Ventricular Stimulation in Post-Myocardial. Fraction and no Ventricular Arrhythmias

Transcription

1 original ARTICLES Ventricular Arrhythmias Risk Evaluation by Microvolt T-wave alternans versus Programmed Ventricular Stimulation in Post-Myocardial Infarction Patients With Preserved Ejection Fraction and no Ventricular Arrhythmias Sorin Pescariu, Daniel Brie, Dana Maximov, Dana Popa, Milovan Slovenski, Adina Ionac, Cristian Mornos, Andreea Dumitrescu, Stefan Iosif Dragulescu REZUMAT Obiectiv: Determinarea fezabilit\]ii MTWA (Microvolt T-wave alternans) pentru evaluarea riscului de aritmie ventricular\ la pacien]ii cu interven]ie de revascularizare complet\ dup\ infarct miocardic, frac]ie de ejec]ie a ventriculului st ng (FEVS) p\strat\ [i f\r\ aritmii ventriculare maligne n antecedente. Material [i metode: Lotul de studiu a fost format din 74 pacien]i (13 femei - 18%, v rst\ medie ani), cu FEVS 45% (FEVS mediu 59 13%) [i f\r\ aritmii ventriculare sus]inute n antecedente, care au fost supu[i interven]iei de revascularizare cu implantare de stent pentru infarct miocardic acut sau recent (boala coronarian\ mono sau bi-vascular\). Dup\ 30 de zile de la interven]ia de revascularizare to]i pacien]ii au efectuat un test de efort MTWA (Heartwave system, Cambridge Heart Inc. 2000) urmat de un studiu electrofiziologic cu stimulare ventricular\ programat\ standard (SVP) (ce a inclus ntre 1 [i 3 stimuli). Rezultate: {aisprezece pacien]i (22%) au fost pozitivi la testul MTWA, 52 pacien]i (70%) au avut un test negativ, iar 6 (8%) un test nedeterminat. La SVP, r\spuns pozitiv - aritmie ventricular\ sus]inut\ - au prezentat doar doi pacien]i cu teste MTWA pozitiv (un pacient a prezentat tahicardie ventricular\ monomorfic\, iar altul tahicardie ventricular\ polimorfic\). La ace[tia a fost implantat un dispozitiv cardioverter - defibrilator. La al]i 12 pacien]i cu r\spuns negativ la SVP, nou\ cu MTWA anterior pozitiv, iar trei cu MTWA negativ, a fost indus\ tahicardie ventricular\ nesus]inut\ ( ntre 10 [i 25 de secunde). Doi pacien]i cu test MTWA pozitiv au refuzat SVP. Sensibilitatea MTWA n detectarea aritmiilor ventriculare a fost de 90%, cu o specificitate de 81%. Valoarea predictiv\ negativ\ a MTWA pentru evenimente aritmice ventriculare a fost de 97%, iar cea pozitiv\ a fost de 14.3%. Urm\rirea medie a fost de 14 luni, f\r\ evenimente aritmice majore n toate cazurile, inclusiv la cei cu cardioverter-defibrilator implantabil. Concluzii: Testul MTWA are o valoare predictiv\ negativ\ bun\ pentru evenimentele aritmice la aceast\ categorie de pacien]i [i poate fi utilizat\ pentru stratificarea riscului. Consider\m c\ la pacien]ii cu MTWA pozitiv este necesar\ investigarea ulterioar\ invaziv\, respectiv SVP. Cuvinte cheie: studiu electrofiziologic, Microvolt T-wave alternans, aritmie ventricular\, stimulare ventricular\ programat\, infarct miocardic abstract Objective: The study objective is to determine the feasibility of Microvolt T-wave alternans (MTWA) for ventricular arrhythmia risk evaluation in patients with complete interventional revascularization after myocardial infarction, preserved left ventricular ejection fraction (LVEF) and no prior malignant ventricular arrhythmias. Material and methods: Study population included 74 patients (13 women - 18%, mean age 56 ± 11 years) with LVEF 45% (mean LVEF 59 ± 13%) and no prior sustained ventricular arrhythmias underwent successfully interventional revascularization with stent implantation for acute or recent myocardial infarction (1 or 2 coronary vessel disease). At 30 days after interventional revascularization all patients underwent MTWA exercise test (Heartwave system, Cambridge Heart Inc. 2000) followed by electrophysiological study with standard programmed ventricular stimulation-pvs (including 1 to 3 extrastimuli). Results: Sixteen patients (22%) were found positive at MTWA test, 52 patients (70%) had a negative test, and 6 patients (8%) had an indeterminate test. At PVS positive response- sustained ventricular arrhythmias were induced in only two patients with previous positive MTWA (one patient with ventricular monomorphic tachycardia, one patient with ventricular polymorphic tachycardia). They were implanted with an implantable cardioverter defibrillator. In 12 patients with negative response at PVS, 9 with previous positive MTWA and 3 with previous negative MTWA, nonsustained (between seconds) ventricular tachycardia was induced. Two cases with positive MTVA refused the PVS. The sensitivity of MTWA test for ventricular arrhythmias was 90%, with 