Therapy For Ventricular Arrhythmias Research Articles

Therapy of ventricular arrhythmias in patients suffering from isolated left ventricular non-compaction cardiomyopathy.

Non-compaction cardiomyopathy (NCCM) is associated with high rates of mortality and morbidity. Knowledge regarding risk stratification, arrhythmogenesis, therapy, and prognosis is limited. The aim of this study was to analyse the outcome of patients suffering from NCCM and ventricular arrhythmias (VAs) focusing on a treatment with implantable cardioverter-defibrillator (ICD) therapy and catheter ablation. We conducted a multicentre observational study on 18 patients with NCCM, who underwent ICD implantation for secondary (n = 12) and primary (n = 6) prevention. In patients with multiple symptomatic episodes of VAs catheter ablation was performed. During a follow-up of 62 ± 42 months, 12 patients (67%) presented with appropriate ICD therapies [ventricular tachycardia (VT): n = 8; ventricular fibrillation (VF): n = 4; VT/VF: n = 3]. Ten patients underwent catheter ablation for VT/VF. Solely endocardial ablation was conducted in eight patients, and in two patients endo- and epicardial ablation was performed within the same procedure. Acute procedural success was achieved in 9/10 patients. Ventricular tachycardia recurrence was observed in two patients and the median arrhythmia free interval was 9.5 months (interquartile range 5.3-21 months). One patient underwent reablation, four patients died due to the underlying NCCM, and one patient received a left ventricular assist device. Ventricular arrhythmias are common in patients suffering from NCCM and ICD therapy may be effective for primary and secondary prevention. In our cohort, consisting of patients with multiple VA episodes and recurrent ICD therapy, catheter ablation offered a safe and effective therapeutically option.

Reduced occurrence of appropriate therapy for ventricular arrhythmias after beta-blocker uptitration following implant of a primary prevention CRT-defibrillator

Background: Absence of beta-blocker use independently predicts appropriate therapy. Following cardiac resynchronisation therapy (CRT) implant, reverse remodelling and protection against bradycardia allows for beta-blocker dose uptitration. The differential dosing effects on the occurrence of a first episode of appropriate therapy in primary prevention CRT-defibrillator (CRT-D) patients remains unstudied.Methods and Results: Changes in beta-blocker dose following CRT-D in consecutive primary prevention patients implanted between 2008 and 2015 were retrospectively studied. Beta-blocker dose was expressed as percent of target dose. Uptitration of beta-blocker dose following implant was calculated as the change in percent of target dose between implant and 6-months follow-up. Results from a prospectively maintained database of all device analysis were used to determine the occurrence of appropriate therapy. A total of 162 patients (68 ± 8 years) were studied. One hundred and ten (68%) patients underwent uptitration (mean 47 ± 19% in target dose) and 52 (32%) remained on a stable beta-blocker dose. During 37 ± 22 months follow-up, the cumulative percent of appropriate therapy was 31% in patient receiving no-uptitration versus 10% in the uptitrated patients (p < 0.001). After correction for known predictors of appropriate therapy, uptitration was independently associated with an OR = 0.263 (CI = 0.103–0.675; p = 0.001) for the occurrence of appropriate therapy. Every 1%-increase in target dose for beta-blocker associated with a significant lower risk for appropriate therapy, OR = 0.982 (CI = 0.965–0.999; p = 0.042).Conclusion: Following implantation of a primary prevention CRT-D, uptitration of beta-blockers associated with a reduced occurrence of a first episode of appropriate therapy for ventricular arrhythmias. An inverse dose–response effect was seen between beta-blocker dose and appropriate therapy.

Ablation Lesion Characterization in Scarred Substrate Assessed Using Cardiac Magnetic Resonance.

