Prescription Of Antiarrhythmic Drugs Research Articles

Abstract 12194: Clinical Application of Virtual Antiarrhythmic Drug Test Using Digital Twins in Patients Who Recurred Atrial Fibrillation After Catheter Ablation

Introduction: We previously reported that a computational modeling-guided antiarrhythmic drug (AAD) test was feasible for assessing diverse AADs in patients with atrial fibrillation (AF). In this study, we took the virtual AAD test (V-AAD) in patients who took AADs after AF catheter ablation (AFCA). Hypothesis: Patients using an effective drug in the VAAD test will have fewer AF recurrences than patients using an ineffective drug. Methods: This single-center retrospective study included 246 patients (72.8% male, 60.7±10.2 years of age, 38.6% paroxysmal AF) prescribed AADs within 3 months after AFCA. Using realistic computational modeling, we evaluated the effects of five AADs (amiodarone, sotalol, dronedarone, flecainide, and propafenone; 2 doses for each drug). Clinical AADs (C-AAD) were chosen at the discretion of the physicians blinded to the V-AAD test. We defined the effective V-AAD as the V-AAD that terminated AF or converted AF to atrial tachycardia (AT) and the best V-AAD as the V-AAD that ended virtual AF the fastest. We compared AF recurrence rates after the AAD prescription depending on the results of the V-AAD test. Results: The ineffective and best V-AAD were administered in 64 (26.0 %) and 70 patients (28.5%). The recurrence rate within a year after using the ineffective, effective, and best V-AAD were 46.9%, 35.7%, and 25.7%, respectively (log-rank p=0.013). The recurrence rate within a year in patients with at least one V-AAD terminating AF and those without was 33.9% and 50.0%, respectively (log-rank p=0.034). The use of best V-AAD (OR 0.43, 95% CI [0.18-0.96]; p=0.042, vs. ineffective V-AAD) is an independent predictor of AF recurrence within a year of using AAD after AFCA. Conclusions: The digital twins-guided V-AAD test was feasible for evaluating the efficacy of multiple AADs in patients with AF who had a high chance of recurrence after AFCA. We need a prospective randomization study to assess the prediction power of the V-AAD test.

Diagnostic evaluation of unexplained ventricular tachyarrhythmias in younger adults.

The diagnostic work-up for cardiac arrest from ventricular tachyarrhythmias occurring in younger adults and structurally normal hearts is variable and often incomplete. We reviewed records for all recipients of a secondary prevention implantable cardiac defibrillator (ICD) younger than 60 years at a single quaternary referral hospital from 2010 to 2021. Patients with unexplained ventricular arrhythmias (UVA) were identified as those with no structural heart disease on echocardiogram, no obstructive coronary disease, and no clear diagnostic features on ECG. We specifically evaluated the adoption rate of five modalities of "second-line"cardiac investigations: cardiac magnetic resonance imaging (CMR), exercise ECG, flecainide challenge, electrophysiology study (EPS), and genetic testing. We also evaluated patterns of antiarrhythmic drug therapy and device-detected arrhythmias and compared them with secondary prevention ICD recipients with a clear etiology found on initial assessment. One hundred and two recipients of a secondary prevention ICD under the age of 60 were analyzed. Thirty-nine patients (38.2%) were identified with UVA and were compared with the remaining 63 patients with VA of clear etiology (61.8%). UVA patients were younger (35.6 ± 13.0vs. 46.0 ± 8.6 years, p < .001) and were more often female (48.7% vs. 28.6%, p = .04). CMR was performed in 32 patients with UVA (82.1%), whereas flecainide challenge, stress ECG, genetic testing, and EPS were only performed in a minority of patients. Overall, the use of a second-line investigation suggested an etiology in 17 patients with UVA (43.5%). Compared to patients with VA of clear etiology, UVA patients had lower rates of antiarrhythmic drug prescription (64.1% vs. 88.9%, p = .003) and had a higher rate of device-delivered tachy-therapies (30.8% vs. 14.3%, p = .045). In this real-world analysis of patients with UVA, the diagnostic work-up is often incomplete. While CMR was increasingly utilized at our institution, investigations for channelopathies and genetic causes appear to be underutilized. Implementation of a systematic protocol for work-up of these patients requires further study.

