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Delayed electrocardiographic changes after percutaneous transluminal septal myocardial ablation in hypertrophic obstructive cardiomyopathy
Journal of Electrocardiology 40 (2007) 356.e1 – 356.e6 www.jecgonline.com
Delayed electrocardiographic changes after percutaneous transluminal septal myocardial ablation in hypertrophic obstructive cardiomyopathy Hangyuan Guo, PhD, MD,a,b,4 Ping Wang, MD,a Yangbo Xing, PhD,a Fang Peng, MD,a Jun Jiang, MD,c Biao Yang, MD,a Binquan You, MD,a Yufang Qiu, MD,a Jong-Dae Lee, MD, PhDb a
Department of Cardiology, Shaoxing People’s Hospital, The First Affiliated Hospital of Shaoxing, University of China, Shaoxing, Zhejiang, China b First Department of Internal Medicine, Medical College, Fukui University of Japan, Fukui, Japan c Department of Cardiology, First Affiliated Hospital of Medical College, Zhejiang University of China, Zheijiang, China Received 22 August 2006; accepted 14 December 2006
Abstract
Objectives: This work aimed to study the delayed electrocardiographic changes, including Q-T interval, corrected Q-T dispersion, and heart rate variability (HRV) 3 years after percutaneous transluminal septal myocardial ablation (PTSMA), in symptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM). Methods: In 26 patients (11 women, 15 men; average age, 37.4 F 11.2 years) with symptomatic and medically refractory HOCM, 1.4 F 0.5 septal branches were occluded with an injection of 3.8 F 1.3 mL of alcohol (95%) to ablate the hypertrophied interventricular septum. Baseline and 3 days and 3 years postprocedure 24-hour Holter electrocardiographic findings were determined. Results: One patient developed complete atrioventricular block requiring permanent pacing. The PR interval was significantly prolonged 3 days after ablation, but recovered 3 years postprocedure. Three days after the procedure, all patients developed right bundle branch block, which was present in 24 patients after 3 years. The QRS duration was significantly prolonged 3 days after ablation and during 3 years of follow-up. There was significant and persistent prolongation of QT interval and transient prolongation of corrected QT dispersion 3 days after ablation and returned to preablation values 3 years postprocedure, but JT interval and corrected JT dispersion were not significantly changed after PTSMA. Heart rate variability data (time domain and frequency domain) 3 days and 3 years after PTSMA, including low frequency, high frequency, root mean squared successive difference interval, and the percent of sinus cycles differing from the preceding cycle by more than 50 milliseconds, significantly increased compared to that before the procedure. Low frequency/high frequency, SD of all normal-to-normal intervals, and SD of 5-minute average normal-to-normal intervals were not significantly changed after PTSMA. Conclusions: Percutaneous transluminal septal myocardial ablation for HOCM induces significant delayed electrocardiographic changes in most patients. The changes include QRS prolongation, new right bundle branch block, persistent QT prolongation, transient QT dispersion and PR prolongation, and changes in HRV data. Electrocardiographic long-term follow-up of a larger series of patients is required to determine the conclusive therapeutic significance. D 2007 Published by Elsevier Inc.
Keywords:
Percutaneous transluminal septal myocardial ablation; Hypertrophic obstructive cardiomyopathy; QT interval; Heart rate variability
Introduction Hypertrophic cardiomyopathy (HCM) is defined as a primary, sometimes familial, and genetically fixed myocar-
4 Corresponding author. Department of Cardiology, Shaoxing People’s Hospital, Shaoxing, Zhejiang 312000, China. Tel.: +86 575 522 8810; fax: +86 571 869 97949. E-mail address: [email protected] 0022-0736/$ – see front matter D 2007 Published by Elsevier Inc. doi:10.1016/j.jelectrocard.2006.12.003
dial hypertrophy. In the obstructive form of the disease (hypertrophic obstructive cardiomyopathy [HOCM]), a dynamic outflow tract obstruction of the left, occasionally also of the right, ventricle can be found. Hypertrophic obstructive cardiomyopathy is the most frequent cause of stress-induced syncope or sudden cardiac death in younger patients. An individual estimation of prognosis is difficult, although several risk factors have been identified.1 Therapeutic approaches, including use of negatively inotropic
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Table 1 Clinical characteristics of 26 patients with HOCM on admission Age (y) Male/female Time since HOCM diagnosis (y) NYHA function class Family history of HOCM or sudden cardiac death (n/total) Systemic hypertension (n/total) Documented supraventricular tachycardia (n/total) History of syncopal attacks (n/total) History of acute heart failure (n/total) Medication b-Blockers (n/total) Calcium antagonists (n/total)
37.4 F 11.2 15/11 7.1 F 3.3 3.0 F 0.6 7/26 10/26 8/26 7/26 10/26 18/26 26/26
substances (b-adrenergic blocking agents and calcium antagonists of the verapamil type), implantation of a DDD pacemaker,2 surgical myectomy,3 and percutaneous septal myocardial ablation (PTSMA) by alcohol-induced septal branch occlusion,4,5 aim to reduce the extent of outflow tract obstruction, thus improving clinical symptoms. Percutaneous transluminal septal myocardial ablation induces myocardial infarction of the subaortic part of the interventricular septum, where the ventricular conduction system begins. One would therefore expect that there will be significant changes in the electrocardiogram (ECG). We present the delayed electrocardiographic changes in a group of 26 patients who underwent the procedure. Methods Study patients Subjects consisted of 26 patients (11 women, 15 men; mean age, 37.4 F 11.2 years) with a mean (FSD) disease duration of 7.1 F 3.3 years. The patients were all symptomatic despite therapy with verapamil (240-480 mg/d) and/ or b-blockers (metoprolol, 100-300 mg/d); 8 patients had verapamil alone and 18 cases took both verapamil and metoprolol. The mean heart functional class (New York Heart Association [NYHA]) was 3.0 F 0.6. The clinical baseline data of the patients are shown in Table 1. Diagnosis of HOCM in all patients was confirmed by clinical and noninvasive criteria. Inclusion criteria were severely symptomatic patients (NYHA functional class z III) despite sufficient drug therapy or with important side effects of medication. Low-level symptomatic patients should be treated only if they have documented high-risk factors for sudden cardiac death. In the treated patients, a left ventricular outflow tract (LVOT) gradient ( z 50 mm Hg at rest and z 70 mm Hg under stress) should be documented. In our study, the LVOT gradient was determined at rest (18 cases), after spontaneous extrasystole (1 case), and after provocation with adrenaline in 7 cases. Patients with previous surgical myectomy or DDD pacemaker implantation were excluded. Before as well as 3 days after the intervention, the systolic pressure gradient of the LVOT was determined by Doppler echocardiography (10 cases were measured by transesophageal echocardiography) and 24-hour Holter ECG was carried out.