This study examined radiofrequency catheter ablation (RFCA) lesions within and around scar by cardiac magnetic resonance (CMR) imaging and histology. Substrate modification by RFCA is the cornerstone therapy for ventricular arrhythmias. RFCA in scarred myocardium, however, is not well understood. We performed electroanatomic mapping and RFCA in the left ventricles of 8 swine with myocardial infarction. Non-contrast-enhanced T1-weighted (T1w) and contrast-enhanced CMR after RFCA were compared with gross pathology and histology. Of 59 lesions, 17 were in normal myocardium (voltage >1.5 mV), 21 in border zone (0.5 to1.5 mV), and 21 in scar (<0.5 mV). All RFCA lesions were enhanced in T1w CMR, whereas scar was hypointense, allowing discrimination among normal myocardium, scar, and RFCA lesions. With contrast-enhancement, lesions and scar were similarly enhanced and not distinguishable. Lesion width and depth in T1w CMR correlated with necrosis in pathology (both; r2= 0.94, p< 0.001). CMR lesion volume was significantly different in normal myocardium, border zone, and scar (median: 397 [interquartile range (IQR): 301 to 474] mm3, 121 [IQR: 87 to 201] mm3, 66 [IQR: 33 to 123] mm3, respectively). RFCA force-time integral, impedance, and voltage changes did not correlate with lesion volume in border zone or scar. Histology showed that ablation necrosis extended into fibrotic tissue in 26 lesions and beyond in 14 lesions. In 7 lesions, necrosis expansion was blocked and redirected by fat. T1w CMR can selectively enhance necrotic tissue in and around scar and may allow determination of the completeness of ablation intra- and post-procedure. Lesion formation in scar is affected by tissue characteristics, with fibrosis and fat acting as thermal insulators.

Percutaneous cryoablation for papillary muscle ventricular arrhythmias after failed radiofrequency catheter ablation.

Catheter ablation of ventricular arrhythmias (VA) from the papillary muscles (PM) is challenging due to limited catheter stability and contact on the PMs with their anatomic complexity and mobility. This study aimed to evaluate the effectiveness of cryoablation as an adjunctive therapy for PM VAs when radiofrequency (RF) ablation has failed. We evaluated a retrospective series of patients who underwent cryoablation for PM VAs when RF ablation had failed. The decision to switch to cryoablation was at the operator's discretion when intracardiac echocardiography (ICE) suggested that cryoablation might be more effective in achieving catheter stability and energy delivery. Sixteen patients underwent cryoablation of PM VAs between 2014 and 2016 after RF ablation was unsuccessful. VAs originated from the anterolateral left ventricle (LV) PM (six patients), posterolateral LV PM (six patients), and right ventricle PM (four patients). VAs were predominantly frequent premature ventricular complexes (PVCs); however, patients with sustained ventricular tachycardia and PVC-triggered VF were also represented. Fifteen of the 16 patients were treated with cryoablation; in one patient, a procedural complication with retrograde aortic access precluded treatment. In all patients treated with cryoablation, contact and stability was confirmed with ICE to be superior to the RF catheter, and there was acute and long-term elimination of VAs. Cryoablation is a useful adjunctive therapy in ablation of PM VAs, providing excellent procedural outcomes even when RF ablation has failed. Cryoablation catheters are less maneuverable than RF ablation catheters and care is required to avoid complications.

Atrial Fibrillation and Ventricular Arrhythmias in ST Segment Elevation Myocardial Infarction: Possibilities of Pharmacotherapy and Non-Pharmacological Treatment

Atrial fibrillation (AF) is the most common tachyarrhythmia complicating ST segment elevation myocardial infarction (STEMI), while ventricular arrhythmias (VA) can, not only be accompanied by a hemodynamic disorder, but in some cases, worsen its prognosis. The article presents a modern view on risk factors for development of AF (elderly age, left ventricle systolic dysfunction, heart failure, etc.), strategy and tactics of AF treatment in patients with STEMI, the indications for its pharmacological cardioversion and electro-impulse therapy. It is shown that I.V. administration of betablockers and in some cases amiodarone for reducing the frequency of ventricular contractions is advisable. Features and argumentative issues of triple antithrombotic therapy in patients with AF with STEMI, the possibilities and indications for the use of double antithrombotic therapy instead of triple one are described. Clinical significance and peculiarities of treatment of various types of VA have been determined, the role of myocardial revascularization, radiofrequency catheter ablation, normalization of electrolyte imbalance, use of beta-blockers and amiodarone in the prevention and therapy of lifethreatening ventricular arrhythmias has been emphasized. The irrationality, and sometimes the risk of carrying out prophylactic antiarrhythmic therapy for AF and VA in the acute stage of STEMI, as well as the role of the implantable cardioverter-defibrillator in primary prevention of death in certain groups of patients with low left ventricle ejection fraction after myocardial infarction was noted. The value of various antiarrhythmic drugs in their effect on the improvement of prognosis in patients after STEMI is estimated. The material is presented based on modern recommendations for the treatment of patients with STEMI, therapy of AF and VA, prevention of sudden cardiac death, as well as data from several controlled studies and own clinical experience of pharmacotherapy of arrhythmias.