Abstract 10986: Use of the “Pill in the Pocket” Approach for Atrial Fibrillation Termination as Determined from the Antiarrhythmic Medication for Atrial Fibrillation (AIM-AF) Study: A Physician Survey on the Prescription of Antiarrhythmic Drugs in the USA and Europe

Introduction: USA and European guidelines recognize that an oral antiarrhythmic drug (AAD) for acute conversion of symptomatic atrial fibrillation (AF) can be effective in AF termination, provided a drug with rapid effect is used and safety precautions are followed. How the ‘pill in the pocket’ (PIP) approach is used in physicians’ practices has not been examined. We performed a survey to understand clinicians’ AAD PIP prescription practices in the USA and Europe. Methods: An online physician survey of 629 cardiologists and interventional electrophysiologists (EPs) was conducted in the USA, Germany, Italy, Sweden, and the UK. Respondents were treating ≥10 AF patients who received AAD therapy and/or had received or were referred for ablation. This exploratory survey contained 96 questions on physician demographics, AF types, and drug treatment practices. Results: Respondents in the USA and Europe, reported PIP use in 24% and 19% of their patients, respectively. Frequency of PIP use was greatest in paroxysmal AF without structural heart disease (SHD; 41%) vs paroxysmal AF with SHD (16%). In contrast to guideline recommendations, PIP was used in persistent AF (pers-AF) in 18% without SHD and in 12% with SHD. Use for pers-AF was highest in the USA and by EPs. For AF without SHD, class IC AADs were used most often (flecainide, 77%; propafenone, 32%), but there was notable use of amiodarone (Amio) (13%) and sotalol (Sot) (13%), the latter more in the USA and by EPs. For AF with SHD, class IC use diminished considerably. PIP was given with a rate control agent (new or chronically, beta blocker &gt; calcium channel blocker) in 71%, while 29% gave PIP AADs without concomitant rate control agents. Optimal arrhythmia frequencies for PIP were felt to be: monthly (13%), q2-3 months (46%), q4-6 months (26%), q7-12 months (11%), and yearly or less (4%), with no notable differences between the USA and Europe, or cardiologists and EPs. Conclusions: Our survey revealed that clinicians in both the USA and Europe use PIP in almost a quarter of their patients, mostly for AF with minimal or no heart disease (guideline appropriate). However, Amio and Sot use for PIP and use of PIP for pers-AF was evident, highlighting the need for further interventions on the appropriate and optimal use of the PIP strategy.

Abstract 12766: Treatment of Patients With Atrial Fibrillation and Heart Failure in the AIM-AF (Antiarrhythmic Medication for Atrial Fibrillation) Study: A Physician Survey on the Prescription of Antiarrhythmic Drugs in the US and Europe

Introduction: ACC/AHA/HRS guidelines recommend dofetilide or amiodarone in patients with atrial fibrillation (AF) and symptomatic heart failure (HF). ESC 2020 guidelines added dronedarone (IA) and sotalol (IIbA) as antiarrhythmic drug (AAD) options for patients with AF and HF with preserved ejection fraction (HFpEF), retaining only amiodarone (IA) for AF and HF with reduced ejection fraction (HFrEF). Dronedarone was also added for patients with normal or mildly impaired (but stable) left ventricular function (IA). In both guidelines, catheter ablation (ABL) may be considered in AF and HFrEF to improve outcomes. Methods: An online survey to understand treatment practice in patients with AF and HF was conducted in the US, Germany, Italy, Sweden, and the UK. Respondents were cardiologists or cardiac electrophysiologists (N=629) actively treating ≥10 patients with AF who received AAD therapy and/or had received or were referred for ABL. The survey comprised 96 questions on physician demographics, AF types, and treatment practices. Results: After AF type and symptom status, presence of HF was the third most cited reason to select rhythm control over rate control (13% of respondents). Overall, 39% preferred first-line ABL over AADs in patients with AF and comorbidities such as HF; yet HFrEF was the top-ranked factor for favoring AADs over ABL by 20%. Amiodarone was the AAD selected most often in HFrEF (81%), and HFpEF (60%), and used less in the US than Europe (particularly in HFrEF: 71% vs 91%). Sotalol was selected by 18% as a typical choice for AF with HFrEF (US 25%, Europe 12%), not in accordance with guideline recommendations; class Ic drugs were also selected in HFrEF (US 8%, Europe 4%) contrary to recommendations. Use of dronedarone (18% vs 27%) and sotalol (26% vs 42%) was less common in the US than Europe in patients with HFpEF; use of class Ic agents, against recommendations, was the same in both regions (18%). Conclusions: Presence of HF is frequently considered by physicians in AF treatment decisions, but treatment patterns indicate divergence from guideline recommendations with several specific AADs. However, the guidelines do not clearly define HF and, in clinical practice, use of non-recommended agents appear acceptable to some in individual circumstances.

