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Several medicines, including cancer therapies, are known to alter the electrophysiological function of ventricular myocytes resulting in abnormal prolongation and dispersion of ventricular repolarization (quantified by multi-lead QTc measurement). This effect could be amplified by other concomitant factors (e.g., combination with other drugs affecting the QT, and/or electrolyte abnormalities, such as especially hypokalemia, hypomagnesaemia, and hypocalcemia). Usually, this condition results in higher risk of torsade de point and other life-threatening arrhythmias, related to unrecognized unpaired cardiac ventricular repolarization reserve (VRR). Being VRR a dynamic phenomenon, QT prolongation might often not be identified during the 10-s standard 12-lead ECG recording at rest, leaving the patient at increased risk for life-threatening event. We report the case of a 49-year woman, undergoing tamoxifen therapy for breast cancer, which alteration of ventricular repolarization reserve, persisting also after correction of concomitant recurrent hypokalemia, was evidenced only after manual measurements of the corrected QT (QTc) interval from selected intervals of the 12-lead ECG Holter monitoring. This otherwise missed finding was fundamental to drive the discontinuation of tamoxifen, shifting to another “safer” therapeutic option, and to avoid the use of potentially arrhythmogenic antibiotics when treating a bilateral pneumonia in recent COVID-19. Supplementary Information The online version contains supplementary material available at 10.1007/s12012-021-09659-w.

Background “Fight-or-flight” reaction to perceived danger may affect operational efficiency of police officers (POs), with negative impact on public safety. Therefore, there is a growing interest for methods to investigate stress occurring during highly-demanding operations. Stress-induced reactions are studied in psychophysiology integrating multiple parameters (ECG, EEG, respiration, electrodermal activity, salivary cortisol ...), most of them unrecordable in real-world dynamic situations. Instead ECG, recordable also during physical activity, quantifies stress-related autonomic modulation (AM) through the analysis of heart rate (HR) and its variability (HRVa). We used ECG and a miniaturized wearable wireless telemetric device (mWTD) to monitor AM changes during realistic police tactical training (rPTT), police tactical driving (PTD), oleoresin capsicum exposure (OCE) and live-fire shooting competitions (LFSC). 20 years of research, aimed to understanding of mechanisms underlying human response in force-on-force scenarios and to design more efficient training methods for POs, are reported. Method We selected data of 185 healthy POs (33.6±4.4 years old) investigated during rPTT with different psycho-physiological impact. Until 2015, ECG was recorded with standard ECG-Holter, then the novel mWTD connected to a standard textile sensors garment (Nuubo) has been used featuring simultaneous recording of 3 ECG and 2 Skin potential responses (SPR) for real-time assessment of transient variation of AM with a novel fast algorithm for integration of time-variant HRV spectral parameters (HRVp) and of Root Mean Square value of the two SPR signals (SPRRMS). Results HR increment varied significantly among individuals undergoing the same tasks. Highest HR values (>180 bpm in 66%) were observed during LFSC, often associated with poor operational score. Standard short-term HRVa was inadequate to evidence short-lasting transient changes of AM response due to acute stress (dominant LF at the beginning of task and at medium workload, relative dominance of HF and inversion of LF/HF ratio at the zenith of HR, in high-stress tasks). Under OCE, 83% of POs were able to perform their tasks, despite typical physical symptoms, high HR increment (peak 161 bpm) and HRV decrement with LF prevalence. Discriminant Analysis of HRVp differentiated between physical and psychological stress (accuracy >80%). During PTD good correlation was found between stress-induced increment of SPR activity and driving demands. Conclusion The mWTD is reliable for on-duty compatible recordings and telemetric transmission of AM during highly-demanding operations of POs. Real-time calculation and monitoring of time-varying spectral HRVp with SPRRMS provide immediate multimodal information on AM response to emotional and physical stress reactions to tactical demands. Discriminant Analysis of HRVp is useful to differentiate psychological and physical stress during police operational activity.

