Long-term outcomes from upgrade to cardiac resynchronisation therapy in ischaemic versus non-ischaemic heart disease.

BACKGROUND: Cardiac resynchronisation therapy (CRT) can be necessary in patients with chronic heart failure, who have already been provided with transvenous cardiac implantable electrical devices. Upgrade procedures revealed controversial results, while long-term outcomes regarding underlying Ischaemic- (ICM) or Non-Ischaemic heart disease (NICM) have yet to be described. METHODS: The Mannheim Cardiac Resynchronisation Therapy Registry (MARACANA) was designed as a retrospective observational single-centre registry, including all CRT implantations from 2013-2021 (n = 459). CRT upgrades (n = 136) were retrospectively grouped to either ICM (n = 84) or NICM (n = 52) and compared for New York Heart Association classification (NYHA), paced QRS-width, left ventricular ejection fraction (LVEF), tricuspid annular plane systolic excursion (TAPSE) and other heart failure modification aspects in the long-term (59.3 ± 5 months). RESULTS: Baseline-characteristics including paced QRS-width, upgrade indications or NYHA-classification were comparable for both groups (group comparison p>.05). The CRT upgrade improved NYHA (ICM: 2.98 ± 0.4 to 2.29 ± 0.7, NICM: 2.94 ± 0.5 to 2.08 ± 0.5) and the LVEF (ICM: 27.2 ± 6.6 to 38.25 ± 8.8, NICM: 30.2 ± 9.4 to 38.7 ± 13.8%) after five years, irrespective of underlying heart disease (each group p < .05, group comparison p>.05). Only ICM revealed significant improvements in TAPSE (15.9 ± 4.1 to 18.9 ± 4.1 mm) and narrowing of the paced QRS-width (185.4 ± 29 to 147.2 ± 16.3 ms) after five years (each p < .05). CONCLUSIONS: Upgrade to CRT might improve heart failure symptoms and left-ventricular systolic function in the long-term, irrespective of underlying ischaemic or non-ischaemic heart disease.

[What is confirmed in the treatment of atrial fibrillation?] / Was ist gesichert in der Therapie von Vorhofflimmern?

Atrial fibrillation is the most common clinically relevant cardiac arrhythmia. Important goals in the treatment of atrial fibrillation are improvement of the quality of life, relief of symptoms and the prevention of stroke. New in the current European guidelines on atrial fibrillation from 2020 is a structured approach with the introduction of the 4S-AF scheme (4S estimation of the risk of stroke, severity of symptoms, degree of severity of atrial fibrillation load and substrate, AF atrial fibrillation) for better characterization of atrial fibrillation and the ABC pathway in the treatment. The decision on the use of anticoagulation should be made after appropriate risk stratification. Depending on the characterization and symptoms of atrial fibrillation, the planning of further treatment should be made with respect to symptom control. Based on recent studies, rhythm-maintaining treatment by means of drugs or catheter ablation is gaining in importance over a strategy purely aimed at controlling the frequency. Integral components of treatment are also the identification and treatment of comorbidities and cardiovascular risk factors as well as the modification of an unhealthy lifestyle.

Septal myocardial scar burden predicts the response to cardiac contractility modulation in patients with heart failure.

We hypothesized that myocardial septal scarring, assessed by cardiac magnetic resonance (CMR) using late gadolinium enhancement (LGE), at the site of cardiac contractility modulation (CCM) lead placement may predict treatment response. Eligible heart failure (HF) patients underwent LGE CMR imaging before CCM device implantation. The response to CCM therapy at follow-up was determined by a change in NYHA class and echocardiographic left ventricular ejection fraction (LVEF) assessment. Patients were classified as responders, if they showed an improvement in either NYHA class or improvement of LVEF by ≥ 5%. 58 patients were included. 67% of patients were classified as responders according to improved NYHA; 55% according to LVEF improvement. 74% of patients were responders if either NYHA class or LVEF improvement was observed. 90% of responders (according to NYHA class) showed septal LGE < 25% at septal position of the leads, while 44% of non-responders showed septal LGE > 25% (p < 0.01). In patients treated with CCM, an improvement of NYHA class was observed when leads were placed at myocardial segments with a CMR- LGE burden less than 25%.

