Torsades De Pointes Related to Transient Marked QT Prolongation Following Successful Emergent Percutaneous Coronary Intervention for Acute Coronary Syndrome
By Kawabata, Mihoko Hirao, Kenzo; Takeshi, Sasaki; Sakurai, Kaoru; Inagaki, Hiroshi; Hachiya, Hitoshi; Isobe, Mitsuaki
Abstract We report 2 patients in whom transient marked QT prolongation occurred after successful emergent percutaneous coronary intervention (PCI) for acute coronary syndrome. One patient developed torsades de pointes. In both cases, the QT interval became markedly prolonged within 24 hours after PCI, and this prolongation persisted for 4 days. The T waves had a giant and bizarre negative shape with a prolonged T-wave peak to T-wave end interval. No new- onset ischemia or congenital long QT syndrome was related to the episodes. The patients had not taken any drugs that could have prolonged the QT interval, and their serum potassium levels were within normal limits. Torsades de pointes following successful PCI for acute coronary syndrome is uncommon, but acquired long QT syndrome should be considered and treated in patients in whom giant and bizarre negative T waves and QT prolongation develop after PCI. (c) 2008 Elsevier Inc. All rights reserved.
Keywords: Torsades de Pointes; Acute coronary syndrome; Long QT syndrome; T-wave peak to T-wave end interval; Transmural dispersion of repolarization
Torsades de Pointes (TdP) is a typical form of potentially life- threatening polymorphic ventricular tachycardia that is associated with a long QT interval. Long QT syndrome (LQTS) is a disorder that involves delayed ventricular repolarization and is classified as either the congenital or acquired form. There are several possible causes of acquired LQTS: medications, electrolyte abnormalities, heart disease, such as bradycardia, congestive heart failure, or myocardial ischemia and other conditions such as cerebrovascular accidents.
Recent studies have shown that a long QT interval is not sufficient to provoke TdP.1-3 Heterogeneity of repolarization throughout the ventricle, which results in QT dispersion (QTD), is a marker of dispersion of ventricular repolarization and electrical instability. This spatial inhomogeneity of repolarization develops in transmural regions as well and is known as transmural dispersion of repolarization (TDR). The interval from QRS onset to T-wave offset and that to T-wave apex correspond to the action potential durations of the midmyocardial M cells (the longest action potentials) and epicardial cells (the shortest action potentials), respectively. Therefore, TDR is reflected in the duration of the interval from T-wave peak to T-wave end (TPE).1,2,4,5 Enhanced TDR allows for the propagation of multiple waves of reentry, which is responsible for TdP by serving as a functional underlying reentrant substrate.6
We describe 2 patients in whom transient marked QT prolongation developed after successful emergent percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). In both patients, the T waves had a giant and bizarre negative shape with a prolonged TPE interval. TdP occurred in 1 patient.
A 71-year-old woman was referred to our hospital for worsening dyspnea and prolonged chest pain lasting 20 minutes. For 3 days before her admission, she had experienced dyspnea and chest pain on effort. She had suffered diabetes for 15 years, hypertension for 6 years, hyperlipidernia for 6 years, and obesity as coronary risk factors.
Upon admission, her consciousness was clouded, and she struggled to breath and wheezed remarkably. She was cyanotic and wet with sweat. Her systemic blood pressure was 209/111 mm Hg, and pulse rate was 140 beats per minute. Cardiopulmonary arrest ensued. After successful cardiopulmonary resuscitation, acute myocardial infarction (AMI) was diagnosed (Fig. 1, left). One hour later, she underwent successful PCI of the proximal left anterior descending artery (LAD), which had 95% stenosis (Fig. 2). Her left ventricular ejection fraction was 60%, and peak creatine kinase level was 2764 IU/L.
