Advances in Antiarrhythmic Drug Therapy

Relation of the Severity of Obstructive Sleep Apnea in Response to Anti-Arrhythmic Drugs in Patients With Atrial Fibrillation or Atrial Flutter

Aim. Catheter ablation (CA) is an effective approach for rhythm control in atrial fibrillation (AF), however antiarrhythmic therapy (AAT) remains important. There is a lack of data about long-term AAT use after CA. This study evaluates AAT after CA for AF.Material and methods. In 2012-2016, EURObservational Research Programme of Atrial Fibrillation Ablation Long-Term (EORP AFA L-T) registry was conducted, which included 476 Russian patients (57,1% — men; mean age — 57,1±8,7 years). The follow-up after CA was 12 months (available in 81,9% of patients). The use of AAT was evaluated prior to hospitalization, during hospitalization for CA, as well as at 3, 6 and 12 months of follow-up.Results. Prior to CA, 439 (92,2%) patients received AAT During CA, 459 (96,4%) patients were treated with AAT. After CA, AAT was used by 463 (97,3%), 370 (94,8%), and 307 (78,7%) patients at 3, 6 and 12 months of follow-up, respectively. There was no arrhythmia recurrence in 187 (47,9%) subjects. Among these patients, 40 (21,4%) received class IC or III AAT. The peak of AAT use was found for class IC agents within 3 months after CA (P<0,05), while for other drugs this trend was not observed. There were no factors associated with AAT usage in patients without arrhythmia recurrence after CA. A positive correlation of arrhythmia non-recurrence with a minimum number of previously used antiarrhythmic agents was revealed (RR=0,85; 95% CI 0,73-0,98; P=0,03).Conclusion. The frequency of AAT use after AF ablation is significantly reduced. However, there is a cohort of patients without documented arrhythmia recurrence still receiving AAT, which requires special attention of physicians. There were no clinical predictors of continued AAT in subjects without arrhythmia recurrence.

The optimal pharmacological treatment for patients early after ablation of atrial fibrillation (AF) is still not clear. We analyzed if concomitant antiarrhythmic drug (AAD) therapy significantly alters early recurrence of AF/atrial tachycardia (AT) following pulmonary vein ablation (PVA). For the first 2months after PVA, 274 patients (age 62±10years; 66% male) were individually scheduled for concomitant treatment with beta-adrenergic blocking agents (BB) or AAD therapy. Primary endpoint of this study was a composite of (1) AF/AT lasting more than 30seconds; (2) symptomatic AF/AT recurrence requiring intervention; or (3) intolerance to the antiarrhythmic agent given. Univariate and multivariate analysis was performed to evaluate predictors for successful AAD therapy. Early after PVA, patients were treated with BB (n=89), flecainide (n=99), sotalol (n=37), dronedarone (n=29), or amiodarone (n=115). Ninety-five patients received a combination of AAD therapy and BB. A total of 369 observation periods were analyzed. Over the first 2months following PVA, AF/AT recurrences were found in 42% of patients. No significant difference regarding freedom from AF/AT recurrence with regard to different drug therapies was observed (P=0.769). In multivariate analysis, none of the parameters were significant to predict success of AAD therapy. In nine observations, AAD therapy was terminated due to side effects presumably related to the respective agent. Following PVA, AAD therapy is not superior to BB treatment for the prevention of early atrial arrhythmias. Furthermore and confirmed by multivariate analysis, no drug was superior to another regarding the maintenance of sinus rhythm.

Antiarrhythmic drug therapy in the Multicenter UnSustained Tachycardia Trial (MUSTT): drug testing and as-treated analysis

Quality of life after the initial treatment of atrial fibrillation with cryoablation versus drug therapy.

Three months of empirical antiarrhythmic drug (AAD) therapy after atrial fibrillation ablation (AFA) is a common practice to prevent early arrhythmia recurrence; the data of influence of this practice on longer term ablation outcomes is limited. The aim of this study was to perform a meta-analysis of published controlled trials comparing temporary AAD therapy after AFA with no AAD therapy in patients after AFA. The primary outcome was recurrence of arrhythmia. 1Eight prospective trials were included. Among 2952 patients, 1991 (67%) had paroxysmal AF, and 967 (32.7%) had persistent AF. In total, 1502 patients were treated with AADs and 1450 patients served as a control group (no AAD therapy). Various class IC-III antiarrhythmics were used. Length of AAD administration varied between 6 and 12weeks after start of AFA. The follow-up duration ranged from 1.5 to 17months after stopping medication. Among AAD treated patients, the recurrence of arrhythmia rate was 30.69 vs. 33.79% in control patients (odd ratio 0.86, 95% CI 0.71-1.06, P = 0.15). In patients who received largely amiodarone, there was a trend for difference in recurrence of atrial arrhythmia (odds ratio 0.60, 95% CI 0.34-1.09, P = 0.09). Short-term post pulmonary vein isolation (PVI) AAD therapy does not substantially reduce overall recurrence of AF after ablation.