Impact of Exercise Restriction on Arrhythmic Risk Among Patients With Arrhythmogenic Right Ventricular Cardiomyopathy.

BackgroundPrior studies have shown a close link between exercise and development of arrhythmogenic right ventricular cardiomyopathy. How much exercise restriction reduces ventricular arrhythmia (VA), how genotype modifies its benefit, and whether it reduces risk sufficiently to defer implantable cardioverter‐defibrillator (ICD) placement in arrhythmogenic right ventricular cardiomyopathy are unknown.Methods and ResultsWe interviewed 129 arrhythmogenic right ventricular cardiomyopathy patients (age: 34.0±14.8 years; male: 60%) with ICDs (36% primary prevention) about exercise participation. Exercise change was defined as annual exercise duration and dose in the 3 years before clinical presentation minus that after presentation. The primary outcome was appropriate ICD therapy for VA. During the 5.1 years (interquartile range: 2.7–10.8 years) after presentation, 74% (95/129) patients reduced exercise dose and 85 (66%) patients experienced the primary outcome. In multivariate analyses, top tertile reduction in exercise duration and dose were both associated with less VA (duration: hazard ratio: 0.23 [95% confidence interval, 0.07–0.81]; dose: hazard ratio: 0.14 [95% confidence interval, 0.04–0.44]). Greater reduction in exercise dose conferred greater reduction in VA (P=0.01 for trend). Patients without desmosomal mutations and those with primary‐prevention ICDs benefited more from exercise reduction (P=0.16 and P=0.06 for interaction); however, 58% (18/31) of athletes who reduced exercise dose by >80% still experienced VA.ConclusionsExercise restriction should be recommended to all arrhythmogenic right ventricular cardiomyopathy patients with ICDs. Patients who are “gene‐elusive” and those with primary‐prevention devices may particularly benefit. Exercise reduction is unlikely to reduce arrhythmia sufficiently in high‐risk patients to alter decision‐making regarding ICD implantation.

The Role of Quinidine in the Pharmacological Therapy of Ventricular Arrhythmias 'Quinidine'.

Historically, quinidine was the first medicine used in the therapy of heart arrhythmias. Studies in the early 20th century identified quinidine, a diastereomer of the antimalarial quinine, as the most potent of the antiarrhythmic substances extracted from the cinchona plant. Quinidine is used by the 1920s, as an antiarrhythmic agent to maintain sinus rhythm after the conversion from atrial flutter or atrial fibrillation and to prevent recurrence of ventricular tachycardia or ventricular fibrillation. Its value in chronic prophylaxis of relapse of ventricular arrhythmia was brought under suspicion after publishing of meta analysis that showed that the application of quinidine increases mortality. Due to numerous proofs of increased risk for the appearance of ventricular arrhythmia and sudden death, as well as a number of other adverse effects and drug interactions, quinidine was withdrawn from use and in the recent years has become unavailable in many countries. On the other hand, recent studies have demonstrated that quinidine is the only oral medication that has consistently shown efficacy in preventing arrhythmias and terminating storms due to recurrent ventricular fibrillation, in patients with Brugada syndrome, idiopathic ventricular fibrillation and early repolarization syndrome. Quinidine is also the only antiarrhythmic drug that normalized the QT interval in patients with the congenital short QT syndrome. The aim of this review is to provide good insight into pro and contra arguments for quinidine use in ventricular arrhythmias evidence based on recently published literature.

Is resynchronization therapy really efficient in Emery Dreifuss muscular dystrophy patients?

