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Background: Regular intensive physical activity is associated with non-pathological changes in cardiac morphology. Differential diagnosis with arrhythmogenic right ventricular cardiomyopathy (ARVC) constitutes a frequent problem, especially in athletes showing ventricular arrhythmias with left bundle branch block morphology.Aim Of the Study: To assess the different clinical and non-invasive instrumental features of the subjects affected by ARVC and by athletes.Methods: Three groups of subjects (40 ARVC patients, 40 athletes and 40 controls, mean age 27 (9) years) were examined with family and personal history, physical examination, 12-lead ECG, 24-h ECG, signal-averaged ECG and 2-D and Doppler echocardiography.Results: 12-Lead ECG was abnormal in 62% of ARVC patients versus 7.5% of athletes and 2.5% of controls (p<0.0001). Ventricular arrhythmias and late potentials were present in 70% and 55% of ARVC subjects, respectively (vs 5% of athletes and 7.5% of controls, p<0.0001). Left ventricular parietal wall thickness and left ventricular end-diastolic diameters were significantly higher in athletes. Both athletes and ARVC patients presented a right ventricular (RV) enlargement compared with controls. Moreover, RV outflow tract, measured on parasternal long axis and at the level of aortic root, was significantly larger in ARVC patients (33.6 (4.7) mm vs 29.1 (3.4) mm and 35.6 (6.8) mm vs 30.1 (2.9) mm; p<0.0001), and RV fractional shortening and ejection fraction were significantly lower in ARVC patients compared with athletes (40 (7.9)% vs 44 (10)%; p=0.05 and 52.9 (8)% vs 59.9 (4.5)%; p<0.0001). A thickened moderator band was found to be present in similar percentage in ARVC patients and athletes.Conclusions: An accurate clinical and instrumental non-invasive evaluation including echocardiography as imaging technique allows to distinguish RV alterations typical of ARVC from those detected in athletes as a consequence of intensive physical activity. [ABSTRACT FROM AUTHOR]

Involvement of cerebral vasoconstriction confirms the complexity of the pathophysiology of neurally mediated syncope, and the need to adopt a comprehensive approach to the study of this problem. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess exercise test results and efficacy of therapy with a β blocker (acebutolol) in ryanodine receptor type 2 (RyR2) mutation carriers with documented ventricular arrhythmias (VAs) and long-term follow-up. Twenty RyR2 mutation carriers belonging to 8 families and regularly followed at our center were analyzed using a study protocol involving electrocardiography, exercise tests off and on β-blocker therapy, 2-dimensional echocardiography, and signal-averaged electrocardiography. Off-therapy exercise testing triggered the onset of VAs at different heart rates (mean 132 ± 13 beats/min) with various patterns that worsened while exercising and disappeared immediately after stopping. The most severe VAs detected were nonsustained ventricular tachycardia in 35% and ventricular couplets in 35%. In the remaining subjects single ventricular premature beats were recorded. In 15% of patients single monomorphic ventricular premature beats were detected and identified to be linked to RyR2 mutations owing to the presence of sudden deaths of their family members and subsequent family screening. Acebutolol made the VAs disappear completely in 20% of subjects and decreased their complexity in 50%, whereas it did not change VAs appreciably in 30% of patients with less complex VAs. After 11 ± 8 years of follow-up 2 patients developed syncope. In conclusion, exercise testing was a fundamental tool for assessing the clinical phenotype and efficacy of therapy in RyR2 mutation carriers and therapy with acebutolol led in most subjects to a decreased complexity of the arrhythmic pattern or to complete suppression. [ABSTRACT FROM AUTHOR]

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a cardiac disease characterized by progressive myocardial atrophy and fibrofatty replacement. Standard electrocardiograms (ECGs) and signal-averaged ECGs (SAECGs) were relatively low cost and repeatable diagnostic tools. In this study, ECGs and SAECGs of patients with ARVC were analyzed with the aim to assess the diagnostic capability of these noninvasive techniques. A total of 205 patients with ARVC were analyzed. ECGs were abnormal in 74% of patients and SAECGs were positive in 60%, with normal ECGs mostly related to mild forms of the disease. The most common electrocardiographic abnormalities were localized right QRS prolongation, poor r wave progression in the right precordial leads, incomplete right branch bundle block, prolonged S-wave upstroke in V(1) to V(3), parietal block, ST-segment elevation in V(1) to V(3), inversion of T waves beyond V(2), and epsilon wave. Low QRS voltages in the precordial leads were frequently present in all patients with ARVC compared with a group of 120 healthy subjects (p = 0.00001). T-wave inversion beyond V(3) characterized subjects with severe right ventricular dilatation, whereas in subjects with left ventricular involvement, T-wave inversion in lateral leads was more commonly detected. Overall, the extent of electrocardiographic abnormalities was related to disease extent. In conclusion, abnormalities in ECGs and SAECGs were frequent in patients with ARVC and correlated with disease extent, even if a stereotypical electrocardiographic pattern did not exist. ECGs and SAECGs remain an important tool for the diagnosis and assessment of ARVC extent. Nonetheless, a normal ECG does not exclude the presence of the disease. [ABSTRACT FROM AUTHOR]

