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Background Permanent atrial pacing usually involves lead placement in the right atrial appendage (RAA). Anatomical studies addressing features predisposing to complications are scanty. Objective To assess the morphology of RAA in the perspective of pacing, including the morphology of tenia sagittalis (TS) and the spatial relationship with the aorta. Methods The gross anatomy of the RAA has been analyzed in a consecutive series of 100 hearts following a case of iatrogenic perforation of the aorta by active fixation lead located in the RAA. Transmural RAA sections were taken from 40 hearts to assess the wall thickness at the level of pectinate muscles (PMs) and of inter-PMs spaces and the distance between adjacent PMs. Results The TS was present in 90% of cases (single trunk, 76%; double trunk, 13%; and triple trunk, 1%), demarcating the proximal antral RAA region (facing the adjacent aorta) from the distal saccular RAA region (facing the pulmonary infundibulum). The RAA free wall in the inter-PMs spaces is usually paper-thin and translucent. Histomorphometric analysis reveals that the RAA wall mean thickness was 1.38 ± 0.05 mm (range 0.64–4.25 mm) at the level of PMs and 0.39 ± 0.23 mm (range 0.09–1.05 mm) at the level of inter-PMs spaces. The mean distance between adjacent PMs was 0.88 ± 0.99 mm (range 0.04–4.12 mm). Conclusion In 90% of hearts, a well-defined TS separates the distal saccular from the proximal antral RAA, the latter being closely adjacent to the ascending aorta. The paper-thin wall between PMs is potentially at risk of perforation, and aortic injury could occur when active fixation leads are anchored in the antral RAA, as demonstrated in an iatrogenic fatal case.

Summary Background Although the effects of air pollution on mortality have been clearly shown in many epidemiological and observational studies, the pro-arrhythmic effects remain unknown. We aimed to assess the short-term effects of air pollution on ventricular arrhythmias in a population of high-risk patients with implantable cardioverter-defibrillators (ICDs) or cardiac resynchronisation therapy defibrillators (ICD-CRT). Methods In this prospective multicentre study, we assessed 281 patients (median age 71 years) across nine centres in the Veneto region of Italy. Episodes of ventricular tachycardia and ventricular fibrillation that were recorded by the diagnostic device were considered in this analysis. Concentrations of particulate matter of less than 10 μm (PM 10 ) and less than 2·5 μm (PM 2·5 ) in aerodynamic diameter, carbon monoxide, nitrogen dioxide, sulphur dioxide, and ozone were obtained daily from monitoring stations, and the 24 h median value was considered. Each patient was associated with exposure data from the monitoring station that was closest to their residence. Patients were followed up for 1 year and then scheduled to have a closing visit, within 1 more year. This study is registered with ClinicalTrials.gov, number NCT01723761. Findings Participants were enrolled from April 1, 2011, to Sept 30, 2012, and follow-ups (completed on April 5, 2014) ranged from 637 to 1177 days (median 652 days). The incidence of episodes of ventricular tachycardia and ventricular fibrillation correlated significantly with PM 2·5 (p 10 . An analysis of ventricular fibrillation episodes alone showed a significant increase in risk of higher PM 2·5 (p=0·002) and PM 10 values (p=0·0057). None of the gaseous pollutants were significantly linked to the occurrence of ventricular tachycardia or ventricular fibrillation. In a subgroup analysis of patients with or without a previous myocardial infarction, only the first showed a significant association between particulate matter and episodes of ventricular tachycardia or ventricular fibrillation. Interpretation Particulate matter has acute pro-arrhythmic effects in a population of high-risk patients, which increase on exposure to fine particles and in patients who have experienced a previous myocardial infarction. The time sequence of the arrhythmic events suggests there is an underlying neurally mediated mechanism. From a clinical point of view, the results of our study should encourage physicians to also consider environmental risk when addressing the prevention of arrhythmic events, particularly in patients with coronary heart disease, advising them to avoid exposure to high levels of fine particulate matter. Funding There was no funding source for this study.

Objective The purpose of this study was to evaluate the impact of adhering to a strict follow up regimen on mid-term efficacy of intraoperative radiofrequency ablation in maintaining sinus rhythm for patients with atrial fibrillation undergoing cardiac surgery. Methods We enrolled 52 patients with atrial fibrillation and valve disease divided in 2 groups: group 1 (26 patients) underwent intraoperative radiofrequency ablation and was followed by a team of skilled cardiologists who treated recurrences with amiodarone and electrical cardioversion; group 2 (26 patients) was treated with intraoperative radiofrequency ablation but patients were thereafter treated by their local hospital or personal cardiologist. Results There were no intraoperative deaths or complications related to radiofrequency ablation. Twenty four months after the operation, freedom from atrial fibrillation was 60% in group 1 and 32% in group 2 (p = 0.02). Group 1 also showed a reduction in atrial volume (p ≤ 0.05). Conclusion Postoperative follow up with electrical and pharmacologic cardioversion combined with radiofrequency ablation achieves higher rate of sinus rhythm maintenance. After ablation, electrical cardioversion is effective even in patients with enlarged left atrium, long history of atrial fibrillation, or previous failed electrical cardioversion.

Aims The remote monitoring of pacemakers and implantable cardioverter defibrillators (ICDs) promotes accurate supervision of the patient and device. Alert settings appear to be a crucial parameter of its efficacy. The purpose of our study was to evaluate various settings for alerts and alert message management in patients with pacemakers and ICDs. Methods and results We prospectively evaluated 282 patients (181 males, 101 females, mean age 72 ± 11 years) who were referred to nine electrophysiological centres in the Veneto region of Italy for a pacemaker (76 patients) or ICD (206 patients) implant in which remote monitoring was activated (Biotronik Home Monitoring®, Biotronik, Berlin, Germany). During a mean follow-up of 382 ± 261 days, we received 106 039 transmissions. In the pacemaker group, the alerts that were most frequently activated were those concerning battery exhaustion, surveying impedances, sensing and threshold measurements, as well as missing transmissions. In the ICD/ICD-cardiac resynchronization therapy group, the alerts nearly always activated were those concerning a detection setoff, battery exhaustion, critical values of impedance, or ineffective maximum energy shock. In both groups, the alarms for heart rate monitoring and supraventricular arrhythmia were activated in fewer cases at higher variability among centres. Conclusions Our study demonstrates that more attention is paid to critical technical data than to patients’ clinical profiles, probably to limit an excessive flow of data into the centre. Accurate alert settings, personalized to the patients' features, are essential for easier and more effective management of patients who are followed remotely.