Should HFrEF patients with NYHA class II expect benefit from CCM therapy? Results from the MAINTAINED observational study.

BACKGROUND: Cardiac contractility modulation (CCM) is an FDA-approved device therapy for patients with refractory systolic heart failure and normal QRS width. Randomized trials demonstrated benefits of CCM primarily for patients with severe heart failure (> NYHA class II). PURPOSE: To better understand individualized indication in clinical practice, we compared the effect of CCM in patients with baseline NYHA class II vs. NYHA class III or ambulatory IV over the 5-year period in our large clinical registry (MAINTAINED Observational Study). METHODS: Changes in NYHA class, left ventricular ejection fraction (LVEF), tricuspid annular plane systolic excursion (TAPSE), NT-proBNP level, and KDIGO chronic kidney disease stage were compared as functional parameters. In addition, mortality within 3 years was compared with the prediction of the Meta-Analysis Global Group in Chronic heart failure risk score. RESULTS: A total of 172 patients were included in the analyses (10% with NYHA class II). Only patients with NYHA class III/IV showed a significant improvement in NYHA class over 5 years of CCM (II: 0.1 ± 0.6; p = 0.96 vs. III/IV: - 0.6 ± 0.6; p < 0.0001). In both groups, LVEF improved significantly (II: 4.7 ± 8.3; p = 0.0072 vs. III/IV: 7.0 ± 10.7%; p < 0.0001), while TAPSE improved significantly only in NYHA class III/IV patients (II: 2.2 ± 1.6; p = 0.20 vs. III/IV: 1.8 ± 5.2 mm; p = 0.0397). LVEF improvement was comparable in both groups over 5 years of CCM (p = 0.83). NYHA class II patients had significantly lower NT-proBNP levels at baseline (858 [175/6887] vs. 2632 [17/28830] ng/L; p = 0.0044), which was offset under therapy (399 [323/1497] vs. 901 [13/18155] ng/L; p = 0.61). Actual 3-year mortality was 17 and 26% vs. a predicted mortality of 31 and 42%, respectively (p = 0.0038 for NYHA class III/IV patients). CONCLUSIONS: NYHA class III/IV patients experienced more direct and extensive functional improvements with CCM and a survival benefit compared with the predicted risk. However, our data suggest that NYHA class II patients may also benefit from the sustained positive effects of LVEF improvement.

Impact of baseline left ventricular ejection fraction on long-term outcomes in cardiac contractility modulation therapy.

BACKGROUND: Cardiac contractility modulation (CCM), being reserved for patients with symptomatic chronic heart failure (HF) and narrow QRS complex under guideline directed medical therapy, can recover initially reduced left ventricular ejection fraction (LVEF); however, the influence of pre-implantation LVEF on long-term outcomes is not fully understood. This study aimed to compare the effects of lower and higher preimplantation LVEF on long-term outcomes in CCM-therapy. METHODS: One-hundred seventy-two patients from our single-centre registry were retrospectively included (2002-2019). Follow-up data were collected up to 5 years after implantation. Patients were divided into Group 1 (baseline LVEF≤ 30%) and Group 2 (≥ 31%). Both groups were compared based on differences in survival, echocardiographic- and clinical parameters including LVEF, tricuspid annular plane systolic excursion (TAPSE), NYHA class or Minnesota living with heart failure questionnaire-score (MLWHFQ). RESULTS: 11% of the patients did have a LVEF ≥31%. Mean LVEF ± SD for both groups were 21.98 ± 5.4 versus 35.2 ± 3.7%, respectively. MLWHFQ (47 ± 21.2 vs. 42±21.4) and mean peak oxygen consumption (VO2, 13.6 ± 4.1 vs. 12.7 ± 2.8 ml/kg/min) were comparable between both groups. LVEF-grouping did not influence survival. Lower baseline LVEF resulted in significantly better recovery of echocardiographic parameters such as LVEF and TAPSE. Irrespective from baseline LVEF, both groups showed nearly comparable improvements for clinical parameters like NYHA-class and MLWHFQ. CONCLUSION: Long-term biventricular systolic recovery potential in CCM-therapy might be better for preimplantation LVEF values ≤30%, whereas clinical parameters such as NYHA-class can improve irrespective from baseline LVEF.