Emery Dreifuss disease (EDMD) is a rare muscular dystrophy mostly caused by a mutation of lamin A/C or emerin genes. Heart involvement leads to arrhythmias, conduction disorders and congestive heart failure. At times, these patients can be candidate to cardiac resynchronization therapy (CRT). To describe characteristics and outcome of EDMD patients receiving CRT. All consecutive EDMD patients implanted with a CRT device for conventional indication were included in the study. Clinical, echocardiographic and device interrogation data were collected during the follow-up period. From 2002 to 2013, 11 EDMD patients received CRT (4 males; mean age 52 ± 5 years). Most of patients underwent an upgrade procedure ( n = 10, 91%) from a pacemaker (2/10) or implantable defibrillator (8/10). Average pacing percentage was 95% before CRT upgrade. Average NYHA was 2.6 ± before implantation. Most patients had right ventricular dysfunction with severe tricuspid regurgitation (75%). Ten out of eleven patients (91%) received CRT-Defibrillators. One patient (9%) required reintervention for pocket hematoma. Median follow-up was 21 months. Average biventricular pacing rate was 98%. Among patients implanted with defibrillators, 8/10 (80%) had appropriate therapies for ventricular arrhythmias while 2/10 (20%) had inappropriate therapies. Median left ventricular ejection fraction as well as median left ventricular end diastolic diameter remained unchanged: 37.5% vs 37% before CRT and 61.5 mm vs 60 mm before CRT respectively. Despite CRT, 6/11 patients (55%) had heart transplantation after an 11 months’ median follow-up period. Despite optimal CRT and apparent stability of the left ventricular dysfunction, heart transplantation is often rapidly necessary in EDMD. Right ventricular dysfunction and severe tricuspid regurgitation may partly explain these patients’ poor prognosis despite CRT.

Predictors and outcomes of cardiac resynchronization therapy extended to the second generator

A proportion of patients who receive cardiac resynchronization therapy with defibrillator (CRT-D) live to receive a second generator. Controversy exists on whether an implantable cardioverter-defibrillator (ICD) should be offered to patients who have normalized or near-normalized left ventricular ejection fraction (LVEF) at the time of generator replacement (GR). The purpose of this study was to evaluate incidence of appropriate ICD therapy after CRT-D GR. This series involved 1026 consecutive patients who underwent CRT-D implant between January 1, 2002 and December 31, 2012. Echocardiography was assessed before the initial device implant and before GR. ICDs were monitored at our device clinic in person or remotely, or both. Of the cohort, 227 patients (22.1%) underwent CRT-D GR at our institution. Approximately 48% of the patients who received new CRT-D generators were no longer meeting the guidelines indication for ICD use at the time of GR. These patients received subsequent appropriate ICD therapies at a significantly lower rate than those with LVEF <35% (12% vs 35%; P < .001). Of these patients, 47 (20.7%) had LVEF improvement to ≥50% at the time of GR. ICD therapy for ventricular arrhythmia in the ischemic group was 18.2%, while no patient in the nonischemic group received ICD therapy from the second generator after GR. Improvement in LVEF after CRT-D GR is associated with significantly reduced incidence of appropriate ICD therapy. Ventricular arrhythmia is less likely to develop with normalized LVEF in nonischemic cardiomyopathy.

Cardiac sympathectomy for the management of ventricular arrhythmias refractory to catheter ablation

Catheter ablation is now a mainstay of therapy for ventricular arrhythmias (VAs). However, there are scenarios where either physiological or anatomical factors make ablation less likely to be successful. The purpose of this study was to demonstrate that cardiac sympathetic denervation (CSD) may be an alternate therapy for patients with difficult-to-ablate VAs. We identified all patients referred for CSD at a single center for indications other than long QT syndrome and catecholaminergic polymorphic ventricular tachycardia who had failed catheter ablation. Medical records were reviewed for medical history, procedural details, and follow-up. Seven cases of CSD were identified in patients who had failed prior catheter ablation or had disease not amenable to ablation. All patients had VAs refractory to antiarrhythmic drugs, with a median arrhythmia burden of 1 episode of sustained VA per month. There were no acute complications of sympathectomy. One of 7 patients (14%) underwent heart transplant. No patient had sustained VA after sympathectomy at a median follow-up of 7 months. Because of anatomical and physiological constraints, many VAs remain refractory to catheter ablation and remain a significant challenge for the electrophysiologist. While CSD has been described as a therapy for long QT syndrome and catecholaminergic polymorphic ventricular tachycardia, data regarding its use in other cardiac conditions are sparse. This series illustrates that CSD may be a viable treatment option for patients with a variety of etiologies of VAs.