Context: The mental health crisis in medicine cannot be explained by burnout alone. Physicians are not immune to this crisis and are known to have higher rates of suicide and depression than the general population. A high prevalence of mental health symptoms has been observed in early medical training., Objectives: This study was completed to characterize medical students' mental well-being and provide guidance for timely intervention., Methods: An annual prospective, voluntary, anonymous, cross-sectional survey of medical students was completed over a 4-year period in medical school from 2016 to 2019. The survey was created based on standardized psychiatric screening tools assessing symptoms of depression, anxiety, burnout, and sleep problems. In each of those years, 1,257 (2016), 1,254 (2017), 1,221 (2018), and 1,220 (2019) enrolled students, respectively, were invited to participate. Data on students' mental health were analyzed in relation to their year of school separately for each survey year utilizing SAS 9.4., Results: A total of 973 students in 2016, 889 students in 2017, 547 students in 2018, and 606 students in 2019 participated in the study. For depression and burnout subscales, an increase in symptom scores were observed every survey year (2016, 2017, 2018, and 2019) by the second or third year of medical school with a clinically significant effect size. Persistently high levels of anxiety were observed throughout medical school, with significant increases after the first year noted in the 2016 and 2017 surveys, but not in the 2018 or 2019 surveys. Similarly, significant changes in sleep disturbance were found in the 2016 and 2017 surveys, but not in 2018 or 2019., Conclusions: Symptoms of burnout, depression, and anxiety were observed throughout all four years of medical school, with increases starting after the first year. Early intervention is needed to support students' mental health and increase access to care and resources., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

Context: Emergency medicine (EM) physicians commonly stabilize patients with acute psychiatric distress, such as suicidal ideation. Research has shown that suicidal ideation is difficult to manage in emergency department (ED) settings and that patients in psychiatric distress are often "boarded" in the ED while awaiting more definitive care., Objectives: To examine the attitudes and experiences of emergency physicians regarding the care of patients in psychiatric distress. Special attention is given to suicidal ideation due to its prevalence in the United States., Methods: A 19 question anonymous survey was sent via email to 55 emergency medicine residency directors throughout Michigan, Ohio, Indiana, and Illinois, who were identified using an Internet search of residency programs in the region. The program directors were asked to distribute the survey to their colleagues and residents. The intent of this procedure was to generate as many survey responses as possible, while obscuring the identities of the respondents. Responses were gathered from October 29, 2019 until January 16, 2020. The survey was designed to assess respondents' self-reported demographic data as well as their experiences with the boarding process, initial examination, final disposition, reevaluation of the patient, physician training and resources, and follow up care. Statistical analysis was performed using a Mann-Whitney U test, significance was set at p<0.01., Results: In total, 47 EM physicians responded to the survey; however, not all of the respondents completed all 19 questions. Ten of 44 respondents (22.7%) reported that they do not perform the initial psychiatric examination themselves and instead defer to a nurse or social worker. Twenty-two of 44 respondents (50.0%) reported that they defer to a social worker when determining the final disposition of psychiatric patients. Respondents reevaluated patients in psychiatric distress statistically significantly less often (p=0.01) compared with patients with cardiac pathology. Additionally, 15 of 38 respondents (39.5%) reported that they did not feel adequately trained to handle psychiatric emergencies, and 36 of 39 respondents (92.3%) of physicians felt that their facility would benefit from additional mental health resources. Thirty five of 39 respondents (89.7%) reported that their facility did not have a system in place to follow up with suicidal patients upon discharge., Conclusions: Caring for patients who are acutely suicidal or in psychiatric distress is complex and more research is needed to optimize treatment strategies. The results of this study indicate that EM physicians may regularly defer to nonphysician providers when evaluating and treating patients in psychiatric distress. A perceived lack of training in psychiatry may contribute to this practice. The results of this study are in accord with previous research that indicated a need for additional psychiatry training in EM residencies., (© 2021 Jack Brodeur et al., published by De Gruyter, Berlin/Boston.)

Context: Although there is little data currently available concerning the primary factors associated with disordered eating behaviors among triathletes, these athletes may be at greater risk. Sports medicine professionals are in a unique position to identify athletes with disordered eating risks., Methods: The purpose of this cross-sectional survey study was to identify the prevalence of disordered eating attitudes and behaviors among a national convenience sample of triathletes. A secondary purpose was to identify "triathlon-specific factors" and "competitive athlete-factors" potentially associated with disordered eating behaviors. The authors hypothesized that certain triathlon-specific factors and competitive athlete factors would be associated with increased rates of self-reported disordered eating behaviors., Results: In a respondent sample of 1,033 adults, multiple competitive athlete factors were associated with a higher risk for disordered eating, whereas triathlon-specific factors were not., Conclusions: In this study sample, disordered eating was not specifically associated with triathlon-specific factors. Rather, disordered eating behaviors were found to be more often associated with associated competitive athlete factors, particularly in the many leanness sports such as running., Competing Interests: The authors declare no conflict of interest.

Aims: The majority of patients with pacemakers are very elderly, many being >85-years old. They often suffer from serious illnesses and have great difficulty in walking. The aim of our study was to compare remote pacemaker monitoring with in-home checks of pacemakers, in terms of applicability, efficacy, and cost in a selected population of debilitated elderly patients., Methods and Results: We selected 72 subjects (mean age 87 ± 8 years) among elderly debilitated patients with Medtronic pacemakers, compatible with the Carelink(®) remote monitoring system (13 patients with DDD pacemaker; 59 patients with single-lead VDD pacemaker). Remote follow-up was compared with in-home checks performed by nurses in 326 patients in similar clinical conditions. A total of 190 transmissions were received by remote monitoring (mean transmissions per month: 7.0; mean per patient: 2.6; range 1-6) during 27 months of follow-up. In this period, seven pacemakers were replaced owing to battery exhaustion, after a mean of 6.7 years from implantation. The occurrence of atrial or ventricular high-rate episodes was reported in 98 transmissions (53%). Nineteen patients died (annual mortality: 11.7%). On comparing the costs borne by the hospital for in-home checks, both for medical personnel and transportation, the estimated average saving was €32 per year per patient., Conclusion: Our study shows that the remote follow-up of pacemakers is a reliable, effective, and cost-saving procedure in elderly, debilitated patients. Moreover, remote controls provided an accurate and early diagnosis of arrhythmia occurrence.