Cardiac Contractility Modulation in Patients with Ischemic versus Non-ischemic Cardiomyopathy: Results from the MAINTAINED Observational Study.

BACKGROUND: Cardiac contractility modulation (CCM) is an FDA-approved device-based therapy for patients with systolic heart failure and normal QRS width who are symptomatic despite optimal drug therapy. The purpose of this study was to compare the long-term therapeutic effects of CCM therapy in patients with ischemic (ICM) versus non-ischemic cardiomyopathy (NICM). METHODS: Changes in NYHA class, KDIGO CKD stage, left ventricular ejection fraction (LVEF), tricuspid annular plane systolic excursion (TAPSE), and NT-proBNP levels were compared as functional parameters. Moreover, observed mortality rates at 1 and 3 years were compared to those predicted by the MAGGIC heart failure risk score, and observed mortality rates were compared between groups for the entire follow-up period. RESULTS: One hundred and seventy-four consecutive patients with chronic heart failure and CCM device implantation between 2002 and 2019 were included in this retrospective analysis. LVEF was significantly higher in NICM patients after 3 years of CCM therapy (35 ± 9 vs. 30 ± 9%; p = 0.0211), and after 5 years, also TAPSE of NICM patients was significantly higher (21 ± 5 vs. 18 ± 5%; p = 0.0437). There were no differences in other effectiveness parameters. Over the entire follow-up period, 35% of all patients died (p = 0.81); only in ICM patients, mortality was lower than predicted at 3 years (35 vs. 43%, p = 0.0395). CONCLUSIONS: Regarding improvement of biventricular systolic function, patients with NICM appear to benefit particularly from CCM therapy.

Determinants of arterial stiffness in patients with atrial fibrillation.

BACKGROUND: Arterial stiffness has emerged as a strong predictor of cardiovascular disease, end-organ damage and all-cause mortality. Although increased arterial stiffness has been described as a predictor of atrial fibrillation, the relationship between arterial stiffness and atrial fibrillation is uncertain. AIM: We assessed arterial stiffness in patients with atrial fibrillation compared with that in a control group. METHODS: We enrolled 151 patients with atrial fibrillation who underwent pulmonary vein isolation (mean age 71.1±9.8 years) and 54 control patients with similar cardiovascular risk profiles and sinus rhythm, matched for age (mean age 68.6±15.7 years) and sex. Aortic distensibility as a measure of arterial stiffness was assessed by transoesophageal echocardiography. Patients with atrial fibrillation were followed over a median of 21 (15 to 31) months. RESULTS: Compared with control patients, patients with atrial fibrillation had significantly lower aortic distensibility (1.8±1.1 vs. 2.1±1.1 10-3mmHg-1; P=0.02). Age (hazard ratio 0.67, 95% confidence interval 0.003 to 0.03; P=0.02) and pulse pressure (hazard ratio -1.35, 95% confidence interval -0.07 to -0.03; P<0.0001) were the strongest predictors of decreased aortic distensibility in the study cohort. This effect was independent of the type of atrial fibrillation (paroxysmal/persistent). During follow-up, decreased aortic distensibility was a predictor of cardiovascular and all-cause hospitalizations, as well as recurrences of atrial fibrillation, with a higher incidence rate of events in patients in the lowest aortic distensibility quartile (P=0.001). CONCLUSIONS: Aortic distensibility was significantly reduced in patients with atrial fibrillation, with age and pulse pressure showing the strongest correlation, independent of the type of atrial fibrillation. Additionally, decreased aortic distensibility was associated with cardiovascular and all-cause hospitalizations, as well as recurrences of atrial fibrillation, which showed a quartile-dependent occurrence.