Alcohol ablation procedure First, a 6-F pacemaker lead was placed through the left femoral vein in the right ventricle. After puncture of the left femoral artery, a catheter was introduced into the left ventricular inflow tract through the aortic valve. After puncture of the right femoral artery, a 7-F guiding catheter was placed into the ascending aorta. The LVOT gradient was then determined at rest (18 cases), after spontaneous extrasystole (1 case), and after provocation with adrenaline in 7 cases. This was followed by the intravenous application of 8000 U of heparin to prevent thromboembolic complications. Then, a more than 0.014-in-thick guide wire angioplasty catheter with a balloon diameter of 2.0 mm and length of 1.0 cm (Natick, Massachusetts, USA; Cobra, Boston Scientific Corp) was placed in the proximal part of the septal branch. After the balloon was inflated to a pressure of 5 to 6 bar, the correct balloon position was determined using an injection of contrast medium into the left coronary main artery, and the supply area of the septal branch was determined using an injection of contrast medium through the balloon catheter. If a reduction in the outflow tract obstruction could be established after 5 to 8 minutes of septal occlusion, myocardial ablation of the septal branch supply area was then carried out by an injection of 95% alcohol. Five milligrams of morphine was administrated before alcohol injection. Ten to 12 minutes later, the balloon catheter was deflated, and the morphologic result was examined by visualizing the left main coronary artery. If a sufficient reduction in the outflow tract gradient through the occlusion of a smaller septal branch proved impossible to attain, then another septal branch was occluded. The patients were sent to the cardiac care unit for postinterventional monitoring after finishing the operation. The vascular sheaths were removed after normalization of the coagulation variables. Three days and 3 years after ablation, all patients underwent 24-hour Holter ECG examination. Electrocardiogram analysis All 24-hour Holter ECG recordings were performed 3 days before and 3 days and 3 years after successful Table 2 Comparison of echocardiographic findings pre-PTMSA and post-PTSMA
LA (mm) LVEDd (mm) LVEDs (mm) LVPW (mm) IVS (mm) SAM MR (mL) EF (%)
Pre-PTSMA
Post-PTSMA (3rd day)
47.6 41.8 25.7 14.3 23.5 2.3 26.7 61.2
47.3 42.3 30.6 14.1 19.1 0.9 15.1 59.5
F F F F F F F F
7.2 5.2 5.3 2.5 3.6 0.7 12.0 14.9
F F F F F F F F
6.5 5.0 5.44 2.8 2.54 0.544 7.244 18.1
Post-PTSMA (3rd year) 44.0 F 7.14,D 42.7 31.3 14.7 16.0 0.7 15.8 60.5
F F F F F F F
6.9 4.84 2.1 3.444,D 0.644 8.844 13.9
LA indicates left atrium; LVEDd, left ventricular end-diastolic diameter; LVEDs, left ventricular end-systolic diameter; LVPW, left ventricular posterior wall; IVS, interventricular septum; SAM, septal anterior movement of mitral valve; MR, mitral regurgitant volume; EF, left ventricular ejection fraction. 4 P b .05 vs pre-PTSMA. 44 P b .01 vs pre-PTSMA (3rd day). D P b .05 vs post-PTSMA (3rd day).
H. Guo et al. / Journal of Electrocardiology 40 (2007) 356.e1 – 356.e6 Table 3 Comparison of electrocardiographic findings pre-PTMSA and post-PTSMA
HR (beats/min) PR interval (ms) QRS width (ms) QT interval (ms) QTcd (ms) JT interval (ms) JTcd (ms) SVT (n/total) PVC 10-20/h (n/total) NSVT (n/total) VT (n/total) AV block (n/total)
Pre-PTSMA
Post-PTSMA (3rd day)
Post-PTSMA (3rd year)
67 F 158 F 94 F 421 F 79 F 327 F 57 F 8/26 5/26 4/26 0/26 0/26
63 F 187 F 129 F 468 F 101 F 339 F 61 F 7/26 6/26 4/26 0/26 1/26a
69 164 120.0 464 81 344 60 7/26 5/26 4/26 0/26 1/26a
10 31 17 42 20 35 26
8 4244 2544 534 214 47 22
F F F F F F F
12 38DD 2944 334 20D 30 28
SVT indicates supraventricular tachycardia; PVC, premature ventricular beat; NSVT, nonsustained ventricular tachycardia; VT, ventricular tachycardia; AV, atrioventricular. a The patient with implanted DDD pacemaker showed periods of sinus rhythm. 4 P b .05 vs pre-PTSMA. 44 P b .01. D P b .05 vs post-PTSMA (3rd day). DD P b .01 vs post-PTSMA (3rd day).