Background: Approximately 3% to 10% of patients with syncope experience episodes while driving. The aim of our study was to identify their clinical and pathophysiological features, estimate the incidence of recurrence, and correlate these characteristics with recurrence., Method: We prospectively studied 40 patients who experienced syncope while driving and 50 subjects who experienced syncope in other situations. All cases underwent upright tilt test (UTT), with simultaneous ECG and beat-to-beat blood pressure recordings, to analyze heart rate variability, total peripheral resistance (TPR), and stroke volume (SV)., Results: Patients who experienced syncope while driving suffered more frequently from hypertension (40% vs 20%) and vasodepressive reactions during the UTT (52% vs 26%). Moreover, these patients had increased heart rates (p=0.007) and lower SVs (p=0.006) during a positive UTT. TPR rose immediately before symptoms appeared only in patients who suffered from nondriving syncope (p=0.006). During a mean follow-up of 1793±573 days, 8 syncopic patients while driving had recurrences (20%) but never while driving. They were older, experienced more episodes of syncope, and had a higher incidence of vasodepressive reactions during UTT., Conclusions: Our study confirms a good prognosis for patients who experience syncope while driving, and indicates that more accurate risk stratification is needed in subjects aged over 50 years, who have had more than 4 episodes of loss of consciousness and vasodepressive reactions during UTT., (Copyright © 2011. Published by Elsevier B.V.)

Aim: We assessed the efficacy, reliability and cost of an in-home control service, devoted to debilitated patients with pacemakers, during long-term follow up., Methods: We admitted 802 patients (mean age 87.8 ± 6.9 years) with pacemakers into our program, which were monitored periodically during in-home visits by nurses. During these controls, patients underwent a standard electrocardiogram with and without magnet, during which stimulation intervals were measured. In-home pacemaker assessments were performed by a portable programmer only for patients with Biotronik pacemakers. Electrocardiograms and technical data were evaluated at hospital, and a report was sent by mail to the patient. Moreover, we compared the costs for the hospital, patients and society between in-home and ambulatory assessments., Results: During 80 months of follow up, 2418 controls were performed. The monthly average of patients who were followed at home was 283.9 ± 23.9. The mean number of controls per month was 30.2 ± 10 (range 4-51). One hundred and twenty-three pacemakers were replaced due to battery exhaustion, after a mean device longevity of 7.4 years (range 4.9-12.4 years). Four hundred and sixty-eight patients died (8.7% annual mortality). Fifteen patients (annual incidence 0.3%) were invited to in-hospital visits for reprogramming. The cumulative cost for in-home assessment were 20.5% lower than conventional in-hospital controls and 66.5% lower if patients are transported by ambulance., Conclusion: Elderly debilitated patients can be monitored by effective and reliable pacemaker assessments at home, alleviating them and their families from the issues that are associated with their transfer from the home to the hospital and concurrently reducing overall costs., (© 2011 Japan Geriatrics Society.)

Objective: The aim of our study was to identify specific age-related hemodynamic changes during upright tilt test in patients with vasovagal syncope., Methods: We studied 115 subjects who were referred to us for unexplained syncope during 65 degrees tilt with pharmacological challenge (s.l. nitrate) by noninvasive monitoring of blood pressure (Finometer). Two derived variables were also considered: total peripheral resistance and stroke volume. The patients were divided into 3 groups by age: Group 1, 10-30 yrs; Group 2, 31-50 yrs; and Group 3, >51 yrs., Results: The test was positive in 65 patients (57%). During the first 20 min of the test, older patients experienced lower increases in heart rate (p<0.00001) and premature reduction of total peripheral resistance (p<0.005) and systolic blood pressure (p<0.005). Group 1 showed more pronounced decreases in stroke volume (p<0.01). No differences emerged between negative and positive patients. In the 5 min that preceded syncope, younger subjects experienced a distinct, transient increase in heart rate immediately before symptom onset (p<0.005). Blood pressure was prematurely and progressively decreased in Group 3, whereas it decreased only in the 90 s prior to syncope in Groups 1 and 2 (p<0.01)., Conclusions: Our results suggest that blunted sympathetic activation occurs during passive orthostatism in older patients. On the other hand, hemodynamic changes before symptom onset seem to indicate as in younger subjects syncope results from an excessive sympathovagal reaction, whereas in older subjects it is related to an overwhelming, progressive central vagal activity that is associated with a defective peripheral sympathetic activation., (Copyright 2010 Elsevier B.V. All rights reserved.)