The QT interval, defined as the interval between QRS onset and end of the T wave (defined as return of the terminal T wave to the isoelectric baseline), increased after PCI (Fig. 3, left). When U waves were present, the QT interval was measured to the nadir of the curve between the T wave and the U wave. It was corrected for heart rate according to Bazett’s formula (QTc = QT/square root of the R-R interval). On day 2, a deep inverted T wave, remarkable QT prolongation, and QTD (Fig. 1, middle) were accompanied by development of incessant TdP (Fig. 4). The serum potassium level was 3.8 mEq/L. The patient had not been given any drug that would have prolonged the QT interval; however, nicorandil, an adenosine triphosphate-sensitive potassium channel opener, had been continuously infused. The medications prescribed after PCI were aspirin, heparin, and ticlopidine. There was no familial history of sudden cardiac death, syncope, or LQTS. Chest pain did not recur. Although intravenous magnesium and lidocaine were ineffective, beta- blockers terminated the electrical storm. The patient was reintubed and sedated, and the QT interval normalized on day 5 (Fig. 1, right). Electrocardiograms (ECGs) showed no signs of new-onset ischemic events. Reevaluation of the coronary artery on day 19 revealed no changes.
A 54-year-old woman was referred to our hospital because of chest pain on exertion that had appeared 1 week earlier. Hypertension had been present for 1 year. She had previously undergone surgery for ovarian cancer.
Fig. 1. The 12-lead ECG series in patient 1 showing dynamic changes in the QT and T-wave peak to T-wave end (TPE) intervals. Left, After successful cardiopulmonary resuscitation, anteroseptal acute myocardial infarction was diagnosed. The QTc interval was 485 milliseconds. Middle, The QTc interval increased maximally on day 2 (QTc = 708 milliseconds) and exhibited a deep inverted T-wave and remarkable prolongation of the TPE interval (200 milliseconds). Right, Both the QT and TPE intervals normalized on day 5 (QTc = 447 milliseconds, TPE = 80 milliseconds). Electrocardiograms over time showed no signs of any new-onset ischemic event.
Fig. 2. Emergent coronary angiography in patient 1 shows 95% stenosis of the proximal LAD. After successful PCI, no other lesions were found.
Upon admission, she had no chest pain; however, ST-T changes were observed on the ECG (Fig. 5, left). Emergent coronary angiography revealed 90% stenosis of the proximal LAD; thus, PCI was performed (Fig. 6).
Percutaneous coronary intervention was successful, and the QT interval increased maximally on day 2 (Figs. 3, 5, middle). The T wave had a deep negative morphology with a prolonged TPE interval. The serum potassium level was 4.0 mEq/L. The patient had not been given any drug that could have prolonged the QT interval. After PCI, nicorandil was infused continuously. Moreover, aspirin, heparin, ticlopidine, angiotensin-converting enzyme inhibitors, and amlodipine were also administered. There had never been any prior evidence of LQTS, and there was no family history of LQTS, syncope, or sudden cardiac death. The patient underwent repeat angiography immediately, which showed no restenosis or new lesion. The maximum creatine kinase level was 305 IU/L, and left ventricular function was preserved. Mexiletine (300 mg daily) was prescribed, and the QTc interval spontaneously shortened to within normal range by day 5 without any episode of malignant arrhythmia (Fig. 5, right).
Fig. 3. Dynamic changes in the QTc interval, QT dispersion, and TPE interval in our patients. In patient 1, the QTc and TPE intervals were measured in lead V^sub 2^, and in patient 2, both intervals were measured in lead V5. The intervals reached maximum length on day 2 and returned to near normal on day 5. Incessant TdP developed in patient 1 on day 2.
We report 2 cases of non-Q-wave myocardial infarction (NQMI) and unstable angina exhibiting marked prolongation of both the QT and TPE intervals, the myocardial ischemia was relieved in the early phase by successful emergent revascularization. In both cases, both the QT and TPE intervals became maximally prolonged on day 2 and returned to near normal on day 5. Incessant TdP developed in the NQMI patient. There were no other factors that might have prolonged the QT interval.
