Prognostic significance of remotely monitored nocturnal heart rate in heart failure patients with reduced ejection fraction.

BACKGROUND: Elevated resting heart rate is a risk factor for cardiovascular events. OBJECTIVE: The purpose of this study was to investigate the clinical significance of nocturnal heart rate (nHR) and 24-hour mean heart rate (24h-HR) obtained by continuous remote monitoring (RM) of implantable devices. METHODS: We analyzed daily-sampled trends of nHR, 24h-HR, and physical activity in patients on ß-blocker therapy for chronic heart failure and with implantable cardioverter-defibrillators or cardiac resynchronization therapy defibrillators (CRT-Ds). Patients were grouped by average nHR and 24h-HR quartile during follow-up to estimate the respective incidence of nonarrhythmic death and device-treated ventricular tachycardia/fibrillation (VT/VF). RESULTS: The study cohort included 1330 patients (median age 69 years [interquartile range 61-77 years]; 41% [n = 550] with CRT-D; median follow-up 25 months [interquartile range 13-42 months]). Compared with patients in the lowest nHR quartile (≤57 beats/min) group, patients in the highest quartile group (>65 beats/min) had an increased risk of nonarrhythmic death (adjusted hazard ratio [AHR] 2.25; 95% confidence interval [CI] 1.13-4.50; P = .021) and VT/VF (AHR 1.98; 95% CI 1.40-2.79; P < .001) and were characterized by the lowest level of physical activity (P ≤ .0004 vs every other nHR quartiles). The highest 24h-HR quartile group (>75 beats/min) showed an increased risk of VT/VF (AHR 2.13; 95% CI 1.52-2.99; P < .001) and a weaker though significant association with nonarrhythmic mortality (AHR 1.80; 95% CI 1.00-3.22; P = .05) as compared with the lowest 24h-HR quartile group (≤65 beats/min). CONCLUSION: In remotely monitored patients with implantable cardioverter-defibrillator/CRT-D on ß-blocker therapy for heart failure, elevated heart rates (nHR >65 beats/min and 24h-HR >75 beats/min) were associated with increased mortality and VT/VF risk. nHR showed a stronger association than 24h-HR with worst prognosis and lowest physical activity.

Computational Investigation of Interactions between Carbon Nitride Dots and Doxorubicin.

The study of carbon dots is one of the frontiers of materials science due to their great structural and chemical complexity. These issues have slowed down the production of solid models that are able to describe the chemical and physical features of carbon dots. Recently, several studies have started to resolve this challenge by producing the first structural-based interpretation of several kinds of carbon dots, such as graphene and polymeric ones. Furthermore, carbon nitride dot models established their structures as being formed by heptazine and oxidized graphene layers. These advancements allowed us to study their interaction with key bioactive molecules, producing the first computational studies on this matter. In this work, we modelled the structures of carbon nitride dots and their interaction with an anticancer molecule (Doxorubicin) using semi-empirical methods, evaluating both geometrical and energetic parameters.

Daily Exposure to Air Pollution Particulate Matter Is Associated with Atrial Fibrillation in High-Risk Patients.

Several epidemiological studies found an association between acute exposure to fine particulate matter of less than 2.5 µm and 10 µm in aerodynamic diameter (PM2.5 and PM10) and cardiovascular diseases, ventricular fibrillation incidence and mortality. The effects of pollution on atrial fibrillation (AF) beyond the first several hours of exposure remain controversial. A total of 145 patients with implantable cardioverter-defibrillators (ICDs), cardiac resynchronization therapy defibrillators (ICD-CRT), or pacemakers were enrolled in this multicentric prospective study. Daily levels of PM2.5 and PM10 were collected from monitoring stations within 20 km of the patient's residence. A Firth Logistic Regression model was used to evaluate the association between AF and daily exposure to PM2.5 and PM10. Exposure levels to PM2.5 and PM10 were moderate, being above the World Health Organization (WHO) PM2.5 and PM10 thresholds of 25 µg/m3 and 50 µg/m3, respectively, on 26% and 18% of the follow-up days. An association was found between daily levels of PM2.5 and PM10 and AF (95% confidence intervals (CIs) of 1.34-2.40 and 1.44-4.28, respectively) for an increase of 50 µg/m3 above the WHO threshold. Daily exposure to moderate PM2.5 and PM10 levels is associated with AF in patients who are not prone to AF.