Since tangential currents are better detectable as magnetic than electric signals at the body surface, magnetocardiographic mapping (MCG) can be more sensitive than ECG to atrial electrophysiologic alteration, such as abnormal interatrial conduction and/or dispersion of atrial repolarization, as mechanisms underlying the occurrence of paroxysmal atrial fibrillation (PAF). We had previously reported that visual analysis of the magnetic field distribution (MFD) dynamics may evidence an inversion of atrial MFD early during the P-wave suggesting atrial repolarization overlapping depolarization along the descending limb of the P-wave (Guida et al 2018). Aim of this study was to systematically evaluate the reproducibility of such observation and to evaluate the reliability of non-invasive MCG imaging of atrial electrophysiology carried out in our unshielded hospital laboratory. Methods MCG was recorded, in sinus rhythm (SR), with an unshielded 36-channel SQUID-system providing about 30–40 fT/√Hz sensitivity in bandwidth DC-250Hz (sampling frequency 1kHz). MCG data of 40 patients with PAF (PAFp) and 40 age-matched healthy controls (HC), with at least two subsequent recordings to evaluate reproducibility and optimal S/N ratio, were retrospectively analyzed. The dynamics of atrial MFD was studied, at 1 ms time resolution, to identify the onset of atrial repolarization (AR), in respect of the P-wave and PR interval duration. To localize atrial sources, the inverse solution was calculated with the Effective Magnetic Dipole (EMD) model, also after subtraction of the atrial repolarization. MCG parameters of atrial electromagnetic vector (EMV) were also calculated. The reproducibility was evaluated with the intraclass correlation coefficient (ICC). Results High resolution analysis of atrial MFD dynamics confirmed that atrial repolarization field overlaps atrial depolarization during the last third of the P-wave in most investigated subjects. Thus, subtraction of average AR MFD is necessary to discover and image the left atrial depolarization pathway. The reproducibility of MCG estimate of atrial MFD and of EMV parameters was good (average ICC >0.7). In PAFp, MCG evidenced abnormality of AR MFD consistent with dispersion of atrial repolarization (Figure 1), as previously reported with simultaneous MCG and MAP recordings (Fenici & Brisinda, 2007); however, such evaluation is reliable only with optimal S/N ratio during the PR interval. Conclusions Unshielded MCG in SR is sensitive enough to non-invasively image atrial electrophysiology. Visual analysis of atrial MFD dynamics with high temporal resolution reproductively confirmed that AR MFD initiates early, within the descending limb of the P-wave, masking the deeper magnetic field generated by left atrial depolarization currents. MCG can image abnormality of AR MFD in PAFp, suggestive of dispersion of atrial action potential duration. Quantitative estimate of atrial EMV parameters differentiates PAFp from HC.

Background The Wolff-Parkinson-White (WPW) syndrome can be associated with sudden cardiac death, therefore risk assessment (RA) with electrophysiological (EP) testing (EPT) is mandatory to identify patients (pts) requiring catheter ablation (CAb). Our retrospective cohort study aimed to evaluate the variability of EP parameters during follow-up of WPW pts and the reliability of trans-esophageal EPT (TEEPT) for RA, evaluation of treatment efficacy, and EP follow-up of untreated athletes/pts. Method Data of 335 WPW pts, studied with TEEPT between 1985 and 2018, were retrospectively analyzed. Anterograde effective refractory period (ERP) of accessory pathways (AP) and of the atrioventricular node, Wenckebach point, shortest preexcited RR intervals (SPERRI) during atrial fibrillation (AF) and/or atrial pacing (At-P) and inducibility of supraventricular arrhythmias were assessed, at rest (supine and standing) and during effort. An AP was defined at high arrhythmogenic risk (HAR) if the anterograde AP-ERP and/or SPERRI (in AF or At-P) were ≤240 ms at rest or ≤200 ms during effort test. All patients were followed-up as outpatients or telephonically, as clinically required. 195 pts (17% female) were included, having exhaustive clinical information, two or more TEEPT and exhaustive clinical follow-up until late 2018. Time-evolution of EP parameters was evaluated, using parametric and non-parametric tests, as appropriate. Results and discussion Median age at first TEEPT was 20 years (IQR 16–29 years). Median follow- up was 44.3 months (IQR 16.4–122.9 months). Two pts (both identified at HAR and scheduled for surgery when ablation was unavailable) died suddenly, at rest. No other serious arrhythmic complication occurred, during the FU. Out of 19 pts (9.7% - Group A) showing enhanced AP conductivity at follow-up (mean ERP/SPERRI shortening: 30.8 ms, range 10–80 ms), 4 pts were found at HAR and underwent CAb. 176 pts (90.3% – Group B) showed a stable or impaired (25% under pharmacological treatment) AP conductivity during the follow-up. Their mean ERP/SPERRI increase was 39.7 ms (range 0–130 ms). Group A pts were significantly younger (20 vs 28 years old; 88% of Group A pts were Conclusions TEEPT is a safe, non-invasive tool to stratify arrhythmogenic risk of WPW pts. Our data suggest that a watchful waiting is safe for low to moderate risk pts. Younger males with an antero-septal Kent bundle may deserve a more intensive EP follow-up. Aggressive therapy should be considered as mandatory only for symptomatic HAR pts, taking into account complications, risk/benefit ratio and pts' preferences. In other cases, medical therapy and watchful observation could be applied safely under periodical TEEPT, as appropriate.

Magnetic field maps from (A) subjects without ischemia, showing a bipolar field map throughout the cardiac cycle, and (B) patients with acute coronary syndrome in whom a distorted, fragmented or multipolar field map characterizes active myocardial ischemia. Maps were recorded with a 15-channel magnetometry device and display the magnetic field distribution at the point of maximum rate of change between the Q and R peaks (QR) and between the R and S peaks (RS). The dipoles observed in subjects without ischemia are generally aligned in the same direction and have only a single positive (red) and single negative (blue) pole. The images from ischemic patients are generally more complex. A wider spread of angles and pole to pole distance, and the presence of more than two peaks are features that generally indicate ischemia.