Background Atrial fibrillation (AF) is a progressive disease. Additionally, delaying AF catheter ablation (AFCA) for a year, during antiarrhythmic drug (AAD) therapy does not reduce the efficacy of this ablation. This study explored AFCA rhythm outcomes based on the diagnosis-to-ablation time (DAT) and AAD responsiveness in participants with either paroxysmal AF (PAF) or persistent AF (PeAF). Methods We included the data of 1,038 participants with AAD-resistant PeAF, all of whom had a clear time point for the diagnosis of PeAF and had undergone an AFCA for the first time. Participants who experienced recurrences of the paroxysmal type, while on AAD therapy, were analyzed as a cohort of AAD-partial-responders; whereas those who consistently maintained a PeAF, while on AAD therapy were analyzed as a cohort of AAD-non-responders. We calculated the DAT cutoff to determine long-term rhythm outcomes, using a maximum log-likelihood approach, based on the Cox proportional hazards regression model. Results Of the participants, 79.8% were male, and the median age was 61 years. The cohort of AAD-non-responders had a higher body mass index and larger left atrial diameter than that of the cohort of AAD-partial-responders. Furthermore, the cohort of AAD-non-responders showed a significantly higher incidence of AF recurrence subsequent to AFCA (adjusted hazard ratio= 1.75, 95% confidence interval: 1.33–2.30; log-rank test: p< 0.001) than that of the cohort of AAD-partial-responders. The log-likelihood graphs of the Cox proportional hazards regression models showed bimodal morphology for the cutoff values of 22 and 40 months. The cutoff value of DAT that most optimally discriminated between rhythm outcomes was 22 months. Conclusions Thus, both the DAT and AAD responsiveness affected the rhythm outcomes of AFCA. Delaying AFCA to a DAT of longer than 22 months was inadvisable, particularly in the participants in whom PeAF progressed to PAF during AAD therapy.

Does atrial fibrillation ablation really reduce stroke rates?

Natural history of potentially lethal ventricular arrhythmias in patients treated with long-term antiarrhythmic drug therapy

Atrial fibrillation (AF) frequently coexists with pulmonary hypertension (PH) and is associated with clinical deterioration, right ventricular dysfunction, and increased mortality. While catheter ablation has demonstrated superiority over anti-arrhythmic drug (AAD) therapy in select AF populations, outcomes in patients with concurrent PH remain poorly characterized. We performed a retrospective cohort study using the TriNetX Research Network. Adults with AF and PH were identified and stratified by treatment with catheter ablation plus AAD or AAD therapy alone. After 1:1 propensity score matching for demographics, comorbidities, and medication use, 9759 patients were included in each cohort. The primary outcomes were major adverse cardiovascular events (MACE) and right heart failure. Secondary outcomes included all-cause mortality, acute myocardial infarction (MI), and stroke. Kaplan-Meier models were used as the primary analysis, with Cox proportional hazards and E-value analysis as sensitivity. Competing risk analyses were performed using Fine-Gray models. Ablation was associated with a 50% reduction in MACE (HR 0.497 [0.467, 0.528], p < 0.001) and 35% reduction in right heart failure (HR 0.647 [0.573, 0.732], p < 0.001). There were also significant reductions in all-cause mortality (HR 0.469 [0.454, 0.488], p < 0.001) and stroke (HR 0.819 [0.728, 0.922], p = 0.001). There was no difference in acute MI (HR 0.982 [0.891, 1.082], p = 0.710). Findings were consistent across Cox sensitivity analyses, E-value analysis, and competing-risk models. In AF patients with PH, catheter ablation with AAD therapy was associated with substantially lower risks of adverse cardiovascular outcomes compared with AAD therapy alone. These findings suggest that catheter ablation is associated with lower risks of adverse cardiovascular outcomes in this high-risk population.