Multicentre experience with the second-generation subcutaneous implantable cardioverter defibrillator and the intermuscular two-incision implantation technique.

INTRODUCTION: The recently developed second-generation subcutaneous implantable cardioverter defibrillator (S-ICD) and the intermuscular two-incision implantation technique demonstrate potential favorable features that reduce inappropriate shocks and complications. However, data concerning large patient populations are lacking. The aim of this multicentre prospective study was to evaluate the safety and outcome of second-generation S-ICD using the intermuscular two-incision technique in a large population study. METHODS AND RESULTS: The study population included 101 consecutive patients (75% male; mean age, 45 ± 13 years) who received second-generation S-ICD (EMBLEM; Boston Scientific, Marlborough, MA) implantation using the intermuscular two-incision technique as an alternative to the standard implantation technique. Twenty nine (29%) patients were implanted for secondary prevention. Twenty four (24%) patients had a previously implanted transvenous ICD. All patients were implanted without any procedure-related complications. Defibrillation testing was performed in 80 (79%) patients, and ventricular tachycardia was successfully converted at less than or equal to 65 J in 98.75% (79/80) of patients without pulse generator adjustments. During a median follow-up of 21 ± 10 months, no complications requiring surgical revision or local or systemic device-related infections were observed. Ten patients (9.9%) received appropriate and successful shocks for ventricular arrhythmias. Three (2.9%) patients experienced inappropriate shocks due to oversensing the cardiac signal (n = 1), noncardiac signal (n = 1), and a combination of both cardiac and noncardiac signals (n = 1), with one patient requiring device explantation. No patients required device explantation due to antitachycardia pacing indications. CONCLUSIONS: According to our multicentre study, second-generation S-ICD implanted with the intermuscular two-incision technique is an available safe combination and appears to be associated with a low risk of complications, such as inappropriate shocks.

A targeted next-generation gene panel reveals a novel heterozygous nonsense variant in the TP63 gene in patients with arrhythmogenic cardiomyopathy.

BACKGROUND: Arrhythmogenic cardiomyopathy (ACM) is associated with arrhythmias and risk of sudden death. Mutations in genes encoding proteins of cardiac intercalated discs account for ∼60% of ACM cases, but the remaining 40% is still genetically elusive. OBJECTIVE: The purpose of this study was to identify the underlying genetic cause in probands with ACM. METHODS: DNA samples from 40 probands with ACM, negative for mutations in the 3 major ACM genes-DSP, PKP2, and DSG2, were screened by using a targeted gene panel consisting of 15 known ACM genes and 53 candidate genes. RESULTS: About half of patients were found to carry rare variant(s) predicted to be damaging; specifically, 9 (22.5%) showed ≥1 variants in genes associated with ACM and/or with other inherited heart diseases and 10 (25%) showed variants in candidate genes. Among the latter, we focused on 2 novel variants in TP63 and PPP1R13L candidate genes (c.796C>T, p.(R266*) and c.1858G>C, p.(A620P), respectively). The encoded proteins p63 and inhibitor of apoptosis stimulating p53 protein are known to be interacting partners. Inhibitor of apoptosis stimulating p53 protein is a shuttling multifunctional protein: in the nucleus it is critical for inhibiting p63 function, whereas in the cytoplasm it regulates desmosome integrity. According to the American College of Medical Genetics and Genomics guidelines, the variant in TP63 has been scored as likely pathogenic and the variant in PPP1R13L as a variant of uncertain significance. Importantly, the mutant TP63 allele leads to nonsense-mediated messenger RNA decay, causing haploinsufficiency. CONCLUSION: Our findings identify TP63 as a putative novel disease gene for ACM, while the possible involvement of PPP1R13L remains to be determined.