PTSMA by means of b3-Channel Digital USB Holter RecorderQ (Advanced Biosensor, Inc., Columbia, SC, USA). The tapes were subsequently analyzed by the PREDICTOR HRVECG arrhythmia analysis program, which allows detection of normal sinus beats and supraventricular and ventricular extrasystoles. After automatic analysis of the tape, the data file was visually reviewed and edited by the investigators. Heart rate variability was performed with the (Arrhythmia Research Technology, Inc., Austin, Texas, USA) HRVECG HRV analysis program. Aberrant ECG complexes, such as premature ventricular beats, electrical noise, or other aberrant ECG signals, and their adjacent RR intervals were rejected from the RR interval generation process and HRV analysis. Time-domain measures were the SD of all normal RR intervals in the entire 24-hour ECG recording (SDNN), the SD of the average normal RR intervals for all 5-minute segments (SDANN), the root mean squared successive difference interval (the square root of the mean of the
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squared differences between adjacent normal RR intervals over the entire 24-hour recording, rMSSD), and the percentage of sinus cycles differing from the preceding cycle by more than 50 milliseconds over the entire 24-hour recording (PNN50). The power spectral analysis of normal-to-normal intervals was computed by fast Fourier transform on 5-minute segments over the 24-hour period. The PREDICTOR HRVECG system provides 4 frequency-domain measures of HRV, namely, low-frequency (LF) power (0.04-0.15 Hz) and high-frequency (HF) power (0.15-0.40 Hz). The following ECG features were noted: basic rhythm, atrioventricular (AV) block, and presence of bundle branch block. QRS duration was measured in all leads and the arithmetical mean was calculated. The longest PR interval was taken for analysis. For QT measurements, an average of 3 consecutive intervals was taken from all leads. JT = QT interval QRS duration. QTc and JTc were calculated using the formula of Bazett for each lead separately. For QTc dispersion (QTcd) and JTc dispersion (JTcd), the difference between the maximum and minimum QTc (JTc) intervals was used. Statistical analysis Data are expressed as mean F SD (x¯ F SD). Frequencies are given for discrete variables. Comparison of continuous variables at various times was carried out using the paired Student t test. All statistical analyses were carried out in an IBM computer with SPSS software (SPSS, Chicago, Ill). A P value b .05 was considered statistically significant.
Results Changes in hemodynamic results and complications during the intervention A mean of 1.4 F 0.5 (1-3) septal branches was occluded by injection of 3.8 F 1.1 mL (range, 2-7.8) of alcohol, 17 cases with 1 septal branch, 6 cases with 2 septal branches, and 3 cases with 3 septal branches. A reduction of LVOT gradient could be attained in all patients. The mean systolic pressure difference in the LVOT at rest decreased from
Fig. 1. Electrocardiographic changes pre-PTSMA and post-PTSMA (top, V1; middle, V3; foot, V5).
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Table 4 Heart rate variability change preprocedure and 3 days and 3 years after PTSMA
LF (bpm2/Hz) HF (bpm2/Hz) LF/HF SDNN (ms) SDANN (ms) rMSSD (ms) PNN50 (% of beats)
Pre-PTSMA
Post-PTSMA (3rd day)
Post-PTSMA (3rd year)
238 F 82 97 F 36 2.5 F 1.1 114 F 37 98 F 37 21 F 9 4.8 F q2.1
315 143 2.2 107 105 32 6.9
308 F 134 F 2.3 F 119 F 109 F 34 F 6.8 F
F F F F F F F
1354 674 0.7 50 48 134 3.04
1294 714 0.9 49 33 114 2.44
4 P b .05 vs pre-PTSMA.
75.8 F 20.1 to 15.6 F 7.1 mm Hg ( P b .01) after balloon occlusion and after occlusion by alcohol to 10.2 F4.9 mm Hg ( P b .01 vs baseline, P b .01 vs balloon occlusion). The postextrasystolic gradient could be reduced from 129.8 F 28.6 to 34.5 F 10.7 mm Hg ( P b .01). One patient developed ventricular fibrillation after the alcohol injection, and sinus rhythm could be restored by 200 j of defibrillation. All patients developed different degrees of heart block during the periprocedural period; 15 patients (57.7%) developed a trifascicular block but only 1 developed a complete AV block, requiring permanent pacemaker implantation. Temporary right bundle branch block occurred in 19 patients (73.1%) and permanent block occurred in 11 patients (42.3%). Three-year clinical course During a 3-year follow-up of 26 cases, there were no deaths. After 3 years, there was a significant improvement in the clinical symptoms, with the NYHA function class improving to 1.4 F 0.6 ( P b .01 vs baseline). Twenty patients (76.9%) had improved subjectively, 5 patients (19.2%) reported no change in their cardiac symptoms, and 1 patient (3.9%) complained of more serious symptoms than during preoperation. There were no serious cardiac complications during follow-up. Echocardiographic findings Left ventricular outflow tract gradients were significantly reduced. The mean SAM phenomenon was acutely reduced from 2.3 F 0.7 to 1.1 F 0.5 ( P b .01). Echocardiography after the operation for 3 days showed new wall motion dyskinesia in the basal septum in all patients. After 3 years, the results of echocardiographic findings could be compared in all patients. The changes in left heart dimensions are shown in Table 2. Compared with baseline values, 15 patients (57.7%) had a reduction of LVOT gradient of more than 50%, whereas 3 (11.5%) showed no significant change. Compared with the acute results, a further reduction in LVOT gradient was shown in 11 patients (42.3%). Electrocardiographic findings The results of electrocardiographic findings could be compared in all patients. The changes in ECG data are shown in Table 3. All ECG data but PR interval and QTcd have no obvious difference between post-PTSMA (third day) and post-PTSMA (third year). One patient developed complete AV block requiring permanent pacing. The mean
heart rate did not change significantly 3 days after the procedure and during follow-up. The PR interval was significantly prolonged 3 days after ablation, but recovered 3 years postprocedure. Three days after the procedure, all patients developed right bundle branch block, which persisted in 24 patients after 3 years. The QRS duration was significantly prolonged 3 days after ablation and during the 3-year follow-up. Typical ECG changes (persistent broadening of the QRS complex and lengthened QT interval) 3 days and 3 years after ablation are shown in Fig. 1. There was significant and persistent prolongation of QT interval and transient prolongation of corrected QT dispersion 3 days after ablation and returned to preablation values 3 years postprocedure, but JT interval and corrected JT dispersion were not significantly changed after PTSMA. Heart rate variability Heart rate variability data (time domain and frequency domain) 3 days and 3 years after PTSMA, including LF, HF, rMSSD, and PNN50, significantly increased compared to that before the procedure. Low frequency/HF, SDNN, and SDANN were not significantly changed after PTSMA (Table 4). Discussion In the treatment of HOCM, surgical myectomy and DDD pacemaker therapy are considered the standard procedural extensions to drug therapy with negatively inotropic drugs. As an alternative to nonsurgical procedure for reducing the LVOT gradient, PTSMA by alcohol-induced septal branch occlusion was introduced. However, long-term electrocardiographic follow-up of a larger patient series has not been sufficiently described.3,5-7 Percutaneous transluminal septal myocardial ablation is a new, investigational, catheter-based treatment for severely symptomatic, medically refractory hypertrophic obstructive cardiomyopathy (HOCM). Left ventricular outflow tract gradient was greatly decreased in patients with HOCM undergoing a PTSMA procedure, and their symptoms were greatly improved without cardiac complications during follow-up.8 Percutaneous transluminal septal myocardial ablation is an effective, nonsurgical treatment method for drug-refractory patients with HOCM.9 Most patients have symptomatic improvement, at least moderate reductions in outflow tract gradients, and possibly improvement in exercise capacity. The most common procedural complication is the development of high-grade AV block necessitating implantation of a permanent pacemaker in 5.6% of patients. Compared with surgical myectomy, PTSMA has the advantage of being minimally invasive, easily repeated, and with relatively low major morbidity and mortality risk for patients with comorbid conditions. The findings from recently initiated international registries will be helpful in assessing the overall success and complication rates with PTSMA.10 Premature sudden cardiac death (SD) is a critical event in the natural history of HCM and occurs during or just after physical exertion in approximately 60% of instances.
