Riccardo Fenici

Biomagnetically localizable multipurpose catheter and method for magnetocardiographic guided intracardiac mapping, biopsy and ablation of cardiac arrhythmias

A multipurpose catheter, specially designed to be biomagnetically localizable and the method for magnetocardiographic (MCG) guided intracardiac electrophysiological recordings, endomyocardial biopsy and ablation of cardiac arrhythmias are described. The catheter features two non-polarizable non-ferrous magnetic electrodes, arranged in such a way that, connected to an external current generator, an electromagnetic field of dipolar configuration can be generated in the heart. The connection is done with twisted pairs of non-ferrous magnetic conductors, to avoid the occurrence of spurious magnetic fields along the catheter during current injection to the electrodes. With this assembly the tip of the catheter can be localized (and driven close to an arrhythmogenic area) by MCG mapping. The same electrodes are feasible for monophasic action potential (MAP) recordings.One or more lumen allow fluid infusion, blood sampling, pressure measurements and introduction of steerable wires, pacing or ablation electrodes, bioptic devices, or optic fibers.On the basis of preoperative MCG three-dimensional localization of the arrhythmogenic substrate, the biomagnetically localizable catheter is driven, under fluoroscopic control, as close as possible to the suspected arrhythmogenic zone. MCG mapping is then performed under pacing, with adjustments of the catheters tip, until the electrically induced magnetic field and catheters localization parameters fit those generated by the spontaneous arrhythmia. MAP is recorded. The catheter position is accepted for ablation when electrophysiological abnormalities are identified in the MCG localized area.

Clinical application of magnetocardiography

Magnetocardiography is a noninvasive contactless method to measure the magnetic field generated by the same ionic currents that create the electrocardiogram. The time course of magnetocardiographic and electrocardiographic signals are similar. However, compared with surface potential recordings, multichannel magnetocardiographic mapping (MMCG) is a faster and contactless method for 3D imaging and localization of cardiac electrophysiologic phenomena with higher spatial and temporal resolution. For more than a decade, MMCG has been mostly confined to magnetically shielded rooms and considered to be at most an interesting matter for research activity. Nevertheless, an increasing number of papers have documented that magnetocardiography can also be useful to improve diagnostic accuracy. Most recently, the development of standardized instrumentations for unshielded MMCG, and its ease of use and reliability even in emergency rooms has triggered a new interest from clinicians for magnetocardiography, leading to several new installations of unshielded systems worldwide. In this review, clinical applications of magnetocardiography are summarized, focusing on major milestones, recent results of multicenter clinical trials and indicators of future developments.

Multiple system atrophy presenting as parkinsonism: clinical features and diagnostic criteria.

To evaluate the possibility that parkinsonian signs may be the only presenting feature of multiple system atrophy (MSA), parkinsonian patients were studied who had no atypical clinical signs and had no symptoms of autonomic dysfunction, but who reported that they had not experienced the anticipated good response to dopaminergic treatment. These stringent criteria identified 20 patients from a series of 298 consecutive parkinsonian outpatients. The following clinical pointers were analysed: (a) rate of disease progression; (b) symmetry of parkinsonian symptoms and signs; (c) occurrence of resting tremor during the first three years from onset. In addition, all patients underwent (d) acute and chronic challenge with dopaminergic drugs; (e) cardiovascular reflex autonomic function tests; (f) high field MRI. Rapid progression of disease was seen in 45% of patients, onset was symmetric in 25%, tremor was absent at onset in 70%, response to dopaminergic drug challenges was inadequate in 40%, abnormal cardiovascular reflexes occurred in 50%, and some abnormal MRI finding occurred in 35% of cases. Each of these features was equally weighted by giving to each patient a 0 to 6 point score corresponding to the number of abnormal findings. Fifteen patients scoring higher than 1 were considered at risk for having MSA: five of them were classified as clinically possible (score 2), six as clinically probable (score 3-4), and four patients were classified as clinically definite multiple system atrophy (score 5). The six pointers considered were variably combined in each patient, none of them being universally abnormal in patients with high scores. The patients were followed up for a mean 2.1 (SEM 0.65) years. All but one of the 10 patients prospectively classified as probable or definite MSA developed unequivocal clinical signs of fully symptomatic MSA. A receiver operator characteristic cure was plotted for the prospective score based on follow up diagnosis. The best compromise for trade off between sensitivity and specificity was a cut off value at a score of 3. The sensitivity and specificity of the individual pointers considered to predict fully symptomatic MSA varied considerably, and no single item could predict whether patients presenting with just parkinsonian signs went on during the two year follow up period to develop fully symptomatic MSA. Instead, the number of abnormalities offered a predictive value for the clinical prognosis of these parkinsonian patients.

Ventricular activation is impaired in aged rat hearts.