Anticoagulation after catheter ablation of atrial fibrillation: An unnecessary evil? A systematic review and meta-analysis.

BACKGROUND: Anticoagulation in patients with atrial fibrillation (AF) is currently based on clinical parameters (CHA2 DS 2 -VASc score) that have been shown to predict cerebrovascular events (CVE). Controversy exists as to whether CVE risk persists unmodified after successful catheter ablation, as observational studies suggest a lower risk of CVE. Current guidelines recommend continued oral anticoagulation (OAC) based on the CHA 2 DS 2 -VASc score risk profile. METHODS: We conducted a systematic literature review of all studies published up to July 31, 2018, that reported CVE after catheter ablation of AF and compared patients on or off OAC. Random-effects models were used to demonstrate the risk of CVE and major bleeding in on-OAC vs off-OAC patients. This analysis was further stratified by CHADS2 and CHA 2 DS 2 -VASc score. RESULTS: We retained 16 studies, 10 prospective cohort and 6 retrospective cohort, that met inclusion criteria, and which enrolled 25 177 patients: 13 166 off-OAC and 12 011 on-OAC. No significant difference in the incidence of CVE emerged between on-OAC and off-OAC patients after AF ablation (risk ratio, 0.66; confidence interval [CI], 0.38, 1.15). Similar results were found after stratification by CHADS2 and CHA 2 DS 2 -VASc score. Off-OAC patients suffered significantly less bleeding than those on OAC (RR, 0.17; CI, 0.09, 0.34). Of note, the percentage of patients with AF recurrence impacts the treatment effect in the two groups ( P = 0.001). CONCLUSIONS: In this metanalysis, the risk-benefit ratio favored the suspension of OAT after successful AF ablation even in patients at moderate-high risk. Whether the reported results can be extended also to non-vitamin K antagonist oral anticoagulants warrants further investigations.

Optimization of coronary sinus lead placement targeted to right-to-left delay in patients undergoing cardiac resynchronization therapy.

AIMS: Anatomical placement of the coronary sinus (CS) lead in basal or mid-ventricular positions of the posterior and lateral walls is associated with a better clinical outcome of cardiac resynchronization therapy (CRT). We hypothesized that optimization of CS lead placement targeted the right-to-left electrical delay (RLD) predicts an additional clinical benefit. METHODS AND RESULTS: The CS lead was placed according to current standards in 90 patients (Conventional group) and at the site of the longest RLD in 121 patients (RLD group). Non-responders were defined as those who died or underwent hospitalization for heart failure or did not improve in their Clinical Composite Score within 6 months. There were 67 (32%) non-responders. Compared with Conventional group, the final CS pacing site was more frequently in the basal segments in the RLD group (40% vs. 23%, P = 0.007); moreover, the RLD ratio (%RLD) of the total QRS width was longer (77 ± 13 vs. 73 ± 15, P = 0.05) and biventricular QRS shortened more from the baseline (-31 ± 21 ms vs. -21 ± 26 ms, P = 0.004). Nevertheless, the rate of non-responders was similar in the RLD and Conventional groups (35% vs. 28%, P = 0.30), as was %RLD (76 ± 16 vs. 75 ± 13, P = 0.66). QRS width during right ventricular (RV) pacing was an independent predictors of adverse outcome, with a 2% increase in the risk of failure for each 1 ms increase in QRS (P = 0.006). CONCLUSION: Optimization of CS lead placement targeted to latest electrical activation does not provide additional clinical benefit to anatomical placement in basal or mid-ventricular positions of the posterior and lateral walls. QRS width during RV pacing was a strong predictor of CRT failure. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT03204864.

Association between air pollution and ventricular arrhythmias in high-risk patients (ARIA study): a multicentre longitudinal study.

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 (PM10) and less than 2·5 µm (PM2·5) 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 PM2·5 (p<0·0001) but not PM10. An analysis of ventricular fibrillation episodes alone showed a significant increase in risk of higher PM2·5 (p=0·002) and PM10 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.