Extent of peri-infarct scar on late gadolinium enhancement cardiac magnetic resonance imaging and outcome in patients with ischemic cardiomyopathy.

BACKGROUND: Only a minority of patients who receive an implantable cardioverter-defibrillator (ICD) on the basis of left ventricular ejection fraction receive appropriate ICD therapy. Peri-infarct scar zone assessed by late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) is a possible substrate for ventricular tachyarrhytmias (VTAs). OBJECTIVE: The aim of our prospective study was to determine whether LGE-CMR parameters can predict the occurrence of VTA in patients with ischemic cardiomyopathy (ICM). METHODS: Two hundred sixteen patients with ICM underwent CMR imaging before primary or secondary ICD implantation and were prospectively followed. We assessed CMR indices and CMR scar characteristics (infarct core and peri-infarct zone) to predict outcome and VTAs. RESULTS: Patients were followed up for 1497 days (interquartile range 697-2237 days). Forty-seven patients (21%) received appropriate therapy during follow-up. Patients with appropriate ICD therapy had smaller core scar (31.5% ± 8.5% vs 36.8% ± 8.9%; P = .0004) but larger peri-infarct scar (12.4% ± 2.6% vs 10.5% ± 2.9%; P = .0001) than did patients without appropriate therapy. In multivariate Cox regression analysis, peri-infarct scar (hazard ratio 1.15; 95% confidence interval 1.07-1.24; P = .0001) was independently and significantly associated with VTAs whereas left ventricular ejection fraction, right ventricular ejection fraction, core scar, and left atrial ejection fraction were not. CONCLUSION: Scar extent of peri-infarct border zone was significantly associated with appropriate ICD therapy. Thus, LGE-CMR parameters can identify a subgroup of patients with ICM and an increased risk of life-threatening VTAs.

Comparison of transvenous vs subcutaneous defibrillator therapy in patients with cardiac arrhythmia syndromes and genetic cardiomyopathies.

BACKGROUND: Inherited arrhythmia syndromes and genetic cardiomyopathies attribute in a significant proportion to sudden cardiac death. Implantable cardioverter defibrillators (ICDs) are the cornerstone in the prevention of sudden death in high-risk patients. However, ICD therapy is also associated with high rates of inappropriate shocks and/or device-related complications especially in young patients. OBJECTIVE: To determine the outcome of high-risk patients with inherited arrhythmia syndromes and genetic cardiomyopathies comparing two defibrillator technologies. METHOD: Between 2010 and 2018, 183 consecutive patients from two large German tertiary care centers were enrolled in the study. The majority of patients (83%) had either cardiac channelopathies or idiopathic ventricular fibrillation without cardiac structural abnormalities, while the remaining 17% had a genetic cardiomyopathy (HCM/ARVC). Eighty-six patients (47%) received a transvenous ICD (TV-ICD), while a subcutaneous ICD (S-ICD) was implanted in another 97 patients (53%). RESULTS: During a mean follow-up of 4.3 years, 30 patients had an appropriate ICD therapy (annual rate 3.8%). Fifteen patients experienced an inappropriate shock (annual rate 1.9%). Lead failure occurred in 17 (9%) patients and was less frequent in the S-ICD group (OR 0.48, 95%CI 0.38-0.62). Adverse defibrillator events, defined as a composite of inappropriate shocks and lead failure requiring surgical revision were significantly lower in the S-ICD group as compared to the TV-ICD group (OR 0.55, 95%CI 0.41-0.72). There was a non-significant trend towards lower appropriate shocks in the S-ICD group, that in combination with all-cause shocks yielded in a significantly higher freedom of any shock in the S-ICD group (RR 39%, p = 0.003). No deaths occurred during follow-up. CONCLUSION: The present data favor the use of the subcutaneous ICD for patients with inherited arrhythmia syndromes and genetic cardiomyopathies who do not need anti-bradycardia pacing.

Perception of atrial fibrillation in dependence of neuroticism.