Physical activity, patient-reported symptoms, and clinical events: Insights into postprocedural recovery from personal digital devices

BackgroundPersonal digital devices may offer insights into patient recovery and an approach for remote monitoring after procedures.ObjectiveTo examine associations between activity measured using personal digital devices, patient-reported outcome measures (PROMs), and clinical events among patients after catheter ablation for atrial fibrillation (AF) or bariatric surgery.MethodsWe aggregated personal digital device, PROM, and electronic health record data in a study conducted at 2 health systems. We used Fitbit devices for step count assessments, KardiaMobile for cardiac rhythm assessments, and PROMs for pain and palpitations over 5 weeks.ResultsAmong 59 patients, 30 underwent AF ablation and 29 bariatric surgery. Thirty-six patients (63%) reported pain. There was no difference in median [interquartile range] daily steps between patients with and those without pain (4419 [3286–7041] vs 3498 [2609–5888]; P = .23). Among AF ablation patients, 21 (70%) reported palpitations. Median daily steps were lower among those with palpitations than among those without (4668 [3021–6116] vs 8040 [6853–10,394]; P = .03). When accounting for within-subject correlation, recordings of AF were associated with a significant mean decrease in median daily steps (–351; 95% confidence interval –524 to –177; P <.01). Patients who received a new antiarrhythmic drug prescription had AF recorded in a median of 5 [5–5] of 5 total weeks, whereas patients who did not receive a new antiarrhythmic recorded AF in a median of 1 [0–3] week (P = .02).ConclusionPersonal digital device and PROM data can provide insight into postprocedural recovery outside of usual clinical settings and may inform follow-up and clinical decision-making. (ClinicalTrials.gov Identifier: NCT03436082)

Association between specific antiarrhythmic drug prescription in the post-procedural blanking period and recurrent atrial arrhythmias after catheter ablation for atrial fibrillation.

PurposeTo evaluate if specific AADs prescribed in the blanking period (BP) after catheter ablation of atrial fibrillation (AF) may be associated with reduced risk of early recurrence (ER) and/or late recurrence (LR) of atrial arrhythmias.MethodsA total of 478 patients undergoing first-time ablation at a single institution were included. Outcomes were: ER, LR, discontinuation of AAD less than 90 days post-ablation, and second ablation. ER was defined as AF, atrial flutter (AFL), or atrial tachycardia (AT) > 30 seconds within BP. LR was defined as AF/AFL/AT > 30 seconds after BP.ResultsOf 478 patients, 14.9% were prescribed no AAD, 26.4% propafenone/flecainide, 34.5% sotalol/dofetilide, 10.7% dronedarone, and 13.6% amiodarone. Patients prescribed amiodarone were more likely to have persistent AF, hypertension, diabetes, and other comorbidities. In unadjusted analyses, there were no differences between groups in relation to ER (log rank P = 0.171), discontinuation of AAD before ninety days post-ablation (log rank P = 0.235), or freedom from second ablation (log rank P = 0.147). After multivariable adjustment, patients prescribed amiodarone or dronedarone were more likely to experience LR than those prescribed no AAD [Adjusted Hazard Ratio (AHR) 1.83, 95% CI 1.10–3.04, p = 0.02; AHR 1.79, 95% CI 1.05–3.05, p = 0.03, respectively].ConclusionFollowing first-time catheter ablation, there were no differences between specific AAD prescription and risk of ER, while those prescribed amiodarone or dronedarone in the BP were more likely to experience LR than those prescribed no AAD, which may represent an association due to confounding by indication.

Эффективность и безопасность фармакологической кардиоверсии фибрилляции предсердий

Currently, atrial fibrillation is the most prevalent supraventricular tachycardia. Selection of management strategy for such patients becomes an important issue for medical practitioners. The review includes issues related to atrial fibrillation management tactics algorithms based on the patients’ age and comorbidities; contemporary approaches to pharmacological therapy of the described type of arrhythmia are reported, peculiar features for prescription of antiarrhythmic drugs of various classes are highlighted.

Evaluation of medical quality and treatment trends of nonvalvular atrial fibrillation in Beijing inpatients.