Right ventricular function assessed by 2D strain analysis predicts ventricular arrhythmias and sudden cardiac death in patients after acute myocardial infarction.

Left ventricular function is a well-established predictor of malignant ventricular arrhythmias, but little is known about the importance of right ventricular (RV) function. The aim of this study was to investigate the importance of RV function for prediction of sudden cardiac death (SCD) or malignant ventricular arrhythmias (VAs) after acute myocardial infarction (MI). A total of 790 patients with acute MI were prospectively included. All patients had 2D strain echocardiography performed to evaluate right ventricular (RV) free wall strain (RVS) and RV mechanical dispersion (MD) defined as the standard deviation of time to peak negative strain in all myocardial segments. The primary composite end point [SCD, admission with VA or appropriate therapy from a primary prophylactic implantable cardioverter-defibrillator (ICD)] was analysed with Cox models. Mean age was 69 ± 12 years, and 74% were male. Thirty-one patients experienced the primary end point during a median follow-up of 898 days (Q1-Q3 704-981). RVS was independently associated with outcome in a multivariable model including age and left ventricular global longitudinal strain; pr 1% change [hazard ratio (HR) 1.08, 95% confidence interval (CI) 1.01-1.15; P = 0.038]. Patients in the lower tertile (poor strain) showed a 10-fold risk of an event compared with the upper tertile (HR 9.8, 95% CI 2.23-42.3; P = 0.002). RV MD was not independently associated with VA/SCD (HR 0.99, 95% CI 0.91-1.09; P = 0.93). RVS proved superior to tricuspid annular plane systolic excursion (TAPSE) (P = 0.03) in the multivariable model. RVS, but not RV MD, was significantly and independently related to SCD/VA in patients with acute MI. Furthermore, RVS was shown to be superior to TAPSE.

Usefulness of Left Atrial Emptying Fraction to Predict Ventricular Arrhythmias in Patients With Implantable Cardioverter Defibrillators.

Impaired left atrial emptying fraction (LAEF) is an important predictor of mortality in patients with heart failure. As it may reflect increased LV wall stress, it might predict ventricular arrhythmia (VA) specifically. This study evaluated the predictive value of LAEF assessed with cardiovascular magnetic resonance (CMR) imaging with respect to appropriate device therapy (ADT) for VA and compared its role with CMR assessed scar size and other risk factors. In total, 229 patients (68% male, 63 ± 10years, 61% ischemic cardiomyopathy) with LV ejection fraction ≤35% who underwent CMR and implantable cardioverter defibrillator (ICD) implantation for primary prevention in 2005 to 2012 were included. CMR was used to quantify LV volumes and function. LV scar size was quantified when late gadolinium enhancement was available (n= 166). Maximum and minimum left atrial volumes and LAEF were calculated using the biplane area-length method. The occurrence of ADT and mortality was assessed during a median follow-up of 3.9years. Sixty-two patients (27%) received ADT. Univariable Cox analysis showed that male gender, creatinine level, minimum left atrial volume, LAEF, and total scar size were significant predictors of ADT. In multivariable Cox analysis, LAEF (hazard ratio 0.75 per 10%, p <0.01), and scar size (hazard ratio 1.03 per g, p= 0.03) remained the only independent predictors of ADT. Patients with both LAEF > median and scar size < median were at low risk (13% ADT at 5years), whereas those with LAEF < median and scar size > median experienced 40% ADT at 5years (log-rank p= 0.01). In conclusion, LAEF independently predicts ADT in patients with primary prevention ICDs. Combined assessment of LAEF and scar sizeidentifies a group with low risk of ADT. Therefore, LAEF assessment could assist in risk stratification for VA to select patients with the highest benefit from ICD implantation.

Clinical decision tool for CRT-P vs. CRT-D implantation: Findings from PROSE-ICD.