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Abnormalities in ventricular repolarization may not be present at rest in some patients but may become apparent under certain conditions.11 Several risk factors are established for prediction of sudden cardiac death caused by ventricular arrhythmias in patients with HCM. QT dispersion (QTd) is thought to reflect the heterogeneity of ventricular repolarization. The relation of QTd with ventricular arrhythmias and sudden cardiac death has been shown by several studies.12-14 Patients with HCM show a prolonged QTc (N 440 milliseconds) and increased QTc dispersion compared with normal subjects. In addition, the degree of left ventricular hypertrophy correlates with maximal QTc. The presence of a prolonged QT with increased regional dispersion may be associated with the occurrence of serious ventricular arrhythmia and sudden death in HCM.15 QT variability is abnormal in patients with HCM and indirectly supports the concept that arrhythmia-related syncope in these patients may be, at least in part, related to an altered control of repolarization.16 The 24-hour QT variability was higher in nonsurvivors than in survivors with HCM. Episodes of nonsustained ventricular tachycardia in untreated patients were more frequent during the nighttime. Twenty-hour QT variability was higher in nonsurvivors than in survivors.17 Although QTd was significantly greater in patients with HCM than in normal controls, its relation to risk factors of sudden death could not be established.18 Increased QT dispersion and JT dispersion are weakly associated with sudden cardiac death in the selected patients with HCM.19 Percutaneous transluminal septal myocardial ablation for HOCM induces significant changes in the resting ECG in most patients, despite the occlusion of a relatively small artery. The changes include new Q waves, new bundle branch block, transient anterior ST-segment elevation, AV block, and transient prolongation of QT interval. JT interval was significantly different from baseline only on the seventh day and at the 6-month followup. These differences were caused by a slightly higher heart rate. JTc interval did not change significantly during followup. No significant changes were found in QT dispersion and QTc dispersion except for QTc-d on the third day. JTcd increased from 73 F 31 milliseconds at baseline to 109 F 39 milliseconds ( P b .05) by the third day. By the ninth day, JTd and JTcd had returned to preablation values.20 Prolongation of QT and QTc intervals has been reported in HOCM, especially in patients with serious ventricular arrhythmias.21,22 QTc prolongation as a result of ablation is at least partly caused by prolongation of the QRS complex. To avoid this influence, we also analyzed the behavior of the JT interval. In contrast to QTc, JTc did not show significant changes. The results of HRV analysis in patients with HCM are conflicting. Most authors think that HRV is reduced in HOCM and well correlated with the degree of subaortic obstruction. Heart rate variability indices are also a sensitive marker of functional status.23 Parasympathetic predominance was shown during autonomic stimulation in patients with HCM. No correlation was found between HRV and echocardiographic measurements under analysis.24 The HRV reduction was more expressed in patients with HCM and family members less than 30 years of age. A significantly reduced SDNN was observed in 54% of patients in the HCM group
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and in 42% of subjects in the members group. Reduced HRV is frequently seen not only in patients with diagnosed HCM, but also in a substantial number of their kindred.25 The values of rMSSD and pNN50 were lower in the patients with HOCM than in the controls before pacing, which were restored to normal levels by the end of the study. Long-term pacing in patients with HOCM restores the sympathovagal balance in the heart by improving vagal activity.26 Our study showed that 1 patient developed complete AV block requiring permanent pacing. The PR interval was significantly prolonged 3 days after ablation, but recovered 3 years postprocedure. Three days after the procedure, all patients developed right bundle branch block, which persisted in 24 patients after 3 years. The QRS duration was significantly prolonged 3 days after ablation and during the 3-year follow-up. There was significant and persistent prolongation of QT interval and transient prolongation of corrected QT dispersion 3 days after ablation and returned to preablation values 3 years postprocedure, but JT interval and corrected JT dispersion were not significantly changed after PTSMA. Heart rate variability data (time domain and frequency domain) 3 days and 3 years after PTSMA, including LF, HF, rMSSD, and PNN50, significantly increased compared to that before the procedure. Low frequency/HF, SDNN, and SDANN were not significantly changed after PTSMA. Left ventricular outflow tract gradient was greatly decreased in patients with HOCM undergoing a PTSMA procedure, and their symptoms were greatly improved without cardiac complications during the 3-year follow-up. Possible complications include different degree of heart block including trifascicular blocks, requiring temporary pacemaker implantation. Percutaneous transluminal septal myocardial ablation is a promising nonsurgical method for the treatment of symptomatic patients with HOCM. Percutaneous transluminal septal myocardial ablation for HOCM induces significant delayed electrocardiographic changes in most patients. The changes include QRS duration, right bundle branch block, QT interval, corrected QT dispersion, and HRV data. Electrocardiographic longterm follow-up of a larger series of patients is required to determine the conclusive therapeutic significance. References 1. Gleichmann U, Seggewiss H. Clinical picture and therapy of hypertrophic cardiomyopathy. Med Klin 1998;93:260. 