HomeCirculationVol. 106, No. 2Ventricular Tachycardia Associated With Myocardial Infarct Scar Free AccessReview ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessReview ArticlePDF/EPUBVentricular Tachycardia Associated With Myocardial Infarct ScarA Spectrum of Therapies for a Single Patient Kyoko Soejima, MD and William G. Stevenson, MD Kyoko SoejimaKyoko Soejima From the Cardiovascular Division, Department of Internal Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Mass. and William G. StevensonWilliam G. Stevenson From the Cardiovascular Division, Department of Internal Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Mass. Originally published9 Jul 2002https://doi.org/10.1161/01.CIR.0000019361.34897.75Circulation. 2002;106:176–179Case: A 73-year-old woman is referred for management of recurrent ventricular tachycardia (VT). She had suffered an inferior wall myocardial infarction in 1970. Fifteen years later, she presented with a wide QRS tachycardia, palpitations, and dizziness. Therapy with amiodarone was initiated but discontinued in 1997 because of toxicity, and she received an implantable cardioverter-defibrillator (ICD). She did well until July 2000, when she had several shocks from the ICD, all of which were preceded by syncope. Interrogation of the ICD confirmed 23 episodes of VT, 20 asymptomatic runs terminated by antitachycardia pacing (ATP), and 3 episodes requiring cardioversion from the ICD. Her left ventricular ejection fraction was 25%. Sotalol failed to prevent VT recurrences and mexiletine produced nausea and tremor.She was referred for catheter ablation. An echocardiogram revealed akinesis of the inferior wall and no left ventricular thrombus. In the electrophysiology laboratory, programmed stimulation induced 5 different morphologies of VT (Figure 1) with rates ranging from 180 to 220 bpm. Because the induced VTs were unstable, producing hypotension and often changing from one VT to another, catheter mapping and ablation were performed largely during sinus rhythm, guided by electrogram characteristics and pacing during sinus rhythm (pace-mapping) that marked the location of the infarct scar and likely reentry paths in the subendocardium. After placement of lines of radiofrequency (RF) lesions through these abnormal regions, only ventricular flutter (280 bpm) was inducible; the slower VTs were no longer inducible. There have been no VT recurrences in the 18 months of follow-up after ablation. Download figureDownload PowerPointFigure 1. Twelve-lead ECGs of the inducible VTs were obtained in the electrophysiology laboratory.DiscussionVentricular arrhythmias associated with myocardial infarction (MI) occur in 2 distinct phases. During the acute phase of infarction, polymorphic VT that degenerates to ventricular fibrillation is most common. In the weeks that follow, the healing infarct undergoes structural changes. Fibrosis creates areas of conduction block and also increases separation of myocyte bundles, slowing conduction through myocyte pathways in the border of the infarct.1,2 These pathways or channels can support stable reentry circuits, leading to monomorphic VT, when an appropriate trigger (such as a change in sinus rate or a premature depolarization) occurs. After surviving the acute phase of the infarct, monomorphic VT may emerge at any time. With present management of myocardial infarction, the incidence of sustained VT is relatively low, and fewer than 5% of infarct survivors have inducible VT when studied early after the infarct.3 Patients with large infarcts, often those who are not successfully reperfused, are at greatest risk for VT. Although the first 6 months after infarction is thought to be the period of greatest risk for VT and sudden death, some patients develop VT much later, as in the case presented above. Whether late development of VT is related to electrical and mechanical remodeling or additional ischemic events contributing to the development of the substrate for the VT is not known. Because the arrhythmia substrate for late VT is relatively fixed, this type of VT tends to be recurrent and difficult to suppress with medications.Antiarrhythmic Drugs and ICDsAntiarrhythmic drugs are frequently prescribed because they alter the electrophysiological properties of the reentrant circuit and suppress potential triggers for the development of VT. However, within 2 years, >40% of patients being treated for sustained VT will experience recurrences.4 There is a risk that a VT recurrence will cause sudden death, particularly in patients with depressed ventricular function and those who have presented with a hemodynamically poorly tolerated VT.5Three recent trials support the superiority of ICDs over antiarrhythmic drug therapy for prolonging survival and preventing sudden death in survivors of sustained ventricular arrhythmias.6,7,8 Thus, an ICD is first-line therapy for these patients. For many patients, placement of an ICD prevents the side effects of antiarrhythmic drugs. The most effective drug, amiodarone, produces side effects in almost 75% patients within 5 years. These side effects include hypothyroidism (5% to 25%), blue skin (1% to 6%), corneal pigmentation (1%), pulmonary toxicity (1% per year), tremor, or other neurological toxicity. ICD risks include device failure, lead fractures, and infection, but these are infrequent. ICDs also provide back-up pacing that protects against bradyarrhythmia.Although ICDs extend survival, they only treat the arrhythmia when it occurs, and do not prevent arrhythmia recurrences. Follow-up is required for the infrequent possibility of device malfunction. Within a year of ICD implantation, 68% of patients have recurrent episodes of VT.6 Most monomorphic VTs can be terminated by antitachycardia pacing, which is painless and often asymptomatic, but some patients require electrical cardioversion via the ICD. When VT initially recurs, and particularly when it becomes frequent, an evaluation is required to address potential aggravating factors, such as myocardial ischemia, electrolyte abnormalities, or decompensated heart failure. Most patients with frequent monomorphic VT require additional therapy to reduce VT episodes.Interactions Between ICDs and Antiarrhythmic AgentsAntiarrhythmic drug therapy decreases the frequency of VT episodes in patients with ICDs and may make the VT more amenable to antitachycardia pacing therapy. For some patients, drug therapy is problematic. The antiarrhythmic agent may slow the sinus rate, causing the patient to be paced, potentially with loss of AV synchrony, or producing adverse hemodynamic effects from right ventricular pacing. Antiarrhythmic agents may slow the rate of VT when it occurs such that it falls below the detect rate of the ICD, or falls into the range where sinus tachycardia can also occur, making distinction of sinus tachycardia from VT difficult. Some drugs, notably amiodarone, can increase the energy required for defibrillation, theoretically reducing the likelihood that ventricular fibrillation would be effectively treated by the ICD.AblationRF catheter ablation is a useful adjuvant therapy for frequent episodes of symptomatic VT. Initial ablation studies used careful mapping during VT to identify a critical part of the VT reentry circuit where the relatively small RF ablation lesions could interrupt reentry. The presence of hemodynamically stable VT facilitated mapping and ablation attempts. Patients with unstable VTs that did not allow detailed mapping were largely excluded from initial ablation attempts. Developments in the understanding of the nature of reentrant circuits and in methods to identify the region of the infarct scar and potential reentrant circuit paths through the scar now allow catheter ablation to be effective for many patients who have multiple and unstable VTs.9,10Catheter mapping systems allow electrophysiological data to be integrated in a 3-dimensional anatomic reconstruction of the ventricle (Figure 2A). The map of the left ventricle in Figure 2A, was created during sinus rhythm. The catheter was moved from point to point around the ventricle. At each point, the electrogram amplitude was plotted and color coded, with normal amplitude areas (>1.5 mV) indicated as purple and progressively lower-amplitude regions indicated by blue, green, yellow, and red regions. This patient has a large infero-posterior low-amplitude region consistent with her prior infarction. The area is much larger than that which can be completely ablated by RF energy; however, additional data can be obtained to focus the ablation to an appropriate region.10Download figureDownload PowerPointFigure 2. A, Voltage map of the left ventricle, constructed with an electroanatomic mapping system by moving the mapping catheter point by point over the endocardial surface, is shown. For each point, the electrogram amplitude is indicated by colors: purple indicates >1.5 mV (normal); blue, green, yellow, and red indicate progressively lower-amplitude abnormal regions. The left ventricle is viewed from the PA projection. The infarct area is identified as the extensive low-voltage area (red, yellow, green colors) in the inferior wall. Sites at which pace mapping and limited entrainment mapping were performed are shown with white tags. The gray regions indicate areas of dense scar that create fixed conduction block. B, The locations of RF lesions placed to interrupt pathways between the mitral annulus and areas of dense scars are shown as red tags. EM indicates entrainment mapping; PM, pace mapping matched.Inducing VT once in the electrophysiology laboratory allows confirmation of the diagnosis. In addition, the QRS morphology of the VT is obtained for use as a rough guide to the location of the reentry circuit in the infarct. In lead V1, a right bundle-branch block–like morphology VT suggests a left ventricular origin, and left bundle-branch block–like morphology predicts an origin in the right ventricle or in the interventricular septum. Dominant S waves in V2, V3, and V4 suggest an exit near the apex. Dominant R waves in these leads suggest an exit closer to the mitral annulus. Then, during sinus rhythm, pacing from the mapping catheter (pace-mapping) at sites around the infarct