Multicentre comparison Of shock efficacy using single-vs. Dual-coil lead systems and Anodal vs. cathodaL polarITY defibrillation in patients undergoing transvenous cardioverter-defibrillator implantation. The MODALITY study.

PURPOSE: An optimal active-can lead configuration during implantable cardioverter defibrillator (ICD) placement is important to obtain an adequate defibrillation safety margin. The purpose of this multicenter study was to evaluate the rate of the first shock success at defibrillation testing according to the type of lead implant (single vs. dual coil) and shock polarity (cathodal and anodal) in a large series of consecutive patients who received transvenous ICDs. METHODS: This was a multicenter study enrolling 469 consecutive patients. Single- versus dual-coil leads and cathodal versus anodal polarity were evaluated at defibrillation testing. In all cases, the value of the energy for the first shock was set to 20 J less than the maximum energy deliverable from the device. RESULTS: A total of 469 patients underwent defibrillation testing: 158 (34 %) had dual-coil and 311 (66 %) had single-coil lead systems configuration, 254 (54 %) received anodal shock and 215 (46 %) received cathodal shock. In 35 (7.4 %) patients, the shock was unsuccessful. No significant differences in the outcome of defibrillation testing using single- versus dual-coil lead were observed but the multivariate analysis showed an increased risk of shock failure using cathodal shock polarity (OR 2.37, 95 % CI 1.12-5.03). CONCLUSIONS: Both single- and dual-coil transvenous ICD lead systems were associated with high rates of successful ICD implantation, and we found no significant differences in ventricular arrhythmias interruption between the two ICD lead systems configuration. Instead, anodal defibrillation was more likely to be successful than cathodal defibrillation.

[Pathophysiology of atrioventricular conduction disturbances in sports practitioners]. / I disturbi di conduzione normali e patologici dello sportivo giovane-adulto.

In athletes practicing endurance sports, atrioventricular conduction disturbances may be physiological. This holds true for first-degree atrioventricular blocks, type 1 second-degree atrioventricular blocks, and slight ventricular activation delays (slurred S wave in V1). On the contrary, right (RBBB) and left bundle branch blocks (LBBB) and fascicular blocks (left anterior [LAH] and left posterior hemiblocks [LPH]), either isolated or associated with RBBB, are rare in asymptomatic athletes. The latter can be the consequence of structural heart disease or primary degeneration of the intraventricular conduction system (Lev-Lenègre disease). In our experience, LPH and LPH+RBBB have always a pattern of familial recurrence. LAH+RBBB may be familial (40-60%). Isolated RBBB is rarely familial. LBBB is never familial. Families with hereditary conduction disorders may also have a history of juvenile sudden death. Patients with LBBB may show coronary artery anomalies. The long-term prognosis of intraventricular conduction disorders in asymptomatic subjects, without apparent heart disease, is unknown.

Should all individuals with a nondiagnostic Brugada-electrocardiogram undergo sodium-channel blocker test?

BACKGROUND: The diagnostic Brugada-electrocardiogram (Br-ECG) is characterized by "coved-type" ST-segment elevation (type 1) in V(1) to V(2)/V(3). The sodium-channel blocker test is clinically used to unmask diagnostic Br-ECG in patients with nondiagnostic "saddle-back" Br-ECG (type 2 and type 3). OBJECTIVE: To assess the prognostic value of the sodium-channel blockers test in individuals with a nondiagnostic Br-ECG. METHODS: We studied 153 consecutive patients (128 men; age 41.7 ± 14.0 years) with a type 2/3 Br-ECG who underwent a sodium-channel blocker test with either flecainide (48%) or ajmaline (52%). Nondiagnostic Br-ECGs were identified during the evaluation of cardiac arrest in 5 patients (3%), syncope in 36 (24%), cascade family screening in 48 (31%), and incidental ECG in 64 (42%). A spontaneous type 1 Br-ECG was systematically excluded by serial ECGs (6.1 ± 0.4) and recording of right precordial leads both at standard and second and third intercostal spaces. RESULTS: The sodium-channel blocker test result was positive in 76 (50%) patients. During a follow-up of 59 ± 33 months, 9 (5.9%) patients experienced events such as syncope (n = 4), appropriate interventions of defibrillator (n = 4), or sudden death (n = 1). A positive sodium-channel blocker test was associated with a significantly higher event rate in symptomatic patients (P = .01) but not in asymptomatic individuals (P = .18). No events occurred among asymptomatic individuals with an incidental nondiagnostic Br-ECG. CONCLUSIONS: In asymptomatic individuals with a nondiagnostic Br-ECG, the incidence of events is low regardless of the sodium-channel blocker test result while in symptomatic patients a positive sodium-channel blocker test result is associated with an adverse arrhythmic outcome and may contribute to risk stratification.