The aims of the present study were to investigate the incidence and characteristics of conduction disorders (CDs) after transcatheter aortic valve implantation (TAVI), to analyze the predictors of permanent pacemaker (PPM) implantation, and to evaluate the outcomes of CDs over time. In particular, we sought to investigate whether the depth of deployment and other technical aspects of valve implantation might predict the need for PPM implantation after TAVI. TAVI has been reported to favor the onset or worsening of CDs often requiring PPM implantation. A total of 70 patients with aortic stenosis due to dystrophic calcification underwent TAVI with third-generation CoreValve Revalving System from May 2007 to April 2009. We collected electrocardiograms at baseline, during TAVI, during hospitalization and at the 1-, 3-, 6-, and 12-month follow-up visits thereafter. The clinical, anatomic, and procedural variables were tested to identify the predictors of PPM implantation. The PPM dependency at follow-up was analyzed. Six patients were excluded from the analysis because of a pre-existing PPM. Of the 64 patients, 32 (50%) had one or more atrioventricular-intraventricular CDs at baseline. TAVI induced a worsening in the CDs in 49 (77%) of the 64 patients, with 25 (39%) requiring in-hospital PPM implantation. On multivariate analysis, the independent predictors of PPM implantation were the depth of the prosthesis implantation (p = 0.039) and the pre-existing right bundle branch block (p = 0.046). A trend in the recovery of the CDs over time was recorded, although 2 patients required PPM implantation 1 month after discharge for late complete atrioventricular block. In conclusion, TAVI often induces or worsens CDs, requiring PPM in more than one third of patients, although a trend in the recovery of CDs during the midterm was recorded. The independent predictors of PPM implantation were the depth of prosthesis implantation and pre-existing right bundle branch block.

The aim of our study was to identify specific age-related hemodynamic changes during upright tilt test in patients with vasovagal syncope.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.The test was positive in 65 patients (57%). During the first 20 min of the test, older patients experienced lower increases in heart rate (p0.00001) and premature reduction of total peripheral resistance (p0.005) and systolic blood pressure (p0.005). Group 1 showed more pronounced decreases in stroke volume (p0.01). 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 (p0.005). 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 (p0.01).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.

A 63-year-old man presented with recurrent syncopal attacks associated with swallowing and right-sided throat pain. Immediately after admission, he presented a 16-s asystolia. The patient's clinical history was unremarkable except for previous postimplant periodontitis. Several episodes of severe bradycardia and sinus pauses, always associated with painful deglutition, were recorded subsequently. X-ray orthopanthomography and magnetic resonance imaging of the neck confirmed several areas of periodontitis around the previous dental implants and right mastoid inflammation. A barium swallow and fibre-optic endoscopy also revealed a small sliding hiatus hernia and distal chronic oesophageal inflammation. Despite complete dental curettage, antibiotics and antigastro-oesophageal reflux therapy, only partial relief of the pain and incomplete resolution of the arrhythmic disorder were obtained after 3 weeks, and the patient underwent pacemaker implantation. At 1-month follow-up, however, he reported the complete relief of the throat pain; subsequent Holter monitoring showed normal sinus rhythm, without pacemaker-induced electrical activity.

ObjectivesWe tested whether 3-dimensional electroanatomical voltage mapping (EVM) may help in the differential diagnosis between idiopathic right ventricular outflow tract (RVOT) tachycardia and arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D).BackgroundRight ventricular EVM has been demonstrated to reliably identify low-voltage regions (“electroanatomical scar”), which in patients with ARVC/D correspond to areas of fibrofatty myocardial replacement.MethodsThe study population comprised 27 patients (15 men and 12 women, age 33.9 ± 8 years) with RVOT tachycardia and no echocardiographic/angiographic evidence of right ventricular (RV) dilation/dysfunction, who underwent EVM and endomyocardial biopsy (EMB) for characterization of ventricular tachycardia (VT) substrate before catheter ablation.ResultsElectroanatomical voltage mapping was normal in 20 of 27 patients (74%, group A), with electrogram voltage >1.5 mV throughout the RV. The other 7 patients (26%, group B) showed ≥1 (1.4 ± 07) RV electroanatomical scar area(s) (bipolar voltage

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.

This study aimed to assess manpower and resource consumption of the HomeGuide workflow model for remote monitoring (Biotronik Home Monitoring [HM], Biotronik SECo. KG, Berlin, Germany) of cardiac implantable electronic devices in daily clinical practice.The model established a cooperative interaction between a reference nurse (RN) for ordinary management, and a responsible physician (RP) for medical decisions in each outpatient clinic. RN reviewed remote transmissions and alerts, addressing critical cases to the RP.A total of 1,650 patients were enrolled in 75 sites: 25% pacemakers (PM), 22% dual-, 27% single-chamber implantable defibrillators (ICD), 2% PM with cardiac resynchronization therapy (CRT), and 24% ICD-CRT. During a median follow-up of 18 (10-31) months, 3,364 HM sessions were performed (74% by the RN, 26% by the RP) to complete 18,478 remote follow-ups. Median duration of remote follow-ups was 1.2 (0.6-2.0) minutes, corresponding to a manpower of 43.3 (4.2-94.8) minutes/month every 100 patients for nurses and 10.2 (0.1-31.1) for physicians (P0.0001). RN submitted 15% of remote transmissions to RP, who decided unscheduled follow-ups in 12% of the cases. The median manpower for phone calls was 1.9 (0.8-16.5) minutes/month every 100 contacted patients. There were 2.84 in-hospital visits/patient, 0.46 of which triggered by HM findings. A cumulative per-patient HM follow-up time of 15.4 minutes (20% of total follow-up time) allowed remote detection of 73% of actionable events.HM implemented in the HomeGuide workflow model required1 hour/month every 100 patients to detect the majority of actionable events with limited administrative workload.