Ventricular arrhythmias (VAs) with left bundle-branch-block and inferior axis morphology (LBBB-IA), suggestive of outflow tract (OT) origin, are a challenge in sports medicine because they can be benign or expression of a silent cardiomyopathy. Non-invasive classification is essential to plan ablation strategy if required. We aimed to evaluating magnetocardiographic (MCG) discrimination of OT-VAs site of origin (SoO). MCG and ECG data of 26 sports activity practitioners, with OT-VAs were analyzed. OT-VAs-SoO was classified with discriminant analysis (DA) of 8 MCG parameters and with invasively-validated ECG algorithms. MCG inverse source-localization merged with magnetic resonance (CMR) provided three-dimensional electro-anatomical imaging (MCG 3D-EAI). ECG classification was univocal in 73%. MCG-DA differentiated right ventricular OT from aortic sinus cusp VAs, with 94.7% accuracy. MCG 3D-EAI confirmed OT-VAs-SoO in CMR images. In cases undergoing ablation, MCG 3D-EAI was confirmed by CARTO 3D-EAI. MCG-DA improves non-invasive classification of OT-VAs-SoO. Further comparison with interventional results is required.

Background: Psychological profile (PsyP) of patients with transient loss of consciousness (TLoC) is evidence of high prevalence of anxiety and depression. However, the mechanistic link between abnormal PsyP and TLoC is still unclear. Aim: This study aimed to evaluate: 1) prevalence of abnormal PsyP in TLoC patients; 2) cardiac autonomic response to head-up tilt test (HUTT) in patients with (PsyP+) or without abnormal PsyP (PsyP–), developing syncope (HUTT+) or not (HUTT–). Methods: Forty-one patients (66% female, mean age 36 ± 15 years), with history of TLoC, underwent PsyP before HUTT. Short-term heart rate variability analysis was carried out under baseline rest condition and at peak heart rate and/or onset of syncope induced by nitroglycerine (NTG), during HUTT. Results: HUTT+ occurred in 17/41 patients, more frequently in females, who had higher levels of anxiety (p < 0.0001). PsyP+ was prevalent in 70.5% of HUTT+ patients (p < 0.05). Among PsyP+ patients HUTT+ had dominant sympathetic modulation (DSM) at rest, which increased at the onset of syncope, whereas in HUTT patients vagal modulation was prevalent at rest. Among NTG-induced HUTT+ patients, fourfold higher increases of very low frequency (VLF) power were found in PsyP– compared with PsyP+. Conclusions: 58% of patients with history of TLoC were PsyP+. In PsyP+ patients, DSM at rest correlates with higher prob­ability of NTG-induced syncope, which occurs with 60% increment of low frequency and 530% increment of VLF power. Conversely, in patients with prevalent vagal modulation at rest and a decrease in VLF power after NTG, syncope did not occur. This supports interpretation of VLF power as an index of stress-induced sympathetic activity.

Background and aim Obesity plays a dominant role in the etiology of atrial fibrillation (AF), and the maintenance of a normal body mass index (BMI) seems to prevent and even reduce the incidence of the arrhythmia's recurrence. We selected 270 patients (pts) to assess whether this therapeutic effect was statistically significant even in Mediterranean patients. Method and results In this retrospective cohort study, we analyzed every symptomatic AF relapse during a total follow-up of 657 patient-years. Clinical data, BMI variations, and pts' history were available in our clinical database. We divided the pts in four groups (Gs), according to their BMI variation during the follow-up: G1, normal weight pts, maintaining their weight; G2, overweight pts, losing weight; G3, overweight pts, maintaining their weight; G4, pts gaining weight. Their follow-up (in months) was normalized according to their AF relapses, thus obtaining a mean AF-free period for each patient. Among the overweight groups, G2 showed the best AF-free period (9.7 months). However, G3 and G4 showed a reduced AF-free interval (4.6 and 1.7 months, respectively). G1, predictably, had the longest AF-free period (10 months). Conclusion The results of the present study confirm that simple non-invasive intervention aimed to normalize BMI and to control risk factors through appropriate lifestyle can be highly effective in reducing the AF burden, by acting on comorbidities and proarrhythmic mechanisms. Therefore, serious attempt should be made to correct risk factors before an ablation therapy is proposed.

