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Background Remote rhythm monitoring with wearable devices is increasingly used especially for early detection of atrial fibrillation/flutter (AF/Afl), being the access to hospital discouraged, especially for frail elderly patients, due to the burden and risk of COVID-19 pandemic. Whereas devices using photo plethysmography (PPG) may misinterpret as AF pulse irregularities due to extrasystoles, patient-directed recording of a single (usually wrist-to-wrist) lead ECG (LEAD I) with hand-held devices or smartwatches have been developed to increase accuracy in AF detection. However, although recent studies validating such devices single-lead ECG recording have shown high sensitivity and specificity, false negative findings such as those reported here are still possible and must be prevented [1]. Purpose Given previous experience of diagnostic uncertainty or failure of the smartwatch ECG (SW-ECG) LEAD I to detect AF/Afl, we have tested if false negative diagnosis could be avoided by recording in addition at least one right precordial (pseudo-V1) lead analyzed by a trained healthcare professional. Method Over one calendar year observation, five patients with previous history of ablated supraventricular arrhythmias suffering sudden palpitations suspected of paroxysmal AF/Afl were instructed to record with their smartwatch at least one precordial lead in addition to LEAD I, to monitor ECG until the termination of symptoms. The SW-ECG strips were sent by telephone for professional interpretation. Diagnostic accuracy based on LEAD I and pseudo-V1 were independently validated by two cardiologists (diagnostic goldstandard - DGS). Results 22 AF/Afl events occurred. Pharmacological cardioversion to sinus rhythm (SR) was obtained in 64%. 192 ECG strips were transmitted. 43,7% of the strips were automatically classified as “not significant” (or “not valid”). Compared to DGS, out of 108 “valid” strips, correct automatic identification of AF/Afl was obtained in 36,4% with LEAD I, in 33,3% with pseudo V1 and in 54,5% with combined leads, respectively. Interestingly, the SW algorithm has wrongly diagnosed as SR, not only LEAD I, but also 39,4% of pseudo-V1 strips, despite clear-cut evidence of typical flutter waves (Figure 1), when RR intervals were regular due to high degree (e.g., 4:1) A-V block. Conclusions With simple instructions, patients (or their relatives) can easily record an additional precordial (pseudo-V1) SW-ECG lead, that may enhance sensitivity and specificity for remote detection of AF/Afl. However, at present, visual interpretation of SW-ECG by a trained healthcare professional is still needed to guarantee 100% correct diagnosis of AF/Afl, crucial to reduce thromboembolic risk and timely initiate the appropriate treatments. The automatic interpretation of SW's ECG could be improved by appropriate training of a machine learning approach to detect and analyze the atrial waveform provided by an additional pseudo-V1 lead. Funding Acknowledgement Type of funding sources: None.

Background Quantitative assessment of individual body adaptability to physical training performed with the purposes of health maintenance is particularly necessary in the elderly age, to avoid the risk of overstrain induced by inappropriate exercises workload and physical stress. For that purpose, heart rate monitors and heart rate variability (HRV) analysis are nowadays commercially available. However, their reliability to guide individualized fitness training in elderly people needs to be tested, knowing that users might not have medical education. Objective To preliminary quantify autonomic nervous system (ANS) responses to graded physical effort and recovery in healthy elderly basing on the parasympathetic nervous system (PNSi), the sympathetic nervous system (SNSi) and the stress (STRi) indices, derived by short-term and time-varying HRV analysis. Methods ECG of a 75 healthy male subject was monitored, from April to November 2020, during three times/week training sessions with a professional bike–ergometer. Each session consisted of 10 minutes baseline rest, 5 minutes warm-up, 30 minutes work and 10 minutes recovery. According to age, the training workload was graded from low (65–75 watt/min), to moderate (75–85 watt/min), semi-intensive (85–95 watt/min) and intensive (95–110 watt/min). For this pilot study, ECG data of only 40 training sessions (10 sessions for each workload to evaluate reproducibility) were analyzed with Kubios Premium software (version 3.4.1), in the time (TD) and frequency (FD) domains, with nonlinear (NL) methods and with time-varying (TV) algorithms. Short-time HRV was calculated from 2-minutes intervals. The PNSi, SNSi and STRi induced by each workload were averaged and compared. Results Average values of PNSi, SNSi and STRi were significantly different (p Conclusions The calculation of PNSi, SNSi and STRi from HRV analysis is an efficient method for quick and simplified quantitative assessment of dynamic ASN adaptation to effort-induced stress from HRV analysis. If confirmed, the method may be useful for safer and even remote monitoring of training/rehabilitation in elderly. However, more detailed evaluation of spectral and NL parameters may be necessary to interpret more complex patterns of abnormal cases. Funding Acknowledgement Type of funding sources: None. Table 1Figure 1