Ischemic heart disease and LQTS
In previous reports, both the QT interval and QTD became prolonged during the early postinfarction period,7,8 reaching a transient peak on day 2 or 3 before returning to baseline on day 4.9 Both were significantly more prolonged in patients with NQMI than in patients with Q-wave myocardial infarction and were most evident in patients in whom the NQMI was most extensive, suggesting that the transmural distribution of necrosis might influence the repolarization. The clinical courses in our cases were similar to those in these reports; however, the QT prolongation was much greater than was reported previously: 491 milliseconds for NQMI patients and 465 milliseconds for Q-wave myocardial infarction patients. In addition, no TdP was observed in the reported series.
Fig. 4. In patient 1, the incessant TdP that developed on day 2 constituted an electrical storm.
Halkin et al.10 reported similar cases with TdP following AMI. They documented pause-dependent TdP during transient obvious QT prolongation in 1.8% of their patients with AMI. In the absence of identifiable causes, they called the LQTS “infarct-related LQTS.” The prominent feature of the ECGs was also deep and inverted T waves. In their patients, the QTc interval increased from 445 +- 58 milliseconds to 558 +- 84 milliseconds by day 2, and the maximum QT prolongation and TdP occurred 3 to 11 days after infarction. Myocardial ischemia itself prolongs the QT interval, however, a study in rats showed that myocardial ischemia and even reperfusion increased QTD and that increased QTD was associated with cardiac arrhythmias.11
Injection of ionic contrast agents into the coronary arteries is known to prolong the QT interval; however, we used nonionic contrast, which has not been shown to affect the QT interval.12 Moreover, although both of our patients underwent repeat coronary angiography for reevaluation with the same nonionic contrast medium, QT prolongation was not observed after the repeat procedures.
Women are 2-3 times more likely to develop TdP than men, and female sex is considered a risk factor for TdP. Both of our patients were women. Chauhan et al. reported that infarct-related QT prolongation was independent of sex.9 In the study of Halkin et al.10 study, 4 of the 8 patients in whom “infarct-related LQTS” developed were women, revealing no sex predilection.
Mechanism of QT prolongation and TdP
The mechanism responsible for the transient changes that occurs in the QT and TPE intervals after coronary events despite relief from ongoing myocardial ischemia is not yet clear. However, marked TPE prolongation suggests that the increase in TDR plays an important role. A disproportionate prolongation of the M-cell action potential, which was also seen in models of subendocardial myocardial infarction, contributes to the development of long QT intervals and augmented TDR.5,6,13
Although it is beyond the scope of this report to uncover the mechanism underlying TPE prolongation and TdP, our cases may provide some clues. Substantially injured endocardium might result in increased TDR. Both of our patients were continuously infused with nicorandil, which is reported to be capable of abbreviating a long QT interval, reducing TDR, and preventing TdP when LQTS is secondary to reduced I^sub Kr^ or I^sub Ks^ but less so when it is due to augmented late I^sub Na^.14 In addition, mexiletine is reported to be very effective in shortening the QT interval and decreasing TDR in LQT3 models and to be valuable in reducing the incidence of arrhythmogenesis in LQT2 models.1,2 Our second patient took mexiletine and had no TdP attacks despite the longer QTc intervals than in patient 1. The medication in our cases might suggest that augmented late I^sub Na^ might have been more involved than reduced I^sub Kr^ or I^sub Ks^ in the infarct-related LQTS and TdP.
Fig. 5. The 12-lead ECG series in patient 2. Left, Upon admission, ST-T change was associated with a normal QT interval. Middle, The QTc interval became prolonged and peaked on day 2 at 756 milliseconds. Of note, the TPE interval also increased markedly (340 milliseconds) and exhibited a giant and bizarre negative T-wave. Right, On day 5, the QT and TPE intervals returned to normal (QTc = 442 milliseconds, TPE = 120 milliseconds).
Fig. 6. Emergent coronary angiogram in patient 2 revealing 90% stenosis of the proximal LAD. Percutaneous coronary intervention was successfully performed.
