- Email: [email protected]
QT dispersion variability and myocardial viability in acute myocardial infarction
International Journal of Cardiology 61 (1997) 61–67
QT dispersion variability and myocardial viability in acute myocardial infarction F. Gabrielli*, L. Balzotti, A. Bandiera Dipartimento di Scienze Cardiovascolari e Respiratorie, Universita` ‘ La Sapienza’, Roma, Italia Received 5 March 1997; accepted 13 June 1997
Abstract The aim of this study was to evaluate QT dispersion in acute and sub-acute stages of myocardial infarction and clarify the relationship between QT dispersion and myocardial viability. We studied 95 patients with acute myocardial infarction. The QT dispersion values were compared to those of a control group of 50 healthy subjects. In the patients with acute myocardial infarction dispersion of ventricular repolarization was evaluated on the standard electrocardiograms obtained at the time of admission and ten days later. Two-dimensional echocardiography examination was performed to assess and compare left ventricular wall motion at different stages. QT dispersion values were increased in patients with acute myocardial infarction and levels were higher in the early than in late phases. A better recovery of QT dispersion was found in those patients who demonstrated improvement of left ventricular contractility. The modifications of QT dispersion can reflect the alterations of myocardial contractility. 1997 Elsevier Science Ireland Ltd. Keywords: QT dispersion; Acute myocardial infarction; Stunned myocardium; Hibernating myocardium
1. Introduction The QT interval reflects the duration of the ventricular electrical systole, determined by the phases of depolarization and repolarization. Modifications of this interval can be the expression of alterations of cardiac electrophysiology, cardiac geometry, autonomic tone [1] and / or pharmacological effects and electrolyte disturbances [2]. Dispersion of ventricular repolarization time is a marker of an inhomogeneous recovery of the excitability in the ventricular mass [3]. The regional heterogeneity of the repolarization time of the ventricular myocardial cells can determine the presence of variations in the QT interval duration among *Corresponding author, Circ. ne Nomentana, 256 00162, Roma, Italy.
different electrocardiographic leads [4–7]. The QT dispersion, defined as the difference between the maximal and minimal QT interval duration in a 12-lead electrocardiogram, represents the expression of the physiological desynchronization of the myocardial excitability recovery. The clinical relevance of QT dispersion has been evaluated by various studies [1,5,8–16]. The assessment of QT dispersion can provide important data in the determination of the risk and / or benefits of antiarrhythmic treatment [1,5,8,9,17–22]. After myocardial infarction QT dispersion evaluation can be useful for identification of the patients at risk for arrhythmias and sudden death [5,10,23,24]. In the present study we evaluated the QT dispersion in acute and sub-acute stages of myocardial infarction and we clarified the relationship between
0167-5273 / 97 / $17.00 1997 Elsevier Science Ireland Ltd. All rights reserved. PII S0167-5273( 97 )00135-6
62
F. Gabrielli et al. / International Journal of Cardiology 61 (1997) 61 – 67
QT dispersion and the presence of myocardial viability.
2. Materials and methods
2.1. Patients The study population consisted of 95 patients with acute myocardial infarction (56 male and 39 female; mean age 63612 years) who, within 12 h of the onset of typical cardiac chest pain, had been admitted to the Coronary Care Unit of the Department of Cardiovascular and Respiratory Sciences of the University of Rome ‘‘La Sapienza’’. The diagnosis of acute myocardial infarction was established by at least two of the following criteria: 1) typical chest pain unresponsive to nitrates; 2) electrocardiographic alterations (Q waves and / or STsegment elevation); 3) rise in serum creatine kinase to at least twice the upper limit of normal. The exclusion criteria were: 1) treatment with drugs influencing the QT interval duration (antiarrhythmic drugs, beta-blockers, positive inotropic agents, tricyclic antidepressants, phenothiazines); 2) patients without sinus rhythm; 3) bundle branch block or preexcitation; 4) preexistent valve disease; 5) pericardial effusion; 6) electrolyte imbalance; in particular patients with serum potassium concentration ,3.7 mEq per l were excluded. Thrombolytic therapy was initiated in 30 patients within 6 h of onset of symptoms. The QT dispersion values in the patients with myocardial infarction were compared to a control group of 50 healthy subjects (30 male and 20 female, mean age 60611 years).
2.2. Analysis of the QT interval The standard electrocardiograms were recorded by means of a 3-channel ECG recorder at a paper speed of 50 mm s -1 . In the patients with acute myocardial infarction we evaluated the electrocardiograms obtained at admission time and ten days later. The analysis was performed by means of a three times enlarged photocopy. The QT interval was measured from the beginning of the QRS complex to
the end of the T wave (defined as the point of return of the T wave to the baseline). The leads where the end of the T wave could not be well determined was not included. Electrocardiograms with less than seven leads available for analysis were excluded. All electrocardiograms were analyzed by two observers and the QT interval was evaluated by an average of three consecutive beats. Each QT interval was correct for the heart rate according to Bazett’s formula (QTc5QT divided by the square root of RR interval). The QT dispersion was determined as the difference between the maximal and minimal QTc interval occurring among any of the 12 leads of the electrocardiogram. Variabilities due to observers were compared. The intraobserver and interobserver variations were, respectively, 1%–1.5% and 1%–2%.