2. Meisel E, Rauwolf T, Burghardt M, et al. Pacemaker therapy of hypertrophic obstructive cardiomyopathy. PIC (Pacing in Cardiomyopathy) Study Group. Herz 2000;25:461. 3. Qin JX, Shiota T, Lever HM, et al. Outcome of patients with hypertrophic obstructive cardiomyopathy after percutaneous transluminal septal myocardial ablation and septal myectomy surgery. J Am Coll Cardiol 2001;38:1994. 4. Seggewiss H. Current status of alcohol septal ablation for patients with hypertrophic cardiomyopathy. Curr Cardiol Rep 2001;3:160. 5. Guo H, Wang J, Chen J, et al. Percutaneous transluminal septal myocardial ablation in hypertrophic obstructive cardiomyopathy: acute results and three-year noninvasive follow-up in 18 patients. Can J Cardiol 2004;20:779. 6. Airoldi F, Di Mario C, Catanoso A, et al. Progressive decrease of outflow gradient and septum thickness after percutaneous alcohol-
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ization of the interventricular septum in hypertrophic obstructive cardiomyopathy. Ital Heart J 2000;1:200. Faber L, Seggewiss H, Welge D, et al. Predicting the risk of atrioventricular conduction lesions after percutaneous septal ablation for obstructive hypertrophic cardiomyopathy. Z Kardiol 2003;92:39. Jiang T, Wu X, Jia C, et al. Percutaneous transluminal septal myocardial ablation in patients with hypertrophic obstructive cardiomyopathy. Chin Med J (Engl) 2002;115:26. Jiang T, Wu X, Jia C. Percutaneous transluminal septal myocardial ablation in patients with hypertrophic obstructive cardiomyopathy: immediately and middle-term follow-up results. Zhonghua Nei Ke Za Zhi 2001;40:663. Rubin DN, Tuzcu EM, Lever HM. Percutaneous transluminal septal myocardial ablation. Curr Cardiol Rep 2000;2:160. Yi G, Poloniecki J, Dickie S, et al. Can the assessment of dynamic QT dispersion on exercise electrocardiogram predict sudden cardiac death in hypertrophic cardiomyopathy? Pacing Clin Electrophysiol 2000;23:1956. zu Vilsendorf DM, Strunk-Mueller C, Gietzen FH, et al. Simultaneous hypertrophic obstructive cardiomyopathy and long QT syndrome: a potentially malignant association. Z Kardiol 2002;91:575 [German]. Gottfridsson C, Wallentin I, Dernevik L, et al. Full ventricular capture indicated by the QT interval function. Pacing Clin Electrophysiol 1998; 21:2171. Saumarez RC, Pytkowski M, Sterlinski M, et al. Delayed paced ventricular activation in the long QT syndrome is associated with ventricular fibrillation. Heart Rhythm 2006;3:771. Dritsas A, Sbarouni E, Gilligan D, et al. QT-Interval abnormalities in hypertrophic cardiomyopathy. Clin Cardiol 1992;15:739. Cuomo S, Marciano F, Migaux ML, et al. Abnormal QT interval variability in patients with hypertrophic cardiomyopathy: can syncope be predicted? J Electrocardiol 2004;37:113.
17. Goktekin O, Ritsushi K, Matsumoto K, et al. The relationship between QT dispersion and risk factors of sudden death in hypertrophic cardiomyopathy. Anadolu Kardiyol Derg 2002;2:226. 18. Baranowski R, Chojnowska L, Michalak E, et al. Analysis of the corrected QT before the onset of nonsustained ventricular tachycardia in patients with hypertrophic cardiomyopathy. Pacing Clin Electrophysiol 2003;26:387. 19. Yi G, Poloniecki J, Dickie S, et al. Is QT dispersion associated with sudden cardiac death in patients with hypertrophic cardiomyopathy? Ann Noninvasive Electrocardiol 2001;6:209. 20. Kazmierczak J, Kornacewicz-Jach Z, Kisly M, et al. Electrocardiographic changes after alcohol septal ablation in hypertrophic obstructive cardiomyopathy. Heart 1998;80:257. 21. Dritsas A, Sbarouni E, Gilligan D, et al. QT interval abnormalities in hypertrophic cardiomyopathy. Clin Cardiol 1992;15:739. 22. Fei L, Slade A, Grace A, et al. Ambulatory assessment of the QT interval in patients with hypertrophic cardiomyopathy: risk stratification and effect of low dose amiodarone. Pacing Clin Electrophysiol 1994;17:2222. 23. Doven O, Sayin T, Guldal M, et al. Heart rate variability in hypertrophic obstructive cardiomyopathy: association with functional classification and left ventricular outflow gradients. Int J Cardiol 2001; 77:281. 24. Bittencourt MI, Barbosa PR, Drumond Neto C, et al. Assessing autonomic function in hypertrophic cardiomyopathy [Portuguese]. Arq Bras Cardiol 2005;85:388. 25. Sosnowski M, Kozakiewicz K, Korzeniowska B, et al. Heart rate variability in patients with hypertrophic cardiomyopathy and in their close relatives. Wiad Lek 2002;55:561 [Polish]. 26. Simantirakis EN, Kochiadakis GE, Kanakaraki MK, et al. Impact of chronic DDD pacing on time-domain indexes of heart rate variability in patients with hypertrophic obstructive cardiomyopathy. Pacing Clin Electrophysiol 1999;22:1808.
