Clinical presentation and outcome of Brugada syndrome diagnosed with the new 2013 criteria

The 2013 HRS/EHRA/APHRS consensus statement recommends the use of V1 and V2 leads recorded in the second and third intercostal spaces (High-ICS) for diagnosis of Brugada syndrome (BrS) creating a new category of patients discovered only with modified leads. The clinical presentation and the arrhythmic risk in these patients are ill defined. This study was aimed at assessing the role of High-ICS in the analysis of BrS and the clinical profile of the patients diagnosed only when ECG leads are moved to upper intercostal spaces

Hydroquinidine Prevents Life-Threatening Arrhythmic Events in Patients With Short QT Syndrome.

Short QT syndrome (SQTS) is a rare and life-threatening arrhythmogenic syndrome characterized by abbreviated repolarization. Hydroquinidine (HQ) prolongs the QT interval in SQTS patients, although whether it reduces cardiac events is currently unknown. This study investigated whether long-term treatment with HQ reduces the occurrence of life-threatening arrhythmic events (LAE) (cardiac arrest or sudden cardiac death) in SQTS patients. In this cohort study on consecutive SQTS patients, 2 analyses were performed: 1) a matched-period analysis for the occurrence of LAE in 17 SQTS patients who received long-term HQ; and 2) a comparison of the annual incidence of LAE off- and on-HQ in 16 SQTS patients who survived a cardiac arrest. A total of 17 patients (82% male, age 29 ± 3 years, QTc before treatment 331 ± 3 ms) received HQ therapy (584 ± 53 mg/day). Therapy was stopped in 2 cases (12%) due to gastrointestinal intolerance, and 15 patients continued treatment for 6 ± 1 year. QTc prolongation was observed in all patients (by 60 ± 6 ms; p < 0.001). We compared the occurrence of LAE during 6 ± 1 years before and after HQ, observing that patients on HQ experienced a reduction in both the rate of LAE from 40% to 0% (p = 0.03) and the number of LAE per patient from 0.73 ± 0.3 to 0 (p = 0.026). Furthermore, the annual rate of LAE in the 16 patients with a previous cardiac arrest dropped from 12% before HQ to 0 on therapy (p = 0.028). We demonstrated for the first time that treatment with HQ was associated with a lower incidence of LAE in SQTS patients. These data point to the importance that quinidine, that in several countries has been removed from the market, remains available worldwide for patients with SQTS. In the present study, therapy with HQ has been proven to be safe, with a relatively low rate of side effects.This work was supported by the Ricerca Corrente Funding scheme of the Italian Ministry of Health. Dr. Bellazzi is a shareholder of Biomeris; and is a stakeholder of Engenome. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Pedro Brugada, MD, served as Guest Editor for this paper.S

Efficacy of automatic mode switching in DDDR mode pacemakers: The most 2 study

Background: Effective automatic mode switching (AMS) algorithms capable of detecting a range of supraventricular tachyarrhythmias is important given evidence of atrial fibrillation (AF), atrial flutter (AFL), and atrial tachycardia (AT) post-implantation of pacemakers. Objectives: The aim of the study was to assess the efficacy, defined as ability to detect a specific atrial rate and activate AMS, of five different AMS mechanisms during simulation of AF, AFL, and AT. Materials and methods: A total of 48 subjects (35 men, 13 women; mean age: 69±8 years) implanted with DDDR pacemakers utilizing five different AMS mechanisms (mean atrial rate, rate cut-off, complex 'fallback' algorithm, retriggerable atrial refractory period, and physiological band 'beat-to-beat') were tested using an external electronic device that simulated the occurrence of supraventricular tachyarrhythmias. AF, AFL, and AT were simulated by delivering low voltage pulse trains at 350, 250 and 160 beats/min, respectively. Results: Mean efficacy for all AMS mechanisms was 81% [range: 57% to 100%] at 350 beats/min, 81% [range: 57-100%] at 250 beats/min, and 79% [range: 57-100%] at 160 beats/min. The AMS mechanisms that yielded 100% efficacy were the rate cut-off and physiological band 'beat-to-beat.' Conclusion: Not all AMS algorithms are equally efficacious at detecting atrial arrhythmias and subsequently activating AMS. Our results suggest that the most efficacious AMS algorithms are those that use rate cut-off and physiological band 'beat-to-beat' to detect supraventricular tachyarrhythmias. © 2007 Springer Science+Business Media, LLC

Gene-specific therapy with mexiletine reduces arrhythmic events in patients with long QT syndrome type 3