The quality of care presented to AF cases in tertiary and non-tertiary hospitals in China remains obscure and needs further investigation. Therefore, we examined the compliance with quality measures (QMs) and clinical performance measures (PMs) that were proposed by the ACC/AHA in 2016 in a Chinese adult population with nonvalvular atrial fibrillation (AF). We also investigated the changes in patients' characteristics, treatment plans, and quality of provided care at different time-points [2011-2016]. We used the datasets from two registry-based studies in Beijing, including the Chinese Atrial Fibrillation Registry (CHINA-AF) investigation. From August 2011 to July 2016, an overall number of 13,439 nonvalvular AF cases were included. Our primary outcome was to determine the compliance rate with two PMs [oral anticoagulant (OAC) use and prothrombin time international normalized ratio (INR)] and six QMs (beta-blocker, ACEI-ARB, and the inappropriate prescription of antiarrhythmic drugs, Sotalol, antiplatelet and OAC, and non-dihydropyridine calcium channel antagonist) over a period of 5 years [2011-2016]. Also, the difference in compliance between tertiary and non-tertiary hospitals was investigated. The compliance with PMs and QMs was variable between tertiary and non-tertiary hospitals. In tertiary hospitals, the total number of inpatient beds was >500, and each bed was equipped with >1.03 health technical personnel and >0.4 nurses. In non-tertiary hospitals, the available beds capacity was <500, and each bed corresponded with 0.7-0.88 health technical personnel and >0.4 nurses. The compliance rates with OAC use steadily increased from 2011-2015 in tertiary hospitals (35%, 35.9%, 37.9%, 45%, and 49%, P<0.001). In non-tertiary hospitals, INR follow-up of warfarin use increased significantly over the years, with rates of 36.2%, 60.5%, 71.6%, 64.3%, and 81.5% (P=0.04), respectively. In terms of QMs, the compliance with the six measure sets was quite similar among tertiary and non-tertiary hospitals avoiding any significant difference over the years (P>0.05). We noted an improvement in medical quality regarding the use of OAC, especially in tertiary hospitals. Meanwhile, the compliance rates of INR follow-up improved in non-tertiary hospitals. However, the compliance rates of other performance and QMs are still low, which are in need of improvement.

Comparison between cryoballoon ablation and radiofrequency catheter ablation for atrial fibrillation in patients on hemodialysis.

BackgroundDifficulties are often encountered while controlling atrial fibrillation (AF), especially in hemodialysis (HD) patients. Previous data revealed that cryoballoon ablation (CBA) for treating paroxysmal atrial fibrillation (PAF) was not inferior to radiofrequency ablation (RFA); however, HD patients were excluded in this prior trial. Thus, the efficacy of CBA for HD patients is still unknown.MethodsThis retrospective study analyzed HD patients who underwent catheter ablation (CA) for AF from August 2011 to June 2019. Patients who received CBA (CBA group) and those who received RFA (RFA group) were compared. The primary endpoint was defined as freedom from a composite outcome (a documented recurrence of any atrial tachyarrhythmia or a prescription of antiarrhythmic drugs) at one year after CA.ResultsThe RFA and CBA groups were composed of 21 and 23 patients, respectively. Freedom from a composite outcome was 58.4% in the RFA group and 68.2% in the CBA group (Log-rank: p = 0.571).ConclusionOur results suggest that patients on HD with AF who were treated with CBA tended to have better outcomes than patients treated with RFA. Therefore, CBA could be a suitable ablation method for HD patients.

Guideline-Concordant Antiarrhythmic Drug Use in the Get With The Guidelines-Atrial Fibrillation Registry.

Antiarrhythmic drug (AAD) therapy for atrial fibrillation (AF) can be associated with both proarrhythmic and noncardiovascular toxicities. Practice guidelines recommend tailored AAD therapy for AF based on patient-specific characteristics, such as coronary artery disease and heart failure, to minimize adverse events. However, current prescription patterns for specific AADs and the degree to which these guidelines are followed in practice are unknown. Patients enrolled in the Get With The Guidelines-Atrial Fibrillation registry with a primary diagnosis of AF discharged on an AAD between January 2014 and November 2018 were included. We analyzed rates of prescription of each AAD in several subgroups including those without structural heart disease. We classified AAD use as guideline concordant or nonguideline concordant based on 6 criteria derived from the American Heart Association/American College of Cardiology/Heart Rhythm Society AF guidelines. Guideline concordance for amiodarone was not considered applicable, since its use is not specifically contraindicated in the guidelines for reasons such as structural heart disease or renal function. We analyzed guideline-concordant AAD use by specific patient and hospital characteristics, and regional and temporal trends. Among 21 921 patients from 123 sites, the median age was 69 years, 46% female and 51% had paroxysmal AF. The most commonly prescribed AAD was amiodarone (38%). Sotalol (23.2%) and dofetilide (19.2%) were each more commonly prescribed than either flecainide (9.8%) or propafenone (4.8%). Overall guideline-concordant AAD prescription at discharge was 84%. Guideline-concordant AAD use by drug was as follows: dofetilide 93%, sotalol 66%, flecainide 68%, propafenone 48%, and dronedarone 80%. There was variability in rate of guideline-concordant AAD use by hospital and geographic region. Amiodarone remains the most commonly prescribed AAD for AF followed by sotalol and dofetilide. Rates of guideline-concordant AAD use were high, and there was significant variability by specific drugs, hospitals, and regions, highlighting opportunities for additional quality improvement.