Background— Endocardial voltage mapping (EVM) identifies low-voltage right ventricular (RV) areas, which may represent the electroanatomic scar substrate of life-threatening tachyarrhythmias. We prospectively assessed the prognostic value of EVM in a consecutive series of patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D). Methods and Results— We studied 69 consecutive ARVC/D patients (47 males; median age 35 years [28–45]) who underwent electrophysiological study and both bipolar and unipolar EVM. The extent of confluent bipolar (P =0.009). In the remaining patients with normal bipolar EVM (n=16; 23%), the use of unipolar EVM unmasked ≥1 region of low-voltage electrogram affecting 26.2% (11.6–38.2) of RV wall. During a median follow-up of 41 (28–56) months, 19 (27.5%) patients experienced arrhythmic events, such as sudden death (n=1), appropriate implantable cardioverter defibrillator interventions (n=7), or sustained ventricular tachycardia (n=11). Univariate predictors of arrhythmic outcome included previous cardiac arrest or syncope (hazard ratio=3.4; 95% confidence interval, 1.4–8.8; P =0.03) and extent of bipolar low-voltage areas (hazard ratio=1.7 per 5%; 95% confidence interval, 1.5–2; P P Conclusions— The extent of bipolar RV endocardial low-voltage area was a powerful predictor of arrhythmic outcome in ARVC/D, independently of history and RV dilatation/dysfunction. A normal bipolar EVM characterized a low-risk subgroup of ARVC/D patients.

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.

Objectives The purpose of this study is to assess the effectiveness of defibrillation testing (DT) in patients undergoing implantable cardioverter-defibrillator (ICD) insertion. Background Although DT is considered a standard procedure during ICD implantation, its usefulness has not been definitively proven. Methods The SAFE-ICD (Safety of Two Strategies of ICD Management at Implantation) study is a prospective observational study designed to evaluate the outcome of 2 strategies: performing defibrillation testing (DT+) versus not performing defibrillation testing (DT−) during de novo ICD implants. No deviation from the centers' current practice was introduced. In all, 2,120 consecutive patients (836 DT+ and 1,284 DT−) age ≥18 years were enrolled at 41 Italian centers from April 2008 to May 2009 and followed up for 24 months until June 2011. The primary endpoint was a composite of severe complications at ICD implant and sudden cardiac death or resuscitation at 2 years. Results The primary endpoint occurred in 34 patients: 12 intraoperative complications (8 in DT+ group; 4 in DT− group) and 22 during follow-up (10 in DT+ group; 12 in DT− group). Overall, the estimated yearly incidence (95% confidence interval) was DT+ 1.15% (0.73 to 1.83) and DT− 0.68% (0.42 to 1.12). The difference between the 2 groups was negligible: 0.47% per year (−0.15 to 1.10). Mortality from any cause was similar at 2 years (adjusted hazard ratio: 0.97 [0.76 to 1.23], p = 0.80). Conclusions In this large cohort of new ICD implants, event rates were similar and extremely low in both groups. These data indicate a limited clinical relevance for DT testing, thus supporting a strategy of omitting DT during an ICD implant. (Safety of Two Strategies of ICD Management at Implantation [SAFE-ICD]; NCT00661037 )

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.

Recent studies have suggested that interlead QT variability on the surface electrocardiogram, defined as QT dispersion, may reflect regional variations in myocardial recovery of excitability.1-4 The finding of a decreased QT dispersion in patients with different heart diseases treated with class III agents, sotalo13 and amiodarone,5T6 further supports this theory. A significant QT dispersion was found both in patients with congenital and acquired long QT interva12,5,7%s and in patients with myocardial infarction. 2,3,g~10 In hypertrophic cardiomyopathy (HC), the presence of electrical instability is a potentially important determinant of sudden death.“-l3 The pathologic substrate of the disease may create the conditions for QT interval prolongation and nonhomogeneous recovery of excitability.14 Dritsas et all5 recently showed a prolonged corrected QT interval (QTc) and increased QTc dispersion in 24 patients with HC compared with normal subjects, but a comparison between patients with and without ventricular arrhythmias was not done. This study assesses QT dispersion in HC patients with and without documented serious ventricular arrhythmias and sudden death. Twenty-six patients with NC (19 males and 7 females, mean age 37 t- 13 years, range 8 to 57) attending our institution for outpatient follow-up evaluation, or referred for risk stratification

Background— The role of implantable cardioverter-defibrillator (ICD) in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia and no prior ventricular fibrillation (VF) or sustained ventricular tachycardia is an unsolved issue. Methods and Results— We studied 106 consecutive patients (62 men and 44 women; age, 35.6±18 years) with arrhythmogenic right ventricular cardiomyopathy/dysplasia who received an ICD based on 1 or more arrhythmic risk factors such as syncope, nonsustained ventricular tachycardia, familial sudden death, and inducibility at programmed ventricular stimulation. During follow-up of 58±35 months, 25 patients (24%) had appropriate ICD interventions and 17 (16%) had shocks for life-threatening VF or ventricular flutter. At 48 months, the actual survival rate was 100% compared with the VF/ventricular flutter–free survival rate of 77% (log-rank P =0.01). Syncope significantly predicted any appropriate ICD interventions (hazard ratio, 2.94; 95% confidence interval, 1.83 to 4.67; P =0.013) and shocks for VF/ventricular flutter (hazard ratio, 3.16; 95% confidence interval, 1.39 to 5.63; P =0.005). The positive predictive value of programmed ventricular stimulation was 35% for any appropriate ICD intervention and 20% for shocks for VF/ventricular flutter, with a negative predictive value of 70% and 74%. None of the 27 asymptomatic patients with isolated familial sudden death had appropriate ICD therapy. Twenty patients (19%) had inappropriate ICD interventions, and 18 (17%) had device-related complications. Conclusions— One fourth of patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia and no prior sustained ventricular tachycardia or VF had appropriate ICD interventions. Syncope was an important predictor of life-saving ICD intervention and is an indication for ICD. Prophylactic ICD may not be indicated in asymptomatic patients because of their low arrhythmic risk regardless of familial sudden death and programmed ventricular stimulation findings. Programmed ventricular stimulation had a low predictive accuracy for ICD therapy.