OBJECTIVE: Atrial fibrillation (AF) is associated with a varying symptom burden, which ranges from completely unawareness to disabling conditions. The present cross-sectional study tried to assess if neuroticism is associated with a greater degree of perception of AF related symptoms. METHODS: 162 patients who were considered for catheter ablation of AF were included. AF related symptom burden was quantified according to the European Heart Rhythm Association (EHRA) score. Personality traits were assessed using the Big Five personality traits (5BT). RESULTS: Female patients reported higher symptom burden. Higher EHRA scores were furthermore associated with treatment with antiarrhythmic agents, digitalis, direct oral anticoagulants (DOAC), and antidepressant treatment, as well as suffering from heart failure or chronic kidney disease. Neuroticism showed a positive correlation to AF related symptom burden with significantly higher neuroticism scores in patients with higher EHRA scores (Rho = 0.41; 95%CI 0.26 to 0.53; p < .001), while no association was demonstrated for the other four personality traits. Multiple linear regression analysis revealed neuroticism as strongest independent predictor for symptomatic AF, followed by treatment with antiarrhythmic agents and DOAC. CONCLUSIONS: Perception of AF related symptoms is a multifactorial process, which in our cohort was independently associated with neuroticism. Patients with higher symptom burden were also more likely to receive antiarrhythmic agents and DOAC, as well as antidepressants. TRIAL REGISTRATION: German registry for clinical studies (DRKS), DRKS00019007.

Arterial Stiffness Is Associated With Increased Symptom Burden in Patients With Atrial Fibrillation.

BACKGROUND: Increased arterial stiffness (AS) has been described as a predictor of atrial fibrillation (AF). This study was performed to assess whether increased AS leads to a higher symptom burden in patients with AF. METHODS: One hundred sixty-two consecutive patients (104 male, 58 female) with diagnosed AF (paroxysmal or persistent) were enrolled. Symptoms most likely attributable to AF were quantified according to the Canadian Cardiovascular Society Severity of Atrial Fibrillation (SAF) scale. AS indices (aortic distensibility, cyclic circumferential strain, and aortic compliance) were characterized using transoesophageal echocardiography. RESULTS: The cohort was divided into asymptomatic to oligosymptomatic (SAF scale 0-1, n = 78 [48.1%]) and symptomatic (SAF scale ≥ 2, n = 84 [51.9%]) patients. Symptomatic patients tended to be younger (median, 75 [interquartile range (IQR) 67-80] vs 71 [65-79]; P = 0.047) and were more likely to be female (22 [28.2%] vs 36 [42.9%]; P = 0.052). Hypertension was more frequent in symptomatic patients. Aortic compliance indices each were reduced in symptomatic patients, most pronounced for aortic compliance (median, 0.05 [IQR 0.03-0.06] vs 0.04 [0.03-0.05] cm/mm Hg; P = 0.01) followed by cyclic circumferential strain (median, 0.09 [IQR 0.07-0.11] vs 0.07 [0.04-0.10]; P = 0.02) and aortic distensibility (10-3 mm Hg-1, median, 1.74 [IQR 1.34-2.24] vs 1.54 [1.12-2.08]; P = 0.03). Multivariable analysis revealed aortic compliance as an independent predictor for symptoms in patients with AF with an odds ratio of 2.6 (95% confidence interval, 1.2-3.4; P = 0.003). CONCLUSIONS: AS contributes to a high symptom burden in patients with AF, emphasizing the prognostic role of AS in the early detection and prevention in patients with AF.

Recurrence of Atrial Fibrillation in Dependence of Left Atrial Volume Index.