Current status of the clinical practice and analysis on the ratioanl prescription of antiarrhythmic drugs in Chinese patients with atrial fibrillation: Results from the Chinese Atrial Fibrillation Registry (CAFR) trial

Objective: To explore the practice patterns and the related factors of oral antiarrhythmic drug (AAD) treatment in Chinese patients with atrial fibrillation (AF), and to evaluate the compliance of AAD application to atrial fibrillation management guidelines. Methods: From August 2011 to August 2016, medical records from 18 014 patients with AF were analyzed based on data from the Chinese Atrial Fibrillation Registry trial. Patients were divided into AAD group (7 788 cases, 43.23%) and non-AAD group (10 226 cases, 56.77%) according to whether AAD was used at baseline or at the time of first use during follow-up. Amiodarone (4 129 cases, 53.02%) and propafenone (3 211 cases, 41.23%) were the mostly prescribed AAD and subgroup analysis was performed accordingly. Medical records were analyzed by random forest regression to evaluate the use of AAD and related factors in patients with AF, and the rationality of AAD was analyzed according to the guidelines for the management of atrial fibrillation. Result: A total of 18 014 patients were included in this study, of which 60.48% (10 895/18 014) were male patients, 22.65% (4 081/18 014) were elderly patients(≥75 years old), there were 7 788 patients (43.23%) in AAD group, and 10 226 patients(56.77%) in non-AAD group. Compared with the non-AAD group, the elderly patients (≥75 years old, 13.74%(1 070/7 788) vs. 29.44%(3 011/10 226)), persistent AF (28.95% (2 250/7 788) 45.80% (4 683/10 226)), heart failure(8.29% (646/7 788) vs. 21.95% (2 245/10 226)), stroke and (or) TIA(12.15% (946/7 788) vs. 19.95% (2 040/10 226)), renal dysfunction(16.36%(1 274/7 788) vs. 29.37% (3 003/10 226)), and high thromboembolism risk(60.17% (4 748/7 788) vs. 76.40% (7 813/10 226)) were less prevalent in the AAD subgroup (P<0.001). Multivariate analysis showed that patients in tertiary hospitals (OR=3.72, 95%CI 3.17-4.37) were more likely to use AAD, elderly patients (≥75 years old, OR=0.47, 95%CI 0.39-0.55), persistent atrial fibrillation (OR=0.66, 95%CI 0.60-0.72), and patients with heart failure (OR=0.54, 95%CI 0.47-0.63), stroke and (or) TIA (OR=0.77, 95%CI 0.68-0.87), renal dysfunction (OR=0.75, 95%CI 0.59-0.95) and high thromboembolism risk(OR=0.7, 95%CI 0.58-0.84) were more likely not to use AAD(P<0.05). In the AAD group, amiodarone and propafenone were the most commonly used AAD, accounting for 53.02% (4 129/7 788) and 41.23% (3 211/7 788), respectively. Multivariate analysis showed that patients with persistent atrial fibrillation (OR=4.57, 95%CI 3.94-5.29) and coronary heart disease (OR=4.14, 95%CI 3.03-5.64), heart failure (OR=2.07, 95%CI 1.48-2.89), non-ischemic cardiomyopathy (OR=4.84, 95%CI 2.41-9.73) were more likely to use amiodarone, and those with normal left ventricular ejection fraction (OR=0.31, 95%CI 0.15-0.65) and low thromboembolism risk (OR=0.78, 95%CI 0.63-0.97) were more likely to use propafenone (P<0.001). The overall incidence of AAD treatment, which was not indicated by the guidelines was 6.5% (480/7 340); 5.1% (212/4 129) in the amiodarone group and 8.3% (268/3 211) in the propafenone group, respectively. Compared with the rational AAD use group, the proportion of irrational drug use was higher in the elderly (≥75 years old) (20.4% (98/480) vs. 12.9% (887/6 860)), patients of high thromboembolism risk (77.1% (379/480) vs. 59.0% (4 047/6 860)), and in non-tertiary hospitals (7.1% (34/480) vs. 3.3% (299/6 860)), but lower in men(50.8% (244/480) vs. 64.5% (4 427/6 860)), P<0.001. Conclusions: The patients with paroxysmal atrial fibrillation, who were treated with AAD, were mostly patients with fewer complications, and the patients who were treated with amiodarone were mostly patients with persistent atrial fibrillation, patients were more likely to complicate with organic heart disease. The incidence of AAD that do not comply with the guidelines was low, and it was more common in non-tertiary hospitals and the elder patients with high thromboembolism risk.