Right ventricular lead perforation is a rare but serious and potentially life-threatening complication of pacemaker or defibrillator lead implantation. This report describes a patient with Brugada syndrome in whom the diagnosis of asymptomatic right ventricular perforation by an implantable cardioverter defibrillator lead was detected 12 days after implantation, thanks to a report from home monitoring system. The patient was admitted to our institution, where the lead was explanted and replaced. This case illustrates the potential lifesaving benefit of the home monitoring system in patients with implantable cardioverter defibrillator.

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.This study aimed to verify the presence of a sympathetic driven increase of cardiac contractility before vasovagal syncope.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.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, p0.05; HF: from 41 ± 21 to 26 ± 16 nu, p0.05). Tissue-Doppler showed a similar increase in Sw in both positive and negative patients but showed a significant decrease of Aw in syncopal subjects (p0.005).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.

Clinico-pathological findings are described in two patients with typical variant angina who died suddenly during an ischemic attack. In both cases, detailed pathologic examination of the coronary arteries disclosed severe focal atherosclerosis of the anterior descending coronary artery. The only distinctive histological finding was new intimal proliferation of smooth muscle cells enmeshed within mucoid substance, superimposed on the old fibrous cap of the plaque. These findings agree with experimental and clinical data which suggest that coronary vasospasm may be related to growth of atherosclerotic plaques. This study provides histological evidence that progression of an atherosclerotic plaque may underlie variant angina and sudden death.

Context Recently, the implantable cardioverter-defibrillator (ICD) has been promoted for prevention of sudden death in hypertrophic cardiomyopathy (HCM). However, the effectiveness and appropriate selection of patients for this therapy is incompletely resolved. Objective To study the relationship between clinical risk profile and incidence and efficacy of ICD intervention in HCM. Design, Setting, and Patients Multicenter registry study of ICDs implanted between 1986 and 2003 in 506 unrelated patients with HCM. Patients were judged to be at high risk for sudden death; had received ICDs; underwent evaluation at 42 referral and nonreferral institutions in the United States, Europe, and Australia; and had a mean follow-up of 3.7 (SD, 2.8) years. Measured risk factors for sudden death included family history of sudden death, massive left ventricular hypertrophy, nonsustained ventricular tachycardia on Holter monitoring, and unexplained prior syncope. Main OutcomeMeasure Appropriate ICD intervention terminating ventricular tachycardia or fibrillation. Results The 506 patients were predominately young (mean age, 42 [SD, 17] years) at implantation, and most (439 [87%]) had no or only mildly limiting symptoms. ICD interventions appropriately terminated ventricular tachycardia/fibrillation in 103 patients (20%). Intervention rates were 10.6% per year for secondary prevention after cardiac arrest (5-year cumulative probability, 39% [SD, 5%]), and 3.6% per year for primary prevention (5-year probability, 17% [SD, 2%]). Time to first appropriate discharge was up to 10 years, with a 27% (SD, 7%) probability 5 years or more after implantation. For primary prevention, 18 of the 51 patients with appropriate ICD interventions (35%) had undergone implantation for only a single risk factor; likelihood of appropriate discharge was similar in patients with 1, 2, or 3 or more risk markers (3.83, 2.65, and 4.82 per 100 person-years, respectively; P=.77). The single sudden death due to an arrhythmia (in the absence of advanced heart failure) resulted from ICD malfunction. ICD complications included inappropriate shocks in 136 patients (27%). Conclusions In a high-risk HCM cohort, ICD interventions for life-threatening ventricular tachyarrhythmias were frequent and highly effective in restoring normal rhythm. An important proportion of ICD discharges occurred in primary prevention patients who had undergone implantation for a single risk factor. Therefore, a single marker of high risk for sudden death may be sufficient to justify consideration for prophylactic defibrillator implantation in selected patients with HCM.

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° 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.

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.

In patients affected by isolated atrial fibrillation, epicardial pulmonary veins ablation can be performed with minimally invasive robotic-guided cardiac surgery techniques. This approach might become a feasible alternative to percutaneous transcatheter procedures. In this case report, we present a totally endoscopic robotic-guided pulmonary veins microwave ablation, on beating heart. A 64-year old male patient affected by paroxysmal atrial fibrillation was scheduled for an epicardial ablation procedure. Through three 1 cm-length port accesses, the "da Vinci" robotic system's camera and arms were introduced in the patient's chest. The pericardial reflections along the superior and inferior vena cava, as well as the transverse sinus, were dissected. Through an additional 0.5 cm-length port, a guidewire was advanced gradually across the transverse sinus, the diaphragmatic surface of the heart and the oblique sinus, finally surfacing outside the thoracic wall through the same port. Once tied to the microwave probe, the guidewire was pulled out carrying the probe inside the chest up to encircle the pulmonary veins. Once in place, a box lesion of the pulmonary veins was produced by microwave. At the 3-month follow up the patient is in sinus rhythm and so far did not longer experienced paroxysmal arrhythmic episodes.

