Ventricular tachycardia future or investigational therapies

Ventricular tachycardia Microchapters
Home
Patient Information
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating Ventricular Tachycardia from other Disorders
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
Diagnostic Study of Choice
History and Symptoms
Physical Examination
Laboratory Findings
Electrocardiogram
Chest X Ray
Echocardiography
Cardiac MRI
Other Diagnostic Tests
Treatment
Medical Therapy
Electrical Cardioversion
Ablation
Surgery
Primary Prevention
Secondary Prevention
Cost-Effectiveness of Therapy
Future or Investigational Therapies
Case Studies
Case #1
Ventricular tachycardia future or investigational therapies On the Web
Most recent articles
Most cited articles
Review articles
CME Programs
Powerpoint slides
Images
Ongoing Trials at Clinical Trials.gov
US National Guidelines Clearinghouse
NICE Guidance
FDA on Ventricular tachycardia future or investigational therapies
CDC onVentricular tachycardia future or investigational therapies
Ventricular tachycardia future or investigational therapies in the news
Blogs on Ventricular tachycardia future or investigational therapies
to Hospitals Treating Ventricular tachycardia future or investigational therapies
Risk calculators and risk factors for Ventricular tachycardia future or investigational therapies

Overview

In recent years, the results of pharmacologic therapy for preventing VAs are disappointing. Therapy limitations are due to variable efficacy, pro-arrhythmic effects, patient compliance, and adverse effects from long-term therapy. in patients with ICDs, adjuvant suppressive therapy as amiodarone and sotalol have been shown to reduce the rate of recurrent VT when compared with beta-blockers or placebo. Pharmacologic therapy (amiodarone or sotalol) with or without adjunctive catheter ablation are recommended by the current guidelines to prevent VT/VF recurrence and reducing ICD shocks

Future or investigational studies

In recent years, the results of pharmacologic therapy for preventing VAs are disappointing. Therapy limitations are due to variable efficacy, pro-arrhythmic effects, patient compliance, and adverse effects from long-term therapy. in patients with ICDs, adjuvant suppressive therapy as amiodarone and sotalol have been shown to reduce the rate of recurrent VT when compared with beta-blockers or placebo. Pharmacologic therapy (amiodarone or sotalol) with or without adjunctive catheter ablation are recommended by the current guidelines to prevent VT/VF recurrence and reducing ICD shocks

The goals of management of VAs include:

• Symptom relief (including syncope, worsening heart failure, and ischemic chest pain
• Improving quality of life
• Reducing implantable cardioverter defibrillator (ICD) shocks,
• Preventing deterioration of left ventricular function
• Reducing risk of arrhythmic death
• Improving overall survival. Treatment of underlying medical conditions, the cardiac disorders, the presence of heart failure, the cause for the arrhythmias, consequences of the VAs, and the risks and benefits of the therapeutic pharmacological or invasive strategy

Recent research and clinical advances allowed to tailor the approach to VA management on the basis of the underlying etiology with higher efficacy. These advances have been focused on:

• The development of diagnostic modalities and imaging tools to identify the arrhythmogenic substrate responsible for VT (focal or scar)
• Genetic screening for markers of channelopathies, and
• Superior mapping and ablation technologies

Non-invasive imaging and diagnostic modalities

Over the past 100 years, cardiologists rely on the following to diagnose VT:

• ECG
• Monitoring strategies
• Limited intracardiac electrodes

As the mechanism of VT has become better understood and defined, the following non-invasive imaging modalities have become an integral part of the diagnostic and management strategy:

• Echocardiography
• Cardiac computed tomography (CT)
• Cardiac magnetic resonance imaging (CMR)
• Nuclear studies

Based on the 2015 European Society of Cardiology Guidelines, If echocardiography fails to provide accurate assessment of ventricular function or underlying structural changes that may be arrhythmogenic (scar size, distribution, and transmurality), perform CMR or CT (extended a class IIa recommendation)

The information derived from these tests are important to:

• Identify structural heart disease
• Assess left and right ventricular function
• Risk-stratify those at highest risk of inducible VT/VF on the basis of scar size in order to select the patients who would benefit most from an ICD
• Serves as a guide for planning ablation procedures

Inherited cardiomyopathies and channelopathies

• Up to half of the families of sudden cardiac arrest victims below 50 years of age are carriers of hereditary cardiomyopathies or cardiac genetic channelopathies

• It is recommended to evaluate patients and first-degree relatives with sudden cardiac arrest caused by inherited cardiovascular disease (diagnosed or suspected) in a dedicated clinic with appropriately trained staff (class I, 2015 Expert Consensus Statement from the Heart Rhythm Society)

• Early identification of a channelopathy or inherited cardiomyopathy can now be done at appropriate centers at a low cost by performing an extended molecular gene panels
• This allows risk stratification of sudden cardiac death and introduction of appropriately timed therapy (lifestyle changes, pharmacologic therapy versus ICD implantation or catheter ablation or both)

• Identification of a potential arrhythmic substrate located in the epicardial right ventricular outflow tract (RVOT) that may trigger VT/VF in some patients with Brugada syndrome has been identified and is considered an example of an important breakthrough in treating genetic arrhythmia syndromes

• Epicardial 3D EAM has shown abnormal low voltage and fractionated late potentials clustered exclusively in the anterior RVOT epicardium.

• Ablation at these sites rendered VT/VF non-inducible in 78% and normalization of the Brugada ECG pattern (coved ST-elevations in V1 and V2) in 89%.