Ventricular arrhythmias are frequently observed in the elderly population secondary to alterations of electrophysiological properties that occur with the normal aging process of the heart. However, the underlying mechanisms remain poorly understood. The aim of the present study was to determine specific age-related changes in electrophysiological properties and myocardial structure in the ventricles that can be related to a structural-functional arrhythmogenic substrate. Multiple unipolar electrograms were recorded in vivo on the anterior ventricular surface of four control and seven aged rats during normal sinus rhythm and ventricular pacing. Electrical data were related to morphometric and immunohistochemical parameters of the underlying ventricular myocardium. In aged hearts total ventricular activation time was significantly delayed (QRS duration: +69%), while ventricular conduction velocity did not change significantly compared with control hearts. Moreover, ventricular activation patterns displayed variable numbers of epicardial breakthrough points whose appearance could change with time. Morphological analysis in aged rats revealed that heart weight and myocyte transverse diameter increased significantly, scattered microfoci of interstitial fibrosis were mostly present in the ventricular subendocardium, and gap junction connexin expression decreased significantly in ventricular myocardium compared with control rats. Our results show that in aged hearts delayed total ventricular activation time and abnormal activation patterns are not due to delayed myocardial conduction and suggest the occurrence of impaired impulse propagation through the conduction system leading to uncoordinated myocardial excitation. Impaired interaction between the conduction system and ventricular myocardium might create a potential reentry substrate, contributing to a higher incidence of ventricular arrhythmias in the elderly population.

Clinical magnetocardiography. 10 years experience at the Catholic University.

Since the introduction, in 1982, of a Biomagnetic facility in the clinical environment, efforts were concentrated to investigate whether magnetocardiography 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 than350 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.

Characterization of Fetal Arrhythmias by Means of Fetal Magnetocardiography in Three Cases of Difficult Ultrasonographic Imaging

Characterization of ultrasound detected fetal arrhythmias is generally performed by means of M‐mode and pulsed Doppler echocardiography (fECHO), sonographic techniques that allow only indirect and approximate reconstruction of the true electrophysiological events that occur in the fetal heart. Several studies demonstrated the ability of fetal magnetocardiography (fMCG) to identify fetal arrhythmias. We report on three women, studied after the 32nd gestational week, who were referred for fMCG because of unsatisfying fetal cardiac visualization with fECHO due to maternal obesity, fetus in constant dorsal position hiding the fetal heart, intrauterine growth retardation, and oligohydramnios. Minor pericardial effusion was present in the third patient and digoxin therapy was given. FMCG were recorded with a 77‐channel MCG system working in a shielded room. Independent Component Analysis (FastICA algorithm) was used to reconstruct fetal signals. The good quality of the retrieved fetal signals allowed real‐time detection of arrhythmias and their classification as supraventricular extrasystoles (SVE), with/without aberrant ventricular conduction and/or atrioventricular block. The time course of the fetal cardiac rhythm was reconstructed for the entire recording duration; hence, fetal heart rate variability could be studied in time and frequency. Since isolated extrasystoles may progress to more hazardous supraventricular tachycardias, the noninvasive antenatal characterization of, even transient, fetal arrhythmias and their monitoring during pregnancy can be of great clinical impact.

Phantom validation of multichannel magnetocardiography source localization

FENICI, R., et al.: Phantom Validation of Multichannel Magnetocardiography Source Localization. Multichannel magnetocardiography (MMCG) is used clinically for noninvasive localization of the site of origin of cardiac arrhythmias. However, its accuracy in unshielded environments is still unknown. The aim of this study was to test the accuracy of three‐dimensional localization of intracardiac sources by means of MMCG in an unshielded catheterization laboratory using a saline‐filled phantom, together with a nonmagnetic catheter designed for multiple monophasic action potential recordings in a clinical setting. A nine‐channel direct current superconducting quantum interference device (DC‐SQUID) system (sensitivity fT/Hz0.5) was used for MMCG from 36 points in a measuring area of 20 × 20 cm. The artificial sources to be localized were dipoles embedded in the distal end of the catheter, placed 12 cm below the sensors plane. Equivalent current dipoles, effective magnetic dipoles, and distributed currents models were used for the inverse solution. The localization error was estimated as the three‐dimensional difference between the physical position of the tip of the catheter and the three‐dimensional localization of the dipoles derived by means of the inverse solution calculated from MMCG data. The reproducibility was tested by repeating the MMCG after repositioning the phantom and the measurement system. The average location error of the catheter dipole was 9 ± 4 mm and was due primarily to imprecise depth estimation. Localization was reproducible within 0.73 mm. The distributed currents model provided an accurate image of current distribution centered over the catheter tip. The authors conclude that MMCG estimation is accurate enough to guarantee proper localization of cardiac dipolar sources even in an unshielded clinical electrophysiological laboratory. (PACE 2003; 26[Pt. II]:426–430)

Nonfluoroscopic localization of an amagnetic stimulation catheter by multichannel magnetocardiography.