BACKGROUND: Long QT syndrome type 3 (LQT3) is a lethal disease caused by gain-of-function mutations in the SCN5A gene, coding for the alpha-subunit of the sodium channel NaV1.5. Mexiletine is used to block late sodium current and to shorten QT interval in LQT3 patients. OBJECTIVES: The aim of this study was to determine whether mexiletine prevents arrhythmic events (arrhythmic syncope, aborted cardiac arrest, or sudden cardiac death) in LQT3 patients. METHODS: The endpoint of this retrospective cohort study, which studied consecutive LQT3 patients who were referred to our center and treated with mexiletine, was to evaluate the antiarrhythmic efficacy of mexiletine by comparing the number of arrhythmic events per patient and the annual rate of arrhythmic events during observation periods of equal duration before and after the beginning of therapy with mexiletine. RESULTS: The study population comprised 34 LQT3 patients, 19 (56%) of whom were male. The median age at beginning of treatment with mexiletine was 22 years, and median QTc interval before therapy 509 ms. The median duration of oral mexiletine therapy was 36 months, at an average daily dose of 8 ± 0.5 mg/kg. Mexiletine significantly shortened QTc (by 63 ± 6 ms; p < 0.0001) and reduced the percentage of patients with arrhythmic events (from 22% to 3%; p = 0.031), the mean number of arrhythmic events per patient (from 0.43 ± 0.17 to 0.03 ± 0.03; p = 0.027), and the annual rate of arrhythmic events (from 10.3% to 0.7%; p = 0.0097). CONCLUSIONS: Besides shortening QTc interval, mexiletine caused a major reduction of life-threatening arrhythmic events in LQT3 patients, thus representing an efficacious therapeutic strategy

Implantable hearing devices in clinical practice. Systematic review and consensus statements

Objective: Implantable hearing devices represent a modern and innovative solution for hearing restoration. Over the years, these high-tech devices have increasingly evolved but their use in clinical practice is not universally agreed in the scientific literature. Congresses, meetings, conferences, and consensus statements to achieve international agreement have been made. This work follows this line and aims to answer unsolved questions regarding examinations, selection criteria and surgery for implantable hearing devices. Materials and methods: A Consensus Working Group was established by the Italian Society of Otorhinolaryngology. A method group performed a systematic review for each single question to identify the current best evidence on the topic and to guide a multidisciplinary panel in developing the statements. Results: Twenty-nine consensus statements were approved by the Italian Society of Otorhinolaryngology. These were associated with 4 key area subtopics regarding pre-operative tests, otological, audiological and surgical indications. Conclusions: This consensus can be considered a further step forward to establish realistic guidelines on the debated topic of implantable hearing devices

Outcomes of Patients with Catecholaminergic Polymorphic Ventricular Tachycardia Treated with β-Blockers

Importance: Patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) may experience life-threatening arrhythmic events (LTAEs) despite β-blocker treatment. Further complicating management, the role of implantable cardioverter defibrillator (ICD) in CPVT is debated. Objective: To investigate the long-term outcomes of patients with RYR2 CPVT treated with β-blockers only and the cost to benefit ratio of ICD. Design, Settings, and Participants: This prospective cohort study conducted from January 1988 to October 2020 with a mean (SD) follow-up of 9.4 (7.5) years included patients who were referred to the Molecular Cardiology Clinics of ICS Maugeri Hospital, Pavia, Italy. Participants included consecutive patients with CPVT who were carriers of a pathogenic or likely pathogenic RYR2 variant with long-term clinical follow-up. Exposures: Treatment with selective and nonselective β-blocker only and ICD implant when indicated. Main Outcome and Measures: The main outcome was the occurrence of the first LTAE while taking a β-blocker. LTAE was defined as a composite of 3 hard end points: sudden cardiac death, aborted cardiac arrest, and hemodynamically nontolerated ventricular tachycardia. Results: The cohort included 216 patients with RYR2 CPVT (121 of 216 female [55%], median [IQR] age 14, [9-30] years). During a mean (SD) follow-up of 9.4 (7.5) years taking β-blockers only, 28 of 216 patients (13%) experienced an LTAE (annual rate, 1.9%; 95% CI, 1.3-2.7). In multivariable analysis, experiencing either an LTAE (hazard ratio [HR], 3.3; 95% CI, 1.2-8.9; P =.02) or syncope before diagnosis (HR, 4.5; 95% CI, 1.8-11.1; P =.001) and carrying a C-terminal domain variant (HR, 18.1; 95% CI, 4.1-80.8; P <.001) were associated with an increased LTAE risk during β-blocker therapy only. The risk of LTAE among those taking selective β-blockers vs nadolol was increased 6-fold (HR, 5.8; 95% CI, 2.1-16.3; P =.001). Conversely, no significant difference was present between propranolol and nadolol (HR, 1.8; 95% CI, 0.4-7.3; P =.44). An ICD was implanted in 79 of 216 patients (37%) who were followed up for a mean (SD) of 8.6 (6.3) years. At the occurrence of LTAE, ICD carriers were more likely to survive (18 of 18 [100%]) than non-ICD carriers (6 of 10 [60%]; P =.01). Conclusions and Relevance: In this cohort study, selective β-blockers were associated with a higher risk of LTAE as compared with nadolol. Independently from treatment, LTAE and syncope before diagnosis and C-terminal domain variants identified patients at higher risk of β-blocker failure, and the ICD was associated with reduced mortality in high-risk patients with CPVT

