Donatella Brisinda

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.

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.

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)

Treating chronic anal fissure with botulinum neurotoxin

Recent reports confirm that the management of chronic anal fissure has undergone extensive re-evaluation during the past few years. This rejuvenation of interest is attributable to the application of neurochemical treatment, which has contributed to the tendency to treat the disease on an outpatient basis. The use of botulinum neurotoxin seems to be a promising and safe approach for the treatment of chronic anal fissure, particularly in patients at high risk for incontinence. Indeed, botulinum neurotoxin has been successfully used selectively to weaken the internal anal sphincter as a treatment for chronic anal fissure. It is also more efficacious than nitrate therapy, and is not related to the patients willingness to complete treatment.

Identification of anti-endothelial cell antibodies in patients with chronic anal fissure

BACKGROUND Recent studies demonstrate that chronic anal fissure can be the consequence of a local ischemic process. Thus hypothesizing that at the perianal level the interaction of immune component with endothelium could constitute a mechanism determining ischemia and hypertonia, the presence or absence of circulating anti-endothelial cell antibodies (AECAs) was determined in the serum of patients with anal fissure. METHODS The study was carried out on 30 patients: 10 with posterior chronic anal fissure (group 1), 10 with grades III and IV hemorrhoids (group 2), and 10 without previous or active anorectal disease, or both (group 3). An indirect immunofluorescence assay on sections of rat kidney tissue was used to identify AECA in the peripheral blood. RESULTS The assay result was positive for AECAs in 12 patients, all with anorectal disease when compared to the control group (P = .001). The basal anal tone was higher in the AECA-positive patients than in the AECA-negative patients (P = .001). CONCLUSIONS Only the patients with anal fissure or hemorrhoids were AECA positive. All healthy controls tested negative for AECA. Although the number of subjects studied is small, the presence of auto-antibodies directed against the endothelial cells in the serum of these patients supports the hypothesis that the endothelium is involved in the anal disease.

Management of bladder, prostatic and pelvic floor disorders with botulinum neurotoxin.

Since its introduction in the late 1970s for the treatment of strabismus and blepharospasm, botulinum toxin (BoNT) has been increasingly used in the interventional treatment of several other disorders characterized by excessive or inappropriate muscle contractions. The use of this pluripotential agent has extended to a plethora of conditions including: focal dystonia; spasticity; inappropriate contraction in most sphincters of the body such as those associated with spasmodic dysphonia, esophageal achalasia, chronic anal fissure, and vaginismus; eye movement disorders; other hyperkinetic disorders including tics and tremors; autonomic disorders such as hyperhidrosis; genitourinary disorders such as overactive and neurogenic bladder, non-bacterial prostatitis and benign prostatic hyperplasia; and aesthetically undesirable hyperfunctional facial lines. In addition, BoNT is being investigated for the control of the pain, and for the management of tension or migraine headaches and myofascial pain syndrome. BoNT injections have several advantages over drugs and surgical therapies in the management of intractable or chronic disease. Systemic pharmacologic effects are rare; permanent destruction of tissue does not occur. Graded degrees of relaxation may be achieved by varying the dose injected; most adverse effects are transient. Finally, patient acceptance is high. In this paper, clinical experience over the last years with BoNT in urological impaired patients will be illustrated. Moreover, this paper presents current data on the use of BoNT to treat pelvic floor disorders.

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.

Concentric Remodeling Detection by Magnetocardiography in Patients with Recent Onset Arterial Hypertension

The aim of this work was to evaluate a number of magnetocardiographic (MCG) indices in their predictive ability for left ventricular (LV) concentric remodeling. Twenty‐five male patients affected by essential hypertension for no longer than 15 months and presenting signs of LV remodeling participated in the study; 25 normal men volunteers of comparable age were evaluated as controls. All participants underwent echocardiography (ECHO), electrocardiography (ECG), and magnetocardiography (MCG). Several MCG based indices were evaluated, namely the QRS Integral, T Integral, QRS‐T Integral, T/QRS Integral, RS Index, and the variations of the electrical cardiac axis (ECA) orientation. MCG indices were compared with ECHO parameters, i.e., left ventricular mass index (LVMI) and relative wall thickness (RWT), and with ECG parameters, i.e., 12‐lead standard ECG LVH Sokolow‐Lyon and Cornell voltages. QRS Integral values for patients and controls were significantly different (P = 0.03), whereas T Integral values showed only a tendency to differentiate between patients and controls (P = 0.15). No significant correlation between MCG and echocardiographic indices in patients was found; RWT showed a tendency to correlate with QRS Integral (r = 0.34, P = 0.17) and with RS Index (r = 0.49, P = 0.15), and LVMI showed a tendency to correlate with the variations of the ECA orientation (r = 0.38, P = 0.10). Our findings, also supported by preliminary results on patients affected by hypertension induced LV hypertrophy, suggest a potential role of MCG in the evaluation of early electrophysiological alterations due to LV concentric remodeling. (PACE 2004; 27[Pt. I]:709–718)

Noninvasive Study of Ventricular Preexcitation Using Multichannel Magnetocardiography

FENICI, R., et al.: Noninvasive Study of Ventricular Preexcitation Using Multichannel Magnetocardiography. In clinical practice, noninvasive classification of ventricular preexcitation (VPX) is usually done with ECG algorithms, which provide only a qualitative localization of accessory pathways. Since 1984, single or multichannel magnetocardiograpy (MMCG) has been used for three‐dimensional localization of VPX sites, but a systematic study comparing the results of ECG and MMCG methods was lacking. This study evaluated the reliability of MMCG in an unshielded electrophysiological catheterization laboratory, and compared VPX classification as achieved with the five most recent ECG algorithms with that obtained by MMCG mapping and imaging techniques. A nine‐channel direct current superconducting quantum interference device (DC‐SQUID) MMCG system (sensitivity is 20 fT/Hz0.5) was used for sequential MMCG from 36 points on the anterior chest wall, within an area 20 × 20 cm . Twenty‐eight patients with Wolff‐Parkinson‐White syndrome were examined at least twice, on the same day or after several months to test the reproducibility of the measurements. In eight patients, the reproducibility of MMCG was also evaluated using different MCG instrumentation during maximal VPX and/or atrioventricular reentrant tachycardia induced by transesophageal atrial pacing via a nonmagnetic catheter. The results of VPX localization with ECG algorithms and MMCG were compared. Equivalent current dipole, effective magnetic dipole, and distributed currents imaging models were used for the inverse solution. MMCG classification of VPX was found to be more accurate than ECG methods, and also provided additional information for the identification of paraseptal pathways. Furthermore, in patients with complex activation patterns during the delta wave, distributed currents imaging revealed two different activation patterns, suggesting the existence of multiple accessory pathways. (PACE 2003; 26[Pt. II]:431–435)