BACKGROUND/AIM: Despite advances in the treatment strategies of patients with atrial fibrillation (AF), the risk of AF recurrences is still over 50%. An increased left atrial volume index (LAVI) reflects left ventricular diastolic dysfunction (DD) and deterioration of the LA function. This study aims to determine AF recurrence following cardioversion (CV) or catheter ablation for AF (pulmonary vein isolation; PVI) in dependence of DD and LAVI. PATIENTS AND METHODS: One hundred and sixty-two patients with paroxysmal or persistent AF in whom either CV or PVI were performed were included and followed over a mean of 22.9±3.8 months. Recurrence was defined as any recurrence of AF that occurred 3 months following the procedure. DD and LAVI were assessed using transthoracic echocardiography (TTE). RESULTS: Recurrent AF occurred in 100 (61.7%) patients, predominantly following CV [CV 41 (76.2%) vs. PVI 59 (54.6%), p<0.0001]. Both DD and an increased LAVI were more common in the recurrence-group [DD 46.0% vs. 14.5%, p=0.0001; LAVI (ml/m2) 49.0±18.6 vs. 26.3±7.0, p<0.0001]. ROC analysis revealed LAVI>36 ml/m2 as cut-off (p<0.0001, AUC=0.92, 95%CI=0.87-0.97, sensitivity=76%, specificity=94%). In the multivariate analysis, DD (HR=1.6, 95%CI=1.3-2.1, p=0.04) and LA enlargement (defined as LAVI>36 ml/m2 with HR=2.1, 95%CI=1.8-2.7, p<0.0001) could be identified as independent predictors of AF recurrence after attempting to control the heart rhythm. CONCLUSION: LA enlargement and DD are independent risk factors associated with AF recurrence after initial successful rhythm control attempt. These findings have implications for timing of either ablation or CV.

Clinical Profile and Long-Term Follow-Up of Children with Brugada Syndrome.

Brugada syndrome (BrS) is a rare channelopathy associated with sudden cardiac death (SCD). Although outcome data of adult cohorts are well known, information on children are lacking. The aim of the present study was to analyze the clinical profile, treatment approach and long-term outcome of children affected with BrS. After a systematic review of the literature compiled from a thorough database search (PubMed, Web of Science, Cochrane Libary, Cinahl), data from a total of 4 studies which included 262 BrS patients were identified. The mean age of patients was 12.1 ± 5.5, 53.8% males and 19.8% spontaneous BrS type I. 80.2% of patients presented BrS ECG I after receiving sodium channel blockers. 76% of these patients were asymptomatic while only 17.9% suffered from recurrent syncope. Around 1.5% of the patients were admitted due to aborted SCD, and 3% suffered from atrial arrhythmias. Electrophysiological work-up was performed in 132 patients. Induction of ventricular tachycardia/ventricular fibrillation using programmed ventricular stimulation was inducible in 16 patients. 56 children received an ICD. 11 patients received quinidine. An electrical storm was documented in 1 patient. Appropriate shocks occured in 16% of the patients over a median follow-up period of 62.2 (54-64). ICD-related complications were observed in 11 patients (19.6%) with a predominance of inappropriate shocks and lead failure and/or fracture. Although BrS in the childhood is rare, diagnosis and management continues to be challenging. ICD therapy is an effective therapy in high-risk children with BrS, however, with relevant ICD-related complications.

Arrhythmic events in Brugada syndrome patients induced by fever.

INTRODUCTION: The Brugada syndrome is associated with arrhythmic events, which may even lead to sudden cardiac death (SCD) as it causes arrhythmic events. A typical Brugada syndrome ECG type I can be triggered at fever situations. The aim of this pooled meta-analysis is to further explore the baseline characteristics and the association of fever to BrS-related arrhythmic events. METHODS: We compiled data from a search of databases (PubMed, Web of Science, Cochrane Library, and Google Scholar). We included 17 studies including 14 case reports and a total of 53 patients. RESULTS: Our population including 53 patients showed a male predominance of 92% with a mean age of 40.6 ± 17.7 years. 58% of patients had a family history of SCD or BrS. Genetic screening was performed in 14 patients (26%) and revealed a SCN5A mutation in 21% of the patients. ICD implantation was initiated in six patients. 75% (n = 39) of patients did not have symptoms before the fever event. Symptoms at fever included life-threatening arrhythmia such as ventricular fibrillation (VF) or ventricular tachycardia (VT; 17%), syncope (13%), and cardiac arrest or aborted SCD (13%). One patient developed electrical storm which led to not aborted SCD. CONCLUSION: Fever is a great risk factor for arrhythmia events in BrS patients. Patients with known fever triggered Brugada syndrome should be surveilled closely during fever and be started on antipyretic therapy as soon as possible.