Patients with ACS should undergo careful ECG monitoring even after successful PCI because transient QT prolongation with TdP may occur even in the absence of any other QT interval-prolonging factors. Although this phenomenon is transient, clinicians must be alert to the appearance of any QT interval prolongation and pleomorphic ventricular tachyarrhythmia.
Torsades de pointes after successful PCI for ACS is uncommon; however, a variant of acquired LQTS should be considered and treated in patients in whom giant and bizarre negative T waves and QT prolongation develop after PCI despite relief of any ongoing myocardial ischemia.
1. Shimizu W, Antzelevitch C. Sodium channel block with mexiletine is effective in reducing dispersion of repolarization and preventing torsade de pointes in LQT2 and LQT3 models of the long- QT syndrome. Circulation 1997;96:2038.
2. Shimizu W, Antzelevitch C. Cellular basis for the ECG features of the LQT1 form of the long-QT syndrome: effects of beta- adrenergic agonists and antagonists and sodium channel blockers on transmural dispersion of repolarization and torsade de pointes. Circulation 1998;98:2314.
3. Antzelevitch C, Shimizu W. Cellular mechanisms underlying the long QT syndrome. Curr Opin Cardiol 2002;17:43.
4. Shimizu W, Antzelevitch C. Differential effects of beta- adrenergic agonists and antagonists in LQT1, LQT2 and LQT3 models of the long QT syndrome. J Am Coll Cardiol 2000;35:778.
5. Yan GX, Antzelevitch C. Cellular basis for the electrocardiographic J wave. Circulation 1996;93:372.
6. El-Sherif N, Caref EB, Yin H, Restivo M. The electrophysiological mechanism of ventricular arrhythmias in the long QT syndrome: tridimensional mapping of activation and recovery patterns. Circ Res 1996;79:474.
7. Moreno FL, Villanueva T, Karagounis LA, Anderson JL. Reduction in QT interval dispersion by successful thrombolytic therapy in acute myocardial infarction. Circulation 1994;90:94.
8. Doroghazi RM, Childers R. Time-related changes in the Q-T interval in acute myocardial infarction: possible relation to local hypocalcemia. Am J Cardiol 1978;41:684.
9. Chauhan VS, Tang AS. Dynamic changes of QT interval and QT dispersion in non-Q-wave and Q-wave myocardial infarction. J Electrocardiol 2001;34:109.
10. Halkin A, Roth A, Lurie I, Fish R, Belhassen B, Viskin S. Pausedependent torsade de pointes following acute myocardial infarction: a variant of the acquired long QT syndrome. J Am Coll Cardiol 2001;38:1168.
11. Lu HR, Yu F, Dai DZ, Remeysen P, De Clerck F. Reduction in QT dispersion and ventricular arrhythmias by ischaemic preconditioning in anesthetized, normotensive and spontaneously hypertensive rats. Fundam Clin Pharmacol 1999; 13:445.
12. Kenigsberg DN, Khanal S, Kowalski M, Krishnan SC. Prolongation of the QTc interval is seen uniformly during early transmural ischemia. J Am Coll Cardiol 2007;49:1299.
13. Yan GX, Antzelevitch C. Cellular basis for the normal T wave and the electrocardiographic manifestation of the long-QT syndrome. Circulation 1998;98:1928.
14. Shimizu W, Antzelevitch C. Effects of a K+ channel opener to reduce transmural dispersion of repolarization and prevent torsade de pointes in LQTl, LQT2, and LQT3 models of the long-QT Syndrome. Circulation 2000; 102:706.
Mihoko Kawabata, MD, PhD,* Kenzo Hirao, MD, PhD, Sasaki Takeshi, MD, Kaoru Sakurai, MD, Hiroshi Inagaki, MD, Hitoshi Hachiya, MD, PhD, Mitsuaki Isobe, MD, PhD
Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan
Received 23 May 2007; accepted 21 September 2007
None of the authors have a conflict of interest or financial relationship related to this manuscript.
* Corresponding author. Department of Cardiovascular Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. Tel.: +81 358035231; fax: +81 358030131.
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