Medical Treatment for Idiopathic VT/Vpcs

APHRS Summit meeting 2016 Medical treatment for idiopathic VT/VPCs

Yoshinori Kobayashi MD Tokai university Hachioji hospital Tokyo, JAPAN Classification of idiopathic VT and VPCs according to mechanism and origin of the tachycardia 1) Triggered activity or enhanced automaticity -origin (successful ablation site)-

(1) Outflow tract a)RV-Outflow tract (Septum, Free wall, RCC, pulmonary artery) b)LV-Outflow tract (LCC, RCC, Sub-aortic valve endocardium, Cardiac summit) (2) Anterior inflow (His bundle area, NCC) (3) Tricuspid annulus (tricuspid annulus) (4) Mitral annulus (mitral annulus) (5) Papillary muscle (left side dominant, left posterior PM> left anterior PM) (6) His-Purkinje system (Purkinje network, bundle branch) (7) Epicardial LV including cardiac summit (GCV, AIVV, Epicardial approach) (8) Crux (Intra-CS, Mid cardiac vein, Epicardial approach)

2) Reentrant mechanism (1) Verapamil sensitive left ventricular tachycardia (Fascicular tachycardia) a) Posterior type b) Anterior type c) Upper-septal type Delayed afterdepolarization (DADs) in adenosine-sensitive VT

Induction of VT during pacing. The small deflection suggesting DADs is noted during pacing on MAP catheter positioned at the site of origin (RVOT). DAD is shown to be facilitated by catecholamine infusion and exercise.

VT was terminated by adenosine, and the termination was associated with abolition of DADs

Lerman BB et al. Heart Rhythm 2007;4:973-976. Signal transduction schema for initiation and termination of cAMP-mediated triggered activity Vagal maneuvers Adenosine

Be-ta blocker Catecholamine Be-ta adrenergic stimulation Exercise and catecholamine increase intracellular cAMP production via stimulation of the Gs protein and induce various cellular responses including acceleration of the L-type calcium channel and Ca release from SR. Then the increase in Ca channel blocker intracellular Ca concentration results in the acceleration of Na-Ca exchanger and Iti, which generates DADs.

Adenosine activates the inhibitory Gi protein via adenosine A1 receptor stimulation and antagonize increased cAMP production. Facilitate Lerman BB et al. Heart Rhythm 2007;4:973-976. Suppress Right and left ventricular outflow tract tachycardia Evidence for a common electrophysiologic mechanism

Iwai S et al. J Cardiovasc Electrophysiol 2006;17:1052-58

What about the mechanism of idiopathic focal VTs originating in the other regions. LVOT-VTs were similarly shown to be adenosine sensitive and verapamil sensitive. Comparison of clinical parameters between RVOT-VT and LVOT-VT

Iwai S et al. J Cardiovasc Electrophysiol 2006;17:1052-58 Autonomic and pharmacological responses of IVT arising from the LVOT

4/5 pts

6/6 pts

4/5 pts

Yamawake N et al. J Cardiovasc Electrophysiol 2007;18:1161-66 Location of the origins of annular IVT and induction of VT by exercise

Patient population： 9 pts with annular VT Tricuspid annulus:3 Mitral annulus: 7 Epicardial origin:3

Mean VT Cycle length : 450±87 ms

6/6 pts: Programmed pacing initiated VT was initiated by exercise and terminated the VT 7/9 pts: Isoproterenol facilitated initiation of the VT

Ip JE et al. Circ Arrhythm Electrophysiol 2014;7:436-444 Response of VT to administration of adenosine, verapamil and Valsalva maneuver

Adenosine terminated VT in 9/9 pts

Verapamil terminated VT Valsalva maneuvor in 2/2 pts Terminated VT in 2/2 pts

Ip JE et al. Circ Arrhythm Electrophysiol 2014;7:436-444 Epicardial origin including the cardiac summit How to measure the MDI

Distribution of the origin of epicardial VT/VPC

Electrophysiological characteristics: ISP: Facilitate the tachycardia occurrence in 10/10 (100%) Pacing: induced the tachycardia in 8/10 (80%) terminated the tachycardia in 10/10 (100%) Adenosine: terminated VT in 8/9 (89%) Entrainment phenomenon (-) B: Distribution of MDI values Cyclic AMP mediated triggered activity in various subgroups. Daniels DV et al. Circulation 2006;113:1659-1666 Anatomical and ECG characteristics of VAs originating in PM

Yamada T et al. Circ Arrhythm Electrophsiol. 2010;3:324-31 Distribution of the origins of PM ventricular arrhythmias and electrophysiological characteristics

Electrophysiological features 1) Refractoriness to verapamil and Na channel blockers 2) Tendency for PVCs rather than VT 3) Inducibility with exercise 4) Lack of inducibility with programmed pacing 5) Focal mechanism proved by mapping system (Centrifugal activation pattern)

Distribution of origin of Non-reentrant mechanism Triggered activity LV papillary muscle or enhanced automaticity

Yamada T et al. JCE. 2009;20:866-72 12.1. Idiopathic Ventricular Tachycardia Recommendations

Class I Catheter ablation is useful in patients with structurally normal hearts with symptomatic, drug-refractory VT arising from the RV or LV or in those who are drug intolerant or who do not desire long-term drug therapy. (Level of Evidence: C)