region and comparing the paced QRS with the VT morphology helped identify the VT reentrant circuit.11 The circuits can be large and multiple circuits are common.In the case presented, 5 different VTs were inducible. Figure 2A shows that pace mapping at a site in the low-voltage infarct region, located between two areas of dense unexcitable scar (gray regions), produced a QRS morphology similar to that of one of the VTs. To gain further confirmation that this region was involved in VT, the mapping catheter was placed at the site and VT was induced. After assessing the pattern of electrical activation, burst pacing was initiated to terminate VT. The effects of pacing (entrainment mapping) confirmed that this site was in the circuit12 (Figure 3). During stable sinus rhythm, a line of RF lesions (line 1) was then created through the target region. After the initial RF line was created, programmed stimulation induced other VT morphologies. On the basis of pace-mapping, additional RF lesions (line 2) were created (Figure 2B), which abolished inducible monomorphic VT. Download figureDownload PowerPointFigure 3. An example of entrainment mapping is shown. VT had been induced by right ventricular pacing. Pacing during VT was then performed from the mapping catheter in the left ventricle. The tachycardia was then promptly terminated by rapid burst pacing (not shown) to restore stable sinus rhythm. At this site, pacing accelerates VT to the pacing rate (cycle length of 280 ms) without changing the QRS morphology of the VT. This often indicates that the pacing site, where the mapping catheter is located, is in the reentry circuit. Additional measurements (the postpacing interval and stimulus to QRS interval) confirm that the site is in the reentry circuit. RF ablation was therefore performed at this and adjacent sites, abolishing VT. Abl indicates ablation catheter; RVA, right ventricular apex; VTCL, ventricular tachycardia cycle length.The Role of VT AblationICDs are first-line therapy for many patients with recurrent VT. When antiarrhythmic drug therapy fails to control symptomatic recurrences of VT, catheter ablation should be considered and can be expected to reduce the frequency of recurrent VT in >75% of patients.9,10,13,14 In experienced centers, ablation is now performed regardless of whether the VT rate is rapid and is associated with hemodynamic collapse. The major procedural risks are related to thromboembolism (1.2%), perforation (0.3%), and vascular access complications.15 The procedures can be long and are facilitated by the use of 3-dimensional reconstructions of the ventricular anatomy.When ablation fails, it is usually because of existence of portions of the reentrant circuits deep to the endocardium where they cannot be interrupted with standard endocardial ablation techniques. Ablation with saline-irrigated cooled ablation catheters and percutaneous epicardial mapping and ablation approaches are being evaluated that may allow some of these VTs to be ablated.16,17 Nonpharmacological therapies, such as RF ablation, have an increasingly important role in the management of VT after myocardial infarction, thus expanding the array of options available to clinicians.FootnotesCorrespondence to William G. Stevenson, MD, Cardiovascular Division, Brigham and Women's Hospital 75 Francis St, Boston, MA 02115. E-mail [email protected] References 1 Wit A, Janse MJ. The Ventricular Arrhythmia of Ischemia and Infarction: Electrophysiological Mechanisms. Mount Kisco, NY: Futura; 1993.Google Scholar2 De Bakker JMT, Van Capelle FJL, Janse MJ, et al. Slow conduction in the infarcted human heart: "zigzag" course of activation. Circulation. 1993; 88: 915–926.CrossrefMedlineGoogle Scholar3 Andresen D, Steinbeck G, Bruggemann T, et al. Risk stratification following myocardial infarction in the thrombolytic era. J Am Coll Cardiol. 1999; 33: 131–138.CrossrefMedlineGoogle Scholar4 The ESVEM investigators. Determinants of predicted efficacy of antiarrhythmic drugs in the electrophysiologic study versus electrocardiographic monitoring trial. Circulation. 1993; 87: 323–329.CrossrefMedlineGoogle Scholar5 Wyse DG, Talajic M, Hafley GE, et al. Antiarrhythmic drug therapy in the multicenter unsustained tachycardia trial (MUSTT): drug testing and as-treated analysis. J Am Coll Cardiol. 2001; 38: 344–351.CrossrefMedlineGoogle Scholar6 The Antiarrhythmics versus Implantable Defibrillators (AVID) Investigators. A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. N Engl J Med. 1997; 337: 1576–1583.CrossrefMedlineGoogle Scholar7 Connolly SJ, Gent M, Roberts RS, et al. Canadian implantable defibrillator study (CIDS); a randomized trial of the implantable cardioverter defibrillator against amiodarone. Circulation. 2000; 101: 1297–1302.CrossrefMedlineGoogle Scholar8 Kuck KH, Cappato R, Siebels J, et al. Randomized comparison of antiarrhythmic drug therapy with implantable defibrillators in patients resuscitated from cardiac arrest. The cardiac arrest study Hamburg (CASH). Circulation. 2000; 102: 748–754.CrossrefMedlineGoogle Scholar9 Marchlinski FE, Callans DJ, Gottlieb CD, et al. Linear ablation lesions for control of unmappable ventricular tachycardia in patients with ischemic and nonischemic cardiomyopathy. Circulation. 2000; 101: 1288–1296.CrossrefMedlineGoogle Scholar10 Soejima K, Suzuki M, Maisel WH, et al. Catheter ablation in patients with multiple and unstable ventricular tachycardias after myocardial infarction: short ablation lines guided by reentry circuit isthmuses and sinus rhythm mapping. Circulation. 2001; 104: 664–669.CrossrefMedlineGoogle Scholar11 Stevenson WG, Sager PT, Natterson PD, et al. Relation of pace mapping QRS configuration and conduction delay to ventricular tachycardia reentry circuits in human infarct scars. J Am Coll Cardiol. 1995; 226: 481–488.Google Scholar12 Stevenson WG, Khan H, Sager P, et al. Identification of reentry circuit sites during catheter mapping and radiofrequency ablation of ventricular tachycardia late after myocardial infarction. Circulation. 1993; 88: 1647–1670.CrossrefMedlineGoogle Scholar13 Stevenson WG, Friedman PL, Sweeney MO. Catheter ablation as an adjunct to ICD therapy. Circulation. 1997; 96: 1378–1380.CrossrefMedlineGoogle Scholar14 Strickberger SA, Man KC, Daoud EG, et al. A prospective evaluation of catheter ablation of ventricular tachycardia as adjuvant therapy in patients with coronary artery disease and implantable cardioverter- defibrillator. Circulation. 1997; 96: 1525–1531.CrossrefMedlineGoogle Scholar15 Hindricks G. The Multicentre European Radiofrequency Survey (MERFS): complications of radiofrequency catheter ablation of arrhythmias. The Multicentre European Radiofrequency Survey (MERFS) investigators of the Working Group on Arrhythmias of the European Society of Cardiology. Eur Heart. 1993; 14: 1644–1653.CrossrefMedlineGoogle Scholar16 Calkins H, Epstein A, Packer D, et al. Catheter ablation of ventricular tachycardia in patients with structural heart disease using cooled radiofrequency energy: results of a prospective multicenter study. Cooled RF Multi Center Investigators Group. J Am Coll Cardiol. 2000; 35: 1905–1914.CrossrefMedlineGoogle Scholar17 Soejima K, Delacretaz E, Suzuki M, et al. Saline-cooled versus standard radiofrequency catheter ablation for infarct related ventricular tachycardias. 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Rosellini E, Lazzeri L, Maltinti S, Vanni F, Barbani N and Cascone M (2019) Development and characterization of a suturable biomimetic patch for cardiac applications, Journal of Materials Science: Materials in Medicine, 10.1007/s10856-019-6327-6, 30:11, Online publication date: 1-Nov-2019. Akhyari P, Barth M and Lichtenberg A (2017) 7.25 Cardiac Patch with Cells: Biological or Synthetic Comprehensive Biomaterials II, 10.1016/B978-0-08-100691-7.00157-9, (482-505), . Castellano D, Blanes M, Marco B, Cerrada I, Ruiz-Saurí A, Pelacho B, Araña M, Montero J, Cambra V, Prosper F and Sepúlveda P (2014) A Comparison of Electrospun Polymers Reveals Poly(3-Hydroxybutyrate) Fiber as a Superior Scaffold for Cardiac Repair, Stem Cells and Development, 10.1089/scd.2013.0578, 23:13, (1479-1490), Online publication date: 1-Jul-2014. 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N, T, M, B, R, M, B, K and P (2014) site appropriate following right ventricle Online publication date: Le A, A, L, S and D in for cardiac therapies, Online publication date: M, M, S, N, A, E, and M as a for and Journal of and Online publication date: and M for myocardial on Biological Online publication date: Rosellini E, Barbani N and P of Scaffolds for Myocardial and of Biomaterials Myocardial . M, J, D and S for cardiac Materials and Online publication date: Akhyari P, Barth M and Lichtenberg A Cardiac Patch with Cells: Biological or Synthetic Comprehensive . S, M, R, J, M and S of for myocardial Journal of Materials Science: Materials in Medicine, Online publication date: N and M Acellular Cardiac as a Scaffold for In and Online publication date: D and A of with Disease, . J, S and D of by Journal of Online publication date: D, A, A, P, S, I, E, S, P, and and Mechanical Within a Myocardial Patch A, Online publication date: K and J and and in . 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A, J, J and de Radiofrequency Catheter Ablation of Ventricular Tachycardia in Patients With an Implantable de Online publication date: F, F, J, J, J, E, J, D and J Cells: Cardiac for and Online publication date: Ventricular Tachycardia and Associated with Electrical the of the Journal of Cardiovascular Electrophysiology, D, S, M and K Catheter ablation of ventricular tachycardia guided by cardiac Online publication date: N Ventricular in The Journal of Cardiovascular Online publication date: and of the and of on the of Journal of Biomaterials Online publication date: T, D, R, K, T, P, N, and R (2017) in the Ventricular Online publication date: K, P, D, R, and R Ventricular With Online publication date: M, and H of the in Myocardial T, H, S, N, and A conduction slowing and conduction A and D, R and The of electroanatomic mapping during radiofrequency ablation of ventricular tachycardia in patients after myocardial infarction, July 106, 2 Originally