The aim of the current study was to evaluate stress levels during routine activities and during a major political event by members of the VI Reparto Mobile, an Italian specialized police unit exclusively deployed for riot and crowd control, which had undergone serious stress and liability consequences after the 2001 G8-Summit in Genoa. The investigation protocol consisted of a psychological assessment at the beginning of the study, evaluation of task-related stress with the Job Content Questionnaire (JCQ) and the Effort-Reward Imbalance questionnaire (ERI) at two time periods, and evaluation of behavioral and clinical outcomes as measured by short-term sickness absences (STSA) throughout the duration of the study. The sample consisted of 290 policemen, representing a 98.6 % participation rate. Results found that unit officers were more emotionally stable, conscientious and open to experiences than the general male population and career soldiers. JCQ and ERI decreased significantly when compared with daily and special event activities (p

To test the feasibility of a novel method to combine magnetocardiographic (MCG) estimate of ventricular repolarization (VR) and multiple monophasic action potential (MultiMAP) recording in spontaneously breathing rodents with percutaneous sub-xyphoid epicardial placement of a MCG-compatible amagnetic catheter (AC), ten Wistar rats (WRs) and ten guinea pigs (GPs) were studied. Under fluoroscopic control, the AC was moved until four stable MAPs were recorded (fixed inter-electrode distance of 1.2 mm). 36-channel DC-SQUID (sensitivity 20 fT Hz(-½)) were used for MCG mapping. MAPs, differentially amplified (BW: DC-500 Hz), were digitized at 1 kHz. AC pacing provided local ventricular effective refractory period (VERP) estimate. MAP duration (MAPd) was measured at 50% and 90% levels of repolarization. Simultaneous MCG mapping and MultiMAP recording were successful in all animals. Average MAPd50% and MAPd90% were shorter in WRs than in GPs (26.4 ± 2.9 ms versus 110.6 ± 14.3 ms and 60.7 ± 5.4 ms versus 127.7 ± 15.3 ms, respectively). VERP was 51 ± 4.8 ms in WRs and 108.4 ± 12.9 ms in GPs, respectively. The MAP amplitude was 16.9 ± 4.5 in WRs and 16.2 ± 4.2 in GPs. MAP and MCG parameters of VR were in good agreement. All animals survived the procedure. Two also survived a second invasive study; one was followed up until natural death at 52 months. Percutaneous MultiMAP recording is minimally invasive, usually avoids animal sacrifice, is compatible with simultaneous surface MCG mapping and might be used for experimental validation of MCG VR abnormality, to study the arrhythmogenic potential of new drugs and/or animal models of ventricular arrhythmias.

Background: To determine the prevalence of anti-beta-adrenoceptors autoantibodies (a{beta}AA) in patients with idiopathic arrhythmias (IA) and to assess whether a{beta}AA are predictive markers for concealed cardiomyopathy in such patients. Methods and Results: Sixty-seven patients (group 1) with IA [25 supraventricular (SVA) and 42 ventricular (VA)]; 14 patients (group 2) with suspected cardiomyopathy, 12 patients with definite cardiomyopathy (group 3); and 19 healthy controls (group 4) were tested with an enzyme immunoassay, using synthetic peptides corresponding to the second extracellular loop of the human {beta}1- and {beta}2-adrenoceptors. Endomyocardial biopsy was performed in 29 patients. As compared with group 4 [3/19 (15.7%)], anti-{beta}1-adrenoceptor autoantibodies (a{beta}1AA) were more frequent in group-1 patients [38/67 (56.7%; P

BACKGROUND: P‐wave duration, its dispersion and signal‐averaged ECG, are currently used markers of vulnerability to atrial fibrillation (AF). However, since tangential atrial currents are better detectable at the body surface as magnetic than electric signals, we investigated the accuracy of magnetocardiographic mapping (MCG), recorded in unshielded clinical environments, as predictor of AF occurrence. METHODS: MCG recordings, in sinus rhythm (SR), of 71 AF patients and 75 controls were retrospectively analyzed. Beside electric and magnetic P‐wave and PR interval duration, two MCG P‐wave subintervals, defined P‐dep and P‐rep, were measured, basing on the point of inversion of atrial magnetic field (MF). Eight parameters were calculated from inverse solution with “Effective Magnetic Dipole (EMD) model” and 5 from “MF Extrema” analysis. Discriminant analysis (DA) was used to assess MCG predictive accuracy to differentiate AF patients from controls. RESULTS: All but one (P‐rep) intervals were significantly longer in AF patients. At univariate analysis, three EMD parameters differed significantly: in AF patients, the dipole‐angle‐elevation angular speed was lower during P‐dep (p

Background Magnetocardiographic mapping (MCG) provides quantitative assessment of the magnetic field (MF) induced by cardiac ionic currents, is more sensitive to tangential currents, and measures vortex currents undetectable by ECG, with higher reported sensitivity of MCG ventricular repolarization (VR) parameters for earlier detection of acute myocardial ischemia. Aims of this study were to validate the feasibility of in-hospital unshielded MCG and to assess repeatability and reproducibility of quantitative VR parameters, considering also possible gender- and age-related variability. Methods MCG of 204 healthy subjects [114 males-mean age 43.4 ± 17.3 and 90 females-mean age 40.2 ± 15.7] was retrospectively analyzed, with a patented proprietary software automatically estimating twelve VR parameters derived from the analysis of the dynamics of the T-wave MF extrema (five parameters) and from the inverse solution with the effective magnetic dipole model giving the effective magnetic vector components (seven parameters). MCG repeatability was calculated as coefficient of variation (CV) ±standard error of the mean (SEM). Reproducibility was assessed as intraclass correlation coefficient (ICC). Results The repeatability of all MCG parameters was 16 ± 1.2 (%) (average CV ± SEM). Optimal (ICC > 0.7) reproducibility was found for 11/12 parameters (mean values) and in 8/12 parameters (single values). No significant gender-related difference was observed; six parameters showed a strong/moderate correlation with age. Conclusion Reliable MCG can be performed into an unshielded hospital ambulatory, with repeatability and reproducibility of quantitative assessment of VR adequate for clinical purposes. Wider clinical use is foreseen with the development of multichannel optical magnetometry.