2.3. Echocardiography In the patients with acute myocardial infarction Two-dimensional echocardiography was performed by parasternal long and short axis, apical four-chambers and apical long axis views. Echocardiographic examinations were performed at admission time and ten days later. The left ventricle was divided into 16 segments. Wall motion abnormalities were assessed according to the following score: 05normal motion; 15 hypokinesia; 25akinesia; 35dyskinesia; 215 hyperkinesia). The wall motion score was represented by the average of the values of all 16 segments.
2.4. Dobutamine echocardiography Dobutamine echocardiography was performed in 48 patients. Dobutamine was administered with an infusion pump at the initial dose of 5 mg kg -1 per min for 5 min; the dose was increased by 5 mg kg -1 per min at 5 min intervals up to a maximal dose of 40 mg kg -1 min -1 . Continuous ECG recording was performed, blood pressure was measured by cuff method every 2 min during and up to 15 min after drug administration. End points for terminating the test were the same as for exercise, except that the maximal dose of drug replaced exercise-induced exhaustion and the added variable: decrease in systolic blood pressure .20 mmHg. Updated on-line images were digited at the following four stages: 1)
F. Gabrielli et al. / International Journal of Cardiology 61 (1997) 61 – 67
baseline, 2) low dose (,20 mg), 3) high dose (.20 mg), and 4) 10 min of recovery.
2.5. Statistical analysis All data were expressed as mean values 6 SD. The patients of the same groups were compared by paired Student’s t-test and the patients of different groups were compared by the use of unpaired t-test. A P value of less than 0.05 was considered as statistically significant.
63
was higher than in the control subjects (68616 ms vs 3464 ms p,0.005) (Fig. 1). In the patients with anterior myocardial infarction (n551) and with inferior infarction (n544) the QT dispersion was, respectively, at admission time 83617 ms and 84620 ms and, ten days later, 67616 ms and 67617 ms. There was no significant difference in the reduction of the QT dispersion between these two groups of patients (219% in the anterior infarction group and 222% in the inferior infarction group).
3.3. Thrombolytic therapy 3. Results
3.1. Normal subjects In the normal subjects QT dispersion amounted to 3464 ms. There were no significant differences in QT dispersion between male (3263 ms) and female (3363 ms) and in age (35 to 50 years, 3165 ms; 51 to 65 years, 3566 ms; 66 to 80 years, 3462 ms).
3.2. Acute myocardial infarction At the time of admission a significantly higher QT dispersion was found in the patients with myocardial infarction than in normal subjects (84619 ms vs 3464 ms; p,0.005). The values of QT dispersion determined ten days later was lower than at admission time (68616 ms vs 84619 ms; p,0.005) but
In the patients treated with thrombolytic therapy (n530) there was a better reduction of QT dispersion values (67617 ms vs 79615 ms; 214%) than in the patients without thrombolysis (81612 ms vs 85611 ms; 23.5%) (Fig. 2).
3.4. QT dispersion and contractility recovery The patients with acute myocardial infarction were divided into two different groups on the basis of left ventricular contractility recovery determined ten days after hospital admission: 45 patients showed a reduction of the wall motion score values and 50 patients showed no improvement of the score values. In the patients with reduction of the wall motion score the QT dispersion was 88628 ms at admission time and 67619 ms ten days later ( p,0.0005). In
Fig. 1. QT dispersion in normal subjects and in patients with myocardial infarction. * p,0.005 vs normal subjects.
64
F. Gabrielli et al. / International Journal of Cardiology 61 (1997) 61 – 67
Fig. 2. Comparison of QT dispersion in patients with (A) and without (B) thrombolysis. * p,0.005.
the patients without improvement of the wall motion score the QT dispersion was 84627 ms at admission time and 74619 ms ten days later ( p,0.001). We found a better reduction of the QT dispersion values in the patients with reduction of the wall motion score values than in the others (224% vs 25%, p,0.05) (Fig. 3). In the group of patients with thrombolytic treatment (n530) there was a better reduction of the QT dispersion in the patients (n520) with wall motion
score improvement (62618 ms vs 80619 ms; 220%) than in the patients (n510) without score reduction (76620 ms vs 80615 ms; 28%).
3.5. QT dispersion and hibernating myocardium In the group of patients with echocardiographic evidence of hibernating myocardium the QT dispersion was 75616 ms at admission time and 50612 ms ten days later ( p,0.005).
Fig. 3. Comparison of QT dispersion in patients with (A) and without (B) stunned myocardium. * p,0.005.
F. Gabrielli et al. / International Journal of Cardiology 61 (1997) 61 – 67
65
Fig. 4. Comparison of QT dispersion in patients with (A) and without (B) hibernating myocardium. * p,0.005.
In the group of patients without presence of hibernating myocardium the QT dispersion was 79615 ms at admission time and 60610 ms ten days later ( p,0.005). There was no significant difference in the QT dispersion reduction between these groups of patients (234% vs 224%) (Fig. 4).