Background— Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a condition associated with the risk of sudden death (SD). Methods and Results— We conducted a multicenter study of the impact of the implantable cardioverter-defibrillator (ICD) for prevention of SD in 132 patients (93 males and 39 females, age 40±15 years) with ARVC/D. Implant indications were a history of cardiac arrest in 13 patients (10%), sustained ventricular tachycardia in 82 (62%), syncope in 21 (16%), and other in 16 (12%). During a mean follow-up of 39±25 months, 64 patients (48%) had appropriate ICD interventions, 21 (16%) had inappropriate interventions, and 19 (14%) had ICD-related complications. Fifty-three (83%) of the 64 patients with appropriate interventions received antiarrhythmic drug therapy at the time of first ICD discharge. Programmed ventricular stimulation was of limited value in identifying patients at risk of tachyarrhythmias during the follow-up (positive predictive value 49%, negative predictive value 54%). Four patients (3%) died, and 32 (24%) experienced ventricular fibrillation/flutter that in all likelihood would have been fatal in the absence of the device. At 36 months, the actual patient survival rate was 96% compared with the ventricular fibrillation/flutter-free survival rate of 72% ( P Conclusions— In patients with ARVC/D, ICD therapy provided life-saving protection by effectively terminating life-threatening ventricular arrhythmias. Patients who were prone to ventricular fibrillation/flutter could be identified on the basis of clinical presentation, irrespective of programmed ventricular stimulation outcome.

Introduction: Intraoperative left atrial radiofrequency (RF) ablation recently has been suggested as an effective surgical treatment for atrial fibrillation (AF). The aim of this study was to verify the outcome of this technique in a controlled multicenter trial. Methods and Results: One hundred three consecutive patients (39 men and 65 women; age 62 ± 11 years) affected by AF underwent cardiac surgery and RF ablation in the left atrium (RF group). The control group consisted of 27 patients (6 men and 21 women; age 64 ± 7 years) with AF who underwent cardiac surgery during the same period and refused RF ablation. Mitral valve disease was present in 89 (86%) and 25 (92%) patients, respectively (P = NS). RF endocardial ablation was performed in order to obtain isolation of both right and left pulmonary veins, a lesion connecting the previous lines, and a lesion connecting the line encircling the left veins to the mitral annulus. Upon discharge from the hospital, sinus rhythm was present in 65 patients (63%) versus 5 patients (18%) in the control group (P < 0.0001). Mean time of cardiopulmonary bypass was longer in the RF group (148 ± 50 min vs 117 ± 30 min, P = 0.013). The complication rate was similar in both groups, but RF ablation-related complications occurred in 4 RF group patients (3.9%). After a mean follow-up of 12.5 ± 5 months (range 4–24), 83 (81%) of 102 RF group patients were in stable sinus rhythm versus 3 (11%) of 27 in the control group (P < 0.0001). The success rate was similar among the four surgical centers. Atrial contraction was present in 66 (79.5%) of 83 patients in the RF group in sinus rhythm. Conclusion: Endocardial RF left atrial compartmentalization during cardiac surgery is effective in restoring sinus rhythm in many patients. This technique is easy to perform and reproducible. Rare RF ablation-related complications can occur. During follow-up, sinus rhythm persistence is good, and biatrial contraction is preserved in most patients. (J Cardiovasc Electrophysiol, Vol. 14, pp. 1289-1295, December 2003)

We describe a 47-year-old man affected with hypertrophic cardiomyopathy and frequent episodes of syncope. During ambulatory Holter monitoring and head-up tilt test, a syncopal attack was associated with sinus arrest and hypotension. This case suggests an additional mechanism of syncope in hypertrophic cardiomyopathy.

We studied 38 patients (mean age 32 +/- 14 years) with arrhythmogenic right ventricular cardiomyopathy (ARVC) to evaluate the clinical significance of histologic features on endomyocardial biopsy specimens as related to signal-averaged electrocardiography (SAECG), spontaneous ventricular arrhythmias, and hemodynamic features. Fifteen patients presented with ventricular tachycardia or fibrillation (sustained ventricular arrhythmias), 23 with other minor arrhythmias. SAECG variables and right ventricular ejection fraction (RVEF) were statistically correlated with the extent of myocardial fibrosis on biopsy in ARVC. An increased percentage of fibrous tissue (> or = 30%) was a significant univariate predictor of late potentials (p = 0.004) and reduced RVEF (p = 0.02). The 18 patients with late potentials had an increased percentage of fibrous tissue (p = 0.01), a reduced RVEF (p = 0.0004), and a higher risk for sustained ventricular arrhythmias (p = 0.05) than the 20 patients without late potentials. RVEF was the most powerful predictor of late potentials (p = 0.004) at multivariate analysis. Moreover, RVEF < or = 50% was associated with an increased risk for development of sustained ventricular arrhythmias (p = 0.02). A SAECG parameter, namely the root-mean-square voltage of the terminal 40 ms at 25 Hz, was an independent predictive factor for the occurrence of sustained ventricular arrhythmias (p = 0.02). Although fibrous tissue may contribute to delayed myocardial activation in ARVC, a reduced RVEF plays an essential role for spontaneous manifestation of sustained ventricular arrhythmias.

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%, P0.001). 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% vs30 days = 77.2%; P0.001). 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%, P0.001). 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.

Objectives . We sought to assess whether structural heart disease underlies the syndrome of right bundle branch block, persistent ST segment elevation and sudden death. Background . Ventricular fibrillation and sudden death may occur in patients with a distinctive electrocardiographic (ECG) pattern of right bundle branch block and persistent ST segment elevation in the right precordial leads. Methods . Sixteen members of a family affected by this syndrome underwent noninvasive cardiac evaluation, including electrocardiography, Holter ambulatory ECG monitoring, stress testing, echocardiography and signal-averaged electrocardiography; two patients had electrophysiologic and angiographic study. Endomyocardial biopsy was performed in one living patient, and postmortem examination, including study of the specialized conduction system, was performed in one victim of sudden death. Results . Five years before a fatal cardiac arrest, the proband had been resuscitated from sudden cardiac arrest due to recorded ventricular fibrillation. Serial ECGs showed a prolonged PR interval, right bundle branch block, left-axis deviation and persistent ST segment elevation in the right precordial leads, in the absence of clinical heart disease. Postmortem investigation disclosed right ventricular dilation and myocardial atrophy with adipose replacement of the right ventricular free wall as well as sclerotic interruption of the right bundle branch. A variable degree of right bundle branch block and upsloping right precordial ST segment was observed in seven family members; four of the seven had structural right ventricular abnormalities on echocardiography and late potentials on signal-averaged electrocardiography. A sib of the proband also had a prolonged HV interval, inducible ventricular tachycardia and fibrofatty replacement on endomyocardial biopsy. Conclusions . An autosomal dominant familial cardiomyopathy, mainly involving the right ventricle and the conduction system, accounted for the ECG changes and the electrical instability of the syndrome.