BackgroundCardiac resynchronization therapy (CRT) devices reduce mortality through pacing-induced cardiac resynchronization and implantable cardioverter defibrillator (ICD) therapy for ventricular arrhythmias (VAs). Whether certain factors can predict if patients will benefit more from implantation of CRT pacemakers (CRT-P) or CRT defibrillators (CRT-D) remains unclear.Methods and resultsWe followed 305 primary prevention CRT-D recipients for the two primary outcomes of HF hospitalization and ICD therapy for VAs. Serum biomarkers, electrocardiographic and clinical variables were collected prior to implant. Multivariable analysis using Cox-proportional hazards model was used to fit the final models. Among 282 patients with follow-up outcome data, 75 (26.6%) were hospitalized for HF and 31 (11%) received appropriate ICD therapy. Independent predictors of HF hospitalization were atrial fibrillation (HR = 1.8 (1.1,2.9)), NYHA class III/IV (HR = 2.2 (1.3,3.6)), ejection fraction <20% (HR = 1.7 (1.1,2.7)), HS-IL6 >4.03pg/ml (HR = 1.7 (1.1,2.9)) and hemoglobin (<12g/dl) (HR = 2.2 (1.3,3.6)). Independent predictors of appropriate therapy included BUN >20mg/dL (HR = 3.0 (1.3,7.1)), HS-CRP >9.42mg/L (HR = 2.3 (1.1,4.7)), no beta blocker therapy (HR = 3.2 (1.4,7.1)) and hematocrit ≥38% (HR = 2.7 (1.03,7.0)). Patients with 0–1 risk factors for appropriate therapy (IR 1 per 100 person-years) and ≥3 risk factors for HF hospitalization (IR 23 per 100-person-years) were more likely to die prior to receiving an appropriate ICD therapy.ConclusionsClinical and biomarker data can risk stratify CRT patients for HF progression and VAs. These findings may help characterize subgroups of patients that may benefit more from the use of CRT-P vs. CRT-D systems.Trial registrationClinicalTrials.gov NCT00733590

Corrigendum.

The Journal of PhysiologyVolume 595, Issue 6 p. 2201-2202 ErratumFree Access Corrigendum This article corrects the following: Therapy for ventricular arrhythmias in structural heart disease: a multifaceted challenge Riccardo Proietti, Jacqueline Joza, Vidal Essebag, Volume 594Issue 9The Journal of Physiology pages: 2431-2443 First Published online: January 27, 2016 First published: 15 March 2017 https://doi.org/10.1113/JP273884AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat There are errors in the article by Proietti et al (2016). Following publication of this Symposium Review, the authors have notified The Journal of two small errors in two of the figures. In Figure 2, panel D was incorrect. The correct version of Figure 2 is: In the abstract figure, the labelling in the top left box should read ‘Low EF (≤35%)’. The correct version of the figure is: Reference Proietti R, Joza J & Essebag V (2016). Therapy for ventricular arrhythmias in structural heart disease: a multifaceted challenge. J Physiol 594, 2431– 2443. doi: 10.1113/JP270534. Volume595, Issue615 March 2017Pages 2201-2202 ReferencesRelatedInformation

Updated ESC guideline: innovations for the treatment of ventricular arrhythmias and recommendations for prevention of sudden cardiac death

The 2015 European Society of Cardiology Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death is an update of the former 2006 European/American guidelines. This new consensus document gives adetailed overview on prevention and therapy of ventricular arrhythmias and sudden cardiac death. This includes detailed discussion of channelopathies and various cardiomyopathies. Gaps in evidence are identified and also discussed. DNA analysis and postmortem assessment in sudden cardiac death victims is for the first time part of these new recommendations. In addition, for the first time recommendations on subcutaneous implantable cardioverter-defibrillator (ICD) and the wearable defibrillator are given. The guidelines strengthen the role of ICD therapy in primary and secondary prevention of sudden cardiac death although data used as the basis for these recommendations are 10-15years old and patients' characteristics including therapeutic options have changed during that time. Systematic reassessment of left ventricular function 6-12weeks after infarction is also included as anew recommendation. The role of catheter ablation in electrical storm and for those presenting with afirst episode of sustained ventricular tachycardia has also been upgraded in the new guidelines. Hopefully, the new guidelines will reach not only cardiologists and help to improve patient care, but also contribute to reducing the high number sudden cardiac deaths in Europe.

Therapy for ventricular arrhythmias in structural heart disease: a multifaceted challenge.