Guinea pigs (GPs) are used for preclinical evaluation of electrophysiologic effects of new drugs, because their myocytes have human-like action potentials and ventricular repolarization's (VR) ion currents. This study was aimed to assess the reliability of magnetocardiographic (MCG) mapping for longitudinal studies of GP cardiac electrical activity. Eighteen anesthetized GPs were investigated with an unshielded 36-channel MCG instrumentation, at the age of 5 months (268.1 +/- 19 g). Twelve GPs survived and were restudied when 14 months old (595.6 +/- 90.5 g). RR, PR, QRS, QT(peak), QT(end), JT(peak), JT(end) and T(peak-end) intervals were measured from MCG waveforms. Magnetic field (MF) maps, equivalent current dipole (ECD) parameters and current density imaging were also analyzed. A significant prolongation of the PR (p < 0.05) and QRS (p < 0.001) intervals was found at 14 months. Gender-related differences of VR intervals were not significant. P(peak) and QRS(peak) MFs were similar in all animals, while T(peak) MF varied interindividually at 5 months and showed a rotation in some animals, at 14 months. The ECD strengths, measured at the P(peak), QRS(peak) and T(peak) were stronger (p < 0.01) at the age of 14 months than at 5 months. In contrast to findings in Wistar rats, age-related and gender-related differences of MCG VR parameters were not significant in GPs. Further work is necessary to clarify the variability of VR MF observed in healthy GPs.

A surgical approach for subdiaphragmatic-programmed electrical stimulation (PES) in mice has been reported by Gutstein et al. [D.E. Gutstein, S.B. Danik, J.B. Sereysky, G.E. Morley, G.I. Fishman, Subdiaphragmatic murine electrophysiological studies: sequential determination of ventricular refractoriness and arrhythmia induction, Am J Physiol Heart Circ Physiol. 285 (3) (2003) H1091-96.]. We developed a percutaneous method to drive a patented magnetocardiography-compatible amagnetic catheter (AC), specifically designed for multiple monophasic action potentials (Multi-MAP) recording, at the epicardium of spontaneously breathing small animals. The aim of this study was to test the feasibility of simultaneous magnetocardiographic (MCG) estimate of ventricular repolarization (VR) and Multi-MAP recording in 5 rats. Under fluoroscopic control, the AC was introduced with a sub-xyphoid puncture, in all animals, and moved at several epicardial sites until 4 stable MAPs were recorded, with a fixed inter-electrode distance of 1 mm. An unshielded 36-channel DC-SQUID system (sensitivity 20 fT/Hz 1 / 2) was used to record the MCG. MAP signals, differentially amplified and filtered at DC-500 Hz, were digitized at 1 kHz. The same AC was used for programmed PES at pacing cycles between 200 and 250 ms. Ventricular effective refractory period (VERP) was evaluated with the accuracy of 2 ms. MAP duration (MAPd) was measured, at 90% levels of repolarization. Simultaneous MCG and MAP recordings were successful in all animals. One rat died for respiratory arrest. Four animals tolerated well the procedure and survived. In WRs, MAPd 90% and VERP were 67 ± 9.4 ms and 69.6 ± 5.6 ms, respectively. This minimally invasive method is well tolerated, avoids animal sacrifice, can be used to validate the accuracy of surface MCG estimate of dispersion of VR and for assessment of arrhythmogenic potential of new drugs.

The Brugada syndrome (BS) is a genetically transmitted arrhythmogenic disease, which requires risk stratification, especially in asymptomatic subjects. Recent studies have shown that magnetocardiographic mapping (MCG) at rest can detect abnormal current distribution located in the RVOT. Here we describe an asymptomatic 28 years old BS patient, studied with 12-lead ECG and 36-channel MCG for three times at rest, under effort and during flecainide (Flec) tests, along a four years follow-up. He had a type 2 BS ECG at rest, but normal physical examination, echocardiogram and MRI. Molecular screening of the SCNC5A open reading frame revealed a de novo missense mutation in the DII–DIII linker, confirming the diagnosis of BS. For MCG assessment of ventricular repolarization (VR), magnetic field (MF) dynamics and MF gradient orientation, were computed during the ST interval and at the T wave peak. Current density reconstruction (CDR) and the strength of the equivalent current dipole (ECD) were calculated during the JT interval, to evidence potentially arrhythmogenic current flowing. In spite of Flec-induced ECG abnormality (typical type-1 ST elevation in V1–V3), MCG didn't show clear-cut variation of VR parameters, which didn't differ from those of healthy controls, at rest and under effort. After Flec, CDR, calculated every 10 ms from the J point, evidenced a change in the direction of the strongest current toward the right ventricular outflow tract, without a significant increase of the JT ECD strength. During the follow-up the patient was asymptomatic and no arrhythmia occurred. Further work is deserved to establish the predictive value of MCG for non-invasive risk stratification in asymptomatic BS patients with abnormal Flec test.

