Anti-tachycardia Pacing for Termination of Rapid Ventricular Tachycardia in Patients with Implantable Cardioverter-Defibrillators.The PITAGORA ICD Trial

Ventricular Tachycardia in Patients with Implantable Cardioverter-Defibrillators. The PITAGORA ICD Trial

M. G

, S. M

, F. M

, V.A. C

, R.M. P

, A.

C

, V. C

, C. P

, S. S

, M. S

, O.

P

, M.C. S

PITAGORA ICD S

I

Introduction

In patients with an implantable cardioverter–defibrillator (ICD) many episodes of rapid monomorphic ventricular tachycardia (VT) may be labelled ventricular fibrillation (VF) by the ICD and treated by painful shocks [1, 2]. Several observational studies have shown that ventricular anti- tachycardia pacing (ATP) is effective in VT termination [1–5].

The PainFREE Rx trial [6] has enrolled 220 patients with coronary artery disease and standard ICD indications, programmed a standardised ventricu- lar detection and therapy algorithm (two burst sequences, eight pulses, 88%) for arrhythmias faster than 188 bpm (320 ms) and showed that:

- 43% of arrhythmias were detected in the traditional VF zone of < 320 ms - 93% of arrhythmias detected in the VF zone were detected as fast VT

(FVT)

- Empirical ATP therapy terminates 85% of FVT episodes with cycle length (CL) from 240 to 320 ms (250–190 bpm) at the first attempt

- The number of shocks saved by enabling ATP for FVT was 396 out of 446 detected episodes

- The low observed incidence of syncopes and FVT acceleration was no greater than that reported in other studies of ICD patients

1

Cardiology Department, San Luigi, S. Currò Hospital, Catania;

Cardiolog y Department, Garibaldi Hospital, Catania;

Cardiology Department, S Sebastiano Hospital, Caserta;

Cardiology Department, Pugliese Ciaccio Hospital, Catanzaro;

5

Cardiology Department, S. Maria degli Ungheresi Hospital, Polistena;

Cardiology

Department, Civile Hospital, Piacenza;

Cardiology Department, Umberto I Hospital,

Enna;

Cardiology Department, S. Antonio Abate, Trapani;

Cardiology Department,

Civico e Benfratelli Hospital, Palermo;

Cardiology Department, Rummo Hospital,

Benevento;

Cardiology Department, Villa Sofia Hospital, Palermo;

Cardiology

Department, Perrino Hospital, Brindisi, Italy

The PainFREE trial [6] concluded that ATP for FVT detected in the VF zone might safely reduce the morbidity of painful shocks. Reducing the shocks could increase patient quality of life, and increase device longevity.

The PainFREE Rx II Study [7] was a prospective, randomised, multi-cen- tre trial that compared the safety and utility of empirical ATP (one burst sequence, eight pulses at 88% coupling interval) with shocks for FVT in a broad ICD population. PainFREE Rx II showed that the first ATP attempt ter- minated 229 of 284 (81%) FVT episodes. Forty out of 47 patients (85%) with FVT episodes presumably had at least one FVT shock prevented by ATP. ATP resulted in a 71% relative reduction in the proportion of shocked episodes.

ATP programming did not lengthen FVT episode duration, its median value was 10.0 s in the ATP arm and 9.7 s in the shock arm. Acceleration of FVT was similarly low between treatment groups: it occurred in 4 of 273 monomorphic VT episodes (2%) in the ATP arm versus 2 of 145 (1%) in the shock arm. Syncope during FVT was rare: it occurred in 2 patients in the ATP group and 1 patient in the shock group.

The process of establishing the clinical role of a new therapeutic strategy, after its feasibility, safety, and efficacy as compared with the conventional therapy have been shown, comprises the conduction of an observational study to confirm results of previous randomised studies in general clinical practice. The main objective of the PITAGORA ICD trial, therefore, is to con- firm the PainFREE II results in Italian clinical practice and to compare, in a randomised design, the termination efficacy of two different ATP sequences (burst eight pulses at 88% and ramp eight pulses starting at 91%).

Methods

Study Design

The PITAGORA ICD trial is a multi-centre, prospective, randomised, single blind study. At least 220 patients will be enrolled in about 24 Italian cardio- logical centres between January 2004 and December 2005. All patients enrolled will give written informed consent according to a protocol approved by local institutional review boards. Commercially available ICDs capable of being programmed for ATP for FVT via VF will be used. Following enrol- ment, patients will be randomised to treatment. ATP will be programmed in a burst configuration for half of them and in a ramp configuration for the other half.

Study Objectives

The main objective is to test the application in Italian clinical practice of

two empirical ATP strategies on spontaneous FVT episodes. The primary end-point is quantification of the termination efficacy of two different sequences (burst eight pulses at 88% and ramp eight pulses starting at 91%).

Secondary objectives are: estimation of the acceleration or syncopal rates associated with ATP treatment of spontaneous FVT episodes; estimation of the percentage reduction in the number of shocks delivered per patient;

evaluation of different possible predictors of ATP success (VT rate, underly- ing disease, anti-arrhythmic drug treatment); evaluation of quality of life and hospitalisations; evaluation of circadian patterns of ventricular arrhyth- mias.

Patient Selection

The inclusion criteria comprise ICD indications (class I–IIA) according to the guidelines and implantation of an ICD capable of ATP for FVT via VF.