4. Discussion In our study it was chiefly found that the patients with acute myocardial infarction showed high QT dispersion values. This dispersion was greater at admission time than ten days later. Our data are in accordance with previous studies that reported a reduction of both QTc interval and QT dispersion in the late phases of myocardial infarction [10,23–25]. An increase in QT dispersion by the induction of myocardial ischaemia using incremental atrial pacing was reported [26]. In these patients a correlation between the extent of coronary artery disease and QT dispersion variability has been hypothesized [26]. The evaluation of QT dispersion was useful for the assessment of arrhythmic events. Various authors determined the prognostic value of the QT dispersion in the stratification of arrhythmic risk during acute myocardial infarction [10,17,23,24,27–30]. In these patients QT dispersion evaluation was found to be
useful in the identification of subjects developing ventricular fibrillation. On the other hand the relationship between wall motion abnormalities and QT dispersion has not been well studied. Different factors may be involved in determining QT dispersion variability. In our study we investigated whether an electrophysiological aspect, characterized by QT dispersion variability, can be related to a mechanical event, determined by modifications of ventricular contractility. The study of patients with acute myocardial infarction represented an important model for the evaluation of both the electrophysiological and mechanical aspects. In fact, electrocardiographic and echocardiographic data, obtained at different stages of myocardial infarction, are an expression of the same physiopathological aspect and represent a good model for studying correlations between electrical and mechanical events. By combining the results of electrocardiographic and echocardiographic data we determined that the reduction of QT dispersion in the late stages of myocardial infarction is related to the left ventricular contractility recovery. In fact the most relevant QT dispersion reduction was found in those patients showing a reduction of the wall motion score index. A relationship between increased QT interval duration and QT dispersion and altered left ventricular systolic function, in patients with and without
66
F. Gabrielli et al. / International Journal of Cardiology 61 (1997) 61 – 67
acute myocardial infarction, was reported [12,31]. In the light of these data the determination of QTc interval duration could be an additional marker in the evaluation of left ventricular systolic dysfunction. The correlation between electrical and mechanical properties of the myocardial fibres can be understood considering that the alteration of impulse conduction may be determined by anatomical and / or biophysical characteristics of the myocardial cells and by their spatial orientation [32]. The relationship between mechanical alterations of the left ventricular wall and modifications of electrical transmembrane potential was well defined. The phenomenon of contraction-excitation feedback was identified as a modification of the mechanical state that precedes or alters the transmembrane electrical potential [3]. Thus, alterations of electrophysiological properties can be determined by modifications of the diameter, pressure and / or function of the left ventricle [3,33,34]. The importance of contractility recovery in the determination of QT dispersion reduction may be underlined by comparing stunned and hibernating myocardium. Our patients with hibernating myocardium, unlike those with stunned myocardium, did not show a significative recovery of QT dispersion. The different trend of QT dispersion, determined by the presence of stunned or hibernated myocardium may reflect the different electrophysiological characteristics of these expressions of myocardial viability. Thrombolytic treatment could play a role in the recovery of the electrophysiological characteristics of myocardial cells [31,35]. In our group of patients receiving thrombolysis and showing a better QT dispersion reduction we found an higher prevalence of stunned myocardium. The main conclusion of our study is that patients with presence of stunned myocardium showed a better QT dispersion reduction. Thus, during acute myocardial infarction, the determination of QT dispersion can define a subgroup of patients with good wall motion recovery. Indeed the recovery of QT dispersion can be an additional marker of the spontaneous recovery of left ventricular contractility.
References [1] Higham PD. Br Heart J 1994;71:508–10.