[Risk stratification in Brugada syndrome]. / Stratificazione del rischio nella sindrome di Brugada.

Individuals with type 1 Brugada ECG pattern may suffer from malignant ventricular arrhythmias (Brugada syndrome). Patients with Brugada syndrome and documented cardiac arrest should receive an implantable cardioverter-defibrillator. In the remaining subjects, the best management is controversial. Many data suggest that patients with syncope, particularly if they have a spontaneous type 1 ECG pattern, have a significant risk. In the remaining population of asymptomatic subjects, the risk is lower but not negligible. How to manage these latter cases is an unsolved issue. The usefulness of the electrophysiological study (EPS) in risk stratification, i.e. inducibility of sustained ventricular tachycardia/fibrillation, is controversial. Indeed, some authors strongly support the prognostic value of EPS, while others completely deny its usefulness. We recently published our experience concerning the usefulness of a combined approach that considered both clinical data and EPS results; 320 patients (258 males, mean age 43 years) with type 1 ECG were enrolled. No patient had previous cardiac arrest; 54% of patients had a spontaneous and 46% a drug-induced type 1 ECG. One third had syncope, two thirds were asymptomatic; 245 patients underwent EPS; 110 patients received an implantable defibrillator. Patients were followed up for 40 months. During follow-up, 17 patients had major arrhythmic events (MAE) (14 resuscitated ventricular fibrillations and 3 sudden deaths). Both spontaneous type 1 ECG and syncope significantly increased the risk (8.6% and 10.4% event rates vs 2.8% and 1.3%). MAE occurred in 14% of subjects with positive EPS, in no subjects with negative EPS, and in 5.3% of subjects without EPS. All MAE occurred in subjects who had ≥ 2 risk factors (syncope, family history of sudden death and positive EPS). Among these patients, those with spontaneous type 1 ECG had a 30% event rate. In subjects with drug-induced type 1 MAE were rare. In conclusion, 1) in subjects with the Brugada type 1 ECG neither a single clinical risk factor nor EPS alone are able to identify subjects at the highest risk; 2) a multiparametric approach (including syncope, family history of sudden death and positive EPS) helps to identify populations at the highest risk; 3) subjects at the highest risk are those with a spontaneous type 1 ECG and ≥ 2 risk factors; 4) the remainder is at low risk.

Management of alert messages in the remote monitoring of implantable cardioverter defibrillators and pacemakers: an Italian single-region study.

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.

Risk stratification in individuals with the Brugada type 1 ECG pattern without previous cardiac arrest: usefulness of a combined clinical and electrophysiologic approach.