81% specificity. The negative predictive value of MTWA for ventricular arrhythmic events was 97% and the positive predictive value was 14.3%. The average follow-up was 14 months without major arrhythmic events for all cases, including those implanted with ICD. Conclusions: The MTWA test has a good negative predictive value for arrhythmic events in this category of patients and can be used for risk stratification. We consider that in patients with positive MTWA, further invasive evaluation, respectively PVS, is necessary. Key Words: electrophysiological study, Microvolt T-wave alternans, ventricular arrhythmia, programmed ventricular stimulation, myocardial infarction 2 nd Cardiology Clinic, Institute of Cardiovascular Disease, Victor Babes University of Medicine and Pharmacy, Timisoara Correspondence to: Sorin Pescariu, Institute of Cardiovascular Disease, 13A G. Adam Str., Timisoara, Tel sorinpescariu@yahoo.com Received for publication: Apr. 13, Revised: Jun. 26, Introduction Patients with reduced left ventricular ejection fraction (LVEF) after myocardial infarction (MI) are at risk of ventricular arrhythmias and many reports regarding risk stratification in these patients have been published. 1-3 Few studies evaluated the risk stratification markers in post-mi patients with preserved LVEF. Risk Sorin Pescariu et al 45

2 stratification is important in patients with preserved LVEF despite the better prognosis of these patients. 4 Microvolt T-wave alternans (MTWA) is a useful marker for identification of high-risk patients post-mi patients with reduced LVEF 30%, or <40%, but the role of MTWA is unknown for risk stratification in post-mi patients with preserved LVEF. 5-7 The study purpose is to determine the feasibility of MTWA for ventricular arrhythmia risk evaluation in patients with complete interventional revascularization after myocardial infarction, preserved LVEF and no prior malignant ventricular arrhythmias. MATERIAL AND Methods Patient population This prospective study enrolled 74 patients (61 men, mean age 56 ± 11 years) with LVEF 45% and no prior sustained ventricular arrhythmias underwent successfully interventional revascularization with stent implantation for acute or recent myocardial infarction (one or two- coronary vessel disease). The diagnosis of MI was based on the clinical course, serum marker activity and ST elevation on electrocardiogram. The LVEF was assessed by modified Simpson rule on echocardiography. We excluded from our study patients with persistent atrial fibrillation/ flutter or those who required a ventricular pacemaker because the MTWA test cannot be interpreted in such circumstances. An informed consent for procedures was obtained from each patient and the study was approved by the local ethics committee. At 30 days after interventional revascularization all patients underwent MTWA exercise test, followed by an electrophysiological study with standard programmed ventricular stimulation. Measurement of MTWA testing Microvolt T wave alternans test was performing using a Heartwave system (Cambrige Heart, Inc., Beadford, Massachusetts) during bicycle exercise. In order to minimize the noise, skin preparation and high resolution electrodes were used. Electrocardiographic leads were placed at standard 12-lead positions and in orthogonal X, Y, Z configuration. The MTWA test was interpreted as positive, negative and indeterminate according to a previously described report. 8 The test was defined as positive if it had sustained alternans with an onset heart rate 110 beats/min or had sustained alternans at resting heart rate, even if the latter is >110 beats/min. Sustained alternans is defined as lasting at least one minute with alternans voltage (Valt) 1.9 μv and alternans ratio 3.0 in any orthogonal lead or two consecutive precordial leads during exercise. The test was defined as negative when the positive criteria were not met and artifact-free data were available showing a heart rate maintained at a level >105 beats/min for at least one min. The test was defined as indeterminate when the results did not meet either the positive or negative criteria. Standard programmed ventricular stimulation After local anesthesia using lidocaine 1%, three 6-Fr quadripolar electrode catheters were inserted percutaneously through the femoral vein and advanced to the high lateral right atrium, across the tricuspid valve, recoded the His bundle electrogram, and to the right apex in all patients. Programmed ventricular stimulation was performed using stimulus duration of 2-ms at amplitude of two