[2] Ahnve S, Gilpin E, Madsen EB, Froelicher V, Henning H, Ross J. Prognostic importance of QTc interval at discharge after acute myocardial infarction: A multicenter study of 865 patients. Am Heart J 1984;108:395–400. [3] Pye MP, Cobbe SM. Mechanisms of ventricular arrythmias in cardiac failure and hypertrophy. Cardiovasc Res 1992;26:740–50. [4] Kautzner J, Gang YI, Camm J, Malik M. Short- and long-term reproducibility of QT, QTc, and QT dispersion measurement in healthy subjects. Pacing Clin Electrophysiol 1994;17:928–37. [5] Day CP, McComb JM, Matthews J, Campbell RWF. Reduction in QT dispersion by sotalol following myocardial infarction. Eur Heart J 1991;12:423–7. [6] Mirvis DM. Spatial variations of QT intervals in normal persons and patients with acute myocardial infarction. J Am Coll Cardiol 1995;5:625–31. [7] Cowan JC, Yussoff K, Moore M, Amos PA, Gold AE, Burke JP, Tansuphaswadikul S, Campbell WF. Importance of lead selection in QT interval measurement. Am J Cardiol 1988;61:83–7. [8] De Ambroggi L, Negroni MS, Monza E, Bertoni T, Schwartz PJ. Dispersion of ventricular repolarization in the long QT syndrome. Am J Cardiol 1991;68:614–20. [9] Priori SG, Napolitano C, Diehl L, Schwarts PJ. Dispersion of the QT interval. A marker of therapeutic efficacy in the idiopathic long QT syndrome. Circulation 1994;89:1681–9. [10] Glancy JM, Garratt CJ, Woods KL, de Bono DP. QT dispersion and mortality after myocardial infarction. Lancet 1995;345:945–8. [11] Penco M, Rosanio S, Tocchi M, Dagianti Jr. A, Vitarelli A, Bandiera A. Effetti del trattamento fibrinolitico sulla dispersione dell’intervallo QT nell’infarto miocardico acuto. Cardiologia 1995;40(Suppl. 2):38. [12] Pye M, Quinn AC, Cobbe SM. QT interval dispersion: a noninvasive marker of susceptibility to arrhythmia in patients with sustained ventricular arrhythmias?. Br Heart J 1994;71:511–4. [13] Buja G, Miorelli M, Turrini P, Melacini P, Nava A. Comparison of QT dispersion in hypertrophic cardiomyopathy between patients with and without ventricular arrhythmias and sudden death. Am J Cardiol 1993;72:973–6. [14] Barr CS, Naas A, Freeman M, Lang CC. Struthers AD. QT dispersion and sudden unexpected death in chronic heart failure. Lancet 1994;343:327–9. [15] Grimm W, Steder U, Menz V, Hoffman J, Maisch B. QT dispersion and arrhythmic events in idiopathic dilated cardiomyopathy. Am J Cardiol 1996;78:458–61. [16] Glancy JM, Garratt CJ, Woods KL, de Bono DP. Use of lead adjustment formulas for QT dispersion after myocardial infarction. Br Heart J 1995;74:676–9. [17] Day CP, McComb JM, Campbell RWF. Reduction in QT dispersion by sotalol following myocardial infarction. Eur Heart J 1991;12:423–7. [18] Cui G, Sen L, Sager P, Uppal P, Singh BN. Effects of amiodarone, sematilide, and sotalol on QT dispersion. Am J Cardiol 1994;74:896–900. [19] Bonatti V, Rolli A, Botti G. Monophasic action potential studies in human subjects with prolonged ventricular repolarization and long QT syndrome. Eur Heart J 1985;6(Suppl. D):131–43. [20] Singh BN. Advantages of beta-blockers versus antiarrhythmic drugs and calcium-channel antagonists in secondary preventions in survivors of myocardial infarction. Am J Cardiol 1989;66:9–20. [21] Ceremuzynski Y, Kleczar E, Kreminska-Pakula M, Kuch J, Nartowicz E, Smielak-Korombel J, Dyduszynski A, Maciejewicz J, Zaleska T, Lazarczyk-Kedzia E, Motyka J, Paczcowska B, Sczaniecka O, Yusif S. Effect of amiodarone on mortality after acute myocardial infarction. J Am Coll Cardiol 1992;20:1056–62.
F. Gabrielli et al. / International Journal of Cardiology 61 (1997) 61 – 67 [22] Hii JTY, Wyse DG, Gillis AM, Duff HJ, Solyo MA, Mitchell LB. Precordial QT interval dispersion as a marker of torsade de pointes. Disparate effects of class Ia antiarrhytmic drugs and amiodarone. Circulation 1992;86:1376–82. [23] Zareba W, Moss AJ, Cessie SI. Dispersione of ventricular repolarization and arrhythmic cardiac death in coronary artery disease. Am J Cardiol 1994;74:550–3. [24] Perkiomaki JS, Koistinen J, Yli-Mayry S, Huikuri HV. Dispersion of QT interval in patients with and without susceptibility to ventricular tachyarrhythmias after previous myocardial infarction. J Am Coll Cardiol 1995;267:174–9. [25] Marinchak RA, Kline RA, Engel TR. Relationship of delayed depolarisation to the QT interval after acute myocardial infarction. Am Heart J 1985;110:742–6. [26] Sporton SC, Taggart P, Suttorn PM, Walker JM, Hardman SM. Acute ischaemia: a dynamic influence on QT dispersion. Lancet 1997;349:306–9. [27] Moller M. QT interval in relation to ventricular arrhythmias and sudden cardiac death in postmyocardial infarction patients. Acta Med Scand 1981;210:73–7. [28] Ahnve S. QT interval prolongation in acute myocardial infarction. Eur Heart J 1985;6(Suppl. D):85–95. [29] Van de Loo A, Avendts W, Hohnoloser SH. Variability of QT dispersion measurements in the surface electrocardiogram in patients with acute myocardial infarction and in normal subjects. Am J Cardiol 1994;74:1113–8.
67
[30] Higham PD, Furniss SS, Campbell RWF. QT dispersion and components of the QT interval in ischaemia and infarction. Br Heart J 1995;73:32–6. [31] Stajer D, Mozina H, Noc M, Rode P. Correlation between QTc interval duration and left ventricular systolic dysfunction in patients with acute myocadial infarction. J Electrocardiol 1993;26:333–40. [32] de Bakker JMT, Van Capelle FJL, Janse MJ, Wilde AA, Coronel R, Becker AE, Dingemans KP, van Hemel NM, Hauer RN. Re-entry as a cause of ventricular tachycardia in patients with chronic heart disease: electrophysiological and anatomic correlation. Circulation 1988;77:589–606. [33] Dean JW, Lab MJ. Arrhythmia in heart failure. Role of mechanically induced changes in electrophysiology. Lancet 1989;2:1309–12. [34] Packer M, Gottlieb SS, Blum MA. Immediate and long-term pathophysiological mechanisms underlying the genesis of sudden cardiac death in patients with congestive heart failure. Am J Med 1987;82(3A):4–10. [35] Moreno FL, Villanueva MT, Karagounis LA, Anderson JL. Reduction in QT interval dispersion by successful thrombolytic therapy in acute myocardial infarction. Circulation 1994;90:94–100.