The unpredictable nature and potentially catastrophic consequences of ventricular arrhythmias (VAs) have obligated physicians to search for therapies to prevent sudden cardiac death (SCD). At present, a low left ventricular ejection fraction (LVEF) has been used as a risk factor to predict SCD in patients with structural heart disease and has been consistently adopted as the predominant, and sometimes sole, indication for implantable cardioverter defibrillator (ICD) therapy. Although the ICD remains the mainstay life-saving therapy for SCD, it does not modify the underlying arrhythmic substrate and may be associated with adverse effects from perioperative and long-term complications. Preventative pharmacological therapy has been associated with limited benefits, but anti-arrhythmic medications have significant side effects profiles. Catheter ablation of VAs has greatly evolved over the last few decades. Substrate mapping in sinus rhythm has allowed haemodynamically unstable VAs to be successfully treated. Both LVEF as an indication for ICD therapy and electro-anatomical mapping for substrate modification identify static components of underlying myocardial arrhythmogenicity. They do not take into account dynamic factors, such as the mechanisms of arrhythmia initiation and development of new anatomical or functional lines of block, leading to the initiation and maintenance of VAs. Dynamic factors are difficult to evaluate and consequently are not routinely used in clinical practice to guide treatment. However, progress in the treatment of VAs should consider and integrate dynamic factors with static components to fully characterize the myocardial arrhythmic substrate.

Primary prevention implantable cardioverter-defibrillator and cardiac resynchronization therapy-defibrillator in elderly patients: results of a Spanish multicentre study.

Currently, there continues to be a lack of evidence regarding outcomes associated with device-based therapy for ventricular arrhythmias in elderly patients, even more in primary-prevention indications. We aimed to describe the follow-up in terms of efficacy and safety of implantable cardioverter-defibrillator (ICD) therapy in a large cohort of elderly patients. Retrospective multicentre study performed in 15 Spanish hospitals. Consecutive patients referred for ICD implantation before 2011 were included. One hundred and sixty-two of 1174 patients (13.8%) ≥75 years were considered as 'elderly'. When compared with those patients <75, this subgroup presented more co-morbid conditions, including hypertension, chronic obstructive pulmonary disease , and renal failure, and more previous hospitalizations due to heart failure (HF). During a mean follow-up of 104.4 ± 3.3 months, 162 patients (14%) died, 120 in the younger age (12.4%), and 42 (24.4%) in the elderly. Kaplan-Meier analysis showed an increased probability of death with increasing age (17, 24, 28, and 69% at 12, 24, 48, and 60 months of follow-up in the elderly group). There was neither difference regarding the rate of appropriate nor inappropriate ICD intervention. In a real-world scenario, elderly patients comprise ∼15% of ICD implantations for primary prevention of sudden cardiac death (SCD). Although the rate of appropriate therapy is similar between groups, the benefit of ICD is attenuated for a major increase in mortality risk among those patients ≥75 years at the moment of device implantation.

Abstract 17176: Prognostic Importance of Defibrillator Appropriate Shocks and Anti Tachycardia Pacing in Mild Heart Failure Patients

Background: Previous studies had shown that patients with heart failure (HF) who receive implantable cardioverter-defibrillator (ICD) for primary prevention are at increased risk for mortality if they receive a shock. However, information about the prognostic importance of therapies [both shock and anti-tachycardia pacing (ATP)] delivered for a different ventricular arrhythmia (VA) rate is limited. Methods: We evaluated the risk for death among 1790 ICD implanted patients from the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy using a time dependent analysis. Patients were categorized to mutually exclusive groups by either the rate of the treated VA (categorized at 200 bpm) or the type of the therapy and VA rate (ATP or shock both categorized at 200 bpm), the reference group was patients that had no device therapy. Results: During a median follow-up time of 4 years 423 patients had appropriate ICD therapy, with 163 receiving therapy for VA&lt; 200 bpm only, and 260 for VA≥200 bpm. ICD therapy for VA≥200 was associated with significant increased mortality (HR=2.27 CI 1.48-3.48, p&lt;.001), while therapy for VA&lt;200 was not different from the no therapy group (HR=1.45 CI=0.86-2.44, p=0.162). Accordingly, in a second model both shocks and ATPs for VA≥200 were associated with increased mortality (HR=2.96 CI 1.91-4.60 p&lt;.001 and HR=2.22 CI 0.96-5.14, p=0.063 respectively), while shocks and ATPs for VA&lt;200 did not differ from the no therapy group (HR=1.43 CI 0.52-3.92 p=0.489 and HR=1.43 CI 0.80-2.56, p=0.232 respectively). Conclusions: In mild HF patients, who receive ICD for primary prevention, mortality is associated with the rate of the arrhythmia rather than the device rendered therapy.