Delayed electrocardiographic changes after percutaneous transluminal septal myocardial ablation in hypertrophic obstructive cardiomyopathy Hangyuan Guo, PhD, MD,a,b,4 Ping Wang, MD,a Yangbo Xing, PhD,a Fang Peng, MD,a Jun Jiang, MD,c Biao Yang, MD,a Binquan You, MD,a Yufang Qiu, MD,a Jong-Dae Lee, MD, PhDb a
Department of Cardiology, Shaoxing People’s Hospital, The First Affiliated Hospital of Shaoxing, University of China, Shaoxing, Zhejiang, China b First Department of Internal Medicine, Medical College, Fukui University of Japan, Fukui, Japan c Department of Cardiology, First Affiliated Hospital of Medical College, Zhejiang University of China, Zheijiang, China Received 22 August 2006; accepted 14 December 2006
Abstract
Objectives: This work aimed to study the delayed electrocardiographic changes, including Q-T interval, corrected Q-T dispersion, and heart rate variability (HRV) 3 years after percutaneous transluminal septal myocardial ablation (PTSMA), in symptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM). Methods: In 26 patients (11 women, 15 men; average age, 37.4 F 11.2 years) with symptomatic and medically refractory HOCM, 1.4 F 0.5 septal branches were occluded with an injection of 3.8 F 1.3 mL of alcohol (95%) to ablate the hypertrophied interventricular septum. Baseline and 3 days and 3 years postprocedure 24-hour Holter electrocardiographic findings were determined. Results: One patient developed complete atrioventricular block requiring permanent pacing. The PR interval was significantly prolonged 3 days after ablation, but recovered 3 years postprocedure. Three days after the procedure, all patients developed right bundle branch block, which was present in 24 patients after 3 years. The QRS duration was significantly prolonged 3 days after ablation and during 3 years of follow-up. There was significant and persistent prolongation of QT interval and transient prolongation of corrected QT dispersion 3 days after ablation and returned to preablation values 3 years postprocedure, but JT interval and corrected JT dispersion were not significantly changed after PTSMA. Heart rate variability data (time domain and frequency domain) 3 days and 3 years after PTSMA, including low frequency, high frequency, root mean squared successive difference interval, and the percent of sinus cycles differing from the preceding cycle by more than 50 milliseconds, significantly increased compared to that before the procedure. Low frequency/high frequency, SD of all normal-to-normal intervals, and SD of 5-minute average normal-to-normal intervals were not significantly changed after PTSMA. Conclusions: Percutaneous transluminal septal myocardial ablation for HOCM induces significant delayed electrocardiographic changes in most patients. The changes include QRS prolongation, new right bundle branch block, persistent QT prolongation, transient QT dispersion and PR prolongation, and changes in HRV data. Electrocardiographic long-term follow-up of a larger series of patients is required to determine the conclusive therapeutic significance. D 2007 Published by Elsevier Inc.
Keywords:
Percutaneous transluminal septal myocardial ablation; Hypertrophic obstructive cardiomyopathy; QT interval; Heart rate variability
Introduction Hypertrophic cardiomyopathy (HCM) is defined as a primary, sometimes familial, and genetically fixed myocar-
4 Corresponding author. Department of Cardiology, Shaoxing People’s Hospital, Shaoxing, Zhejiang 312000, China. Tel.: +86 575 522 8810; fax: +86 571 869 97949. E-mail address: [email protected] 0022-0736/$ – see front matter D 2007 Published by Elsevier Inc. doi:10.1016/j.jelectrocard.2006.12.003
dial hypertrophy. In the obstructive form of the disease (hypertrophic obstructive cardiomyopathy [HOCM]), a dynamic outflow tract obstruction of the left, occasionally also of the right, ventricle can be found. Hypertrophic obstructive cardiomyopathy is the most frequent cause of stress-induced syncope or sudden cardiac death in younger patients. An individual estimation of prognosis is difficult, although several risk factors have been identified.1 Therapeutic approaches, including use of negatively inotropic
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Table 1 Clinical characteristics of 26 patients with HOCM on admission Age (y) Male/female Time since HOCM diagnosis (y) NYHA function class Family history of HOCM or sudden cardiac death (n/total) Systemic hypertension (n/total) Documented supraventricular tachycardia (n/total) History of syncopal attacks (n/total) History of acute heart failure (n/total) Medication b-Blockers (n/total) Calcium antagonists (n/total)
37.4 F 11.2 15/11 7.1 F 3.3 3.0 F 0.6 7/26 10/26 8/26 7/26 10/26 18/26 26/26
substances (b-adrenergic blocking agents and calcium antagonists of the verapamil type), implantation of a DDD pacemaker,2 surgical myectomy,3 and percutaneous septal myocardial ablation (PTSMA) by alcohol-induced septal branch occlusion,4,5 aim to reduce the extent of outflow tract obstruction, thus improving clinical symptoms. Percutaneous transluminal septal myocardial ablation induces myocardial infarction of the subaortic part of the interventricular septum, where the ventricular conduction system begins. One would therefore expect that there will be significant changes in the electrocardiogram (ECG). We present the delayed electrocardiographic changes in a group of 26 patients who underwent the procedure. Methods Study patients Subjects consisted of 26 patients (11 women, 15 men; mean age, 37.4 F 11.2 years) with a mean (FSD) disease duration of 7.1 F 3.3 years. The patients were all symptomatic despite therapy with verapamil (240-480 mg/d) and/ or b-blockers (metoprolol, 100-300 mg/d); 8 patients had verapamil alone and 18 cases took both verapamil and metoprolol. The mean heart functional class (New York Heart Association [NYHA]) was 3.0 F 0.6. The clinical baseline data of the patients are shown in Table 1. Diagnosis of HOCM in all patients was confirmed by clinical and noninvasive criteria. Inclusion criteria were severely symptomatic patients (NYHA functional class z III) despite sufficient drug therapy or with important side effects of medication. Low-level symptomatic patients should be treated only if they have documented high-risk factors for sudden cardiac death. In the treated patients, a left ventricular outflow tract (LVOT) gradient ( z 50 mm Hg at rest and z 70 mm Hg under stress) should be documented. In our study, the LVOT gradient was determined at rest (18 cases), after spontaneous extrasystole (1 case), and after provocation with adrenaline in 7 cases. Patients with previous surgical myectomy or DDD pacemaker implantation were excluded. Before as well as 3 days after the intervention, the systolic pressure gradient of the LVOT was determined by Doppler echocardiography (10 cases were measured by transesophageal echocardiography) and 24-hour Holter ECG was carried out.