QT dispersion variability and myocardial viability in acute myocardial infarction F. Gabrielli*, L. Balzotti, A. Bandiera Dipartimento di Scienze Cardiovascolari e Respiratorie, Universita` ‘ La Sapienza’, Roma, Italia Received 5 March 1997; accepted 13 June 1997
Abstract The aim of this study was to evaluate QT dispersion in acute and sub-acute stages of myocardial infarction and clarify the relationship between QT dispersion and myocardial viability. We studied 95 patients with acute myocardial infarction. The QT dispersion values were compared to those of a control group of 50 healthy subjects. In the patients with acute myocardial infarction dispersion of ventricular repolarization was evaluated on the standard electrocardiograms obtained at the time of admission and ten days later. Two-dimensional echocardiography examination was performed to assess and compare left ventricular wall motion at different stages. QT dispersion values were increased in patients with acute myocardial infarction and levels were higher in the early than in late phases. A better recovery of QT dispersion was found in those patients who demonstrated improvement of left ventricular contractility. The modifications of QT dispersion can reflect the alterations of myocardial contractility. 1997 Elsevier Science Ireland Ltd. Keywords: QT dispersion; Acute myocardial infarction; Stunned myocardium; Hibernating myocardium
1. Introduction The QT interval reflects the duration of the ventricular electrical systole, determined by the phases of depolarization and repolarization. Modifications of this interval can be the expression of alterations of cardiac electrophysiology, cardiac geometry, autonomic tone [1] and / or pharmacological effects and electrolyte disturbances [2]. Dispersion of ventricular repolarization time is a marker of an inhomogeneous recovery of the excitability in the ventricular mass [3]. The regional heterogeneity of the repolarization time of the ventricular myocardial cells can determine the presence of variations in the QT interval duration among *Corresponding author, Circ. ne Nomentana, 256 00162, Roma, Italy.
different electrocardiographic leads [4–7]. The QT dispersion, defined as the difference between the maximal and minimal QT interval duration in a 12-lead electrocardiogram, represents the expression of the physiological desynchronization of the myocardial excitability recovery. The clinical relevance of QT dispersion has been evaluated by various studies [1,5,8–16]. The assessment of QT dispersion can provide important data in the determination of the risk and / or benefits of antiarrhythmic treatment [1,5,8,9,17–22]. After myocardial infarction QT dispersion evaluation can be useful for identification of the patients at risk for arrhythmias and sudden death [5,10,23,24]. In the present study we evaluated the QT dispersion in acute and sub-acute stages of myocardial infarction and we clarified the relationship between
0167-5273 / 97 / $17.00 1997 Elsevier Science Ireland Ltd. All rights reserved. PII S0167-5273( 97 )00135-6
62
F. Gabrielli et al. / International Journal of Cardiology 61 (1997) 61 – 67
QT dispersion and the presence of myocardial viability.
2. Materials and methods
2.1. Patients The study population consisted of 95 patients with acute myocardial infarction (56 male and 39 female; mean age 63612 years) who, within 12 h of the onset of typical cardiac chest pain, had been admitted to the Coronary Care Unit of the Department of Cardiovascular and Respiratory Sciences of the University of Rome ‘‘La Sapienza’’. The diagnosis of acute myocardial infarction was established by at least two of the following criteria: 1) typical chest pain unresponsive to nitrates; 2) electrocardiographic alterations (Q waves and / or STsegment elevation); 3) rise in serum creatine kinase to at least twice the upper limit of normal. The exclusion criteria were: 1) treatment with drugs influencing the QT interval duration (antiarrhythmic drugs, beta-blockers, positive inotropic agents, tricyclic antidepressants, phenothiazines); 2) patients without sinus rhythm; 3) bundle branch block or preexcitation; 4) preexistent valve disease; 5) pericardial effusion; 6) electrolyte imbalance; in particular patients with serum potassium concentration ,3.7 mEq per l were excluded. Thrombolytic therapy was initiated in 30 patients within 6 h of onset of symptoms. The QT dispersion values in the patients with myocardial infarction were compared to a control group of 50 healthy subjects (30 male and 20 female, mean age 60611 years).
2.2. Analysis of the QT interval The standard electrocardiograms were recorded by means of a 3-channel ECG recorder at a paper speed of 50 mm s -1 . In the patients with acute myocardial infarction we evaluated the electrocardiograms obtained at admission time and ten days later. The analysis was performed by means of a three times enlarged photocopy. The QT interval was measured from the beginning of the QRS complex to
the end of the T wave (defined as the point of return of the T wave to the baseline). The leads where the end of the T wave could not be well determined was not included. Electrocardiograms with less than seven leads available for analysis were excluded. All electrocardiograms were analyzed by two observers and the QT interval was evaluated by an average of three consecutive beats. Each QT interval was correct for the heart rate according to Bazett’s formula (QTc5QT divided by the square root of RR interval). The QT dispersion was determined as the difference between the maximal and minimal QTc interval occurring among any of the 12 leads of the electrocardiogram. Variabilities due to observers were compared. The intraobserver and interobserver variations were, respectively, 1%–1.5% and 1%–2%.