We read with much interest the article by Pappone et al1 and the accompanying editorial,2 which revive the long-lasting debate about the appropriate clinical approach to asymptomatic Wolff-Parkinson-White (WPW) patients, balancing between the need to prevent sudden cardiac death and the need to avoid invasiveness and potential complications of unnecessary catheter ablation (CA). We agree with the editorial statements that “Current data including the present study cannot justify a more aggressive ablation approach in the asymptomatic WPW patient,” that “it is yet to be convincingly demonstrated as superior in the real world to the natural history in asymptomatic WPW patients,” and that “ablation provided at the asymptomatic stage has not been demonstrated to produce …

Magnetocardiographic (MCG) mapping is increasingly used for the non-invasive study of coronary artery disease (CAD), cardiomyopathy (CMP) and arrhythmias. MCG study of small animals with ischemia or CMP would provide useful experimental models for the interpretation of abnormal human patterns. The aim of this study was to assess the range of normality of MCG ventricular repolarization parameters, in intact adult rats.10 adult Wistar rats (weight 250 - 350 grams) were investigated with a 36-channel MCG mapping instrumentation (sensitivity is 20 fT/ radical Hz, at 1 Hz), designed for clinical recordings in unshielded hospital laboratories. To assess ventricular repolarization, MCG Q-T(peak), Q-T(end), J-T(peak), J-T(end), T(peak)-T(end) intervals were measured. MCG imaging was obtained by automatic calculation of isofield contour maps, and with inverse source localization based on the Equivalent Current Dipole and Effective Magnetic Dipole models, in a semi-infinite space with homogeneous conductance. Magnetic field (MF) orientation, dynamics and stability during the J-T(end) segment were also calculated. After averaging 300 s of continuous MCG recording, the S/N ratio was good enough for reproducible reconstruction of both atrial and ventricular magnetic maps and for three-dimensional localization of the underlying cardiac generators. Clear gender-related differences in ventricular repolarization duration were found, evidenced by significantly longer Q-T(end), J-T(end) and T(peak)-T(end) intervals in females. The differences in MF orientation, and stability during the J-T(end) segment were not significant. For J-T(peak) MF dynamics, only the ratio between the strengths of the positive and negative poles was significantly lower in the female group ( p0.05).Contactless MCG recording is a novel approach, which simplifies non-invasive mapping in small animals. In normal rats, gender-related differences of ventricular repolarization parameters equivalent to those reported in previous ECG studies were demonstrated.

Objective The aim of this study was to determine whether or not heart rate variability (HRV) analysis during the first 20 min of head-up tilt testing could predict whether patients will develop syncope after nitroglycerine administration. Design 64 patients with previous loss of consciousness underwent head-up tilt testing with the Italian protocol, which involves the administration of nitroglycerine after 20 min of tilt. HRV parameters were analysed from 5 min intervals selected during pretest supine rest (phase 1), the first 5 min (phase 2) and the last 5 min (phase 3) of passive 20 min of tilting, prior to the administration of nitroglycerine. Differences in power (ms 2 ) of the spectral components between the various phases of tilting were calculated for each patient and expressed as Δ. Results 20 patients (group 1, 9 women, mean age 43.2±24.5 years) had a syncope during tilt testing after nitroglycerine, while the other 44 (group 2, 24 women, mean age 41±20.5 years) did not. In group 1, the HRV spectral parameters high frequency (HF) and total power (TP) had a significant decrement from phases 2 to 3 (p=0.012 and 0.027, respectively), while in group 2 the average HF and TP values did not change. The Δ of spectral parameters between phases 2 and 3 were able to differentiate between the two groups and to predict syncope after nitroglycerine administration (p Conclusions HRV analysis within the first 20 min of passive tilting demonstrated that patients with nitroglycerine-induced syncope are characterised by a progressive decrement of parasympathetic activity, which does not occur in patients with a negative response to nitroglycerine. If confirmed on a wider population, HRV analysis could replace nitroglycerine administration and shorten the duration of the tilt test.

