was overcome by manufacturing custom non ferromagnetic electrocatheters (Fenici/

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C.N.R., Patented). At least three simultaneously recorded standard ECG, one MCG and up to four intracavitary signals, were usually stored in analog form on a 14 channel Racal FM tape recorder for further off-line computer analysis. With an average level of noise in the order of about 50 fY/Hz, it was possible to record, in our unshielded hospital laboratory, good quality MCGs during invasive electrophysiology [7, 10, 16].

Results

MCG classification of Ventricular Preexcitation In an ongoing perspective study on 80 patients with cardiac preexcitation, 70 subjects with overt preexcitation (65 Kent-type and 5 Mahaim-type) were magnetically studied. Five different MCG patterns of cardiac preexcitation were reproducibly found in patients with different Kent-type accessory pathways (APs) locations [8, 9, 11, 14, 15, 16, 18]. MCG localization of the ventricular preexcited area was accurate, provided that during mapping a sufficient degree of ventricular preexcitation was spontane-

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A ously present, or pharmacologically obtained by intravenous infusion of verapamil (54/65 Kent pts and 1/5 Mahaim pts). MCG localization of the Kent bundle was inadequate in 11/65 WPW patients because of insufficient degree of ventricular preexcitation during mapping and could not be attempted in patients with concealed accessory pathways (10/ 80 pts). A striking interindividual reproducibility of ventricular depolarization sequences was observed (Fig. 3, 9A) during the delta wave, in patients with similar Kent bundle's localization. It was left-toright and back-to-front for left free-wall AP, rightto-left and usually backward for right free-wall AP [14]. Septal pathways produced mainly right-to-left activation and could be subdivided in two main subgroups: inferior and superior. The former (posteroseptal) with caudo-cranial activation, the latter with variable depolarization sequences (ante-

roseptat and atypical septat). Thus MCG classification of ventricular preexcitation was possible. Moreover MCG mapping after Ajmaline-induced block of the accessory pathways was helpful to confirm the site of insertion of the AP with respect to the interventricular septum. As a matter of fact, right sided septal APs generate an inverted magnetic field and depolarize the septum from right to left, therefore in the opposite direction with respect to the normal septal activation wavefront [15, 16]. In patients with left APs (Fig. 4), the magnetic field pattern can be rather similar during both preexcitation and Ajmaline-induced normal AV conduction. Nevertheless MCG localization of ventricular preexcitation is always left-sided in respect of the ECDs calculated during normal septal activation. Aside the typical dipolar pattern found in the majority of the patients, 22/24, with right preexcitation of the interventricular septum [15,

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