Background: Previous studies proposed as one of the main mechanisms involved in neurally mediated syncope, the stimulation of ventricular mechanoreceptors as the final trigger for vagal discharge., Objectives: This study aimed to verify the presence of a sympathetic driven increase of cardiac contractility before vasovagal syncope., Methods: We studied 23 patients with recurrent syncope. All underwent a 60 ° tilt with pharmacologic challenge (sublingual spray nitrate). Two conditions were used to assess autonomic activity by heart rate variability analysis: in a supine position after 5 min of rest and after 15 min of tilt. Simultaneously, cardiac contractility was quantified by tissue-Doppler echocardiography at the base of the free walls of left ventricle. The peak myocardial velocities during systole (Sw) and late diastole (Aw) were considered., Results: Passive tilt induced a significant increase of the low frequency component (LF) as well as a decrease of the high frequency component (HF) in positive patients (LF: from 49 ± 18 to 65 ± 18 nu, p<0.05; HF: from 41 ± 21 to 26 ± 16 nu, p<0.05). Tissue-Doppler showed a similar increase in Sw in both positive and negative patients but showed a significant decrease of Aw in syncopal subjects (p<0.005)., Conclusions: Our results do not show an increase in ventricular contractility before tilt-induced syncope, or in presence of a valuable increase of sympathetic activity. Instead, we observe a reduction of atrial contractility, which may be a contributory component in the pathogenesis of vasovagal syncope., (Copyright © 2008 Elsevier Ireland Ltd. All rights reserved.)

Aims: Epidemiological studies show that peak exposure to air pollution is associated with increased morbidity and mortality from cardiovascular events. Panel and controlled exposure studies show that particulate matter (PM) may influence the parasympathetic regulation of the heart. The aim of this study was to concurrently measure individual exposure to PM of various sizes, heart rate variability (HRV), and electrical instability in patients with myocardial infarction., Methods and Results: Personal exposures to PM(10), PM(2.5), and PM(0.25) was measured over 24 h in 39 patients (36 males, 3 females; mean age 60.3 years) with prior myocardial infarction (>6 months). Simultaneously, a 24 h ECG was recorded and then analysed for HRV and ventricular arrhythmias. Breath condensate and blood samples also were collected at the end of monitoring to measure several indexes of inflammation. Negative correlation was found between HRV and exposure to PM(0.25) in a group of patients not taking beta-blockers. More severe ventricular arrhythmias were observed at the highest concentrations of PM(10) and PM(2.5). Indexes of inflammation in either breath condensate or blood did not correlate with PM exposures., Conclusion: Our study shows that exposure to ultrafine particles is associated with autonomic dysregulation in selected patients with myocardial infarction. More severe arrhythmias occur at the highest exposures to larger particles. Nevertheless, the underlying mechanisms remain hypothetical because inflammation may be evoked by PM or be related to the disease itself.

Background: Vasovagal syncope (VVS) results from a complex interaction among afferent vagal and sympathetic signals, cortical modulation and bulbar integration. The aim of our study was to evaluate the modifications of autonomic activity during Upright Tilt Test (UTT) in patients with unexplained syncope, and to correlate these changes with the specific cardiovascular reactions induced., Methods and Results: We studied 90 patients with a mean age of 44+/-17 yrs. Frequency domain analysis of heart rate variability (HRV) (normalized units) was performed on 2 periods of 300 beats: at baseline and after 5 min of 60 degrees tilt. UTT was positive in 56 patients (62%). The responses were cardioinhibitory in 8, vasodepressive in 15, mixed in 33. Baseline LF and HF components did not show significant difference between subjects with positive or negative test (HF: 39+/-21 versus 41+/-22; LF: 50+/-22 versus 49+/-23). HRV during UTT showed similar changes in patients with positive or negative test. However, subjects with mixed or cardioinhibitory reactions were characterized by a relevant increase of LF during UTT (from 47+/-23 to 66+/-21), whereas the others by a non-significant decrease of the same component (from 57+/-19 to 51+/-31)., Conclusions: Patients developing a reflex cardioinhibitory reaction during UTT were characterized by an increase of sympathetic activity during the test, that might represent an essential factor to induce a stronger vagal reaction on the sinus node. On the contrary, in subjects with vasodepressive reactions an inadequate enhancement of the sympathetic drive, probably causing a failure of peripheral vasoconstriction, was evidenced.

Aims: The aims of our study were to evaluate late potential changes during long-term follow-up in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) and to correlate these results with echocardiographic findings and sustained ventricular tachycardia (VT) occurrence., Methods and Results: We studied 31 patients (22 males and 9 females; mean age 29+/-16) during 8 years of follow-up by signal-averaged ECG (SAECG) and echocardiography. Ten subjects experienced episodes of sustained VT. During follow-up, all the SAECG parameters showed a progressive significant increase in late potentials. In contrast, echocardiographic indices did not show evidence of relevant modifications. Patients with sustained VT were characterized by significantly lower left and right ventricular ejection fractions, longer values of filtered QRS at 25/40/80-250 Hz filters, and longer high-frequency low-amplitude (HFLA) signals at 25-250 Hz at baseline. The analysis of SAECG modification during follow-up indicated that only HFLA signals at 25-250 Hz increased significantly in the sustained VT group., Conclusion: We detected a progressive increase in delayed ventricular conduction by SAECG not associated with significant echocardiographic changes. Therefore, the conduction disturbance seems to increase independently from anatomical alterations. The baseline SAECG and echocardiographic parameters, more than their modifications during follow-up, appear to be useful in identifying patients with sustained VT.