2.3. Echocardiography In the patients with acute myocardial infarction Two-dimensional echocardiography was performed by parasternal long and short axis, apical four-chambers and apical long axis views. Echocardiographic examinations were performed at admission time and ten days later. The left ventricle was divided into 16 segments. Wall motion abnormalities were assessed according to the following score: 05normal motion; 15 hypokinesia; 25akinesia; 35dyskinesia; 215 hyperkinesia). The wall motion score was represented by the average of the values of all 16 segments.
2.4. Dobutamine echocardiography Dobutamine echocardiography was performed in 48 patients. Dobutamine was administered with an infusion pump at the initial dose of 5 mg kg -1 per min for 5 min; the dose was increased by 5 mg kg -1 per min at 5 min intervals up to a maximal dose of 40 mg kg -1 min -1 . Continuous ECG recording was performed, blood pressure was measured by cuff method every 2 min during and up to 15 min after drug administration. End points for terminating the test were the same as for exercise, except that the maximal dose of drug replaced exercise-induced exhaustion and the added variable: decrease in systolic blood pressure .20 mmHg. Updated on-line images were digited at the following four stages: 1)
F. Gabrielli et al. / International Journal of Cardiology 61 (1997) 61 – 67
baseline, 2) low dose (,20 mg), 3) high dose (.20 mg), and 4) 10 min of recovery.
2.5. Statistical analysis All data were expressed as mean values 6 SD. The patients of the same groups were compared by paired Student’s t-test and the patients of different groups were compared by the use of unpaired t-test. A P value of less than 0.05 was considered as statistically significant.
63
was higher than in the control subjects (68616 ms vs 3464 ms p,0.005) (Fig. 1). In the patients with anterior myocardial infarction (n551) and with inferior infarction (n544) the QT dispersion was, respectively, at admission time 83617 ms and 84620 ms and, ten days later, 67616 ms and 67617 ms. There was no significant difference in the reduction of the QT dispersion between these two groups of patients (219% in the anterior infarction group and 222% in the inferior infarction group).
3.3. Thrombolytic therapy 3. Results
3.1. Normal subjects In the normal subjects QT dispersion amounted to 3464 ms. There were no significant differences in QT dispersion between male (3263 ms) and female (3363 ms) and in age (35 to 50 years, 3165 ms; 51 to 65 years, 3566 ms; 66 to 80 years, 3462 ms).
3.2. Acute myocardial infarction At the time of admission a significantly higher QT dispersion was found in the patients with myocardial infarction than in normal subjects (84619 ms vs 3464 ms; p,0.005). The values of QT dispersion determined ten days later was lower than at admission time (68616 ms vs 84619 ms; p,0.005) but
In the patients treated with thrombolytic therapy (n530) there was a better reduction of QT dispersion values (67617 ms vs 79615 ms; 214%) than in the patients without thrombolysis (81612 ms vs 85611 ms; 23.5%) (Fig. 2).
3.4. QT dispersion and contractility recovery The patients with acute myocardial infarction were divided into two different groups on the basis of left ventricular contractility recovery determined ten days after hospital admission: 45 patients showed a reduction of the wall motion score values and 50 patients showed no improvement of the score values. In the patients with reduction of the wall motion score the QT dispersion was 88628 ms at admission time and 67619 ms ten days later ( p,0.0005). In
Fig. 1. QT dispersion in normal subjects and in patients with myocardial infarction. * p,0.005 vs normal subjects.
64
F. Gabrielli et al. / International Journal of Cardiology 61 (1997) 61 – 67
Fig. 2. Comparison of QT dispersion in patients with (A) and without (B) thrombolysis. * p,0.005.
the patients without improvement of the wall motion score the QT dispersion was 84627 ms at admission time and 74619 ms ten days later ( p,0.001). We found a better reduction of the QT dispersion values in the patients with reduction of the wall motion score values than in the others (224% vs 25%, p,0.05) (Fig. 3). In the group of patients with thrombolytic treatment (n530) there was a better reduction of the QT dispersion in the patients (n520) with wall motion
score improvement (62618 ms vs 80619 ms; 220%) than in the patients (n510) without score reduction (76620 ms vs 80615 ms; 28%).
3.5. QT dispersion and hibernating myocardium In the group of patients with echocardiographic evidence of hibernating myocardium the QT dispersion was 75616 ms at admission time and 50612 ms ten days later ( p,0.005).
Fig. 3. Comparison of QT dispersion in patients with (A) and without (B) stunned myocardium. * p,0.005.
F. Gabrielli et al. / International Journal of Cardiology 61 (1997) 61 – 67
65
Fig. 4. Comparison of QT dispersion in patients with (A) and without (B) hibernating myocardium. * p,0.005.
In the group of patients without presence of hibernating myocardium the QT dispersion was 79615 ms at admission time and 60610 ms ten days later ( p,0.005). There was no significant difference in the QT dispersion reduction between these groups of patients (234% vs 224%) (Fig. 4).