This study was performed to: (1) evaluate the accuracy of noninvasive magnetocardiographic (MCG) localization of an amagnetic stimulation catheter; (2) validate the feasibility of this multipurpose catheter; and (3) study the characteristics of cardiac evoked fields. A stimulation catheter specially designed to produce no magnetic disturbances was inserted into the heart of five patients after routine electrophysiological studies. The catheter position was documented on biplane cine x‐ray images. MCG signals were then recorded in a magnetically shielded room during cardiac pacing. Noninvasive localization of the catheters tip and stimulated depolarization was computed from measured MCG data using a moving equivalent current‐dipole source in patient‐specific boundary element torso models. In all five patients, the MCG localizations were anatomically in good agreement with the catheter positions defined from the x‐ray images. The mean distance between the position of the tip of the catheter defined from x‐ray fluoroscopy and the MCG localization was 11 ± 4 mm. The mean three‐dimensional difference between the MCG localization at the peak stimulus and the MCG localization, during the ventricular evoked response about 3 ms later, was 4 ± 1 mm calculated from signal‐averaged data. The 95% confidence interval of beat‐to‐beat localization of the tip of the stimulation catheter from ten consecutive beats in the patients was 4 ± 2 mm. The propagation velocity of the equivalent current dipole between 5 and 10 ms after the peak stimulus was 0.9 ± 0.2 m/s. The results show that the use of the amagnetic catheter is technically feasible and reliable in clinical studies. The accurate three‐dimensional localization of this multipurpose catheter by multichannel MCG suggests that the method could be developed toward a useful clinical tool during electrophysiological studies.

Nonfluoroscopic Localization of an Amagnetic Catheter in a Realistic Torso Phantom by Magnetocardiographic and Body Surface Potential Mapping

This study was performed to evaluate the accuracy of multichannel magnetocardiographic (MCG) and body surface potential mapping (BSPM) in localizing three‐dimensionally the tip of an amagnetic catheter for electrophysiology without fluoroscopy. An amagnetic catheter (AC), specially designed to produce dipolar sources of different geometry without magnetic disturbances, was placed inside a physical thorax phantom at two different depths, 38 mm and 88 mm below the frontal surface of the phantom. Sixty‐seven MCG and 123 BSPM signals generated by the 10 mA current stimuli fed into the catheter were then recorded in a magnetically shielded room. Non‐invasive localization of the tip of the catheter was computed from measured MCG and BSPM data using an equivalent current dipole source in a phantom‐specific boundary element torso model. The mean 3‐dimensional error of the MCG localization at the closer level was 2 ± 1 mm. The corresponding error calculated from the BSPM measurements was 4 ± 1 mm. At the deeper level, the mean localization errors of MCG and BSPM were 7 ± 4 mm and 10 ± 2 mm, respectively. The results showed that MCG and BSPM localization of the tip of the AC is accurate and reproducible provided that the signal‐to‐noise ratio is sufficiently high. In our study, the MCG method was found to be more accurate than BSPM. This suggests that both methods could be developed towards a useful clinical tool for nonfluoroscopic 3‐dimensional electroanatomical imaging during electrophysiological studies, thus minimizing radiation exposure to patients and operators.

Cardiovascular autonomic nervous system evaluation in Parkinson disease and multiple system atrophy

BACKGROUND Autonomic nervous system dysfunction (ANSd) heralds or follows motor symptoms (MS) in Parkinson disease (PD), but may precede years and progress more rapidly in multiple system atrophy (MSA). Cardiac dysautonomia severity correlates with disabling symptoms thus a Cardiac Autonomic Nervous System Evaluation protocol (CANSEp) is useful to assess ANSd in PD and MSA patients. METHODS AND RESULTS Consecutive patients with PD or MSA were studied. The severity of MS was quantified with UPDR III and Hoehn/Yahr scales. CANSEp consisted of the 5-test Ewing protocol (EP) and Heart Rate Variability analysis (HRVa), in time-domain (TD) and frequency-domain (FD). 36 patients with parkinsonian symptoms (23 PD, 13 MSA) and 40 healthy controls were studied. Parkinsonism was more severe in MSA, comparing UPDR III and Hoehn/Yahr scales (p<0.0001). Higher EPs scores were found in MSA (mean 5.1±1.98) compared to PD (mean 3.5±2) and controls (score 0.25±0.1). TD and FD-HRVa were abnormal in PD and MSA, compared to controls. In PD depression of vagal tone was predominant during sleep, whereas in MSA depression of sympathetic tone prevailed during daily activity. CONCLUSIONS Whereas its specificity is very high, the sensitivity of the EP was only 43.5% in PD and 76.9% in MSA. HRVa improved diagnosis accuracy in 10 patients, unidentified by the EP alone, with overall sensitivity of 65.2% in PD and 92.3% in MSA. Thus CANSEp provides a better assessment of cardiovascular dysautonomia in parkinsonian syndromes, useful to differentiate PD from MSA and to address clinical and pharmacological management.