Clinical and Prognostic Significance of Idiopathic Left Bundle-Branch Block in Young Adults.

AIMS: LBBB is rare in healthy young adults, and its long-term prognosis is uncertain. METHODS: 56 subjects (aged <50 years), in whom an LBBB was discovered by chance in the absence of clinical and echocardiographic evidence of heart disease, were collected in a multicenter registry. RESULTS: 69% were males. Mean age at the time of discovery of LBBB was 37 ± 11 years. Mean QRS duration was 149 ± 17 m sec and 35% had left axis deviation. All patients had a normal echocardiogram, except for left ventricular dyssynchrony; 37 patients underwent coronary angiography (30) or myocardial scintigraphy during effort Eriksson and Wilhelmsen (2005), and in all cases obstructive coronary artery disease was excluded. In 2/30 patients who underwent coronary angiography, an anomalous origin of the CX artery from the right coronary sinus was found. Thirty patients underwent cardiac magnetic resonance; in 60% it was normal, while in 40% it revealed late enhancement, which in 33% was localized in the basal septum, suggesting fibrosis of the left bundle branch. During follow-up (12+/10 years, median 10 years) no sudden death occurred. At the end of follow-up, all patients were alive, except for one who suffered accidental death. Two patients (3.5%) underwent PM implantation owing to syncope. The echocardiogram at the end of follow-up revealed LV dysfunction in only one patient. CONCLUSIONS: In young adults without apparent heart disease, LBBB is a heterogeneous condition. In the vast majority of cases, the prognosis is good and no ventricular dysfunction occurs over time. However, as only 18% of our patients were aged >60 years at the end of follow-up, we cannot establish the prognosis in older age-groups.

Management of Pacemaker Implantation during COVID-19 Infection.

The management of device implantation during the COVID-19 infection has not well defined yet. This is the first case of complete atrioventricular block in a symptomatic patient affected by the COVID-19 infection treated with early pacemaker implantation to minimize the risk of virus contagion.

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.

Cardiac arrest and Brugada syndrome: Is drug-induced type 1 ECG pattern always a marker of low risk?

BACKGROUND: Patients diagnosed as affected by Brugada syndrome (BrS) on the basis of a drug-induced type 1 ECG pattern (type1) are regarded as at low risk for cardiac arrest. We tested whether this assumption matches reality. METHODS: The study population included 26 patients from our group and 217 patients from three studies published between 2002 and 2013, all of them with aborted cardiac arrest (ACA) and in whom a previously unrecognized type1 (spontaneous or drug-induced) was discovered after the event, thus leading to the diagnosis of BrS. RESULTS: Among our 26 patients, a drug-induced type1 was detected in 11 (42%) and only 1/11 showed a spontaneous pattern during follow-up; of 6 patients with syncope before ACA, 4 (67%) had only a drug-induced pattern. ICD shocks rates were similar in both spontaneous and drug-induced groups (57% and 45%). Early on, year 2002, the percentage of drug-induced type1 after ACA was much lower (14%) and has progressively increased to approximately 50%. CONCLUSIONS: If drug-induced type1 carries low arrhythmic risk, it should seldom be the only marker for BrS after an ACA. In studies on patients after an unexpected ACA, a drug-induced type1 leads to the diagnosis of BrS more often than anticipated. This contrasts with prospective studies focusing on patients already diagnosed as BrS and which consider drug-induced type1 as a marker of low risk. Contrary to current views, it is possible that not all patients with a drug-induced BrS type1 are at low risk of future events.

Clinical outcome of patients with the Brugada type 1 electrocardiogram without prophylactic implantable cardioverter defibrillator in primary prevention: a cumulative analysis of seven large prospective studies.