4. Discussion In our study it was chiefly found that the patients with acute myocardial infarction showed high QT dispersion values. This dispersion was greater at admission time than ten days later. Our data are in accordance with previous studies that reported a reduction of both QTc interval and QT dispersion in the late phases of myocardial infarction [10,23–25]. An increase in QT dispersion by the induction of myocardial ischaemia using incremental atrial pacing was reported [26]. In these patients a correlation between the extent of coronary artery disease and QT dispersion variability has been hypothesized [26]. The evaluation of QT dispersion was useful for the assessment of arrhythmic events. Various authors determined the prognostic value of the QT dispersion in the stratification of arrhythmic risk during acute myocardial infarction [10,17,23,24,27–30]. In these patients QT dispersion evaluation was found to be
useful in the identification of subjects developing ventricular fibrillation. On the other hand the relationship between wall motion abnormalities and QT dispersion has not been well studied. Different factors may be involved in determining QT dispersion variability. In our study we investigated whether an electrophysiological aspect, characterized by QT dispersion variability, can be related to a mechanical event, determined by modifications of ventricular contractility. The study of patients with acute myocardial infarction represented an important model for the evaluation of both the electrophysiological and mechanical aspects. In fact, electrocardiographic and echocardiographic data, obtained at different stages of myocardial infarction, are an expression of the same physiopathological aspect and represent a good model for studying correlations between electrical and mechanical events. By combining the results of electrocardiographic and echocardiographic data we determined that the reduction of QT dispersion in the late stages of myocardial infarction is related to the left ventricular contractility recovery. In fact the most relevant QT dispersion reduction was found in those patients showing a reduction of the wall motion score index. A relationship between increased QT interval duration and QT dispersion and altered left ventricular systolic function, in patients with and without
66
F. Gabrielli et al. / International Journal of Cardiology 61 (1997) 61 – 67
acute myocardial infarction, was reported [12,31]. In the light of these data the determination of QTc interval duration could be an additional marker in the evaluation of left ventricular systolic dysfunction. The correlation between electrical and mechanical properties of the myocardial fibres can be understood considering that the alteration of impulse conduction may be determined by anatomical and / or biophysical characteristics of the myocardial cells and by their spatial orientation [32]. The relationship between mechanical alterations of the left ventricular wall and modifications of electrical transmembrane potential was well defined. The phenomenon of contraction-excitation feedback was identified as a modification of the mechanical state that precedes or alters the transmembrane electrical potential [3]. Thus, alterations of electrophysiological properties can be determined by modifications of the diameter, pressure and / or function of the left ventricle [3,33,34]. The importance of contractility recovery in the determination of QT dispersion reduction may be underlined by comparing stunned and hibernating myocardium. Our patients with hibernating myocardium, unlike those with stunned myocardium, did not show a significative recovery of QT dispersion. The different trend of QT dispersion, determined by the presence of stunned or hibernated myocardium may reflect the different electrophysiological characteristics of these expressions of myocardial viability. Thrombolytic treatment could play a role in the recovery of the electrophysiological characteristics of myocardial cells [31,35]. In our group of patients receiving thrombolysis and showing a better QT dispersion reduction we found an higher prevalence of stunned myocardium. The main conclusion of our study is that patients with presence of stunned myocardium showed a better QT dispersion reduction. Thus, during acute myocardial infarction, the determination of QT dispersion can define a subgroup of patients with good wall motion recovery. Indeed the recovery of QT dispersion can be an additional marker of the spontaneous recovery of left ventricular contractility.
References [1] Higham PD. Br Heart J 1994;71:508–10.