to three times the diastolic threshold, with up to three extrastimuli at basic drive cycle lengths, 600 ms and 400 ms respectively, starting at apex, then at outflow tract. Coupling intervals of extrastimuli were decreased in 10-ms interval until coupling interval of 180 ms was reached or refractoriness of all extrastimuli was reached. The endpoint of electrophysiology was the induction of sustained ventricular tachycardia (>30 s in duration or associated with hemodynamic compromise requiring earlier intervention) or the completion of stimulation protocol. The induction of ventricular fibrillation was defined prospectively as an indeterminate result. Follow-up All patients were followed for an average of 14 months. Clinical follow-up was obtained as regular interval. Arrhythmic events during follow-up were defined as: 1. Sustained ventricular tachycardia or ventricular fibrillation; 2. Appropriate ICD therapy for ventricular tachyarrhythmia with documentation of the rhythm leading to the shock by stored electrograms by the device; 3. Sudden cardiac death Statistical analysis All results are expressed as mean ± standard deviation. Sensivity, specificity, positive and negative predictive value, and the predictive accuracy of eventfree prediction were evaluated. 46 TMJ 2008, Vol. 58, No. 1-2

3 Results A number of 74 patients (61 men, 82%) evaluated in this study. (Table 1) The mean age of this cohort was 56 ± 11 years, and the mean left ventricular ejection fraction 59 ± 13%. All patients had acute or recent myocardial infraction (one or two coronary vessel disease) that underwent successfully interventional revascularization with stent implantation. At 30 days after interventional revascularization all patients underwent MTWA exercise test followed by electrophysiological study with standard programmed ventricular stimulation as describe earlier. Table 1. Patients characteristics. Number 74 pts Male/Female ratio 61 (82%) / 13 (18%) Age, mean ± SD 56 ± 11years Left ventricular ejection fraction, mean ± SD 59 ± 13 % Myocardial infarction - anterior 40 pts (54%) - inferior 27 pts (36%) - lateral 7 pts (10%) Figure 1. T-wave alternas positive test. Alternas precordial trend summary. The microvolt TWA test was positive in 16 patients (22%), negative in 52 patients (70%), while 6 patients (8%) had an indeterminate test. (Fig. 1,2) Figure 2. T-wave alternas positive test. Alternans vector trend summary. Indeterminate test was primarily due to frequent ectopic beats or the inability to achieve the target heart rate of >105 beats/min. Previous report in the MI population with reduced LV function has combined positive and indeterminate microvolt TWA into one abnormal group. In our study we separated patients with a positive microvolt TWA test from patients with an indeterminate microvolt TWA test. At electrophysiological study, sustained ventricular arrhythmias were induced in two patients (both with previous positive microvolt TWA test), one with ventricular monomorphic tachycardia and one with ventricular polymorphic tachycardia, with hemodinamic deterioration requiring immediate cardioversion. (Figs. 3-5) These patients received a cardioverter implantable defibrillator. In 12 patients (nine with positive microvolt TWA test, three with negative microvolt TWA test) with negative response on programmed ventricular stimulation nonsustained ventricular tachycardia (between s) was induced. Two patients with positive microvolt TWA refused the electrophysiological study with programmed ventricular stimulation. The sensitivity of predictive value of microvolt TWA for ventricular arrhythmic events was 90%, with 81% specificity. The negative predictive value of microvolt TWA for ventricular arrhythmic events was 97% and the positive predictive value was 14.3%. Sorin Pescariu et al 47

4 Figure 3. Ventricular programmed stimulation. Induction of sustained ventricular tachycardia. Figure 4. Ventricular programmed stimulation. Sustained ventricular tachycardia. in this type of patients (prior MI, preserved LVEF) and can be used for risk stratification. The most common mechanism of sudden cardiac death after acute MI is ventricular tachyarrhythmia.9 The risk of sudden cardiac death among post-mi with preserved LVEF is considered low in patients who benefit of early revascularization. Arrhythmic events have a lower incidence in patients with preserved cardiac function than in patients with reduced cardiac function. Numerous studies evaluate the risk of sudden cardiac death in patients with reduced LVEF after MI. Little