Aims: Patients with the Brugada type 1 ECG (Br type 1) without previous aborted sudden death (aSD) who do not have a prophylactic ICD constitute a very large population whose outcome is little known. The objective of this study was to evaluate the risk of SD or aborted SD (aSD) in these patients. Methods and results: We conducted a meta-analysis and cumulative analysis of seven large prospective studies involving 1568 patients who had not received a prophylactic ICD in primary prevention. Patients proved to be heterogeneous. Many were theoretically at low risk, in that they had a drug-induced Br type 1 (48%) and/or were asymptomatic (87%), Others, in contrast, had one or more risk factors. During a mean/median follow-up ranging from 30 to 48 months, 23 patients suffered SD and 1 had aSD. The annual incidence of SD/aSD was 0.5% in the total population, 0.9% in patients with spontaneous Br type 1 and 0.08% in those with drug-induced Br type 1 (P = 0.0001). The paper by Brugada et al. reported an incidence of SD more than six times higher than the other studies, probably as a result of selection bias. On excluding this paper, the annual incidence of SD/aSD in the remaining 1198 patients fell to 0.22% in the total population and to 0.38 and 0.06% in spontaneous and drug-induced Br type 1, respectively. Of the 24 patients with SD/aSD, 96% were males, the mean age was 39 ± 15 years, 92% had spontaneous Br type 1, 61% had familial SD (f-SD), and only 18.2% had a previous syncope; 43% had a positive electrophysiological study. Multiple meta-analysis of individual trials showed that spontaneous Br type 1, f-SD, and previous syncope increased the risk of SD/aSD (RR 2.83, 2.49, and 3.03, respectively). However, each of these three risk factors had a very low positive predictive value (PPV) (1.9-3.3%), while negative predictive values (NPV) were high (98.5-99.7%). The incidence of SD/aSD was only slightly higher in patients with syncope than in asymptomatic patients (2% vs. 1.5%, P = 0.6124). Patients with SD/aSD when compared with the others had a mean of 1.74 vs. 0.95 risk factors (P = 0.026). Conclusion: (i) In patients with Br type 1 ECG without an ICD in primary prevention, the risk of SD/aSD is low, particularly in those with drug-induced Br type 1; (ii) spontaneous Br type 1, f-SD, and syncope increase the risk. However, each of these risk factors individually has limited clinical usefulness, owing to their very low PPV; (iii) patients at highest risk are those with more than one risk factor.

Optimization of coronary sinus lead placement targeted to the longest right-to-left delay in patients undergoing cardiac resynchronization therapy: The Optimal Pacing SITE 2 (OPSITE 2) acute study and protocol.

AIMS: Left ventricular (LV) lead positioning at the site of delayed electrical activation is associated with better response to cardiac resynchronization therapy (CRT). We hypothesized that a long electrical conduction delay between right ventricular (RV) and coronary sinus (CS) leads during RV pacing (RLD index) is correlated with a better clinical outcome METHODS AND RESULTS: RLD is measured intraprocedurally, during RV pacing, as the time interval between the intracardiac electrograms of RV and CS leads. Initially, we did a prove-of-concept, feasibility, acute study in 97 patients who underwent CRT implantation. The CS lead position was assessed in the 40° right anterior oblique and 40° left anterior oblique views and assigned to one of 11 prespecified segments of a schematic eyeball depiction of the LV walls. Acute outcomes were QRS width during biventricular (BIV) pacing. The longest RLD were found in the basal and mid lateral segments; these accounted for 82% and 78%, respectively, of the total QRS width (%RLD). %RLD was inversely correlated with BIV-paced QRS (P  =  0.0001). A similar slope was present either in the 78 patients with preserved atrioventricular (AV) conduction and in the 19 without AV conduction (- 0.34 vs - 0.27, P  =  0.7). CONCLUSION: We showed that RLD can be used to guide lead placement at the time of CRT implantation and that it is correlated with BIV-QRS width, an indirect predictor of clinical outcome. Based on these findings we started the prospective, multicenter Optimal Pacing SITE 2 (OPSITE 2) trial with the objective to demonstrate a relationship between RLD and clinical outcomes assessed as death, hospitalization for heart failure, New York Heart Association class, and clinical composite score. The protocol is provided.