Background Out of millions of patients (pts) screened every year for chest pain in emergency departments (EDs) only 10% to 20% are affected by an acute coronary syndrome (ACS) or angina due to ischemic heart disease (IHD). Unless ECG recording and serum markers are clearly positive, most of them must undergo complete clinical workout to exclude IHD prior to discharge. Moreover, since even effort-ECG and echocardiography don't exhaustively rule-out IHD, second-level exams are frequently needed, enhancing hospitalization time and related costs. Magnetocardiography (MCG) is increasingly reported as a sensitive, non-invasive, radiation-free method with high negative predictive value (PV) to rule out IHD. Purpose Retrospective cohort study to evaluate the reliability likelihood of unshielded MCG (uMCG) as a tool for rapid rule-out of IHD. Method Rest uMCG data of 263 patients (pts), all chest-pain free at the moment of MCG scan, were retrospectively analyzed. uMCG was recorded with a 36-channel SQUID system (intrinsic sensitivity 30 fT/√Hz, above 1Hz), for 90 seconds. With proprietary software, 13 MCG parameters were automatically calculated from T-wave magnetic field (T-MF): 5 parameters quantifying the dynamics of the MF extrema and eight, obtained from inverse solution with the equivalent magnetic dipole (EMD) model, quantifying the spatial dynamics of the T-wave effective magnetic vector (T-EMV). Pts were stratified as follows: – Group A, chest pain pts, with IHD confirmed by subsequent SPECT and coronary angiography (mean age 66±11 years, 36.7% female); – Group B, chest pain pts, with IHD excluded by subsequent SPECT or coronary angiography (mean age 59±10 years, 28.8% female); – Group C, healthy control subjects (mean age 25±7 years, 48.6% female). Only 60 pts in each group were randomly selected for the analysis. Non-parametric Kruskal-Wallis tests were used to compare the 13 MCG predictors among groups. Linear discriminant analysis was employed to assess likelihood ratios (LHR) and PVs, considering a mean IHD prevalence of 13% (range 10–20%) in chest-pain pts. Results Positive LHR was 9, while the negative LHR was 0.3, resulting in a helpful reduction of the pre-test probability of IHD. Whereas positive PV ranges from 51 to 70%, hardly confirming IHD diagnosis, negative PV ranges from 92 to 96%, giving confidence for a safe IHD rule-out. Conclusions Automatic analysis of T-MF and of T-EMV dynamics from rest MCG provided impressive negative LHR and PV values that, if confirmed in prospective multicenter trials, would rank MCG as a useful tool for quick and early triage of pts with acute chest pain and still non-diagnostic ECG and enzyme patterns, to rule-out those whose symptoms are of non-ischemic origin. Interestingly, a similar high negative PV has been recently reported using MCG QRS predictors. Thus, even better results could be expected by combining algorithms for automatic assessment of both T-wave and QRS predictors. Funding Acknowledgement Type of funding sources: None.