One of the most important mechanisms proposed in the pathogenesis of neurally mediated syncope considers the stimulation of myocardial mechanoreceptors as the final trigger leading to reflex hypotension and bradycardia. The aim of our study was to analyze the modifications of systolic and diastolic velocities of the left ventricle by tissue Doppler echocardiography, during the upright tilt test, to confirm the presence of an increased ventricular contractility before syncope. We evaluated 47 patients (mean age 43 years) with unexplained syncope and 13 healthy subjects. Three echocardiographic recordings were collected: at baseline, during the initial 5 minutes of the test, and after 15 minutes of tilt. The upright tilt test was positive in 28 patients. During the test, all of them had a similar, significant, progressive reduction of left ventricular end-diastolic volume, left atrial area, and left atrial volume. In contrast, the left ventricular ejection fraction showed an early, more pronounced decrease in those with positive tests. By tissue Doppler echocardiography, the systolic waves remained almost unchanged, and the early filling waves decreased similarly in those with positive or negative findings and the controls. In contrast, the atrial filling waves showed a significant decrease only in patients with positive tests. In conclusion, our study did not find increased ventricular contractility before syncope. In contrast, a decreased atrial contribution to ventricular filling characterized patients with positive upright tilt test results, which, we postulate, may be an important contributory factor to vasovagal syncope.

Tetralogy of Fallot is the most common cyanotic congenital heart disease, with a good outcome after total surgical correction. In spite of a low perioperative mortality and a good quality of life, late sudden death remains a significant clinical problem, mainly related to episodes of sustained ventricular tachycardia and ventricular fibrillation. Fibro-fatty substitution around infundibular resection, intraventricular septal scar, and patchy myocardial fibrosis, may provide anatomical substrates of abnormal depolarization and repolarization causing reentrant ventricular arrhythmias. Several non-invasive indices based on classical examination such as ECG, signal-averaging ECG, and echocardiography have been proposed to identify patients at high risk of sudden death, with hopeful results. In the last years other more sophisticated invasive and non-invasive tools, such as heart rate variability, electroanatomic mapping and cardiac magnetic resonance added a relevant contribution to risk stratification. Even if each method per se is affected by some limitations, a comprehensive multifactorial clinical and investigative examination can provide an accurate risk evaluation for every patient.

Introduction: Surgical repair of tetralogy of Fallot is complicated by the occurrence of ventricular tachycardia (VT). Among different indexes proposed to assess prognosis of these patients, the study of QRS and repolarization provided useful information. Controversial results come from the analysis of signal-averaging ECG (SAECG). The aim of our study was to identify patients operated for tetralogy of Fallot at higher risk of sudden death by means of SAECG., Methods and Results: Sixty-six consecutive patients, mean age 26 +/- 10 years, were studied 17.7 +/- 5.8 years after total correction for tetralogy of Fallot using standard ECG, 24-hour Holter recordings, SAECG, and echocardiography. The following variables were measured: standard QRS duration, filtered QRS duration (fQRS), high-frequency and low-amplitude signal duration (HFLA), root mean square of the mean voltage in the terminal portion of filtered QRS (RMS), left and right end-diastolic volumes, and ejection fractions. During a mean follow-up period of 7.3 +/- 3.1 years, 12 patients had episodes of sustained VT and two of them suddenly died. All patients had complete right bundle branch block. Patients with VT were characterized by a significantly longer fQRS duration at all filter settings. On the contrary, there was no difference in standard QRS duration in patients with or without VT. At a multivariate analysis, left ventricular ejection fraction and fQRS were independent predictors for VT., Conclusions: A longer fQRS duration is associated with an increased risk in developing malignant ventricular arrhythmias in asymptomatic patients after total correction of tetralogy of Fallot.

Background: Severe ventricular arrhythmias represent one of the main causes of mortality after repair of tetralogy of Fallot. Their appearance is primarily caused by the large ventricular scar created by surgical intervention. However, the role of autonomic activity as a modulating factor should be considered. The aim of our study was to evaluate this activity in a low-risk group of patients operated on for TOF and its correlation with the occurrence of sustained ventricular tachycardia., Methods and Results: The study group included 38 patients with a mean age of 31 +/- 10 years, selected out of 76 subjects operated on for total correction of tetralogy of Fallot. After a mean interval of 21.9 +/- 6 years from surgical procedure, they underwent electrocardiography, echocardiography, and time domain heart rate variability (HRV) analysis obtained by 24-hour Holter monitoring. Thirty-five healthy subjects comprised the control group for HRV analysis. During a mean follow-up of 6.2 +/- 3 years, 8 patients experienced episodes of sustained ventricular tachycardia. Among different HRV parameters, the standard deviation of all normal beat intervals showed a significant reduction in this group of patients (91.7 +/- 19 versus 133.4 +/- 46, P < .02). Echocardiographic examination demonstrated an increased left ventricular end diastolic volume (85.6 +/- 55 versus 61.3 +/- 13 mL/m(2), P < .05) and a reduced left ventricle ejection fraction (53.9 +/- 9 versus 61.0 +/- 6 %, P < .01) in arrhythmic patients. QRS duration was similar in patients with or without sustained ventricular tachycardia., Conclusions: Patients after surgical correction of tetralogy of Fallot, considered to be at low risk, showed a significant incidence of severe ventricular arrhythmias. HRV analysis seems to be a useful method for identifying arrhythmic patients, and the standard deviation of all normal beat intervals appears to be the more helpful index.