Current status of antiarrhythmic drug use and safety assessment in Chinese patients with atrial fibrillation

Objective: To investigate the current status of antiarrhythmic drugs (AADs) use in Chinese patients with atrial fibrillation(AF) and assess the safety of AADs in this patient cohort. Methods: From January 2011 to December 2013, a total of 4 008 AF patients treated with AADs was enrolled in this study and patients were followed up for 24 months. Detailed information of prescribed drug, the causes of drug discontinuation and side effects were recorded. Results: Amiodarone was prescribed to 64.3%(2 579 cases) and propafenone to 31.1%(1 247 cases) of the enrolled patients, only 148 patients(3.7%) were treated with sotalol and 34 patients (0.8%) were treated with moracizine. The prevalence of heart failure (4.0%(102/2 579) vs. 1.4%(17/1 247, P<0.001), coronary heart disease (13.5% (348/2 579) vs. 7.4%(93/1 247), P<0.001) and non-ischemic cardiomyopathy (3.1%(78/2 579) vs. 0.7%(9/1 247), P<0.001) was significantly higher in patients treated with amiodarone than in the patients treated with propafenone. During the follow-up period, the discontinuation rate of amiodarone, propafenone, sotalol and moracizine was 28.8%(743/2 579), 25.1%(313/1 247), 14.2%(21/148) and 32.4%(11/34) respectively. The reasons of discontinuing amiodarone were: follow physicians' decision (75.7%, 563 cases), no effect (3.0%, 22 cases), side effects (4.3%, 32 cases) and patients' own decision (17.0%, 126 cases). The side effects of amiodarone included thyroid dysfunction (56.3%, 18 cases), bradycardia (12.5%, 4 cases), interstitial pneumonitis/pulmonary interstitial fibrosis (6.2%, 2 cases) and others (gastrointestinal symptom, rash, hepatic dysfunction, etc.). Conclusions: Amiodarone and propafenone are the most common AADs used in Chinese patients with atrial fibrillation. The prescription of AADs is essentially in accordance to the guideline of AF treatment. However, the discontinuation rates of AADs are high in Chinese AF patients. Lacking of better AADs is still a major problem in AF pharmacotherapy. Clinical Trial Registry Chinese Clinical Trial Registry, ChiCTR-OCH-13003729.

April 2016 at a glance. Focus on cardiac remodeling, biomarkers and treatment.

Mohamed et al. show the long-term effects of volume overload induced by aortacaval shunt in mice followed by serial echocardiography until the development of reduced left ventricular ejection fraction (LVEF) and heart failure (HF). Transition to HF was characterized by reduced sarcomeric titin phosphorylation, a cause of increased sarcomeric stiffness, activation of calcium/calmodulin-dependent protein kinase II, decreased protein kinase B (Akt) phosphorylation, high oxidative stress, and increased apoptosis. These changes were worsened in Akt-deficient mice showing the critical role of this kinase.1 Tenascin-C is a large glycoprotein which appears in the extracellular matrix following tissue injury or tumor formation. Yokokawa et al. have measured it in 123 patients with dilated cardiomyopathy undergoing endomyocardial biopsy. Patients with high myocardial tenascin had worse cardiac remodeling and poorer outcomes. Diabetes and HF severity were independent determinants of its content.2 Suematsu et al. have compared valsartan and LCZ696 with a control group in streptozotocin induced diabetic mice. Compared with control and with valsartan groups, administration of LCZ696 improved LVEF and reduced LV ANP mRNA, the LV fibrotic area and TGF-β levels.3 Atrial flutter-related tachycardiomyopathy is a specific form of cardiac remodeling. Brembilla-Perot et al. report the 6 months follow-up of 1269 patients who underwent radiofrequency ablation for atrial flutter. A marked improvement in LVEF was shown in 56% of the patients who had a reduced LVEF before ablation. An ischemic etiology and prescription of antiarrhythmic drugs were associated with a lower likelihood of LVEF improvement. Patients who improved their LVEF had similar outcomes as those with a normal LVEF at baseline whereas those with a persistent low LVEF post-ablation had an almost 3-fold higher mortality rate.4 Ovchinnikova et al. have measured circulating microRNAs in 137 patients with acute HF, 20 with chronic HF, 8 with dyspnea caused by COPD exacerbation, and 41 healthy controls. Plasma levels of miRNAs were decreased in the patients with acute HF compared with all the other groups with 15 of the 226 miRNAs measured that showed a larger than a 4-fold difference. Among them, 12 were different also in the validation cohort and a prognostic value was shown for 7 of them so that their further drop within 48 hours after admission was associated with an increased risk of 180-day mortality.5 Another study shows that liver function exams were abnormal in up to 40% of the patients with acute HF enrolled in ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) and increased serum bilirubin had prognostic value also at multivariable analysis.6 Sleep-disordered breathing (SDB) is found in over half of the patients with HF and is associated with reduced quality of life and poor prognosis. Pearse and Cowie have reviewed the classification, pathophysiology, prognosis and treatment options for patients with HF and SDB. The results of the most recent trials, including SERVE-HF, are discussed.7 The effects of chronic subcutaneous (SQ) BNP administration were evaluated by McKie et al. in a double-blind, placebo controlled study in patients with asymptomatic LV dysfunction who underwent plasma volume expansion at baseline and after 12 weeks. Compared with placebo, chronic SQ, twice daily, BNP administration was associated with an increase in urinary sodium and cGMP excretion and in urine flow with a tendency to a different glomerular filtration rate response to volume expansion and to a lower LV mass.8