AIMS: Risk stratification in individuals with type 1 Brugada electrocardiogram (ECG) pattern (type 1 ECG) for primary prevention of sudden death (SD). METHODS AND RESULTS: Three hundred and twenty patients (258 males, median age 43 years) with type 1 ECG were enrolled. No patient had previous cardiac arrest. Fifty-four per cent of patients had a spontaneous and 46% a drug-induced type 1 ECG. One-third had syncope, two-thirds were asymptomatic. Two hundred and forty-five patients underwent electrophysiologic study (EPS) and 110 patients received an implantable cardiac defibrillator (ICD). During follow-up [median length 40 months (IQ20-67)], 17 patients had major arrhythmic events (MAE) (14 resuscitated ventricular fibrillation (VF) and three SD). Both a spontaneous type 1 ECG and syncope significantly increased the risk (2.6 and 3.0% event rate per year vs. 0.4 and 0.8%). Major arrhythmic events occurred in 14% of subjects with positive EPS, in no subjects with negative EPS and in 5.3% of subjects without EPS. All MAE occurred in subjects who had at least two potential risk factors (syncope, family history of SD, and positive EPS). Among these patients, those with spontaneous type 1 ECG had a 30% event rate. CONCLUSION: (1) In subjects with the Brugada type 1 ECG, no single clinical risk factor, nor EPS alone, is able to identify subjects at highest risk; (2) a multiparametric approach (including syncope, family history of SD, and positive EPS) helps to identify populations at highest risk; (3) subjects at highest risk are those with a spontaneous type 1 ECG and at least two risk factors; (4) the remainder are at low risk.

[Brugada syndrome: diagnosis and risk stratification]. / Sindrome di Brugada: diagnosi e stratificazione del rischio.

Brugada syndrome is a genetic disease, leading to a functional reduction in sodium channel current. This anomaly occurs in the absence of other demonstrable cardiac anomalies. The ECG diagnostic pattern is characterized by coved ST-segment elevation in V1-V3 leads. Brugada syndrome may be complicated by malignant ventricular arrhythmias and sudden death. Risk stratification in individuals with type 1 Brugada ECG pattern for primary prevention of sudden death is an unsolved issue. Recognized risk factors for sudden death are spontaneous type 1 ECG pattern, syncope, or documented cardiac arrest. Family history of sudden death is a controversial risk factor. However, all these factors have a low positive predictive value. The prognostic significance of electrophysiological study (EPS) is debated. There is a consensus about the low predictive value of a positive EPS and a low specificity. However, while some authors deny at all its usefulness, others suggest that EPS is useful when considered together with other clinical risk factors. According to Brugada brothers our personal data suggest that (i) in subjects with type 1 Brugada ECG no single clinical risk factor nor EPS alone are able to identify subjects at the highest risk; (ii) a multiparametric approach (including syncope, family history of sudden death and positive EPS) helps to identify populations at the highest risk; (iii) subjects at the highest risk are those with a spontaneous type 1 ECG and at least two risk factors; (iv) the remaining are at low risk.

Unexplained syncope, Brugada-like ECG and minimal structural right ventricular abnormalities: which is the right diagnosis?

We describe a 65-year-old man with unexplained syncope, Brugada ECG pattern and right ventricular abnormalities. To reach a diagnosis of Brugada syndrome, a variety of diseases have to be excluded. This case report shows how difficult the differential diagnosis is, particularly with arrhythmogenic right ventricular cardiomyopathy, after documentation of minimal structural RV abnormalities; invasive examination may be required. In this case, three-dimensional electroanatomical bipolar voltage mapping revealed a scar area in the right ventricle in the absence of clear-cut kinetic abnormalities, but the sensitivity of this method and specificity in patients without confirmed arrhythmogenic right ventricular cardiomyopathy have not been defined.

Pacemaker malfunctions in Danon's disease.

We describe a case of a 30-year-old man with Danon's disease, an X-linked genetic disorder due to deficiency of lysosomal-associated membrane protein 2 with secondary intracytoplasmatic glycogen and autophagic material storage. This disease is characterized by skeletal muscle involvement, mental retardation, ophthalmic abnormalities, and cardiac disease. In this patient, cardiac involvement was characterized by hypertrophic cardiomyopathy in young age, preexcitation, and parossistic atrioventricular block. The patient underwent to an implantable cardioverter defibrillator implantation for conduction disorders and for primary prevention of sudden death, a frequent event in Danon's disease. This case report describes cardiac involvement with conduction disorders and multiple pacemaker malfunctions in Danon's disease.