The aim of our study was to assess the arrhythmic profile in patients with primary pulmonary hypertension (PPH) and its correlation with autonomic features, echocardiographic indexes and pulmonary function. We studied 9 subjects with a mean age of 42 +/- 11 years. All underwent echocardiography, 24-hour Holter monitoring, and cardiopulmonary exercise testing. Left ventricle ejection fraction was normal (65 +/- 6%). The right ventricle end diastolic volume was increased (108 +/- 32 ml/m2) with a slight reduction of ejection fraction (49 +/- 5%). Right ventricle systolic pressure was increased (91 +/- 25 mmHg). Heart rate variability analysis showed evidence of a reduced standard deviation of all NN intervals (SDNN) compared with the control group (102.8 +/- 32 versus 156.1 +/- 32, p < 0.005). Patients with significant ventricular arrhythmias had a lower SDNN, and lower baseline and effort PO2 (SDNN: 87.0 +/- 15 versus 115.4 +/- 38; baseline PO2: 63.2 +/- 12% versus 78.8 +/- 7%; effort PO2: 50.7 +/- 13% versus 68.7 +/- 19%). The patients with SDNN lower than 90 ms were characterized by a higher right ventricle systolic pressure (115.0 +/- 22.9 mmHg versus 79.2 +/- 17.8 mmHg, p = 0.035). The patients who experienced syncope had higher SDNN (131.7 +/- 36 versus 88.4 +/- 20, p < 0.05), higher effort PO2 (77.5 +/- 14 mmHg versus 52.3 +/- 14 mmHg, p < 0.03). The patients with PPH evidenced an increased sympathetic activity. Premature ventricular beats were more frequent in those subjects with higher adrenergic drive and lower oxygen saturation. Patients with episodes of syncope seem to have a relatively higher vagal activity, and effective mechanisms of adjustment in blood oxygenation during effort.

The identification of subjects with arrhythmogenic right ventricular cardiomyopathy (ARVC) at higher risk for sudden death is an unresolved issue. An influence of the autonomic activity on the genesis of ventricular arrhythmias was postulated. Heart rate variability (HRV) analysis provides a useful method to measure autonomic activity, and is a predictor of increased risk of death after myocardial infarction. For these reasons, the aim of the study was to evaluate HRV and its correlations with ventricular arrhythmias, heart function, and prognostic outcome in patients with ARVC. The study included 46 patients with ARVC who were not taking antiarrhythmic medications. The diagnosis was made by ECG, echocardiography, angiography, and endomyocardial biopsy. Exercise stress test and Holter monitoring were obtained in all patients. Time-domain analysis of HRV was expressed as the standard deviation of all normal to normal NN intervals (SDNN) detected during 24-hour Holter monitoring. Thirty healthy subjects represented a control group for HRV analysis. The mean follow-up was 10.8 +/- 1.86 years. SDNN was reduced in patients with ARVC in comparison with the control group (151 +/- 36 vs 176 +/- 34, P = 0.00042). Moreover, there was a significant correlation of this index with the age of the patients (r = - 0.59, P < 0.001), with the left (r = 0.44, P = 0.002) and right (r = 0.47, P = 0.001) ventricle ejection fraction, with the right ventricular end diastolic volume (r = - 0.62, P < 0.001), and with the ventricular arrhythmias, detected during the same Holter record used for HRV analysis (patients with isolated ventricular ectopic beats < 1,000/24 hours, 184 +/- 34; patients with isolated ventricular ectopic beats > 1,000/24 hours and/or couplets, 156 +/- 25; patients with repetitive ventricular ectopic beats (> or = 3) and/or ventricular tachycardia, 129 +/- 25; P < 0.001). During follow-up two patients showed a transient but significant reduction of SDNN and a concomitant increase of the arrhythmic events. In eight patients an episode of sustained ventricular tachycardia occurred, but the mean SDNN of this subgroup did not differ from the mean value of the remaining patients (152 +/- 15 vs 150 +/- 39; P = NS). Only one subject died after heart transplantation during follow-up (case censored). Time-domain analysis of HRV seems to be a useful method to assess the autonomic influences in ARVC. A reduction of vagal influences correlates with the extent of the disease. The significant correlation between SDNN and ventricular arrhythmias confirmed the influences of autonomic activity in the modulation of the electrical instability in ARVC patients. However, SDNN was not predictive of spontaneous episodes of sustained ventricular tachycardia.

Objectives: The study was done to define the role of the autonomic nervous system in postoperative tetralogy of Fallot., Background: Subsequent to surgical correction of tetralogy of Fallot, patients are at long-term risk of sudden death owing to ventricular electrical instability. The status of the sympathetic nervous system in these patients, known to play an important role in other patients at risk, remains unknown., Methods: We used (123)I metaiodobenzylguanidine (MIBG) with tomographic imaging, combined with assessment of heart rate variability (HRV), to evaluate the activity of the sympathetic nervous system. We analyzed 22 patients who had undergone total correction of tetralogy of Fallot: 13 with either no or minor ventricular arrhythmias, and 9 with sustained ventricular tachycardia or ventricular fibrillation., Results: Analysis of HRV revealed a reduction in vagal control and sympathetic dominance in all patients compared with a healthy control group of 20 subjects. A significant difference was found in the standard deviation of all the adjacent intervals between normal beats (SDNN) in patients with or without severe ventricular arrhythmias. A significant reduction in uptake of (123)I MIBG was demonstrated 30 min after IV injection, and a trend toward reduction after 5 h, associated with reduced washout indices. These data reflect a decrease in the number of nerve endings in the right and left ventricular walls, and an inhomogeneous distribution of the adrenergic nervous system. The uptake of MIBG was significantly reduced in the patients at risk of ventricular tachycardia or fibrillation., Conclusions: Subsequent to surgical correction of tetralogy of Fallot, the positive correlation between myocardial uptake of MIBG, SDNN and the QRS dispersion confirmed the usefulness of analysis of the adrenergic nervous system to stratify patients at risk of life-threatening arrhythmias.