Background— Although radiofrequency catheter ablation (RFA) has evolved from an experimental procedure to an important treatment option for atrial fibrillation, the relative safety and efficacy of catheter ablation relative to that of antiarrhythmic drug (AAD) therapy has not been established. Methods and Results— Two separate systematic reviews were conducted: one on RFA and the other on AAD to provide accurate and broadly representative estimates of the clinical efficacy and safety of both therapies in the treatment of atrial fibrillation. Electronic searches were conducted in EMBASE and MEDLINE from 1990 to 2007. For the RFA review, all study designs were accepted. For the AAD review, articles were limited to prospective studies on the following drugs of interest: amiodarone, dofetilide, sotalol, flecainide, and propafenone. Data were extracted by 1 reviewer, with a second reviewer performing independent confirmation of extracted data. Sixty-three RFA and 34 AAD studies were included in the reviews. Patients enrolled in RFA studies tended to be younger (mean age, 55 versus 62 years), had longer duration of atrial fibrillation (6.0 versus 3.1 years), and had failed a greater number of prior drug trials (2.6 versus 1.7). The single-procedure success rate of ablation off AAD therapy was 57% (95% CI, 50% to 64%), the multiple procedure success rate off AAD was 71% (95% CI, 65% to 77%), and the multiple procedure success rate on AAD or with unknown AAD usage was 77% (95% CI, 73% to 81%). In comparison, the success rate for AAD therapy was 52% (95% CI, 47% to 57%). A major complication of catheter ablation occurred in 4.9% of patients. Adverse events for AAD studies, although more common (30% versus 5%), were less severe. Conclusions— Studies of RFA for treatment of atrial fibrillation report higher efficacy rates than do studies of AAD therapy and a lower rate of complications.