Background Sports motoring and racing imply high physical and psychological stress, during pre-competition phases and the competition itself. Therefore, there is growing interest of racing teams for new technologies providing real-time monitoring of psychophysiological reactions of pilots to highly-demanding driving and vehicle dynamics, to improve personalized training, while reducing human risks and costs. Professional Driving Simulators (PDS) are ideal to assess in real-time vehicle dynamics under any kind of programmable virtual driving conditions, but a direct connection with the driver's physiology is still limited. A novel wearable system and software have been developed, providing simultaneous assessment of pilot's stress reactions, by real-time calculation and monitoring of time-variant heart rate variability (TV-HRV) spectral parameters (SP) and of skin potential response (SPR), in correlation with vehicle's dynamics. Purpose This study aimed to demonstrate the reliability of the method in detecting the pilot's stress induced by different driving demands. Methods 10 volunteers (age 26±2.3 years) were enrolled to pilot a racing car under realistic conditions simulated by the DIM® PDS (Vi-grade). The study protocol consisted of 5-minutes baseline rest, sitting in the cockpit; 5-minutes driving along a straight highway without obstacles; 6-minutes of medium-stress slalom between cones, avoiding collision; 8-minutes racing 4 laps on a race track, at maximum possible speed, but avoiding crashes. ECG and SPR signals were acquired (1 Khz sample rate), with the Vi-BioBox connected to textile wearable sensors. A proprietary software was developed to analyze and stream the TV-HRV and SPR data in real-time to WINTAX4 data logging software for automotive racing industry. Real-time assessment of the pilot's stress was based on the integration of transient changes of HRV-SP and of the Root Mean Square value of two SPR signals (SPRRMS). To validate the accuracy of the real-time HRV analysis, all data were analyzed also off-line with Kubios Premium 3.4.1. software. Results The Vi-BioBox signals were adequate for real-time calculation and monitoring of transient variations of HRV-SP. A good correlation was found between transient stress-induced increment of pilots' SPRRMS values and the occurrence of driving errors (pink-red spots automatically transferred onto the race track – Figure 1). A good match was found between the real-time HRV values calculated by the VI-BioSoft and their off-line calculation with Kubios (v. 3.4.1 Premium). Two pilots, suffering simulator sickness, had prodromal alteration of cardiac autonomic modulation. Conclusion The integration of a Vi-grade PDS with the novel system for real-time calculation and telemetric monitoring of time-variant HRV and SPRRMS provides immediate information about pilot's autonomic response to driving demands and emotional reaction to vehicle's dysfunction, driving errors and bad performance. Funding Acknowledgement Type of funding sources: None. Figure 1

Introduction Parkinsonian syndromes of different nature feature autonomic nervous system dysfunction (ANSd) which may herald or follow motor symptoms (MS) in Parkinson disease (PD), but anticipate by years and progress more rapidly in multiple system atrophy (MSA). Abnormal Heart Rate Variability (HRV) has been reported in both PD and MSA. Purpose This study aimed to evaluating if HRV analysis (HRVa) could contribute to differentiate PD from MSA and to guide early and more appropriate treatment and prognostic assessment. Methods 66 consecutive parkinsonian patients (pts) (48 males, 18 females) (mean age 63.8±10 y) were enrolled between 2010 and 2020. Initial clinical diagnosis was MSA (19), PD (20), PD with autonomic impairment (PD-AI) (10), Lewy body disease (2), supranuclear palsy (3), undefined Parkinsonism (UP) (12). The severity of MS was quantified with UPDRS and Hoehn/Yahr scales. HRV was analyzed with linear (TD and FD) and non-linear (NL) methods (Kubios Premium 3.4.1), during daily activity and NREM sleep (2-minutes intervals) and during REM sleep (1-minute Interval). 44/66 underwent also ASN functional evaluation with the Ewing protocol. Data of 52 age-matched healthy subjects (HS) were used for comparison. For statistical analysis, SPSS software (version 21) was used. Discriminant Analysis (DA) was applied to identify the more relevant parameters differentiating PD from MSA and classifying “undefined” cases. Prolonged follow-up (f-up) provided clinical diagnostic certainty, as goldstandard for validation of HRVa classification accuracy. Results UPDRS and Hoehn/Yahr scores were higher in MSA than in PD (p Most of HRV parameters of 34 pts with certain diagnosis (17 MSA and 17 PD) whose f-up was completed, were significantly different from those of HS. VLFpower and recurrence plot parameters calculated during active wakefulness were different (p F1 = (vlfpw%ar* − 0,087) + (rprec* − 0,319) + (rpshen*10.81) + (−20,53) Comparative classification accuracy of HRVa, Ewing score, UPDRS and Hoehn/Yahr scales is shown in Table 1. Attempting prognostic risk assessment by applying F1 to HRV data of pts with PD-AI and of pts with UP, those classified as MSA according to F1 showed the worst clinical outcome during the f-up. Conclusions This study confirms that a higher degree of prevailing sympathetic ASNd in MSA compared to PD can be identified by a combination of Linear and NL HRV parameters, and correctly differentiate with high (88,2%) predictive accuracy all pts with certain diagnosis verified during prolonged f-up. Moreover, HRVa might be useful for earlier prognostic stratification of pts with parkinsonian symptoms of uncertain nature and to improve clinical and pharmacological management. Funding Acknowledgement Type of funding sources: None.