Impact of Sacubitril/Valsartan on the Long-Term Incidence of Ventricular Arrhythmias in Chronic Heart Failure Patients.

BACKGROUND: Sacubitril/valsartan decreased the risk of sudden cardiac death (SCD) in patients suffering from heart failure with reduced ejection fraction (HFrEF). However, long-term data are sparse. OBJECTIVE: The aim of the present study was to compare the incidence of life-threatening arrhythmias consisting of ventricular tachycardia and/or ventricular fibrillation before and after initiation of sacubitril/valsartan treatment. METHODS: Out of 12,000 patients with HFrEF from 2016-2018, 148 patients were newly prescribed sacubitril/valsartan, but the long-term data of only 127 patients were available and included in this study. RESULTS: Patients with an average age of 66.8 ± 12.1 had a median left ventricular ejection fraction (LVEF) of 25% (interquartile range (IQR) 5.00-45.00) and 30% (IQR 10.00-55.00, p < 0.0005) before and after sacubitril/valsartan treatment, respectively. Systolic blood pressure decreased from 127.93 ± 22.01 to 118.36 ± 20.55 mmHg (p = 0.0035) at 6 months of follow-up. However, in 59 patients with a long-term outcome of 12 months, ventricular arrhythmias persistently increased (ventricular fibrillation from 27.6 to 29.3%, ventricular tachycardia (VT) from 12% to 13.8%, and nonsustained VT from 26.6 to 33.3%). CONCLUSIONS: Sacubitril/valsartan does not reduce the risk of ventricular tachyarrhythmias in chronic HFrEF patients over 12 months of follow-up.

Implantable cardioverter-defibrillator in Brugada syndrome: Long-term follow-up.

BACKGROUND: Brugada syndrome (BrS) is associated with sudden cardiac death (SCD). Although implantable cardioverter-defibrillator (ICD) implantation is recommended, the long-term outcomes and follow-up data with regard to ICD complications have led to controversy. HYPOTHESIS: In the present study, we described the data assimilated in a total of 11 studies, analyzing the outcome in 747 BrS patients receiving ICD. METHODS: Data were performed and analyzed after a systematic review of literature compiled from a thorough database search (PubMed, Web of Science, Cochrane Library, and Cinahl). RESULTS: The mean age of patients receiving ICD was (43.1 ± 13.4, 82.5% males, 46.6% spontaneous BrS type I). Around 15.3% of the patients were admitted due to SCD and 10.4% suffered from atrial arrhythmia. Appropriate shocks were documented in 18.1% of the patients over a mean follow-up period of 82.3 months (47.5-110.4). The following complications were recorded: lead failure and fracture (5.4%), lead perforation (0.7%), lead dislodgement (1.7%), infection (3.9%), pain (0.4%), subclavian vein thrombosis (0.3%), pericardial effusion (0.1%), endocarditis (0.1%), psychiatric problems (1.5%), pneumothorax (0.7%). Inappropriate shocks were documented in 18.1% of the patients. The management of inappropriate shocks was achieved by pulmonary vein isolation (0.5%), drug treatment with sotalol (1.3%) or sotalol with beta-blocker (0.3%) and hydroquinidine (0.1%). CONCLUSIONS: ICD therapy in BrS is associated with relevant ICD-related complications including a substantial risk of inappropriate shocks more frequently in symptomatic BrS patients.

Impact of Antiarrhythmic Drugs on the Outcome of Short QT Syndrome.