Objective: The aim of the study was to assess the prevalence, sensitivity, specificity and predictive value of the signal-averaged ECG in patients with arrhythmogenic right ventricular cardiomyopathy and different forms of ventricular arrhythmias., Methods: The signal averaged ECG in 138 patients and 146 healthy subjects (control group), using a three bandpass filter system (25-250, 40-250, 80-250 Hz), was considered abnormal when at least two parameters were abnormal at each filter setting. Patients were divided into three groups according to the extent of the right ventricular enlargement (mild, moderate, extensive), and into five groups according to the type of ventricular arrhythmia., Results: The signal averaged ECG was abnormal in 57% of the patients and in 4% of the healthy subjects. The sensitivity was 57%, specificity 95% and positive predictive value 92%. The signal averaged ECG was abnormal in 94.4% of patients with the extensive form of the disease, in 77.7% of patients with the moderate form and in 31.8% of patients with the minor form, demonstrating good correlation with the extent of the disease. According to the type of ventricular arrhythmia, a higher correlation was found between signal averaged ECG abnormality and sustained ventricular tachycardia with superior axis (94.4%, P<0. 02); the correlation for the other arrhythmias varied from 16.6% to 55.8%., Conclusion: There is a closer correlation between the signal averaged ECG and extent of disease than with the presence of ventricular arrhythmias. The signal averaged ECG is not helpful in diagnosing minor forms of the disease, but since it is a non-invasive method, it may be useful in evaluating progression of the disease., (Copyright 2000 The European Society of Cardiology.)

We evaluated the incidence of atrial fibrillation in 189 patients (92 males, 97 females, mean age 75 +/- 12 yrs, range 41-100 yrs) with pacemaker, during a mean follow-up of 5.5 yrs (range 1-24 yrs). The indications for implant were: complete AV block (115 pts), second degree Möbitz 2 AV block (51 pts), bifascicular block (5 pts), sick sinus syndrome (14 pts), symptomatic bradycardia (4 pts). The mode of stimulation considered were VVI (105 pt), VVI rate responsive (21 pts), single lead VDD (43 pts), DDD (20 pts). The occurrence of retrograde VA conduction in patients with VVI or VVI rate responsive pacing was also evaluated. Atrial fibrillation occurred in 40 pts (21%). The highest incidence was evidenced in patients with sick sinus syndrome (9 pts, 64%), and in patients with VVI stimulation (28 pts, 27%). On the contrary, the lowest incidence was found in single lead VDD stimulation (4 pts, 9%). The patients with dual chamber pacing showed a relatively high incidence of the arrhythmia (5 pts, 25%). Atrial fibrillation occurred in 9 out of 32 patients with retrograde VA conduction, and in 22 out of 94 patients without retrograde conduction (28% versus 23%, p = NS). In conclusion, it is confirmed that patients with sick sinus syndrome are at high risk for atrial fibrillation. Single lead VDD stimulation seems to be the better mode of pacing in preventing atrial fibrillation, while dual chamber pacing showed minor efficacy. The presence of retrograde VA conduction could not predict the occurrence of the arrhythmia.

The aim of our study was to analyze how the clinical history and the main clinical characteristics of patients suffering from loss of consciousness may influence the results of the upright tilt test. A series of 745 patients (333 males, 412 females; mean age 44 +/- 18 years) with recurrent episodes of syncope or presyncope underwent complete clinical and noninvasive laboratory examination, including vagal maneuvers and upright tilt test (60 degrees for 45 min). Cardiological and neurological findings were normal in every case. Upright tilt test was positive in 462 patients (62%). Patients with presyncope showed a lower positivity compared to patients with syncope (70.2% vs 42.9%, P < 0.001). Younger patients (< 25 years) displayed highest upright tilt test positivity (68.5%), while familial occurrence of syncope or presyncope, results of vagal maneuvers, and different gender did not correlate with the results of the test. The time interval between the last syncopal episode and the day of upright tilt test negatively influenced the proportion of positive tests (> 30 days = 45.1% vs < 30 days = 77.2%; P < 0.001). Patients with more than three syncopal episodes in the 2 months preceding the test showed a higher upright tilt test positivity (83.9% vs 64.5%, P < 0.001). In conclusion, upright tilt test seems to be more sensitive in young patients with syncopal episodes during symptomatic periods. These findings suggest both an individual and temporal variability in autonomic nervous system activity, the implication of which are relevant to the indications for testing as well as the analysis of results.

We evaluated the influence of sympathetic stimulation, induced by mental stress test, on signal-averaged ECG in 30 healthy subjects and in 30 patients with previous myocardial infarction. Both patient and control groups underwent three consecutive signal-averaged ECG: under basal conditions, during a continuous mental stress test, and 5 min after the mental stress test. The signal-averaged ECG parameters, analyzed by mean of a bandpass filter of 25-250 and 40-250 Hz, were: the filtered QRS duration, the duration of the low-amplitude high frequency signals in the terminal portions of the QRS complex below 40 microV (HFLA), and the root mean square voltage in the last 40 ms of the filtered QRS (RMS). The mathematical stress test was considered effective when the heart rate increased by at least 15 beats/min, remaining stable for the total duration of the signal-averaged ECG acquisition. A significant reduction of the filtered QRS duration and HFLA with a simultaneous increase of RMS were found in control group, while no significant changes occurred in patient group. These results indicate that the sympathetic nervous system may affect the results of signal-averaged ECG, probably by influences on intraventricular conduction, in healthy subjects. On the contrary, myocardial alterations in ischemic heart disease induce modification of signal-averaged ECG not influenced by autonomic nervous system activity.