Background Magnetocardiography (MCG) is under clinical evaluation as a novel, sensitive, radiation-free method for first-level non-invasive diagnosis of ischemic heart disease (IHD) and for rule-out of acute coronary syndromes (ACS) in chest pain patients with still normal ECG and serum markers. So far, multichannel MCG has been mainly performed with cryogenic sensors (SQUIDs). Alternatively, to reduce costs and/or to bring MCG to the patient bedside, novel non-cryogenic technologies have been developed, based on small induction coils or optically pumped magnetometers (OPMs). The magnetic field (MF) resolution of OPMs is nowadays comparable to that of the SQUIDs. However, OPMs operate in zero-field mode and consequently need magnetic shielding. Thus, presently used OPMs technology is not suitable for unshielded MCG. On the contrary, Miniature Scalar Atomic Magnetometers (MFAM™) operating in the total-field mode, with a sensitivity better than 2pT/√Hz to about 400Hz, were reported to detect the cardiac MF in an unshielded environment. This study aimed to investigate whether the MFAM, originally developed for geophysics and magnetic anomaly detection, could be suitable for MCG in an unshielded hospital laboratory for clinical electrophysiology (UHEPL). Method Recordings were performed in the north-south direction, with sensors parallel to sources and tilted 30°. A dual-sensor MFAM module was used: one sensor, placed as close as possible to the source of interest, to detect its MF, and the other, more distant, to detect and subtract in real-time the background electromagnetic noise. The magnetic signal was acquired at 1-kHz sampling frequency (bandwidth DC-250 Hz). Signal averaging (SA) and digital filtering of RF noise (notch 50 Hz, LP 100 Hz) were used to improve the signal to noise ratio (S/Nr). First, the recordings were performed with a simplified phantom, filled with saline, using our amagnetic catheter to simulate current dipoles (CDs) of different geometry. Then MCG was attempted in 15 heathy volunteers (HV) (age 22–73 years) and compared with their SQUID MCG (Figure 1C, D). Results After SA of 200 beats and filtering average peak-to-peak noise was 2–4 pT. S/N ratio (≥10 in the phantom (with 1 mA CDs) was twice lower in MFAM MCG. However ventricular MCG was feasible in all HV. On the contrary atrial MCG was adequate in one case only. Figure 1 summarizes the performance of the MFAM in UHEPL: (A) typical MFAM noise spectra. (B) 36-point SQUID MCG at the R wave peak, (C) MFAM-MCG signal taken at the fifth right parasternal intercostal space, D) SQUID MCG at same position for comparison. Conclusions MFAM sensors were sufficiently stable to record MCG of several minutes in our UHEPL. The present sensitivity of MFAM is adequate for clinical MCG of ventricular de/repolarization (i.e. for detection/rule out of IHD/ACS), but not of atrial electrophysiology. A better performance is foreseen with development of more efficient gradiometer technology. Figure 1. Comparison between MFAM and SQUID Funding Acknowledgement Type of funding source: None