Alcohol ablation procedure First, a 6-F pacemaker lead was placed through the left femoral vein in the right ventricle. After puncture of the left femoral artery, a catheter was introduced into the left ventricular inflow tract through the aortic valve. After puncture of the right femoral artery, a 7-F guiding catheter was placed into the ascending aorta. The LVOT gradient was then determined at rest (18 cases), after spontaneous extrasystole (1 case), and after provocation with adrenaline in 7 cases. This was followed by the intravenous application of 8000 U of heparin to prevent thromboembolic complications. Then, a more than 0.014-in-thick guide wire angioplasty catheter with a balloon diameter of 2.0 mm and length of 1.0 cm (Natick, Massachusetts, USA; Cobra, Boston Scientific Corp) was placed in the proximal part of the septal branch. After the balloon was inflated to a pressure of 5 to 6 bar, the correct balloon position was determined using an injection of contrast medium into the left coronary main artery, and the supply area of the septal branch was determined using an injection of contrast medium through the balloon catheter. If a reduction in the outflow tract obstruction could be established after 5 to 8 minutes of septal occlusion, myocardial ablation of the septal branch supply area was then carried out by an injection of 95% alcohol. Five milligrams of morphine was administrated before alcohol injection. Ten to 12 minutes later, the balloon catheter was deflated, and the morphologic result was examined by visualizing the left main coronary artery. If a sufficient reduction in the outflow tract gradient through the occlusion of a smaller septal branch proved impossible to attain, then another septal branch was occluded. The patients were sent to the cardiac care unit for postinterventional monitoring after finishing the operation. The vascular sheaths were removed after normalization of the coagulation variables. Three days and 3 years after ablation, all patients underwent 24-hour Holter ECG examination. Electrocardiogram analysis All 24-hour Holter ECG recordings were performed 3 days before and 3 days and 3 years after successful Table 2 Comparison of echocardiographic findings pre-PTMSA and post-PTSMA
LA (mm) LVEDd (mm) LVEDs (mm) LVPW (mm) IVS (mm) SAM MR (mL) EF (%)
Pre-PTSMA
Post-PTSMA (3rd day)
47.6 41.8 25.7 14.3 23.5 2.3 26.7 61.2
47.3 42.3 30.6 14.1 19.1 0.9 15.1 59.5
F F F F F F F F
7.2 5.2 5.3 2.5 3.6 0.7 12.0 14.9
F F F F F F F F
6.5 5.0 5.44 2.8 2.54 0.544 7.244 18.1
Post-PTSMA (3rd year) 44.0 F 7.14,D 42.7 31.3 14.7 16.0 0.7 15.8 60.5
F F F F F F F
6.9 4.84 2.1 3.444,D 0.644 8.844 13.9
LA indicates left atrium; LVEDd, left ventricular end-diastolic diameter; LVEDs, left ventricular end-systolic diameter; LVPW, left ventricular posterior wall; IVS, interventricular septum; SAM, septal anterior movement of mitral valve; MR, mitral regurgitant volume; EF, left ventricular ejection fraction. 4 P b .05 vs pre-PTSMA. 44 P b .01 vs pre-PTSMA (3rd day). D P b .05 vs post-PTSMA (3rd day).
H. Guo et al. / Journal of Electrocardiology 40 (2007) 356.e1 – 356.e6 Table 3 Comparison of electrocardiographic findings pre-PTMSA and post-PTSMA
HR (beats/min) PR interval (ms) QRS width (ms) QT interval (ms) QTcd (ms) JT interval (ms) JTcd (ms) SVT (n/total) PVC 10-20/h (n/total) NSVT (n/total) VT (n/total) AV block (n/total)
Pre-PTSMA
Post-PTSMA (3rd day)
Post-PTSMA (3rd year)
67 F 158 F 94 F 421 F 79 F 327 F 57 F 8/26 5/26 4/26 0/26 0/26
63 F 187 F 129 F 468 F 101 F 339 F 61 F 7/26 6/26 4/26 0/26 1/26a
69 164 120.0 464 81 344 60 7/26 5/26 4/26 0/26 1/26a
10 31 17 42 20 35 26
8 4244 2544 534 214 47 22
F F F F F F F
12 38DD 2944 334 20D 30 28
SVT indicates supraventricular tachycardia; PVC, premature ventricular beat; NSVT, nonsustained ventricular tachycardia; VT, ventricular tachycardia; AV, atrioventricular. a The patient with implanted DDD pacemaker showed periods of sinus rhythm. 4 P b .05 vs pre-PTSMA. 44 P b .01. D P b .05 vs post-PTSMA (3rd day). DD P b .01 vs post-PTSMA (3rd day).
PTSMA by means of b3-Channel Digital USB Holter RecorderQ (Advanced Biosensor, Inc., Columbia, SC, USA). The tapes were subsequently analyzed by the PREDICTOR HRVECG arrhythmia analysis program, which allows detection of normal sinus beats and supraventricular and ventricular extrasystoles. After automatic analysis of the tape, the data file was visually reviewed and edited by the investigators. Heart rate variability was performed with the (Arrhythmia Research Technology, Inc., Austin, Texas, USA) HRVECG HRV analysis program. Aberrant ECG complexes, such as premature ventricular beats, electrical noise, or other aberrant ECG signals, and their adjacent RR intervals were rejected from the RR interval generation process and HRV analysis. Time-domain measures were the SD of all normal RR intervals in the entire 24-hour ECG recording (SDNN), the SD of the average normal RR intervals for all 5-minute segments (SDANN), the root mean squared successive difference interval (the square root of the mean of the
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squared differences between adjacent normal RR intervals over the entire 24-hour recording, rMSSD), and the percentage of sinus cycles differing from the preceding cycle by more than 50 milliseconds over the entire 24-hour recording (PNN50). The power spectral analysis of normal-to-normal intervals was computed by fast Fourier transform on 5-minute segments over the 24-hour period. The PREDICTOR HRVECG system provides 4 frequency-domain measures of HRV, namely, low-frequency (LF) power (0.04-0.15 Hz) and high-frequency (HF) power (0.15-0.40 Hz). The following ECG features were noted: basic rhythm, atrioventricular (AV) block, and presence of bundle branch block. QRS duration was measured in all leads and the arithmetical mean was calculated. The longest PR interval was taken for analysis. For QT measurements, an average of 3 consecutive intervals was taken from all leads. JT = QT interval QRS duration. QTc and JTc were calculated using the formula of Bazett for each lead separately. For QTc dispersion (QTcd) and JTc dispersion (JTcd), the difference between the maximum and minimum QTc (JTc) intervals was used. Statistical analysis Data are expressed as mean F SD (x¯ F SD). Frequencies are given for discrete variables. Comparison of continuous variables at various times was carried out using the paired Student t test. All statistical analyses were carried out in an IBM computer with SPSS software (SPSS, Chicago, Ill). A P value b .05 was considered statistically significant.