Brugada type 1 electrocardiogram: Should we treat the electrocardiogram or the patient?

Patients with a Brugada type 1 electrocardiogram (ECG) pattern may suffer sudden cardiac death (SCD). Recognized risk factors are spontaneous type 1 ECG and syncope of presumed arrhythmic origin. Familial sudden cardiac death (f-SCD) is not a recognized independent risk factor. Finally, positive electrophysiologic study (+EPS) has a controversial prognostic value. Current ESC guidelines recommend implantable cardioverter defibrillator (ICD) implantation in patients with a Brugada type 1 ECG pattern if they have suffered a previous resuscitated cardiac arrest (class I recommendation) or if they have syncope of presumed cardiac origin (class IIa recommendation). In clinical practice, however, many other patients undergo ICD implantation despite the suggestions of the guidelines. In a 2014 cumulative analysis of the largest available studies (including over 2000 patients), we found that 1/3 of patients received an ICD in primary prevention. Interestingly, 55% of these latter were asymptomatic, while 80% had a + EPS. This means that over 30% of subjects with a Brugada type 1 ECG pattern were considered at high risk of SCD mainly on the basis of EPS, to which a class IIb indication for ICD is assigned by the current ESC guidelines. Follow-up data confirm that in clinical practice single, and often frail, risk factors overestimate the real risk in subjects with the Brugada type 1 ECG pattern. We can argue that, in clinical practice, many cardiology centers adopt an aggressive treatment in subjects with a Brugada type 1 ECG pattern who are not at high risk. As a result, many healthy persons may be treated in order to save a few patients with a true Brugada Syndrome. Better risk stratification is needed. A multi-parametric approach that considers the contemporary presence of multiple risk factors is a promising one.

Event rates and risk factors in patients with Brugada syndrome and no prior cardiac arrest: a cumulative analysis of the largest available studies distinguishing ICD-recorded fast ventricular arrhythmias and sudden death.

BACKGROUND: All available studies that have addressed the issue of risk stratification in patients with type 1 Brugada electrocardiographic (ECG) pattern have considered a combined end point constituted by implantable cardioverter-defibrillator-recorded fast ventricular arrhythmias (ICD-FVA) and sudden death (SD) in patients without ICD. OBJECTIVE: As ICD-FVA are only a surrogate of SD, we tried to focus on the prognostic value of classical risk factors by separating patients with ICD-FVA from those without ICD who suffered SD. METHODS: We made a cumulative analysis of the largest available studies. Studies were selected in which the incidence of FVA and SD could be determined in patients with and without ICD separately. In addition, we tried to analyze the prognostic value of risk factors in patients with and without ICD separately. RESULTS: A total of 2176 patients were recruited from 5 studies, about one-third of whom had an ICD and two-thirds did not. Event rates per 1000 patient-years of follow-up were 31.3 (25­39) and 6.5 (4-10) in patients with and without ICD, respectively (P < .001). When considering FVA in patients with ICD, each single risk factor (spontaneous type 1 ECG pattern, familial juvenile SD, and +EPS) displayed limited clinical value, mainly owing to its low specificity (21%-61%) and low positive predictive value (9%-15%). CONCLUSIONS: In patients with type 1 Brugada ECG pattern, most arrhythmic events occur in patients with an ICD while SD is rare in patients without an ICD. While we have an acceptable ability to predict ICD-FVA, we have insufficient data to predict SD.

Long-term effect of continuing sports activity in competitive athletes with frequent ventricular premature complexes and apparently normal heart.