Operational stress is a complex matter. It requires a better understanding based on scientific knowledge of the psychophysiology of stress to improve training methods for officer’s survival and prevention of post-traumatic stress disorders. This study aimed to assess the reliability and sensitivity of heart rate and of heart rate variability (HRV) as possible objective methods to quantify police operational stress (OS) in the real world and to differentiate the contribution of overlapping physical stress (PhS) during realistic training scenarios. 12-lead ECG of 113 police officers (POs) were continuously monitored during rest, daily activity (control state), and during 172 realistic tactical training scenarios requiring the use of force and/or of shooting firearms (OS, with or without associated PhS). Baseline physiological and psychological measurements were collected on the days of the training session. POs behavior and tactical outcome were rated by police instructors and documented with multiple video cameras. Real-time imaging of tactical stress was tempted with time-varying (TV) spectral HRV analysis (HRVa). Quantitative estimates of time-domain (TD), frequency-domain (FD), and nonlinear HRV parameters were computed from standard (300 and 120 seconds) and very short-term (60 and 30 seconds) intervals. The study was approved by a local Institutional Review Board. TV spectral HRVa provided dynamic imaging of transient cardiac autonomic adaptation induced by OS and/or PhS. Quantitative estimation of the majority of TD and FD HRV parameters were not significantly affected by shortening the length of the explored time-segments from 300 to 30 seconds, as demonstrated by the intraclass correlation coefficient analysis (> 0.70). Discrimination analysis of HRV parameters allowed a differentiation between rest and stress conditions and between mental and physical stress. HRVa provides dynamic imaging and quantification of transient stress-induced autonomic adaptation in police officers during realistic tactical training scenarios.

This study was performed to evaluate the changes in magnetocardiographic (MCG) source localization results when the geometry and the topology of the volume conductor model were altered. Boundary element volume conductor models of three patients were first constructed. These so-called reference torso models were then manipulated to mimic various sources of error in the measurement and analysis procedures. Next, equivalent current dipole localizations were calculated from simulated and measured multichannel MCG data. The localizations obtained with the reference models were regarded as the "gold standard." The effect of each modification was investigated by calculating three-dimensional distances from the gold standard localizations to the locations obtained with the modified model. The results show that the effect of the lungs and the intra-ventricular blood masses is significant for deep source locations and, therefore, the torso model should preferably contain internal inhomogeneities. However, superficial sources could be localized within a few millimeters even with nonindividual, so called standard torso models. In addition, the torso model should extend long enough in the pelvic region, and the positions of the lungs and the ventricles inside the model should be known in order to obtain accurate localizations.

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 catheter's 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.

The interesting reading of the excellent articles by Pathak et al. [(1,2)][1] triggered us to retrospectively review a cohort of 1,068 consecutive patients with atrial fibrillation (AF), to evaluate whether the correlation between body mass index (BMI) and AF behavior could also be verified in an

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.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 (p0.0001). Higher EP's 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.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.

The purpose of this study was to assess, in patients with ventricular preexcitation, the time dependent physiological variation of antegrade conduction properties in the AV node and in accessory pathways (Aps) as a function of autonomic tone variation induced by posture and physical effort, using noninvasive transesophageal atrial pacing. In 74 WPW patients (mean age 21.31 +/- 9.46 yrs), AV node and Kent antegrade effective refractory periods (at pacing cycle lengths 600, 400, and 320 ms), Wenckebach point, shortest preexcited RR intervals during sustained atrial fibrillation (AF) or atrial pacing, as well as the inducibility of AV reentry tachycardia (AVRT) and AF/flutter (AFL) were assessed. All measurements were carried out at rest, in supine and upright positions, and during effort. A second study was carried out approximately 3 months after the first study. The coefficient of variation (CVs) and reproducibility (CRs) were calculated. For each parameter, the differences between the mean of the two studies were not statistically significant. The CVs and CRs ranged between 0.4% and 4% and between 2 and 28 ms, respectively. AF was induced in 40 (54%) of 74 patients at the first study and in 30 (40.5%) of 74 patients at the second study. AVRT was induced in 33 (45%) of 74 patients at the first study and in 38 (51.3%) of 74 patients at the second study. The reproducibility was 45% for AF/AFL and 65% for reentry tachycardia. Transesophageal atrial pacing is a reliable method for noninvasive reproducible evaluation of antegrade electrophysiological properties of both the AV node and APs in WPW patients. However, the effect of autonomic balance variation has to be taken into account and precisely defined because it may significantly affect the inducibility of supraventricular arrhythmias and the estimation of the absolute values of the vulnerable parameters.