Exclusion criteria are: patient life expectancy less than 1 year due to a non- cardiac chronic disease; patient on heart transplant list which is expected within 1 year; patient’s age less than 18 years; unwillingness or inability of patient to provide written informed consent; patient’s enrolment in, or inten- tion to participate in, another clinical study during the course of this study;

patient’s inaccessibility for follow-up at the study centre; presence of ventric- ular tachyarrhy thmias associated with reversible causes; presence of Brugada syndrome, long QT syndrome, or hypertrophic cardiomyopathy;

presence of other electrical implantable devices, such as neurostimulators or others; mechanical tricuspid valve.

Study Size and Duration

The study will enrol a minimum of 220 patients within 2 years. The study will continue for a period of 12 months after the enrolment of the last patient; total study duration will thus be approximately 3 years.

The sample size has been chosen in order to have a collection of episodes comparable with those in the PainFREE Rx trial [6].

Device Programming

The device will be programmed according to the randomisation as shown in Table 1. Since only the FVT are considered for analysis, type and program- ming of VT therapies are left to the investigators’ discretion. FVT and VF detection zones will be identical for all patients (Fig. 1):

- VF detection zone < 320 ms

- Optional VT detection zone > 320 ms

- FVT detection zone > 240 ms and < 320 ms

Data Collection Before Device Implantation

Baseline clinical data will be collected at study enrolment. These data include a complete clinical history particularly designed to capture cardiopulmonary symptoms and the occurrence and characteristics of ventricular arrhythmias before randomisation.

Follow-Up

Patients will be evaluated at follow-up visits as per clinical practice.

Whenever the patients have episodes, an unscheduled follow-up visit will be performed as soon as possible. At each visit, the patient’s clinical status will

Table 1. First FVT therapy programming in the two study arms

Burst ATP arm Ramp ATP arm

Group treatment ATP 8 pulses ATP 15 pulses

Therapy no. 1

Amplitude 8 V 8 V

Pulse width 1.6 ms 1.6 ms

Therapy type Burst Ramp

Number of initial pulses 8 8

R–S1 interval (%RR) 88% 91%

Interval decrement 10 ms 10 ms

Minimum interval 200 ms 200 ms

Number of sequences 1 1

NID VF 18/24 18/2

RNID VF 9/12 9/12

FVT therapies nos. 2–6 Shock Shock

FVT, fast ventricular tachycardia; NID, number of interval detection; RNID, redetection

240 ms 250 bpm

320 ms 188 bpm

OPTIONAL VT ZONE VF ZONE

FVT ZONE

240 ms 250 bpm

320 ms 188 bpm

OPTIONAL VT ZONE VF ZONE

FVT ZONE

Fig. 1. Study programming

be recorded and the ICD interrogated; each stored arrhythmic event will be analysed and collected by save-to-disk procedures.

For patients not showing up at scheduled follow-up visits, they or their relatives will be contacted to know some about their life status.

Anti-arrhythmic Drug Therapy

Anti-arrhythmic drug therapy is left to the physician’s discretion.

Data Analysis

Only the first ATP therapy will be considered as the basis for determining treatment success or failure. Success rates will be determined by episode.

They will be corrected to take into account multiples episodes using the gen- eralised estimating equations (GEE) method.

Appendix

Active study sites and investigators of PITAGORA ICD study are:

S. Luigi–S. Currò – Catania: Michele Gulizia, Giuseppina Francese; Garibaldi – Catania: Salvatore Mangiameli, Giuseppe Doria; S Sebastiano – Caserta: Franco Mascia, Pasquale Golino; Pugliese Ciaccio – Catanzaro: Vincenzo Antonio Ciconte, Roberto Ceravolo; ASL 10 – Polistena: Rocco Mario Polimeni, Giuseppe Meduri;

Civico – Palermo: Stefano Sammartano, Umberto Giordano; Cannizzaro – Catania:

Francesco Lisi, Francesco Liberti; Civile – Milazzo: Ludovico Vasquez, Francesco Badessa; Umberto I – Enna: Vasco Calogero, Carmelo Battaglia; Villa Sofia – Palermo:

Orazio Pensabene; S. Giovanni di Dio – Agrigento: Ignazio Vaccaro, Calogero Catalano; Papardo – Messina: Giuseppe Busà, Santina Patané; S. Antonio Abate – Trapani: Calogero Puntrello; Muscatello – Augusta: Giacomo Chiarandà, Gianfranco Muscio; S. Elia – Caltanissetta: Salvatore Giglia; Vittorio Emanuele – Catania: Alfredo Virgilio, Antonio Circo; Civile – Ragusa: Vincenzo Spadola, Guglielmo Piccione;

Iazzolino – Vibo Valentia: Michele Comito; Ferrari – Castrovillari: Giovanni Bisignani, Giovanni Sanpasquale; G. Rummo – Benevento: Marino Scherillo, Domenico Capobianco; Moscati – Avellino: Giuseppe De Fabrizio, Francesco Rotondi;

Clinica Mediterranea – Napoli (Naples): Pasquale Nocerino; Monaldi – Napoli (Naples): Lucio Santangelo, Cavallaro; Perrino – Brindisi: Maria Cristina Scianaro, G.

Ignone; Civile – Piacenza: Alessandro Capucci, Giovanni Quinto Villani.

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