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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.

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.

It has been demonstrated that Doppler waveform of the hepatic vein (normally triphasic) is transformed into a biphasic or monophasic waveform in cirrhotic patients. The compressive mechanism of liver tissue has been considered up till now the cause of this change. Moreover, cirrhotics show, after USCA injection, a much earlier HVTT due to intrahepatic shunts. Our aim was to prospectively evaluate the correlation between Doppler pattern of hepatic vein and HVTT of a second-generation USCA; we also correlated HVTT with the most common indexes of portal hypertension.We enrolled 38 participants: 33 cirrhotics and 5 healthy controls. Doppler shift signals were obtained from the right hepatic vein. To characterize the hepatic vein pattern, we used the hepatic vein waveform index (HVWI). This index becomes1 with the appearance of the triphasic waveform. We recorded a clip from 20 s before to 2 min after a peripheral intravenous bolus injection of 2.4 ml of USCA (sulfur hexafluoride).The time employed by USCA to cross the liver from the hepatic artery and portal vein to the hepatic vein was defined as HA-HVTT and PV-HVTT, respectively.Cirrhotics with low HVWI showed an earlier transit time; participants with higher HVWI had a longer transit time (Abnormal hepatic vein Doppler waveform in cirrhotic patients could be due to intrahepatic shunts. HVTT could be useful in the non-invasive evaluation of portal hypertension.E’ stato dimostrato che il pattern flussimetrico delle vene epatiche (normalmente trifasico) si trasforma in un pattern bifasico o monofasico nei pazienti cirrotici. La causa di questa alterazione è stata considerata fino ad ora la presenza di meccanismi di compressione generati dal tessuto epatico. Inoltre i pazienti cirrotici presentano dopo somministrazione di mezzo di contrasto un tempo di transito precoce per presenza di shunts intraepatici. Il nostro obiettivo è stato di valutare in maniera prospettica il pattern flussimetrico delle vene epatiche e il tempo di transito di un mezzo di contrasto ecografico di II generazione; abbiamo inoltre correlato il tempo di transito con i più comuni indici di ipertensione portale.Sono stati arruolati 38 pazienti: 33 cirrotici e 5 controlli sani. Il segnale Doppler è stato ottenuto dalla vena epatica di dx. Per meglio caratterizzare il pattern flussimetrico della vena epatica abbia utilizzato un indice dell’onda epatica chiamato HVWI. Tale indice diventa maggiore di 1 in presenza di un’onda trifasica. E’ stato registrato un clip 20 s prima e 2 min dopo la somministrazione di un bolo di 2.4 mL di mdc ecografico (esafluoruro di zolfo). Il tempo impiegato dal mdc per attraversare il fegato dall’arteria epatica e dalla vena porta alla vena epatica sono stati denominati HA-HVTT e PV-HVTT.I cirrotici con basso HVWI hanno mostrato un tempo di transito precoce; i partecipanti con elevato HVWI un tempo di transito più prolungato (E’ stato dimostrato che il pattern flussimetrico delle vene epatiche (normalmente trifasico) si trasforma in un pattern bifasico o monofasico nei pazienti cirrotici. La causa di questa alterazione è stata considerata fino ad ora la presenza di meccanismi di compressione generati dal tessuto epatico. Inoltre i pazienti cirrotici presentano dopo somministrazione di mezzo di contrasto un tempo di transito precoce per presenza di shunts intraepatici. Il nostro obiettivo è stato di valutare in maniera prospettica il pattern flussimetrico delle vene epatiche e il tempo di transito di un mezzo di contrasto ecografico di II generazione; abbiamo inoltre correlato il tempo di transito con i più comuni indici di ipertensione portale.Sono stati arruolati 38 pazienti: 33 cirrotici e 5 controlli sani. Il segnale Doppler è stato ottenuto dalla vena epatica di dx. Per meglio caratterizzare il pattern flussimetrico della vena epatica abbia utilizzato un indice dell’onda epatica chiamato HVWI. Tale indice diventa maggiore di 1 in presenza di un’onda trifasica. E’ stato registrato un clip 20 s prima e 2 min dopo la somministrazione di un bolo di 2.4 mL di mdc ecografico (esafluoruro di zolfo). Il tempo impiegato dal mdc per attraversare il fegato dall’arteria epatica e dalla vena porta alla vena epatica sono stati denominati HA-HVTT e PV-HVTT.I cirrotici con basso HVWI hanno mostrato un tempo di transito precoce; i partecipanti con elevato HVWI un tempo di transito più prolungato (

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.

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.

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.