In patients with severe chronic heart failure, many deaths are sudden due to life-threatening ventricular arrhythmias. Supraventricular arrhythmias such as paroxysmal or chronic atrial fibrillation may also cause serious complications in those patients due to acute loss of atrial contraction, pump failure during rapid ventricular response and embolic events. Two therapeutic strategies are currently available for therapy and prevention of malignant ventricular arrhythmias and subsequent sudden arrhythmic death: antiarrhythmic drug therapy and implantable defibrillators. However, selection of the most beneficial strategy for the individual patient to reduce the risk of sudden death remains a major challenge in cardiology. Betablockers exert a favorable antiarrhythmic action without increasing proarrhythmia, thus betablockers may serve as a basic medication in patients at risk for sudden death. However, the general use of antiarrhythmic drug therapy for symptomatic ventricular arrhythmias is not recommended, as these drugs have been shown to increase mortality in patients with severe congestive heart failure due to proarrhythmic or negative inotropic effects (e.g. class Ia antiarrhythmics). Even class III antiarrhythmic drugs such as amiodarone, which has been studied sufficiently in patients with left ventricular dysfunction, is not effective enough for significant reduction of cardiac mortality in patients with symptomatic ventricular arrhythmias and depressed ventricular function (e.g. EMIAT, CAMIAT). But as a positive result of available studies, amiodarone does not increase mortality in those patients. Dofetilide has also not been shown to prolong life significantly by suppressing malignant ventricular arrhythmias (DIAMOND-Study). In patients with symptomatic ventricular arrhythmias or aborted sudden death, ICD therapy has been proven to be superior to antiarrhythmic drug therapy in cardiac mortality reduction as a secondary prevention strategy (e.g. AVID, CASH, CIDS). For primary prevention of sudden arrhythmic death in high risk patients, 2 studies (MADIT, MUSST) have already demonstrated favorable results, decreasing mortality by ICD therapy in selected patient populations with partly-reduced ventricular function and unsustained but inducible ventricular tachycardias. This topic is, however, undergoing further evaluation by ongoing trials (e.g. MADIT II, SCD-HeFT). From available data, antiarrhythmic drug therapy in high risk patients is not justified on a routine basis, whereas ICD therapy as a secondary and perhaps primary prevention strategy will significantly reduce cardiac mortality in patients with severe heart failure. Sotalol, a class III antiarrhythmic agent, has recently been shown to reduce ICD-shock delivery which indicates that concomitant drug therapy in patients with an ICD device already implanted may be beneficial in terms of reducing ICD discharges due to ventricular and supraventricular tachycardias. In patients with paroxysmal atrial fibrillation and congestive heart failure, restitution of sinus rhythm is the primary therapeutic goal which can be safely achieved by amiodarone and dofetilide (DIAMOND). In the latter, continuous monitoring of the patient is mandatory because of increased risk of torsade de pointes arrhythmias during the first days of drug administration. In patients with chronic atrial fibrillation rate control and anticoagulation with warfarin is the primary therapeutic option, which can be achieved with either drug treatment (Digoxin, betablockers, amiodarone) or by His bundle ablation with subsequent pacemaker insertion.