The long-term outcome of athletes with frequent ventricular premature complexes (VPCs) and apparently normal heart has not been fully clarified. To evaluate the clinical and prognostic significance of VPCs and the influence of continuing sports activity during follow-up, we studied 120 healthy athletes (96 men; median age 16 years) in whom frequent VPCs (>100 VPCs/24 hours) were discovered by chance during preparticipation screening. All athletes were followed up for a median of 84 months. During follow-up, 96 underwent serial 24-hour Holter recording and 62 underwent serial echocardiography. The median number of VPCs/24 hours on basal Holter was 3,760. During follow-up, 81 athletes continued sports activity, whereas 39 did not. No athlete died or developed overt heart disease. The median number of VPCs/24 hours decreased in both athletes who continued sports activity and those who did not (from 3,805 to 1,124, p <0.0001 and from 5,787 to 1,298, p <0.0001, respectively). During follow-up, left ventricular ejection fraction slightly decreased to <55% in 9 of 62 athletes who, in respect to the remaining 53, had more VPCs/24 hours both in the basal state (12,000 vs 3,880) and during follow-up (10,702 vs 1,368), and a longer follow-up (95 vs 36 months). In conclusion, (1) frequent VPCs in athletes without heart disease have a long-term benign prognostic significance, (2) sporting activity does not modify this benign outcome, (3) during follow-up, the burden of VPCs decreases whether or not subjects continue sports activity, and (4) in 14.5% of athletes, ejection fraction slightly decreases over time.

[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.

Does long-lasting sports practice increase the risk of atrial fibrillation in healthy middle-aged men? Weak suggestions, no objective evidence.

BACKGROUND: Some authors have suggested that sports activity can increase the risk of atrial fibrillation in healthy middle-aged men. Therefore, sport activity, although it prevents coronary artery disease, might be the cause of a potentially dangerous arrhythmia. METHODS: To verify this assumption, we critically analyzed the current literature including original articles, reviews and meta-analyses. RESULTS AND CONCLUSIONS: All published articles showed several limitations. The data provided by published studies support the following conclusions: the incidence of atrial fibrillation in sporting middle-aged men is rare (<0.5% per year); a possible facilitating effect on atrial fibrillation is limited to vigorous endurance exercise, not to less vigorous sports; there are no convincing data to demonstrate that sport itself may be the cause of atrial fibrillation in healthy middle-aged men; and a facilitating effect of long-lasting sport cannot be excluded in middle-aged individuals with cardiovascular disorders. Nevertheless, the beneficial effects of exercise should offset this supposed risk, which, albeit increased, remains low.

[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.

Influence of training on the number and complexity of frequent VPBs in healthy athletes.

OBJECTIVE: Frequent ventricular premature beats (VPBs) may be discovered during preparticipation screening in asymptomatic apparently healthy athletes. Some authors hypothesize that they may be a manifestation of 'athlete's heart' and suggest a deconditioning period, which should document a regression of arrhythmias, to exclude a concealed disease. METHODS: To test this hypothesis, we analysed 87 asymptomatic healthy athletes with frequent VPB (>100/24 h). Of these, 44 (group D) underwent at least 3 months' detraining, whereas 43 (group C) continued sporting activity. Athletes underwent 24-h Holter monitoring at the baseline after 5.2 ± 4 (group D) and 7.2 ± 5 (group C) months. RESULTS: Basal characteristics were similar in both groups. Comparison of the basal and follow-up Holter results revealed no significant difference in the mean number of VPB/24 h in either group. In group D, the number of VPB/24 h declined from 8126 ± 8129 to 7998 ± 10 976 (P = 0.48), whereas in group C it rose from 6027 ± 6374 to 6600 ± 8590 (P = 0.51). VPB either disappeared or were markedly reduced (<100 VPB/24 h) in 2/44 (4.5%) group D and 4/43 (9%) group C athletes.In neither group did the number of couplets or nonsustained ventricular tachycardia change significantly. CONCLUSION: In healthy athletes, frequent VPBs discovered by chance during preparticipation screening may not be a manifestation of 'athlete's heart', but may depend on other causes; in the latter case screening may simply reveal a pre-existing asymptomatic phenomenon; the usefulness of detraining in ascertaining eligibility for sport should be further investigated.

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.