In diabetic patients, the pathophysiologic mechanisms of exercise-induced left ventricular (LV) dysfunction remain controversial. In this study, the role of myocardial contractility recruitment in determining an abnormal LV response to isometric or dynamic exercise has been investigated in 14 diabetic patients with autonomic dysfunction. Ischemic heart disease was excluded by the absence of LV wall motion abnormalities induced by isotonic and isometric exercise and by coronary angiography. Left ventricular and myocardial function were studied at rest, and during isometric and isotonic exercise, by two-dimensional echocardiography; moreover, recruitment of an inotropic reserve was assessed by postextrasystolic potentiation at rest and at peak handgrip. An abnormal response of LV ejection fraction to isometric (9/14) or to dynamic (8/14) exercise was frequent in study patients. In these patients, baseline myocardial contractility was normal, and the significant increase in ejection fraction by postextrasystolic potentiation indicated a normal contractile reserve (65 +/- 7% vs. 74 +/- 6%, p = 0.001). Nevertheless, the downward displacement of LV ejection fraction-systolic wall stress relationships during exercise suggests an inadequate increase in myocardial contractility. However, the abnormal ejection fraction at peak handgrip was completely reversed by postextrasystolic potentiation (67 +/- 6% vs. 58.1 +/- 10%, p = 0.008), a potent inotropic stimulation independent of the integrity of adrenergic cardiac receptors. A defective inotropic recruitment, despite the presence of a normal LV contractile reserve, plays an important role in deexercise LV dysfunction in diabetic patients with autonomic neuropathy.

This study was performed to establish whether signal-averaged electrocardiography can aid in the diagnosis of the familial form of arrhythmogenic right ventricular cardiomyopathy in order to determine the severity of the disease and to predict ventricular arrhythmias. In arrhythmogenic right ventricular cardiomyopathy there is a fatty fibrous substitution of myocardium, which is the substrate for delayed myocardial activation; this is responsible for the abnormalities seen on the signal-averaged electrocardiogram (SAECG). Seventy-five members of 11 families, both healthy and with various forms of the disease, were studied using a signal-averaged electrocardiographic technique. Forty-seven members, 16 with a severe and 31 with a minor form of the disease, were found to be affected. Forty-three subjects had abnormal results on the SAECG; of these, 39 had the disease (100% in patients with widespread disease and 74.1% in patients with a minor form), whereas the other 4 had no sign of the disease. Only 44.1% of the subjects with an abnormal SAECG had ventricular arrhythmias, whereas 76% of the subjects with ventricular arrhythmias had an abnormal SAECG. In contrast, 90.6% of patients with an abnormal SAECG had the disease, and only subjects with arrhythmogenic right ventricular cardiomyopathy had ventricular arrhythmias. The abnormality on the SAECG appears to be correlated with the severity of the disease. Signal-averaged electrocardiography does not seem useful in diagnosing the minor forms of the disease and it does not give precise information about electrical instability in these patients.

We studied long-term variability of QT-dispersion in three patients with hypertrophic cardiomyopathy (Maron III) and ventricular fibrillation. Late potentials were absent on signal-averaged electrocardiogram. ST-segment depression was recorded in all three patients at Holter monitoring, and in two during exercise stress testing, nonsustained ventricular tachycardia was present in only one patient. The maximal correct QT-interval and corrected QT-dispersion (QTcd) were measured retrospectively, both off-drug and under treatment with amiodarone and beta-blocker (two patients), or sotalol alone (one patient). Ten age- and sex-matched normal subjects, and 13 hypertrophic cardiomyopathy patients without ventricular arrhythmias formed the control groups. QTcd-values in the control groups never exceeded 80 ms and mean values of 30.1 +/- 10.1 ms and 44.1 +/- 7.9 ms respectively, were found. During long-term follow-up, QTcd increased progressively in two of the three patients with ventricular fibrillation, and at the time of the event all showed a value > 100 ms. Sotalol, but not the amiodarone reduced QTcd. QTcd seems to be a powerful predictor of ventricular electrical instability in the absence of other specific markers, and a promising guide for effective pharmacological therapy.

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, p0.001; 11.1 +/- 4 vs. 15.2 +/- 4, p0.01; 15.2 +/- 4 vs. 18.9 +/- 5, p0.05); 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.

In 24 subjects presenting with apparently idiopathic ventricular arrhythmias, a final diagnosis of arrhythmogenic right ventricular cardiomyopathy was formulated following global evaluation of the clinical, cross-sectional echocardiography and angiographic findings, and the observation of myocardial atrophy with fibrous-fatty substitution in right ventricular endomyocardial biopsy. All patients had good effort tolerance, and a normal cardiac silhouette. Ventricular arrhythmias with a left bundle branch block pattern were present in 23 cases (sustained ventricular tachycardia, nonsustained ventricular tachycardia, ventricular couplets, and ventricular premature complexes); 1 patient experienced an episode of ventricular fibrillation. A nearly constant electrocardiographic feature was T wave negativity in the right precordial leads. Cross-sectional echocardiography and hemodynamic studies showed that right ventricular impairment consisted only of localized structural and dynamic abnormalities; in a few cases the left ventricle was segmentally involved. Familial occurrence was present in 29% of the cases. No case of sudden death was observed during follow-up. These findings confirm that the concealed form of arrhythmogenic right ventricular cardiomyopathy is a cause of so-called "idiopathic" ventricular arrhythmias in subjects with apparently "normal hearts". Echocardiographic and angiographic investigations may lead to the correct diagnosis.