Atrial fibrillation (AF) is common in patients with hypertrophic cardiomyopathy (HCM) and is associated with increased morbidity, heart failure (HF) exacerbations, and adverse long-term outcomes. Although catheter ablation is an established rhythm-control strategy, data comparing its long-term clinical outcomes with anti-arrhythmic drug (AAD) therapy in patients with HCM remain limited. To compare long-term clinical outcomes of catheter ablation versus medical therapy with AADs in patients with HCM and AF. We conducted a retrospective cohort study using the TriNetX Research Network, a global federated database of electronic health records. Adult patients with HCM and AF between January 2010 and December 2020 were identified and stratified according to treatment with catheter ablation or AAD therapy. Outcomes included all-cause mortality, HF exacerbations, AAD-related adverse events, all-cause hospitalization, ischemic stroke, repeat ablation, need for cardioversion, need for long-term AAD use, and atrioventricular nodal ablation. A 1:1 propensity score matching (PSM) analysis was performed to balance baseline characteristics. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate hazard ratios (HRs). After PSM, 3144 patients were included (1572 in each cohort) with a mean follow-up of approximately 3.4 years. Catheter ablation was associated with lower all-cause mortality compared with AAD therapy (9.5% vs. 14.8%; HR: 0.60; 95% CI: 0.49-0.74; p < 0.001). Ablation was also associated with reduced risk of HF exacerbations (38.4% vs. 43.3%; HR: 0.79; 95% CI: 0.71-0.88; p < 0.001) and fewer AAD-related adverse events (8.4% vs. 11.2%; HR: 0.71; 95% CI: 0.55-0.93; p = 0.011). Rates of all-cause hospitalization (HR: 0.93; p = 0.11) and ischemic stroke (HR: 0.78; p = 0.10) were similar between groups. In this large real-world cohort of patients with HCM and AF, catheter ablation was associated with lower mortality, reduced HF hospitalizations, and decreased AAD therapy-related adverse events, as compared with medical therapy. These findings suggest that catheter ablation may provide meaningful clinical benefits in selected patients with HCM and AF, although prospective studies are needed to confirm these observations.

