Predictive value of unshielded magnetocardiographic mapping to differentiate atrial fibrillation patients from healthy subjects.

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 < 0.05) and higher during P-rep (p < 0.001) intervals. The space-trajectory during P-rep and the angle-dynamics during P-dep were higher (p < 0.05), whereas ratio-dynamics P-dep was lower (p < 0.01), in AF. At DA, with a combination of MCG and clinical parameters, 81.5% accuracy in differentiating AF patients from controls was achieved. At Cox-regression, the angle-dynamics P-dep was an independent predictor of AF recurrences (p = 0.037). CONCLUSIONS: Quantitative analysis of atrial MF dynamics in SR and the solution of the inverse problem provide new sensitive markers of vulnerability to AF.

Magnetocardiographic classification and non-invasive electro-anatomical imaging of outflow tract ventricular arrhythmias in recreational sport activity practitioners.

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.

Psychophysiological evaluation of patients with transient consciousness loss of uncertain origin.

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 prob-ability 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.

Unshielded magnetocardiography: Repeatability and reproducibility of automatically estimated ventricular repolarization parameters in 204 healthy subjects.

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.

Hepatic vein transit time of second-generation ultrasound contrast agent: new tool in the assessment of portal hypertension.

PURPOSE: 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. METHODS: 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 becomes >1 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. RESULTS: Cirrhotics with low HVWI showed an earlier transit time; participants with higher HVWI had a longer transit time (p < 0.001). HVTT was earlier as MELD, Child-Pugh score and spleen diameter increased. Patients with ascites and varices of large size had significantly shorter transit times. CONCLUSIONS: 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.

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 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. 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.

Percutaneous method for single-catheter multiple monophasic action potential recordings during magnetocardiographic mapping in spontaneously breathing rodents.

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.

Anti-ß-adrenoceptors autoimmunity causing 'idiopathic' arrhythmias and cardiomyopathy.

BACKGROUND: To determine the prevalence of anti-ß-adrenoceptors autoantibodies (aßAA) in patients with idiopathic arrhythmias (IA) and to assess whether aßAA 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 ß1-and ß2-adrenoceptors. Endomyocardial biopsy was performed in 29 patients. As compared with group 4 [3/19 (15.7%)], anti-ß1-adrenoceptor autoantibodies (aß1AA) were more frequent in group-1 patients [38/67 (56.7%; P<0.01): 27/42 (64.2%; P<0.001) with VA and 11/25 (44%; P<0.05) with SVA]. 3 of the group 1 patients also had anti-ß2-adrenoceptor autoantibodies (aß2AA). 4 were positive for aß2AA only. Biopsy performed in 11/67 group 1 patients was abnormal in all. Of them, 7/8 (87.5%) with VA and 3/3 (100%) with SVA were positive for aß1AA. PCR analysis from paraffin blocks of the 11 group 1 biopsied patients was negative for EV, EBV, HCV, AV, PVB19, INF A/B,HSV1/2, HHV6 and HHV8 viral genomes. CONCLUSIONS: The second extracellular loop of the ß-adrenoceptor is the molecular target of specific autoantibodies. Positivity for aß1AA predicts abnormal histological findings in 90% of IA patients and suggests that autoimmunity might play an arrhythmogenic role.