We studied in detail 17 patients presenting with monomorphic repetitive ventricular rhythms having left bundle branch block morphology and right axis deviation. All had an apparently normal heart at physical examination. At chest radiography, three patients had mild cardiomegaly, and at electrocardiography, five patients had inverted T waves beyond V2. Five patients had syncope or near syncope. In seven patients the tachycardia occurred on effort. One patient died suddenly. The patients were extensively investigated, using cross-sectional echocardiography, complete haemodynamic and angiographic studies, electrophysiology and histology, to search for any structural basis of the arrhythmias. Tachycardia was sustained in 8 patients, nonsustained in 3, and consistent with accelerated idioventricular rhythm and repetitive paroxysmal ventricular tachycardia in 5 and 1 patients, respectively. Despite the differences in clinical and arrhythmologic features, similar abnormalities of right ventricular structure and/or wall motion were detected in all patients, consistent with localized forms of right ventricular cardiomyopathy. Different antiarrhythmic drugs were successfully used in twelve patients (the four patients with accelerated idioventricular rhythm were not treated). The patient who died suddenly had previously had a sustained ventricular tachycardia and was being treated by beta-blockade. Postmortem study revealed massive fibro-adipose substitution of the right ventricular free wall and pulmonary infundibulum.

The incidence and types of rhythm and conduction disturbances in 11 male and 6 female patients with congenitally corrected transposition of the great arteries and no other intrinsic complicating anomalies were studied. Patient age ranged from 5 to 54 years; follow-up ranged from 5 to 37 years. Surface electrocardiograms were recorded in each patient; 15 also underwent 24-hour Holter monitoring and 10 underwent electrophysiologic study. The conduction system of a 54-year-old woman who died suddenly, with complete atrioventricular (AV) block since age 30 years, was studied by serial histologic sections. Fifteen patients were asymptomatic and 2 reported repeated episodes of palpitation since childhood. Ten patients presented with a normal PR interval and 2 with first-degree AV block (12%). Five patients had complete AV block (29%), but none had had it at birth; first- and second-degree AV block preceded complete AV block in 2 patients. The morphologic pattern and duration of QRS suggested a junctional rhythm in 4 patients and an idioventricular pacemaker in 1 patient. Electrophysiologic studies confirmed that the complete AV block site was supra-Hisian in 2 patients and proximal to the His bundle bifurcation in 1 patient. However, histologic investigation disclosed fibrosis and disruption of the proximal nonbifurcating His bundle in the patient who died suddenly. In 2 patients with recurrent supraventricular tachycardia, electrophysiologic studies suggested reentry through James fibers (or dual AV nodal pathway) in 1 and the presence of a left lateral accessory AV pathway in the other. Holter monitoring showed a high incidence of ventricular arrhythmias.

Thirty-two members of a family were studied. Three of them died in their youth and had evidence of arrhythmogenic right ventricular (RV) dysplasia. The other 29 members underwent clinical examination, electrocardiography, chest x-ray and M-mode and 2-dimensional echocardiography. Fourteen patients found to have structural abnormalities of the right ventricle underwent 24-hour ambulatory electrocardiographic recording and symptom-limited bicycle stress testing. Hemodynamic and angiographic studies were performed in 6 of these patients. In this family the arrhythmogenic RV dysplasia showed a wide variation of abnormalities, ranging from mild, local alterations to generalized involvement of the right ventricle. The patients were separated into 3 groups on the basis of both the clinical profile and noninvasive/invasive studies: (1) 3 subjects who died suddenly; (2) 3 subjects who had severe ventricular arrhythmias; and (3) 8 subjects in whom RV impairment was not associated with any significant arrhythmias. There was no close relation between the severity of the RV abnormality and presence of ventricular arrhythmias. The variability of the RV abnormality and the high prevalence of this condition in this family is consistent with a genetic pattern of autosomal dominance with incomplete penetrance.

A family with occurrence of juvenile sudden death and effort polymorphous ventricular tachycardias is reported. Nineteen members aged 9 to 63 years were investigated. Four of them died suddenly in their youth. Postmortem investigation performed in 2 deceased subjects disclosed an apparently normal heart at macroscopy but fibro-fatty substitution of the right ventricular free wall was noted at histologic examination. The 14 living members underwent physical examination, resting electrocardiography, chest X-radiography, Holter monitoring, exercise stress testing, and M-mode and cross-sectional echocardiography. Four patients underwent hemodynamic and electrophysiologic studies. All 14 subjects had normal physical examination as well as normal electrocardiographic and cardiothoracic indices. Localized right ventricular structural and dynamic abnormalities were noted at cross-sectional echocardiographic and angiographic investigation of 9 of the patients. The right ventricular volumes in these subjects were normal or slightly increased. In 7 of them, polymorphous ventricular tachycardias were induced by exercise stress testing. The arrhythmias which were responsive to beta-blockade, do not seem to depend on reentry. Enhanced automaticity appeared to be the more likely mechanism of their production. These data demonstrate that right ventricular cardiomyopathy may occur in an occult form with life-threatening electrical instability.

Right ventricular pathologic involvement, with autopsy evidence of fibrous and fatty infiltration of the right ventricle, was investigated in members of families in which cases of juvenile sudden death had occurred. Seventy-two subjects from nine families were studied. Sixteen died at a young age and 56 are living. Postmortem investigation in 11 cases (mean age at death 24 years) revealed massive replacement of the right ventricular free wall by fat or fibrous tissue. In the 56 living patients clinical examination included an electrocardiogram (ECG) at rest, ambulatory ECG recording, posteroanterior and lateral chest roentgenograms, M-mode and two-dimensional echocardiograms and exercise stress tests. In 14 patients, hemodynamic, angiographic and electrophysiologic studies were also carried out; right ventricular endomyocardial biopsy was performed in four. Structural and dynamic right ventricular impairment was detected in 30 living patients (mean age 25 years), and concomitant mild left ventricular abnormalities were present in 4. In eight of the nine families studied at least two members were affected. Ventricular arrhythmias (Lown grade greater than or equal to 4a) were recorded in more than half of the cases. The data reveal that right ventricular dysplasia shows a familial clustering and causes electrical instability that may place affected subjects at risk of sudden death. The mean age of these subjects suggests that the disease is manifested at a young age with a polymorphic clinical and arrhythmic profile. Finally, because this disease is a primary disorder of the ventricular myocardium, it should be included among the cardiomyopathies.