Purpose: Galectin 3 (Gal 3) – biomarker of fibrosis is increased in serum patients with atrial fibrillation (AF) and metabolic syndrome (MetS). We propose that Gal 3 can impact on progression of the arrhythmia. Objective of the study is to evaluate the role of Gal 3 in predicting the effect of antiarrhythmic drug therapy in patients with AF and MetS. Method: 180 patients with MetS (IDF, 2005) and paroxysmal (n = 100) or persistent (n = 80) AF were examined. Groups did not differ significantly by gender, age, eGFR (p > 0,05), volumes left and right atrium. The examination includes: medical history, anthropometry, echocardiography, serum Gal 3 (ELISA). Patients were taking antiarrhythmic drugs: amiodarone (32%), beta-blockers (42%), sotalol (12%), propafenone (14%) during 16,7 ± 6,9 months. After that we analyzed the clinical data and the effectiveness of antiarrhythmic drug therapy, which is considered effective if there were no reported paroxysms of AF during follow-up. Results: Serum Gal 3 in patients with persistent AF was higher compared to patients with paroxysmal AF (1,02 [0,52;3,14] and 0,54 [0,41;1,31] ng/ml, р = 0,03). In patients with 1-2 paroxysms in month serum Gal 3 was higher than in patients with 1-2 paroxysms in year (1,31 [0,92;4,21] and 0,53 [0,41;0,72] ng/ml, р < 0,001). Serum Gal 3 in patients with recurrent paroxysms of AF and without the effect of antiarrhythmic therapy was higher than in patients without recurrent paroxysms of AF irrespective of antiarrhythmic drug (1,31 [0,75,2,49] and 0,50 [0,41;0,72] ng / ml, p < 0.001). The multivariate regression analysis demonstrated that Gal 3 is an independent predictor of non-effective antiarrhythmic drug therapy of AF (OR = 2,38, 95% CI 1,12-5,04, p = 0.024). In patients with AF and MetS who had serum Gal 3 above 0,77 ng/ml (cut-off point on ROC-curve) the risk of non-effective antiarrhythmic therapy was in 3,6 fold higher during follow-up the study (RR = 3,6, 95% CI 1,6-7,9, p = 0,002). Conclusions: The level of serum galectin 3 in patients with persistent atrial fibrillation is higher than in patients with paroxysmal. Patients with higher level of galectin 3 have a higher risk of non-effective antiarrhythmic drug therapy, that may be an additional indication for surgical treatment.