Class IIa 1. EP testing is reasonable for diagnostic evaluation in patients with structurally normal hearts with palpitations or suspected outflow tract VT. (Level of Evidence: B)

2. Drug therapy with beta blockers and/or calcium channel blockers (and/or IC agents in RVOT VT) can be useful in patients with structurally normal hearts with symptomatic VT arising from the RV. (Level of Evidence: C)

3. ICD implantation can be effective therapy for the termination of sustained VT in patients with normal or near normal ventricular function and no structural heart disease who are receiving chronic optimal medical therapy and who have reasonable expectation of survival for more than 1 y. (Level of Evidence: C) ACC/AHA/ESC 2006 guidelines foe management of patients with ventricular arrhythmias And the prevention of sudden cardiac death. Circulation 2006;114:e385-484 Previously reported success rate of catheter ablation in various subtypes of idiopathic VT/VPCs

RVOT 80-95% LVOT (Endocardial) 70-80% LVOT (Epicardial) 60-80% Near sinus of Valsalva 70-90% Tricuspid or mitral anuli 80-90% LV Papillary muscle 50-70% Cardiac crux 50-80%

Fascicular VT (verapamil-sensitive) 90-100% Effect of be-ta blockers on the frequency of VPCs, symptoms and circadian variation Randomized placebo-control study Pre-drug RVOT-VT 25 pts: Atenolol 50-100mg/day 27 pts: placebo group

Propranolol attenuated circadian variation of VPCs originating RVOT

Post-drug

Atenolol significantly reduced PVC count, basic HR and symptoms

Krittayaphon R et al. AHJ 2002;144:e15 Hayashi H et al. AJC 1999;84:99 12.1. Idiopathic Ventricular Tachycardia Recommendations

Class IIa 1. EP testing is reasonable for diagnostic evaluation in patients with structurally normal hearts with palpitations or suspected outflow tract VT. (Level of Evidence: B)

3. ICD implantation can be effective therapy for the termination of sustained VT in patients with normal or near normal ventricular function and no structural heart disease who are receiving chronic optimal medical therapy and who have reasonable expectation of survival for more than 1 y. (Level of Evidence: C) ACC/AHA/ESC 2006 guidelines foe management of patients with ventricular arrhythmias And the prevention of sudden cardiac death. Circulation 2006;114:e385-484 Spatial distribution of Pd potential and Pp potential in 6 patients with ILVT using CARTO

2 specific local potentials can be detected at the left posteroseptal region

I I

II II

V1 V1

40ms

MAP * * * MAP * * *

Pd potential defined as a slow or fragmented Pp potential defined as spiky potential potential preceding QRS complex preceding QRS complex >40msec >0msec

J Arrhythm. 2015; 31(5): 261–267 Schematic presentation of the distribution of Pd and Pp potential

Case1 Case2 Case3 RAO view PP PP PP

PD PD PD Case4 Case5 Case6

PP PP PP

PD PD PD

Pd potential Pp potential Pd-Pp fusion potential J Arrhythm. 2015; 31(5): 261–267 Effects of lidocaine and verapamil on the conduction of Pd region

Both lidocaine and verapamil prolongs the Pd-Pp interval during the entrainment pacing and the tachycardia. Because both drugs increased the conduction time over the SCZ, the SCZ contains both the depressed sodium- channel-dependent tissue and the calcium channel dependent tissue.

Tsuchiya T et al. JACC 2001;37:1415 Pilsicainide-induced verapamil sensitive ILVT

At the successful ablation site, both DPs and PPs could be recorded.

Because the mechanism of ILVT is reentry with excitable In the baseline study, sustained VT could not be gap, increased conduction delay within the reentry circuit induced by RV programmed pacing, while after by pilsicainide is likely mechanism for the induction and low-dose of pilsicainide it became inducible with perpetuation of the tachycardia. reproducibility. Nagai T et al. PACE 2006;29:549 Summary 1) Idiopathic ventricular arrhythmias (VA:VT/VPC) has a variety of origins which are distributed In both right and left ventricles.

2) The underlying mechanism of most of IVAs except the fascicular VT have been shown to be cAMP-mediated triggered activity (delayed after-depolarization) or enhanced automaticity.

3) Thus, these arrhythmias are supposed to be sensitive to be-ta blockers and calcium channel blockers, and sometimes susceptible to Na channel blockers too.

4) Although the catheter ablation has been shown to be highly effective in suppressing this category of the arrhythmias, the success rate in the IVAs originating in several specific regions such as epicardium and papillary muscles remains relatively low. In such refractory patients to catheter ablation, the role of medical treatment including hybrid therapies still remains as one of therapeutic options.

5)In the patients with fascicular tachycardia (verapamil-sensitive VT), catheter ablation is very effective, therefore the role of the antiarrhythmic therapy is relatively low.

6) When the programmed pacing cannot induce the fascicular VT even under the use of ISP, a low dose of Na channel blocker may facilitate the induction of the tachycardia, rendering it possible to assess the mechanism and activation of the tachycardia. Thank you for your attention

Mt. Erevest on the shiluette of Mt. Nuptse