information is available with respect to the prognostic value of risk stratification markers in post-mi patients with preserved LVEF. Accurate identification of patients at increased risk for sustained ventricular arrhythmias is critical for development of effective strategies to prevent sudden cardiac death. In our study, microvolt TWA test has a low positive predictive value (14.3%), thus, for risk stratification of sudden cardiac death further investigation is needed. Because sensitivity and negative predictive value of microvolt TWA test in our study were high (90% and 97%), the test could be used in the primary screening of patients for risk of ventricular arrhythmias in this population. The positive predictive value of microvolt TWA could be improved when the test is combined with other noninvasive markers, such as NSVT and ventricular late potential.10 We consider that in patients with positive microvolt TWA further evaluation, including electrophysiological study with programmed ventricular stimulation, is needed. The average follow-up was 14 months without major arrhythmic event for all patients, including those with an ICD. Study limitations The study is limited because of reduced number of patients included. Medical and interventional treatment played an important role in evolution of post-mi patients and the incidence of ventricular arrhythmias can be influenced by this. We did not include in our study other risk of ventricular arrhythmias variable such of signaled average electrocardiography and autonomic imbalance markers (heart-rate variability, baroreflex sensitivity and heart rate turbulence). The microvolt TWA test was indeterminate in some patients because they could not achieve a heart rate of at least 105 beats per minute with exercise or due to frequent ectopic ventricular beats. Discussion Conclusion Our study demonstrate that microvolt TWA has a good negative predictive value for arrhythmic events The MTWA test has a good negative predictive value for arrhythmic events in post-mi patients with Figure 5. Ventricular programmed stimulation. Sustained ventricular tachycardia converted with external electric shock to synus rhythm. 48 TMJ 2008, Vol. 58, No. 1-2

5 preserved LVEF and can be used for risk stratification. We consider that in patients with positive MTWA further invasive evaluation, respectively programmed ventricular stimulation, is necessary. REFERENCES 1. Julian DG, Camm AJ, Frangin G, et al. European Myocardial Infarct Amiodarone Trial Investigators. Randomised trial of effect of amiodarone on mortality in patients with left-ventricular dysfunction after recent myocardial infarction: EMIAT. Lancet 1997;349: Makikallio TH, Hoiber S, Kober L, et al. TRACE Investigators Fractal analysis of heart rate dynamics as a predictor of mortality in patients with depressed left ventricular function after acute myocardial infarction (TRAndolapril Cardiac Evaluation.) Am J Cardiol 1999;83: Farrell TG, Bashir Y, Cripps T, et al. Risk stratification for arrhythmic events in postinfarction patients based on heart rate variability, ambulatory electrocardiographic variables and the signal-averaged electrocardiogram. J Am Coll Cardiol 1991;18: Ikeda T, Yoshino H, Sugi K, et al. Predictive value of microvoltage T- wave alternans for sudden cardiac death in patients with preserved cardiac function after acute MI: results of a collaborative cohort study. J Am Coll Cardiol 2006;48: Hohnloser SH, Ikeda T, Bloomfield DM, et al. T-wave alternans negative coronary patients with low ejection and benefit from defibrillator implantation. Lancet 2003;362: Bloomfield DM, Steinman RC, Namerow PB, et al. Microvolt T-wave alternans distinguishes between patients likely and patients not likely to benefit from implanted cardiac defibrillator therapy. A solution to the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II conundrum. Circulation 2004;110: Bloomfield DM, Bigger JT, Steinman RC, et al. Microvolt T-wave alternans and the risk of death or sustained ventricular arrhythmias in patients with left ventricular dysfunction. J Am Coll Cardiol 2006;47: Bloomfield DM, Hohnloser SH, Cohen RJ. Interpretation and classification of microvolt T wave alternans tests. J Cardiovasc Electrophysiol 2002;13: Myerburg RJ, Kessler KM, Castellanos A. Sudden cardiac death: epidemiology, transient risk, and intervention assessment Ann Intern Med 1993;119: Ikeda T, Saito H, Tanno K, et al. T-wave alternans as a predictor for sudden cardiac death after myocardial infarction Am J Cardiol 2002;89: Sorin Pescariu et al 49