Background: The aim of this study was to evaluate the normal values of the most common indexes used in the analysis of ventricular late potential in 102 young male subjects., Methods: The recordings were performed by means of a Marquette electronics Hi-Resolution ECG Mac 15, with filters at 25-250 Hz, 40-250 Hz and 80-250 Hz. The parameters obtained were: filtered QRS duration (QRSD), high-frequency low-amplitude signals duration (HFLA), and the root mean square of the signal expressed in the terminal portion of QRS (RMS). The body surface was also evaluated., Results: QRSD (121.23 ms-113.9 ms-99.9 ms); RMS (105 uV-42.77 uV-34.3 uV); HFLA (17.5 ms-29.3 ms-29.3 ms). The comparison between our results and those proposed by other authors for normal subjects showed different results, particularly concerning the filtered QRS duration. We suppose that these discrepancies may be due to the different instrumentations used and to the different age and sex of the study population., Conclusions: From these results we confirm that a normal range for each index must be done for homogeneous groups of subjects for age and sex, in healthy subjects as well as for different heart disease.

The purpose of this study was to assess the long-term results of a single lead VDD pacing system (Phymos MPS) in 85 patients (48 males, 37 females, mean age 74 +/- 9 years). The system, which incorporates two atrial floating electrodes (Phymos 830-S), was implanted for second- or third-degree Mobitz II AV block. The percentage of AV synchronized pacing, the presence of fusion beats due to short AV delay, and the occurrence of supraventricular arrhythmias was evaluated by Holter monitoring at 6-month intervals. Over a mean period of follow-up of 44 months (range 2-56), over 90% of AV synchronized pacing events were noted in 74 patients (87%). The presence of persistent fusion beats was detected in 12 patients (14%). In ten patients the pacemaker was reprogrammed to VVI mode for supraventricular arrhythmias (7 patients, 8.2%) or unsatisfactory atrial sensing (3 patients, 3.5%). One pacemaker was removed for pocket infection and two for battery depletion. These observations support the use of VDD single lead pacing to combine a physiological mode of stimulation with simple implantation techniques.

To evaluate heart rate variability (expressed as the standard deviation of RR intervals) within 5 years of follow-up, we studied 20 patients (14 males, 6 females, mean age 44 +/- 12 years) who underwent orthotopic heart transplantation. Six measurements were taken: one in the first 3 weeks after transplantation, and the others once annually, for 5 years. Twenty healthy subjects (mean age 44 +/- 7 years) constituted the control group. Heart rate variability increased significantly in the first 3 years of follow-up (7.2 +/- 1 vs. 11.1 +/- 4, p < 0.001; 11.1 +/- 4 vs. 15.2 +/- 4, p < 0.01; 15.2 +/- 4 vs. 18.9 +/- 5, p < 0.05); in the following years this trend slackened and values did not reach a statistically significant difference (18.9 +/- 5 vs. 21.4 +/- 5; 21.4 +/- 5 vs. 22.5 +/- 5). The mean standard deviation was invariably greater in the control group (63.6 +/- 12). These findings show that sinus rhythm variability in the denervated heart progressively increased over 5 years of follow-up. The absence of presynaptic uptake, which is responsible for adrenergic hypersensitivity to circulating catecholamines and intrinsic cardiac reflexes, does not appear to cause this phenomenon, since these mechanisms are not able to evolve in time after cardiac transplantation. Therefore, an enhanced beta-adrenergic receptors density or affinity to circulating catecholamines or a limited sympathetic reinnervation may be the more probable underlying mechanism.

The purpose of this study was to define the history and prognosis of 12 patients (8 males, 4 females) with syncope of unknown origin (5 to 15 episodes), who developed prolonged asystole or complete AV block during the upright tilt test (UTT). The mean age (+/- SD) of the patients was 29 +/- 7.4 years, and all had normal neurological and cardiological findings on evaluation. These patients were selected from a larger group of 92 cases with positive UTT out of a total of 136 subjects who were referred for recurrence of syncope. Neither clinical nor autonomic nervous system evaluation distinguished these 12 patients from those with positive UTT. Following UTT, therapy was initiated and consisted of transdermal scopolamine in four, disopyramide in two, and beta-blockers in four patients. During follow-up (mean, 17 +/- 5.4 months), four patients had recurrences but none experienced episodes of life-threatening syncope. These patients do not show an enhanced risk of sudden death, and drug therapy seems to improve their clinical course. Only long-term follow-up would correctly identify a subgroup at higher risk.

We describe three athletes who had syncope after (case 1) or during (cases 2, 3) hyperventilation. During the episode, ECG showed prolonged sinus arrest. Clinical data and noninvasive investigations were normal and the phenomenon was not reproducible. Electrophysiological study after autonomic blockade allowed a prolonged intrinsic heart rate in case 1, and abnormal corrected sinus node recovery time in cases 1 and 2. During follow-up, symptomatic sinus arrest provoked by deep inspiration occurred in case 3. These cases document prolonged asystole of unknown etiology, secondary to hyperventilation, and probably caused by different vagally-mediated mechanisms.