Background Heart rate variability analysis (HRVa) is increasingly used to evaluate stress-induced adaptation of the autonomic nervous system (ANS), basing on electrocardiogram (ECG) recorded with novel wearable wireless devices (WWD) for physiological monitoring. However, in order to transfer ECG data to mobile phones efficiently, WWD use low sampling frequency (SF), usually ∼100 Hz, thus much lower than the 0.5–1 kHz, previously suggested to optimize R–R intervals detection, precise enough for HRVa in the time-domain (TD), frequency-domain (FD) and with nonlinear (NL) methods. Moreover, the latter are sensitive to SF as a function of data length. Aim Aim of this study was to quantify the relative error (RE%) of HRVa, when calculated from ECG downsampled at 100 Hz, compared with that digitized at 1 kHz, considering different data lengths. Methods ECG of four healthy professional pilots was continuously recorded with a WWD (Vi-grade, Udine), at 1 kHz SF, while driving a professional simulator, inducing different degree of psychophysiological stress by changing suddenly the vehicle's behavior without advising the driver. TD, FD and NL HRV parameters were calculated (Kubios 3.0.2, Finland), from time intervals of 300, 120, 60 and 30 seconds, of ECG downsampled at 100 Hz SF from original recordings acquired at 1 kHz SF (assumed as goldstandard). The RE% and the intraclass correlation coefficient (ICC) were calculated. Results A good correlation (ICC ≥0.79–0.84) was found for the majority of HRV parameters, in both driving conditions, for all selected intervals lengths. The average RE% ranged between zero and 3%, increasing if the length of the interval selected for HRVa was lower than 60 second (Table 1). However higher RE was occasionally found. In Figure 1, an example of HRVa calculated from 2 minutes tachogram's segments, at 100 Hz (left) and at 1 kHz SF (right) is shown. Conclusions Compared to 1 kHz SF, downsampling ECG at 100 Hz doesn't affect significantly HRVa for data lengths between 5 and 1 minutes. However, for shorter time intervals the RE increases. This must be taken into account if HRVa is used to track transient short-lasting changes of ASN modulation induced by acute stress. Figure 1 Funding Acknowledgement Type of funding source: None

Background Although clinical assessment of cardiac autonomic modulation (CAM) usually relies on off-line heart rate variability analysis (HRVa), measured under stationary conditions according to guidelines, there is a growing interest, in sports medicine and psychophysiology, for the reliable evaluation of acute changes of CAM occurring under real-world dynamics (i.e. acute stress induced by competitions or critical situations). The aim of this study was to test, with a standardized clinical protocol inducing enhancement of sympathetic/vagal modulation, the reliability of a novel system for continuous monitoring and telemetric transmission of transient CAM changes, provided by real-time calculation of time-variant HRV parameters (HRVp) and Skin Potential Response (SPR). Methods All measurements were performed in the laboratory for clinical electrophysiology. The Vi-BioBox system consists of a wearable wireless mini-recording device connected to a textile electrode garment and hands electrodes. 3 ECG and 2 SPR signals are continuously recorded (1 kHz sampling-rate) and streamed in real-time to Wintax4 (Magneti-Marelli) data logging for real-time calculation and monitoring of spectral HRVp and of the Root Mean Square value of two SPR signals (SPRRMS) with a proprietary custom software. 10 healthy volunteers (mean age 32.4±16.8 y, 50% males) underwent a 5-steps protocol: 1) 10-minutes baseline supine; 2) 10-minutes Head-up tilting 70° (HUTT); 3) 10-minutes supine recovery); 4) 20-minutes mental stress (“Mensa” preliminary Tests); 5) exercise-test at bicycle-ergometer. 12-lead ECG was continuously recorded also with Mortara Surveyor/X-Scribe and Time-variant HRVp were also calculated off-line with Kubios (3.0.2) software. Statistical analysis was performed with SPSS 21. Results The quality of the Vi-BioBox signals was optimal for reproducible real-time calculation and monitoring of time-variant HRV parameters. Baseline SPRRMS activity ranged between 0.01 and 0.8 mV, with wide interindividual variability. A significant (p Conclusion Real-time monitoring of time-variant spectral HRVp and of SPRRMS was reliable and reproducible. SPRRMS is an independent sensitive marker of sympathetic activation, which anticipates increments of VLF, LF and is useful to interpret CAM underlying of LF/HF changes. Real-time monitoring of CAM may be useful to improve the mechanistic understanding of acute psychophysiological stress-reactions, dysautonomic syncope, arrhythmic events initiation and for telemedicine (i.e. continuous remote monitoring of CAM in patients with heart failure). Figure 1. Real-time monitoring of HRV-SPR Funding Acknowledgement Type of funding source: None