Short QT syndrome (SQTS) is associated with sudden cardiac arrest. There are limited data on the impact of antiarrhythmic drugs on the outcome of SQTS. Materials and Methods: We studied data that describe the clinical outcome of 62 SQTS patients treated with antiarrhythmic drugs, who were recruited from a pool of patients diagnosed in our institution and also from known databases after a systematic search of the published literature. Results: Sixty-two SQTS patients treated with antiarrhythmic drugs were followed up over a median timeframe of 5.6 years (interquartile range 1.6-7.7 years). Six patients, in particular, received multiple drugs as a combination. Of the 55 patients treated with hydroquinidine (HQ), long-term prophylaxis was documented in 41 patients. Fourteen patients stopped treatment due to the following reasons: gastrointestinal intolerance (n = 4), poor compliance (n = 8), and no QTc prolongation (n = 2). Of the 41 patients treated with HQ, the QTc interval increased from 313.5 ± 17.2 to 380.1 ± 21.2 ms. Thirteen of the 41 patients suffered from at least one or more ventricular tachyarrhythmias (VAs) before HQ initiation. VAs are reduced in incidence after HQ treatment (13/41: 31% versus 3/41: 7.3%, p < 0.001). Conclusion: HQ increases the corrected QT interval and prevents VAs in the majority of the patients in this cohort. HQ is safe for use in SQTS patients, particularly due to its low rate of side effects. Other antiarrhythmic drugs might be useful, but the data justifying their use are sparse.

Cardioprotective Effects of Dronedarone Mediated by the Influence on the Expression of Urokinase-Type Plasminogen Activator Receptor.

PURPOSE: Dronedarone is a multichannel-blocking antiarrhythmic drug for the treatment of atrial fibrillation. Observational data hypothesized a cardioprotective effect. In an in vitro endothelial cell-platelet model, we evaluated the molecular atheroprotective effects of dronedarone. METHODS: Following a 24-h incubation of human umbilical vein endothelial cells (HUVECs) with dronedarone (concentration 50, 100, and 150 ng/mL), they were then stimulated for 1 h with lipopolysaccharide (LPS) and were subsequently incubated in direct contact with thrombin-activated platelets. After incubation, the expression of CD40L and CD62P on platelets, and the expression of ICAM-1, VCAM-1, urokinase-type plasminogen activator receptor (uPAR), and membrane type 1 matrix metalloproteinase (MT1-MMP) on endothelial cells were measured by flow cytometry. RESULTS: Preincubation with 150 ng/mL of dronedarone reduced the expression of uPAR on endothelial cells after proinflammatory stimulation with LPS and also by direct endothelial contact with activated platelets (p = 0.0038). In contrast, the expression of CD40L and CD62P on platelets after proinflammatory stimulation with thrombin was significantly increased through direct preincubation with 50/100/150 ng/mL of dronedarone. However, dronedarone had no effects on the expression of MT1-MMP and ICAM-1 in HUVECs. CONCLUSION: In this in vitro analysis, dronedarone directly increased platelet activation but showed significant direct effects on endothelial cells and indirect effects on platelets on selected markers of atherosclerosis.

Long-term follow-up of implantable cardioverter-defibrillators in Short QT syndrome.

BACKGROUND: Short QT syndrome (SQTS) is associated with sudden cardiac death and implantable cardioverter-defibrillator (ICD) implantation is recommended in this rare disease. However, only a few SQTS families have been reported in literature with limited follow-up data. OBJECTIVES: In the recent study, we describe the outcome data of 57 SQTS patients receiving ICD implantation. This includes seven SQTS families consecutively admitted to our hospital between 2002 and 2017 as well as patients reported in published literature. METHODS: Seven SQTS patients admitted to our hospital were followed up. Additionally, 7 studies out of a total of 626 researched articles were identified through systematic database search (PubMed, Web of Science, Cochrane Library, and Cinahl) and their data analyzed according to our model. RESULTS: Complications during a median follow-up time of 67.4 months (IQR 6-162 months) were documented in 31 (54%) patients. Inappropriate shocks were seen in 33% due to T wave oversensing (8.7%), supraventricular tachycardia (19%), lead failure and fracture (21%). Further complications were infection (10%), battery depletion (7%) and psychological distress (3.5%). Appropriate shocks were documented in 19%. Three patients (5%) were treated with s-ICD due to recurrent complications of transvenous ICD. CONCLUSION: ICD therapy is an effective therapy in SQTS patients. However, it is also associated with significant risk of device-related complications.