Outcomes of Patients With Catecholaminergic Polymorphic Ventricular Tachycardia Treated With β-Blockers

Importance: Patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) may experience life-threatening arrhythmic events (LTAEs) despite β-blocker treatment. Further complicating management, the role of implantable cardioverter defibrillator (ICD) in CPVT is debated. Objective: To investigate the long-term outcomes of patients with RYR2 CPVT treated with β-blockers only and the cost to benefit ratio of ICD. Design, settings, and participants: This prospective cohort study conducted from January 1988 to October 2020 with a mean (SD) follow-up of 9.4 (7.5) years included patients who were referred to the Molecular Cardiology Clinics of ICS Maugeri Hospital, Pavia, Italy. Participants included consecutive patients with CPVT who were carriers of a pathogenic or likely pathogenic RYR2 variant with long-term clinical follow-up. Exposures: Treatment with selective and nonselective β-blocker only and ICD implant when indicated. Main outcome and measures: The main outcome was the occurrence of the first LTAE while taking a β-blocker. LTAE was defined as a composite of 3 hard end points: sudden cardiac death, aborted cardiac arrest, and hemodynamically nontolerated ventricular tachycardia. Results: The cohort included 216 patients with RYR2 CPVT (121 of 216 female [55%], median [IQR] age 14, [9-30] years). During a mean (SD) follow-up of 9.4 (7.5) years taking β-blockers only, 28 of 216 patients (13%) experienced an LTAE (annual rate, 1.9%; 95% CI, 1.3-2.7). In multivariable analysis, experiencing either an LTAE (hazard ratio [HR], 3.3; 95% CI, 1.2-8.9; P = .02) or syncope before diagnosis (HR, 4.5; 95% CI, 1.8-11.1; P = .001) and carrying a C-terminal domain variant (HR, 18.1; 95% CI, 4.1-80.8; P < .001) were associated with an increased LTAE risk during β-blocker therapy only. The risk of LTAE among those taking selective β-blockers vs nadolol was increased 6-fold (HR, 5.8; 95% CI, 2.1-16.3; P = .001). Conversely, no significant difference was present between propranolol and nadolol (HR, 1.8; 95% CI, 0.4-7.3; P = .44). An ICD was implanted in 79 of 216 patients (37%) who were followed up for a mean (SD) of 8.6 (6.3) years. At the occurrence of LTAE, ICD carriers were more likely to survive (18 of 18 [100%]) than non-ICD carriers (6 of 10 [60%]; P = .01). Conclusions and relevance: In this cohort study, selective β-blockers were associated with a higher risk of LTAE as compared with nadolol. Independently from treatment, LTAE and syncope before diagnosis and C-terminal domain variants identified patients at higher risk of β-blocker failure, and the ICD was associated with reduced mortality in high-risk patients with CPVT

Transcatheter Mitral Valve Repair With the MitraClip Device for Prior Mitral Valve Repair Failure: Insights From the GIOTTO-FAILS Study

BACKGROUND: Minimally invasive mitral valve repair has a favorable risk-benefit profile in patients with significant de novo mitral regurgitation. Its role in patients with prior mitral valve repair is uncertain. We aimed to appraise the outcome of patients undergoing transcatheter edge-to-edge repair (TEER) with prior transcatheter or surgical mitral valve repair (SMVR).METHODS AND RESULTS: We queried the Italian multicenter registry on TEER with MitraClip, distinguishing naive patients from those with prior TEER or (SMVR). Inhospital and long-term clinical/echocardiographic outcomes were appraised. The primary outcome was the occurrence of death or rehospitalization for heart failure. A total of 2238 patients were included, with 2169 (96.9%) who were naive to any mitral intervention, 29 (1.3%) with prior TEER, and 40 (1.8%) with prior SMVR. Several significant differences were found in baseline clinical and imaging features. Respectively, device success was obtained in 2120 (97.7%), 28 (96.6%), and 38 (95.0%, P=0.261) patients; procedural success in 2080 (95.9%), 25 (86.2%), and 38 (95.0%; P=0.047); and inhospital death in 61 (2.8%), 1 (3.5%), and no (P=0.558) patients. Clinical follow-up after a mean of 14 months showed similar rates of death, cardiac death, rehospitalization, rehospitalization for heart failure, and their composite (all P&gt;0.05). Propensity score-adjusted analysis confirmed unadjusted analysis, with lower procedural success for the prior TEER group (odds ratio, 0.28 [95% CI, 0.09-0.81]; P=0.019) but similar odds ratios and hazard ratios for all other outcomes in the naive, TEER, and SMVR groups (all P&gt;0.05).CONCLUSIONS: In carefully selected patients, TEER can be performed using the MitraClip device even after prior TEER or SMVR