• BRAVE Study is a multicenter randomized study (ablation in Brugada Syndrome for the Prevention of VF episodes) is being planned to assess long-term outcomes of catheter ablation in patients with Brugada syndrome

Future of medical management of ventricular tachycardia in structural heart disease

It has been challenging to develop efficacious anti-arrhythmic drugs for VAs with a limited adverse-effect profile.

• Intravenous amiodarone and sodium channel blockers (lidocaine and procainamide) remain the preferred drug regimen in the acute setting
• Intravenous sotalol has been shown to terminate sustained VT acutely with a higher efficacy versus lidocaine
• Neither amiodarone nor lidocaine has been shown to improve survival or neurologic outcomes in patients with pulseless VT/VF and out-of-hospital cardiac arrest
• intravenous procainamide has been shown to be more efficacious in tachycardia termination and was associated with fewer major cardiovascular events than amiodarone in the acute treatment of hemodynamically tolerated acute treatment of VT
• The effect was consistently observed even in those with structural heart disease as well as when adjusted for age and sex.
• Catheter ablation has been shown to be more efficacious in terms of morbidity primary outcome than escalation of anti-arrhythmic drug therapy (amiodarone or mexiletine or both) but no significant difference in terms of mortatlity
• Meta-analysis studies have shown that there is no significant difference between between anti-arrhythmic drugs versus catheter ablation for preventing recurrent VT in patients with ICDs in terms of risk reduction of VT as well as all-cause mortality

• After successful VT ablation, amiodarone may be safely reduced or discontinued to avoid potential long-term adverse effects and reduce mortality, without an increase risk in VT recurrence

• Nifekalant, a pure potassium channel blocker that has been approved for use in Japan for VT since 1999, has not been shown to be superior to amiodarone in treating out-of-hospital cardiac arrest or shock-resistant sustained VT/VF

• Azimilide (another class III agent) which is not approved in the US has been shown to reduce VAs and appropriate ICD shocks in patients with cardiomyopathies (SHIELD trial)

Future for implantable device therapy

• According to several randomized controlled trials for secondary prevention in both ischemic cardiomyopathy and NICM, ICDs can reduce the risk of sudden cardiac death in addition to guideline-directed medical therapy
• the benefit from ICD For primary prevention of sudden cardiac death has been modest particularly in NICM, primarily because of a lower rate of spontaneous VT/VF.
• An observation by DANISH investigators has been shown that there is no significant overall mortality benefit from primary prevention ICD implantation in patients with NICM and symptomatic heart failure (the DANISH investigators). However, patients younger than 59 years derive significant benefit from the ICD which means that this observation is seems to be age-dependent.
• Young patients with channelopathies and syndromes who are also at high risk for fatal VAs have a significant risk of intravascular lead-related complications and inappropriate shocks.
• This is why ICD arrhythmia detection and programming algorithms have been refined over time to include:
  • Higher minimum cutoff rates
  • Extended detection time for VT
  • Anti-tachycardia pacing
  • Morphology discriminators to minimize the risk of inappropriate shocks
  • The development of an entirely subcutaneous ICD (S-ICD) system with efficacy similar to that of conventional ICD in terminating VT/VF has been a major advance in device technology

Future of Invasive mapping and catheter ablation

• Catheter ablation guided by 3D EAM has emerged as an effective therapeutic option in patients with recurrent and sustained monomorphic VT, arrhythmia-induced cardiomyopathy, recurrent ICD shocks, intolerance to anti-arrhythmic medications, or a combination of these
• Catheter ablation of VT has a reported complication rate ranging from 5 to 7% according to different studies and has low periprocedural mortality and VT termination in up to 70% of cases.
• The recurrence rate, however, remains high; 26 to 50% of patients experience recurrent VT during long-term follow-up
• The success rate of catheter ablation for scar-mediated VT is higher in ischemic cardiomyopathy.
• Substrate-guided VT ablation remains the preferred approach particularly when the arrhythmia is poorly tolerated.
• in patients with ischemic cardiomyopathy, it has been shown that an extensive substrate-based approach is superior to targeting clinical VT (15.5% VT recurrence in substrate-guided versus 48.3% in the clinical VT target group) (The VISTA trial)
• The limitation in achieving higher success in NICM may be related to the more heterogeneous distribution of disease as well as transmurality and epicardial extension of scar
• Recent studies suggest that ablation results in improved quality of life, freedom from ICD shocks, and improved transplant-free survival.
• Limited data available that shows no proven mortality benefit yet for VT ablation in structural heart disease (randomized controlled trials)
• The long-term success of open irrigated radiofrequency (RF) catheter ablation of monomorphic VT associated with coronary artery disease showed reduced ICD shocks and VT episodes with improved quality of life at 6 months. At 3-year follow-up, non-recurrence resulted in decreased amiodarone use and hospitalizations (THE RMOCOOL VT trial)
• Other investigational and clinically tested techniques that could potentially improve substrate characterization, procedural outcomes and minimize complications include:
  • Use of irrigated and contact force ablation catheters
  • Incorporation of pre-procedural and intra-procedural imaging
  • Ablation of deep myocardial substrate with bipolar RF ablation
  • Transcoronary alcohol injection
  • Coronary coil embolization
  • Epicardial ablation
  • Surgical cryoablation
  • Remote magnetic navigation
  • Stereotactic ablative radiotherapy

However, concrete data on the efficacy of these techniques is lacking and further studies are needed.