Background Nowadays research on Autonomous Driving Systems (ADS) and attention towards novel technology allowing real-time assessment of car drivers' psycho-physiological status is growing, to quantify driver's stress during semi-autonomous or autonomous driving assistance and to investigate human reaction to different types of ADS. We present a system for automatic stress detection with combined machine learning analysis of Skin Potential Response (SPR) and electrocardiographic (ECG) recordings to compare the driver's stress reaction during both manual and autonomous driving sessions carried out in a dynamic professional drive simulator (PDS). Methods All data were acquired after informed consent from 14 healthy volunteers (HVs) in the Vi-grade (Udine) PDS. Two SPR signals (one from each hand) and three chest ECG leads were recorded. A Motion Artifact (MA) removal algorithm was used to remove motion artifacts from SPR signals. A cleaned, single SPR signal, obtained as the RMS value by combining the two original signals, was then sent together with the time-variation of heart rate (HR) to a Machine Learning (ML) classification algorithm, i.e., a Support Vector Machine (SVM), based on some specific features of this signal. The output of the SVM provides a series of labels, that indicate the presence or lack of stress episodes during the driving experiment. Stress occurrence was also independently quantified with heart rate variability (HRV) analysis in the time (TD) and frequency (FD) domains and with non-linear (NL) methods. Results All participants completed the driving protocol consisting of two subsequent sessions, one with conventional manual (MD) and the other with autonomous (AD) driving settings, along a highway where some unexpected events occurred, inducing different level stress response. Figure 1 shows an example of time variant changes of the RMS SPR signal and of the HR of one tested individual during both experimental settings. A simultaneous increase of both SPR and HR signal is apparent during the stress episodes correctly identified by the SVM (gray shadows). Discriminant analysis of FD (VLF, LF and HF) and NL (SD1, SD2, Entropy and Recurrence Plot) HRV parameters, independently assessed by two researchers blind to SVM results, differentiated between stress induced by MD and AD (accuracy: 88,4% cross-correlated) in good agreement with automatic SVM assessment. In general stress level was lower during the AD, being all HRV parameters not significantly modified from baseline rest. SPR amplitude eventually increased also during AD, but SVM efficiently differentiated between AD and MD stress anyhow. Conclusions The proposed method for automatic assessment of stress reactions of car drivers with SVM of SPR and HR signals is reliable, in both MD and AD scenarios. The results seem to evidence that MD is in general more demanding than AD inducing higher activation of sympathetic nervous system, especially in critical situations. Figure 1. Time variance of SPR and HR. Funding Acknowledgement Type of funding source: None

More and more sophisticated assisted/autonomous vehicles are becoming available in the market. Automation levels 2 and 3 have been given for settled just a couple of years ago, and the path to fully autonomous car seemed to have no obstacles. In reality, OEMs started recently realizing that the impact of semi and/or fully robotized cars on drivers as well as on passengers is all but predictable. VI-grade has more than ten years experience with developing turn-key solution driving simulators, and has been working for more than five years on a research project to collect meaningful bio-signals from the driver during simulator sessions, in collaboration with the BACPIC of the Catholic University of Sacred Heart and the DPIA of the University of Udine. Recently, a collaboration with the Human Inspired Technology Research Center of University of Padova allowed the extension of the assessment at physio-emotional level.