Objectives. Because sudden death due to complete atrioventricular (AV) block or ventricular arrhythmias is the most dramatic event in myotonic dystrophy, we assessed the relation of cardiac disease to cytosine—thymine—guanine (CTG) triplet mutation in adults affected with myotonic dystrophy. Background. The myotonic dystrophy mutation, identified as an unstable deoxyribonucleic acid (DNA) sequence (CTG) prone to increase the number of trinucleotide repeats, produces clinical manifestations of the disease in skeletal muscle, the heart and many organ systems. Methods. Forty-two adult patients underwent electrocardiography and echocardiography; in addition, signal-averaging electrocardiography was performed in 22, and 24-h Holter monitoring was recorded in 32. The diagnosis was established by neurologic examination, electromyography, muscle biopsy and DNA analysis. The patients were then classified into three subgroups on the basis of the number of CTG trinucleotide repeat expansions: E1= 18 patients with 0 to 500 CTG repeats; E2= 12 patients with up to 1,000 repeats; E3+ E4= 10 patients with up to 1,500 repeats and 2 patients with >1,500 repeats. Results. The incidence of normal electrocardiographic (ECG) results was found to be significantly different in the three subgroups (55%, 50%, 17% in E1, E2, E3+ E4, respectively, p = 0.04), with the highest values in the group with fewer repeat expansions. The incidence of complete left bundle branch block was also significantly different among the groups (5% in E1, 0% in E2, 42% in E3+ E4, p = 0.01) and was directly correlated with the size of the expansion. A time-domain analysis of the signal-averaged ECG obtained in 12 patients in E1, 4 in E2, 5 in E3and 1 in E4showed that abnormal ventricular late potentials were directly correlated with CTG expansion (33% in E1, 75% in E2, 83% in E3+ E4, p = 0.05). Moreover, the incidence of ventricular couplets or triplets showed a positive correlation with size of CTG expansion (0 in E1, 0 in E2, 29% in E3+ E4, chi square 0.02). Conclusions. Our findings suggest that the involvement of specialized cardiac tissue, accounting for severe AV and intraventricular conduction defects, is related to CTG repeat length. In addition, the presence of abnormal late potentials directly correlates to CTG expansion. Abnormal late potentials, caused by slowed and fragmented conduction through damaged areas of myocardium, represent a substrate for malignant reentrant ventricular arrhythmias. In the future, therefore, molecular analysis of DNA should identify patients with cardiac disease at high risk for development of AV block or lethal ventricular arrhythmias.

Summary: We evaluated the progression of conduction system and myocardial disease in 17 asymptomatic myotonic dystrophy patients by clinical evaluation, electrocardiography, vector cardiogmphy , and echocardiography. An exercise test was done in 10 patients. After 8 years, a follow-up study of 12 of the 17 original patients was done with a similar protocol. During this period, 2 patients died: one of sudden death while the other had acute left ventricular failure. In our first control study, we found EKG abnormalities in 15 of our patients, consisting mostly of conduction defects or pseudonecrotic patterns. In our second control, all patients had conduction system disease and, in addition, 3 of them had premature ventricular beats. One patient developed dilated cardiomyopathy. In 6 patients, structural involvement of the right ventricle was found. We conclude that even in asymptomatic myotonic dystrophy patients a conduction system deficit is present and progresses, and cardiac death may occur in about 12% of these patients.

In 24 cases of arrhythmogenic right ventricular (RV) dysplasia, the electrovectorcardiographic (ECG-VCG) behavior of T horizontal (wave and loop) was analyzed and the data compared with RV angiographic volumes. Arrhythmogenic RV dysplasia was diagnosed on the basis of echocardiographic and angiographic data in all subjects. At ECG, T wave was negative in V1 in nine subjects (37%), in V1-V2 in six (25%), in V1-V3 in two (8%), in V1-V4 in one (4%), in V1-V5 in two (8%), and in V1-V6 in four (16%). Nine subjects (37%) presented a bifid T wave in V2-V4. At VCG, T horizontal loop showed three morphologic characteristics: (1) counterclockwise rotation with a mean axis range of +15 degrees to -10 degrees (average, +5 degrees); (2) a figure-eight pattern with a mean axis range of +10 degrees to -40 degrees (average, -17 degrees); and (3) clockwise rotation with a mean axis range of -40 degrees to -110 degrees (average, -70 degrees). T wave changes seem to be primary and independent from QRS changes. RV and diastolic volumes ranged from 100 to 320 m1/m2 (average, 169 +/- 69). The extension of T wave negativity on precordial leads has a direct relationship with RV enlargement (r = 0.89, p less than 0.01). T changes are probably caused by dislocation of the left ventricle backwards secondary to RV dilatation, asynchronous RV repolarization, or intraparietal RV conduction defects.

In 1992, Brugada and Brugada reported a distinct subgroup of patients with episodes of "idiopathic"polymorphic ventricular tachycardia or ventricular fibrillation characterized by a unique electrocardiographic (ECG) pattern, which consisted of right bundle branch block and ST-segment elevation from V1 to V2-V3. As in patients with long QT syndrome, the ECG changes and the ventricular electrical instability could not be explained by structural heart disease, myocardial ischemia, or electrolyte disturbances. The syndrome can be inherited and predominantly affects males. Clinical presentation includes cardiac arrest or syncope caused by rapid ventricular tachycardia or fibrillation characteristically occurring at rest or during sleep. The clinical outcome of affected patients is poor unless they receive an implantable cardioverter defibrillator. The ECG pattern and the electrical ventricular instability have been explained by the dispersion of repolarization between the right ventricular epicardium and endocardium, which predisposes to local reexcitation of myocytes with different action potential durations. A disease-causing missense mutation in the cardiac sodium channel gene SCN5A has been recently reported in patients with Brugada syndrome. It is mandatory for the clinician to carefully rule out any organic heart disease before suggesting a diagnosis of Brugada syndrome, because the typical ECG pattern with the risk of sudden arrhythmic death is also observed in patients with structural heart diseases in the setting of arrhythmogenic right ventricular cardiomyopathy.