Pharmacological and non-pharmacological therapy for arrhythmias in the pediatric population: EHRA and AEPC-Arrhythmia Working Group joint consensus statement

In children with structurally normal hearts, the mechanisms of arrhythmias are usually the same as in the adult patient. Some arrhythmias are particularly associated with young age and very rarely seen in adult patients. Arrhythmias in structural heart disease may be associated either with the underlying abnormality or result from surgical intervention. Chronic haemodynamic stress of congenital heart disease (CHD) might create an electrophysiological and anatomic substrate highly favourable for re-entrant arrhythmias. As a general rule, prescription of antiarrhythmic drugs requires a clear diagnosis with electrocardiographic documentation of a given arrhythmia. Risk-benefit analysis of drug therapy should be considered when facing an arrhythmia in a child.Prophylactic antiarrhythmic drug therapy is given only to protect the child from recurrent supraventricular tachycardia during this time span until the disease will eventually cease spontaneously.In the last decades, radiofrequency catheter ablation is progressively used as curative therapy for tachyarrhythmias in children and patients with or without CHD. Even in young children, procedures can be performed with high success rates and low complication rates as shown by several retrospective and prospective paediatric multi-centre studies. Three-dimensional mapping and non-fluoroscopic navigation techniques and enhanced catheter technology have further improved safety and efficacy even in CHD patients with complex arrhythmias. During last decades, cardiac devices (pacemakers and implantable cardiac defibrillator) have developed rapidly. The pacing generator size has diminished and the pacing leads have become progressively thinner. These developments have made application of cardiac pacing in children easier although no dedicated paediatric pacing systems exist.

Quel traitement anti-arythmique pour la fibrillation atriale paroxystique ?

Only symptomatic patients with paroxysmal AF will be prescribed anti-arrhythmic drugs in order to prevent recurrences. Anti-arrhythmic drugs' efficacy in maintaining sinus rhythm is around 50 to 70 % at one year. Anti-arrhythmic drug prescription is associated with potentially life-threatening pro-arrhythmic effects. Anti-arrhythmic drug prescription should be tailored to each patient after carefully evaluating the risk/benefit ratio. Pulmonary veins isolation might be proposed in case of symptomatic paroxysmal AF after failure of anti-arrhythmic drug therapy.

Cardioversion for Atrial Fibrillation: Does Inflammation Matter?

m t A s s e p p t I p t n The long-term maintenance of sinus rhythm after cardioersion for atrial fibrillation (AF) has long been acknowledged s problematic. Even after initial successful restoration of sinus hythm, some 53% patients will return to AF over the followng months, whereas only approximately 25% remain in sinus hythm at 5 years.1,2 This is despite an aggressive rhythm ontrol strategy, using serial attempts at cardioversion and oncomitant antiarrhythmic drug prescription. More recently, he advent of catheter-based (and surgical-based) technologies as offered the potential of a cure for AF, with some promising esults,3 but even after these procedures, recurrence, often symptomatic, is common, further highlighting the difficulties ncountered in maintaining sinus rhythm.4,5 What contributes to the poor results of cardioversion and ong-term maintenance of sinus rhythm? Structural and lectrical remodeling within the atria may perpetuate AF— hat is, “AF begets AF”—admittedly in an experimental oat model.6 These remodeling changes include progressive eft atrial dilatation and increasing atrial fibrosis,7 the loss of ate adaptation, and the prolongation of atrial conductivity.8 alcium may also accumulate within atrial myocytes, hereby shortening the atrial refractory period, and hence, romoting the propagation of multiple wavelet reentry ciruits.7 The net result is that the biophysical properties of trial tissue are altered at microscopic and macroscopic evels in AF,9 thereby serving to perpetuate the arrhythmia. Does inflammation have a role in this, contributing to the erpetuation and maintenance of AF? Although the precise timulus for the initiation of these atrial changes remains oorly understood, an increasing body of evidence suggests hat inflammation may be central to this pathogenic proess.10 The histology of atrial biopsies taken from patients ith AF has demonstrated evidence of inflammatory infilrates and oxidative damage within the atrial tissue.11,12 Of ourse, these changes may clearly be a consequence of the arious underlying co-morbidities that commonly associate ith AF (e.g., ischemic heart disease, hypertension, diabees mellitus). However, this observation holds true even for hose with lone AF, thereby raising the possibility that nflammation may still play some role in the initiation of F, at least in this patient group.12 Systemic indexes of inflammation are also reported in F.10 For example, C-reactive protein (CRP) is a circulating cute-phase reactant and is considered the prototypic downtream marker of inflammation.13,14 CRP is synthesized by he liver in response primarily to interleukin-6 (IL-6) but also o interleukin-1. Many markers of inflammation exist, but