Action Pistol Shooting, implies high degree of physical and psychological stress, however cardiovascular adaptation during competition has not been studied so far.We studied six healthy males athletes, during the Italian National Dynamic Pistol Shooting Championship. ECG was monitored and blood pressure (BP) manually measured along the match.Mean heart rate (HR) was close to 100 bpm per minute in all but one shooters. Marked tachycardia, above 180 beats per minute was recorded in four shooters, during "field course" stages. In two cases the heart rate under stress reached about 200 bpm, for the occurrence of paroxysmal atrial arrhythmias. BP behavior was different among the six shooters with mean systolic values ranging between 140 and 170 mmHg and maximal systolic values between 160 e 240 mmHg.Action Pistol Shooting induces acute elevation of HR and BP, which may reach abnormal values and can be associated with impaired performance and score. Further study is warranted in shooters undergoing combat-like tournaments to evaluate unperceived cardiovascular stress and their coping capability.

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

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

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.

Using a bipolar suction electrode technique, right atrial monophasic action potential (RA MAP) was recorded in 18 patients surely free from any kind of arrhythmia. Two morphologically different kinds of RA AMP were obtained: the former exhibiting an evident transition between phase 1-2 (plateau) and phase 3 of repolarization (FP), the latter without any appreciable palteau (FL). Electrophysiological properties of human myocardial atrial tissue have been investigated by microelectrode technique. The two types of MAP recorded by us resemble the former the action potential obtained from conducting specialized fiber, the latter the action potential of contractile fibers. A statistically significant difference in RA MAP duration measured at 90% level of repolarization (D 90%) was found between the two kinds of MAP: therefore we suggest to perform quantitative evaluations and pharmaco-ogical investigations only including MAPs of similar morphology. The intraindividual variation coefficient of D 90% may be considered an expression of the range of variability of repolarization duration in man; we suggest that only MAPs of similar configuration should be accepted for its calculation in order to avoid errors of evaluation.

His Bundle Electrogram (HBE) was recorded in 20 patients with Mobitz type II block. All patients were clinically evaluated and a history of syncope was carefully investigated. These patients were prospectively followed (mean follow up: 20,4 months). ECG showed LBBB in 9 patients, RBBB + LAHI in 6, RBBB + LPH in 3, LAH in 1, left axis deviation in 1. In all patients HBE revealed prolungation of H-Q interval and localization of block within the His-Purkinje system (within H in 4) distal to H in 16. In 9 patients intermittent complete heart block localized within the H-P system was documented during HBE recording. 15 patients (75%) experienced syncopal attacks. All patients underwent implantation of permanent demand pace-maker, without further episodes of syncope. Since the site of block is the most important determinant of prognosis, in all patients with Mobitz type II block, whether or not symptoms are present, prophylactic implantation of pace-maker is indicated, because high incidence of progression to complete heart block, with potential risk of Adams-Stokes syndrome and sudden death.

A method is presented for the non-invasive recording of His bundle electrical activity from the body surface in man. Several bipolar ECG leads were employed: precordial, Frank "x" and Frank "z". Signals were filtered (30-300 Hz), highly amplified (5 x 104) and averaged. Digital averaging was performed on line by a microcomputer (OTE Biomedica Neuroaverager mod. 1172). Surface investigation was performed in 10 patients affected by different conduction pathology simultaneously with HBE recordings for diagnostic purpose and in 5 normal volunteers only incruently. Highly repeatable electrical deflections (B waves) were recorded in the PR segment. In all patients a good correspondence between surface (B wave) and intracardiac (H wave) was found. Atrial pacing and pharmacological test were used in order to ascertain the real source of B wave.

For clinical purpose, poligraphyc signals are analyzed: systolic time intervals (STI) and all other significative magnitudes are measured. A system of modular programs (ATS), in Assembler and Fortran IV languages, digitalizes, filters and analyzes three simultaneous analogical signals: ECG, PCK and CP. ATS, adapted polynomial and gonyometrics leats-squares smoothings to the signals for leaving-out spikes and drifts, employs algorhythms that, by a statistic knowledge of the thresholds of the fist derivative of each signal and of the globality of smoothed signals, converge to the measures of the required significative magnitudes. A statistic investigation (on 100 samples) showed that ATS is better than every manual analysis in terms of efficiency, speed and amount of information. In conclusion ATS program is suitable for clinical purposes.