[2] Ahnve S, Gilpin E, Madsen EB, Froelicher V, Henning H, Ross J. Prognostic importance of QTc interval at discharge after acute myocardial infarction: A multicenter study of 865 patients. Am Heart J 1984;108:395–400. [3] Pye MP, Cobbe SM. Mechanisms of ventricular arrythmias in cardiac failure and hypertrophy. Cardiovasc Res 1992;26:740–50. [4] Kautzner J, Gang YI, Camm J, Malik M. Short- and long-term reproducibility of QT, QTc, and QT dispersion measurement in healthy subjects. Pacing Clin Electrophysiol 1994;17:928–37. [5] Day CP, McComb JM, Matthews J, Campbell RWF. Reduction in QT dispersion by sotalol following myocardial infarction. Eur Heart J 1991;12:423–7. [6] Mirvis DM. Spatial variations of QT intervals in normal persons and patients with acute myocardial infarction. J Am Coll Cardiol 1995;5:625–31. [7] Cowan JC, Yussoff K, Moore M, Amos PA, Gold AE, Burke JP, Tansuphaswadikul S, Campbell WF. Importance of lead selection in QT interval measurement. Am J Cardiol 1988;61:83–7. [8] De Ambroggi L, Negroni MS, Monza E, Bertoni T, Schwartz PJ. Dispersion of ventricular repolarization in the long QT syndrome. Am J Cardiol 1991;68:614–20. [9] Priori SG, Napolitano C, Diehl L, Schwarts PJ. Dispersion of the QT interval. A marker of therapeutic efficacy in the idiopathic long QT syndrome. Circulation 1994;89:1681–9. [10] Glancy JM, Garratt CJ, Woods KL, de Bono DP. QT dispersion and mortality after myocardial infarction. Lancet 1995;345:945–8. [11] Penco M, Rosanio S, Tocchi M, Dagianti Jr. A, Vitarelli A, Bandiera A. Effetti del trattamento fibrinolitico sulla dispersione dell’intervallo QT nell’infarto miocardico acuto. Cardiologia 1995;40(Suppl. 2):38. [12] Pye M, Quinn AC, Cobbe SM. QT interval dispersion: a noninvasive marker of susceptibility to arrhythmia in patients with sustained ventricular arrhythmias?. Br Heart J 1994;71:511–4. [13] Buja G, Miorelli M, Turrini P, Melacini P, Nava A. Comparison of QT dispersion in hypertrophic cardiomyopathy between patients with and without ventricular arrhythmias and sudden death. Am J Cardiol 1993;72:973–6. [14] Barr CS, Naas A, Freeman M, Lang CC. Struthers AD. QT dispersion and sudden unexpected death in chronic heart failure. Lancet 1994;343:327–9. [15] Grimm W, Steder U, Menz V, Hoffman J, Maisch B. QT dispersion and arrhythmic events in idiopathic dilated cardiomyopathy. Am J Cardiol 1996;78:458–61. [16] Glancy JM, Garratt CJ, Woods KL, de Bono DP. Use of lead adjustment formulas for QT dispersion after myocardial infarction. Br Heart J 1995;74:676–9. [17] Day CP, McComb JM, Campbell RWF. Reduction in QT dispersion by sotalol following myocardial infarction. Eur Heart J 1991;12:423–7. [18] Cui G, Sen L, Sager P, Uppal P, Singh BN. Effects of amiodarone, sematilide, and sotalol on QT dispersion. Am J Cardiol 1994;74:896–900. [19] Bonatti V, Rolli A, Botti G. Monophasic action potential studies in human subjects with prolonged ventricular repolarization and long QT syndrome. Eur Heart J 1985;6(Suppl. D):131–43. [20] Singh BN. Advantages of beta-blockers versus antiarrhythmic drugs and calcium-channel antagonists in secondary preventions in survivors of myocardial infarction. Am J Cardiol 1989;66:9–20. [21] Ceremuzynski Y, Kleczar E, Kreminska-Pakula M, Kuch J, Nartowicz E, Smielak-Korombel J, Dyduszynski A, Maciejewicz J, Zaleska T, Lazarczyk-Kedzia E, Motyka J, Paczcowska B, Sczaniecka O, Yusif S. Effect of amiodarone on mortality after acute myocardial infarction. J Am Coll Cardiol 1992;20:1056–62.
F. Gabrielli et al. / International Journal of Cardiology 61 (1997) 61 – 67 [22] Hii JTY, Wyse DG, Gillis AM, Duff HJ, Solyo MA, Mitchell LB. Precordial QT interval dispersion as a marker of torsade de pointes. Disparate effects of class Ia antiarrhytmic drugs and amiodarone. Circulation 1992;86:1376–82. [23] Zareba W, Moss AJ, Cessie SI. Dispersione of ventricular repolarization and arrhythmic cardiac death in coronary artery disease. Am J Cardiol 1994;74:550–3. [24] Perkiomaki JS, Koistinen J, Yli-Mayry S, Huikuri HV. Dispersion of QT interval in patients with and without susceptibility to ventricular tachyarrhythmias after previous myocardial infarction. J Am Coll Cardiol 1995;267:174–9. [25] Marinchak RA, Kline RA, Engel TR. Relationship of delayed depolarisation to the QT interval after acute myocardial infarction. Am Heart J 1985;110:742–6. [26] Sporton SC, Taggart P, Suttorn PM, Walker JM, Hardman SM. Acute ischaemia: a dynamic influence on QT dispersion. Lancet 1997;349:306–9. [27] Moller M. QT interval in relation to ventricular arrhythmias and sudden cardiac death in postmyocardial infarction patients. Acta Med Scand 1981;210:73–7. [28] Ahnve S. QT interval prolongation in acute myocardial infarction. Eur Heart J 1985;6(Suppl. D):85–95. [29] Van de Loo A, Avendts W, Hohnoloser SH. Variability of QT dispersion measurements in the surface electrocardiogram in patients with acute myocardial infarction and in normal subjects. Am J Cardiol 1994;74:1113–8.
67
[30] Higham PD, Furniss SS, Campbell RWF. QT dispersion and components of the QT interval in ischaemia and infarction. Br Heart J 1995;73:32–6. [31] Stajer D, Mozina H, Noc M, Rode P. Correlation between QTc interval duration and left ventricular systolic dysfunction in patients with acute myocadial infarction. J Electrocardiol 1993;26:333–40. [32] de Bakker JMT, Van Capelle FJL, Janse MJ, Wilde AA, Coronel R, Becker AE, Dingemans KP, van Hemel NM, Hauer RN. Re-entry as a cause of ventricular tachycardia in patients with chronic heart disease: electrophysiological and anatomic correlation. Circulation 1988;77:589–606. [33] Dean JW, Lab MJ. Arrhythmia in heart failure. Role of mechanically induced changes in electrophysiology. Lancet 1989;2:1309–12. [34] Packer M, Gottlieb SS, Blum MA. Immediate and long-term pathophysiological mechanisms underlying the genesis of sudden cardiac death in patients with congestive heart failure. Am J Med 1987;82(3A):4–10. [35] Moreno FL, Villanueva MT, Karagounis LA, Anderson JL. Reduction in QT interval dispersion by successful thrombolytic therapy in acute myocardial infarction. Circulation 1994;90:94–100.