Attention à l'emploi de la flécaïnide chez l'hémodialysé

Cardiac arrhythmias are frequent by hemodialyzed patients and may lead to the prescription of antiarrhythmic drugs among which flecainide. However there is for this latter a wide interindividual variability in the dose–plasma concentration relationship because of a genetically controlled polymorphic metabolism. That explains why it is not possible to adjust dose only to renal clearance. It becomes even more difficult at hemodialysis stage, especially if hepatic insufficiency and/or certain medications join to it. So this antiarrhythmic drug has to be cautiously initiated and plasma concentrations have to be carefully monitored to avoid side effects, sometimes crippling as in our observation, sometimes as cardiac complications.

Exploring the effect of transient exposure on the risk of acute events by means of time‐window designs: an application to fluoroquinolone antibacterials and arrhythmia

To compare different strategies in allocating time-window at risk and in choosing optimal comparator in the setting of proarrhythmic effects of antibacterial fluoroquinolones. A population-based cohort study. Resident population of a Northern Italian Province. The study cohort comprised 75 226 patients who received at least one prescription for fluoroquinolone from 1997 to 1999. Cohort members who experienced at least an antiarrhythmic drug prescription and/or hospitalisation with diagnosis of arrhythmia during the follow-up were identified. Trends in incidence rates of arrhythmia according to different strategies in allocating time-windows at risk were calculated. Standardised incidence ratios were obtained by comparing arrhythmic events experienced by the study cohort during the time-windows at risk with those expected from both external (unexposed target population) and internal (study cohort during reference time-windows) comparators. The rate of arrhythmia was 21.0 per 100 000 person-weeks during the in-treatment period, remained stable during the following week, and progressively decreased until to converge to 7.7 per 100 000 person-weeks from 16th weeks after stop of exposure. Standardised incidence ratios were 2.35 (95%CI: 1.82, 2.99) and 1.86 (1.44, 2.37) according to external and internal comparators respectively. Evidence of linear increasing of proarrhythmic effect with the length of the antibacterial therapy appeared from every approaches, but it was stronger by using internal comparator. Time-windows designs should be performed by allocating the time-windows at risk and comparing outcome events observed in the cohort during these periods with those experienced by the same cohort during an adequate reference period.

Population based study of use of anticoagulants among patients with atrial fibrillation in the community

Several randomised controlled trials have shown that warfarin treatment for patients with atrial fibrillation substantially reduces their risk of stroke.1 Studies have found low treatment rates among patients with atrial...

Low energy transvenous cardioversion of short duration atrial tachyarrhythmias in humans using a single lead system.

The purpose of this study was to investigate the efficacy and safety of atrial cardioversion using an endocardial single lead system presently used for ventricular defibrillation. The study population consisted of 26 recipients of an ICD in combination with a conventional endocardial single lead system with the proximal spring electrode as anode in the SVC and the distal as cathode in the apex of the RV. Atrial tachyarrhythmias were induced by right atrial burst pacing. If the arrhythmia sustained > 1 minute, biphasic shocks synchronized with the R wave were delivered using the implanted device, beginning with an energy of 4 J. If 4 J failed to terminate the arrhythmia, energy was increased stepwise, if the first shock was successful, a step-down testing was performed after reinduction of atrial tachyarrhythmias. The mean atrial defibrillation threshold was 2.3 +/- 1.2 J (range, 0.5-5 J). A total of 154 shocks were delivered and no adverse effects were observed. The mean defibrillation threshold for atrial flutter was somewhat lower than that for AF (1.8 +/- 1 J vs 2.7 +/- 1.4 J, P = 0.08). There was no correlation between the atrial defibrillation threshold and a history of previously occurring atrial tachyarrhythmias, the kind of the underlying heart disease, a prescription of antiarrhythmic drugs, the dimension of the LA, the LVEF, or the ventricular DFT. Internal atrial cardioversion of short duration atrial tachyarrhythmias using a transvenous single lead system designed for ventricular defibrillation is feasible and safe at low energies, and may have important clinical applications.