Helicobacter pylori virulent strains have been shown to affect cardiovascular diseases through molecular mimicry mechanisms. Silent autoimmune myocarditis has been hypothesized to be the cause of idiopathic dysrhythmias (IA). The aim of this study is to assess the prevalence of virulent H. pylori strains in patients affected by IA. In this study,54 patients (40 men, mean age 44 ± 17 years) affected by IA and 50 healthy subjects (34 men, mean age 45 ± 9) were evaluated. IA, defined as dysrhythmias with no evidence of other cardiac pathology, were either supraventricular (SVA, 23 patients; mean age 45 ± 15 years) or ventricular (VA, 31 patients; mean age 42 ± 18 years). H. pylori infection and gastrointestinal (GI) symptoms were evaluated. H. pylori strains expressing the cytotoxin-associated gene A (cagA) and the vacuolating-cytotoxin A (vacA) were also assessed through western blot. The prevalence of H. pylori is similar in IA patients and in controls (42 vs. 44%; p > 0.05); H. pylori infection is observed in 48 and 39% of the patients are affected by SVA and VA, respectively. The prevalence of CagA-positive strains is increased in IA patients compared to controls (65 vs. 42%; p < 0.01); similarly, the prevalence of VacA-positive strains is also increased in IA patients (74 vs. 46%; p < 0.006). Excluding belching, infected patients did not show any difference in GI symptoms, when compared to non-infected subjects. From this study it is concluded that there is an epidemiological link between CagA and VacA-positive H. pylori strains in IA patients.

Fourteen patients (ten men and four women; mean age, 37 years) with lone atrial fibrillation (AF) (1 to 18 months' duration) were evaluated by thyroid function tests, two-dimensional echocardiography, hemodynamics, coronary angiography, and left ventricular endomyocardial biopsy, because of unresponsiveness to the usual antiarrhythmic therapy. The results of the T3, T4, TSH, and TRH tests were normal in all patients; cardiac valves and ventricular and atrial sizes (left atrium less than 40 mm) were within the normal limits; also normal were LVEDP (less than or equal to 10 mm Hg) and EF (greater than 0.50). Histologic findings were abnormal in all cases, with three patients showing cardiomyopathic changes, three other patients showing active myocarditis (lymphocytic in two and eosinophilic in one), and eight patients with nonspecific necrosis or fibrosis or both. Steroids (prednisone; 50 mg/m2 of body surface area daily) used in addition to antiarrhythmic therapy in patients with eosinophilic and lymphocytic active myocarditis were able to cause reversion to sinus rhythm, while the other patients continued to have AF. This study documents that occult myocardial diseases (myocarditis, cardiomyopathy, and nonspecific necrosis or fibrosis) can underlie "primary" AF. The addition of steroids to antiarrhythmic therapy in patients with refractory AF and histologic evidence of active myocarditis seems to be useful in controlling the arrhythmia.

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.

Objective More than two decades of research work have shown that magnetocardiographic mapping (MCG) is reliable for non-invasive three-dimensional electroanatomical imaging (3D-EAI) of arrhythmogenic substrates. Magnetocardiographic mapping is now become appealing to interventional electrophysiologists after recent evidence that MCG-based dynamic imaging of atrial arrhythmias could be useful to classify patients with atrial fibrillation (AF) before ablation and to plan the most appropriate therapeutic approach. This article will review some key-points of 3D-EAI and discuss what is still missing to favor clinical applicability of MCG-based 3D-EAI. Methods Magnetocardiographic mapping is performed with a 36-channel unshielded mapping system, based on DC-SQUID sensors coupled to second-order axial gradiometers (pick-up coil 19 mm and 55-70 mm baselines; sensitivity of 20 fT/Sqrt[Hz] in above 1 Hz), as part of the electrophysiologic investigation protocol, tailored to the diagnostic need of each arrhythmic patient. More than 500 arrhythmic patients have been investigated so far. Results The MCG-based 3D-EAI has proven useful to localize well-confined arrhythmogenic substrates, such as focal ventricular tachycardia or preexcitation, to understand some causes for ablation failure, to study atrial electrophysiology including spectral analysis and localization of dominant frequency components of AF. However, MCG is still missing software tools for automatic and/or interactive 3D imaging, and multimodal data fusion equivalent to those provided with systems for invasive 3D electroanatomical mapping. Conclusion Since there is an increasing trend to favor interventional treatment of arrhythmias, clinical application of MCG 3D-EAI is foreseen to improve preoperative selection of patients, to plan the appropriate interventional approach and to reduce ablation failure.

Cardiac arrhythmias are frequent in the elderly population, perhaps secondary to an increased prevalence of hypertension and coronary artery disease as well as aging related changes resulting in loss of pacemaker cells and degenerative alteration of the conduction system. Independent from underlying structural heart disease, advanced age alone appears to be a risk factor for increased susceptibility to ventricular arrhythmia. However, the electrophysiological basis of this phenomenon is still unclear. Thus, it is important to assess and to define the underlying arrhythmogenic substrate. The aim of the present study was to identify a likely structural-functional ventricular arrhythmogenic substrate in aged hearts. For this purpose ventricular activation patterns were measured in control (n = 4) and aged (n = 10) in vivo rat hearts by recording unipolar electrograms with an epicardial, 1 mm resolution, 8 times 8 electrode array, during pacing and spontaneous or induced ventricular ectopic beats. Our results in aged hearts suggest that peripheral conduction system might be involved in perpetuating sequences of ventricular ectopic beats, regardless of their origin.