Abstract 18861: Effects of Class III Antiarrhythmics on ICD Therapies and Clinical Outcomes: A Meta-analysis of Randomized Controlled Trials

Introduction: Implantable cardioverter defibrillators (ICD) prolong survival in patients with heart failure, reduced left ventricular ejection fraction (LVEF &lt;= 35%) and/or sustained ventricular arrhythmias (VA) by terminating VA with either anti-tachycardia pacing (ATP) or shock. However, ICD therapies are associated with significant pain, psychological distress, and increased risk for hospitalization and mortality. Antiarrhythmic drugs are commonly used to reduce frequency of VA in patients with ICD. We attempt to study the effects of class III antiarrhythmics on the frequency of ICD therapies, hospitalization and mortality. Methods: PubMed database was queried to identify prospective randomized controlled trials comparing class III antiarrhytmics to placebo on a standard background medical therapy in patients with an ICD and prior history of sustained VA (spontaneous/ treated/ induced) and/or sudden cardiac death. Information on appropriate ICD therapy, hospitalization and mortality was extracted. Fixed effect analysis was used when I2 ≤ 25% and p &gt;0.1, otherwise random effect analysis was performed. Results: After reviewing 2931 articles, seven trials that studied Amiodarone, Sotalol, Azimilide or Celivarone were included. A total of 2117 patients (87% males, mean age 63.8 years, mean LVEF 32.8%) were analyzed. 50.6% of the patients had at least one appropriate ICD therapy delivered and 4.5% died during the follow up. Antiarrhythmic drug usage significantly reduced the number of patients receiving ICD therapy by 55% (OR=0.45, 95% confidence interval [CI] 0.26-0.77, P=.004). There was no significant difference in mortality between treatment and placebo arms. Only 2 of the 7 trials reported number of hospitalizations and the sample size was insufficient for analysis. Conclusions: Class III antiarrhythmics significantly reduced ICD therapy for VA with no significant change in mortality.

Abstract 10920: Programmed Ventricular Stimulation for Risk Stratification in the Brugada Syndrome: A Pooled Analysis

Introduction: The role of programmed ventricular stimulation (PVS) in identifying Brugada syndrome patients at highest risk for sudden death is uncertain. Objective: To investigate the utility of PVS to predict future cardiac arrests or ICD therapy for ventricular arrhythmias in Brugada syndrome patients. Methods: We performed a systematic review and pooled analysis of prospective observational studies of Brugada syndrome patients with no history of sudden cardiac arrest who underwent PVS. We estimated incidence rates and relative hazards of cardiac arrest or ICD shock. Results: We analyzed individual-level data from 8 studies, comprising 1312 patients who experienced 65 cardiac events (median follow-up of 38.3 months). A total of 527 patients were induced into arrhythmias with up to triple extrastimuli. Induction was associated with cardiac events during follow-up (HR 2.66, 95%CI 1.44-4.92, P&lt;0.001). Event risks were inversely proportional to the number of extrastimuli causing induction (HR for each fewer extrastimulus protocol relative to individuals not induced 1.69, 95%CI 1.25-2.29, P&lt;0.001). Annual event rates varied substantially by syncope history, presence of spontaneous type 1 ECG pattern, and arrhythmia induction (0.23%, 95%CI 0.05-0.68 [no induced arrhythmia with up to double extrastimuli]; 0.45%, 95%CI 0.01-2.49 [induced arrhythmia]) and highest risk occurring among individuals with syncope and spontaneous type 1 patterns (2.55%, 95%CI 1.58-3.89 [no induced arrhythmia]; 5.60%, 95%CI 2.98-9.58 [induced arrhythmia]; ( Figure ). Conclusion: In Brugada syndrome patients, arrhythmias induced with PVS associate with future ventricular arrhythmia risk. Induction with fewer extrastimuli is associated with higher risk. However, clinical risk factors are important determinants of arrhythmia risk, and lack of induction does not necessarily portend low ventricular arrhythmia risk particularly in patients with high-risk clinical features.