Results Changes in hemodynamic results and complications during the intervention A mean of 1.4 F 0.5 (1-3) septal branches was occluded by injection of 3.8 F 1.1 mL (range, 2-7.8) of alcohol, 17 cases with 1 septal branch, 6 cases with 2 septal branches, and 3 cases with 3 septal branches. A reduction of LVOT gradient could be attained in all patients. The mean systolic pressure difference in the LVOT at rest decreased from
Fig. 1. Electrocardiographic changes pre-PTSMA and post-PTSMA (top, V1; middle, V3; foot, V5).
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Table 4 Heart rate variability change preprocedure and 3 days and 3 years after PTSMA
LF (bpm2/Hz) HF (bpm2/Hz) LF/HF SDNN (ms) SDANN (ms) rMSSD (ms) PNN50 (% of beats)
Pre-PTSMA
Post-PTSMA (3rd day)
Post-PTSMA (3rd year)
238 F 82 97 F 36 2.5 F 1.1 114 F 37 98 F 37 21 F 9 4.8 F q2.1
315 143 2.2 107 105 32 6.9
308 F 134 F 2.3 F 119 F 109 F 34 F 6.8 F
F F F F F F F
1354 674 0.7 50 48 134 3.04
1294 714 0.9 49 33 114 2.44
4 P b .05 vs pre-PTSMA.
75.8 F 20.1 to 15.6 F 7.1 mm Hg ( P b .01) after balloon occlusion and after occlusion by alcohol to 10.2 F4.9 mm Hg ( P b .01 vs baseline, P b .01 vs balloon occlusion). The postextrasystolic gradient could be reduced from 129.8 F 28.6 to 34.5 F 10.7 mm Hg ( P b .01). One patient developed ventricular fibrillation after the alcohol injection, and sinus rhythm could be restored by 200 j of defibrillation. All patients developed different degrees of heart block during the periprocedural period; 15 patients (57.7%) developed a trifascicular block but only 1 developed a complete AV block, requiring permanent pacemaker implantation. Temporary right bundle branch block occurred in 19 patients (73.1%) and permanent block occurred in 11 patients (42.3%). Three-year clinical course During a 3-year follow-up of 26 cases, there were no deaths. After 3 years, there was a significant improvement in the clinical symptoms, with the NYHA function class improving to 1.4 F 0.6 ( P b .01 vs baseline). Twenty patients (76.9%) had improved subjectively, 5 patients (19.2%) reported no change in their cardiac symptoms, and 1 patient (3.9%) complained of more serious symptoms than during preoperation. There were no serious cardiac complications during follow-up. Echocardiographic findings Left ventricular outflow tract gradients were significantly reduced. The mean SAM phenomenon was acutely reduced from 2.3 F 0.7 to 1.1 F 0.5 ( P b .01). Echocardiography after the operation for 3 days showed new wall motion dyskinesia in the basal septum in all patients. After 3 years, the results of echocardiographic findings could be compared in all patients. The changes in left heart dimensions are shown in Table 2. Compared with baseline values, 15 patients (57.7%) had a reduction of LVOT gradient of more than 50%, whereas 3 (11.5%) showed no significant change. Compared with the acute results, a further reduction in LVOT gradient was shown in 11 patients (42.3%). Electrocardiographic findings The results of electrocardiographic findings could be compared in all patients. The changes in ECG data are shown in Table 3. All ECG data but PR interval and QTcd have no obvious difference between post-PTSMA (third day) and post-PTSMA (third year). One patient developed complete AV block requiring permanent pacing. The mean
heart rate did not change significantly 3 days after the procedure and during follow-up. The PR interval was significantly prolonged 3 days after ablation, but recovered 3 years postprocedure. Three days after the procedure, all patients developed right bundle branch block, which persisted in 24 patients after 3 years. The QRS duration was significantly prolonged 3 days after ablation and during the 3-year follow-up. Typical ECG changes (persistent broadening of the QRS complex and lengthened QT interval) 3 days and 3 years after ablation are shown in Fig. 1. There was significant and persistent prolongation of QT interval and transient prolongation of corrected QT dispersion 3 days after ablation and returned to preablation values 3 years postprocedure, but JT interval and corrected JT dispersion were not significantly changed after PTSMA. Heart rate variability Heart rate variability data (time domain and frequency domain) 3 days and 3 years after PTSMA, including LF, HF, rMSSD, and PNN50, significantly increased compared to that before the procedure. Low frequency/HF, SDNN, and SDANN were not significantly changed after PTSMA (Table 4). Discussion In the treatment of HOCM, surgical myectomy and DDD pacemaker therapy are considered the standard procedural extensions to drug therapy with negatively inotropic drugs. As an alternative to nonsurgical procedure for reducing the LVOT gradient, PTSMA by alcohol-induced septal branch occlusion was introduced. However, long-term electrocardiographic follow-up of a larger patient series has not been sufficiently described.3,5-7 Percutaneous transluminal septal myocardial ablation is a new, investigational, catheter-based treatment for severely symptomatic, medically refractory hypertrophic obstructive cardiomyopathy (HOCM). Left ventricular outflow tract gradient was greatly decreased in patients with HOCM undergoing a PTSMA procedure, and their symptoms were greatly improved without cardiac complications during follow-up.8 Percutaneous transluminal septal myocardial ablation is an effective, nonsurgical treatment method for drug-refractory patients with HOCM.9 Most patients have symptomatic improvement, at least moderate reductions in outflow tract gradients, and possibly improvement in exercise capacity. The most common procedural complication is the development of high-grade AV block necessitating implantation of a permanent pacemaker in 5.6% of patients. Compared with surgical myectomy, PTSMA has the advantage of being minimally invasive, easily repeated, and with relatively low major morbidity and mortality risk for patients with comorbid conditions. The findings from recently initiated international registries will be helpful in assessing the overall success and complication rates with PTSMA.10 Premature sudden cardiac death (SD) is a critical event in the natural history of HCM and occurs during or just after physical exertion in approximately 60% of instances.
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Abnormalities in ventricular repolarization may not be present at rest in some patients but may become apparent under certain conditions.11 Several risk factors are established for prediction of sudden cardiac death caused by ventricular arrhythmias in patients with HCM. QT dispersion (QTd) is thought to reflect the heterogeneity of ventricular repolarization. The relation of QTd with ventricular arrhythmias and sudden cardiac death has been shown by several studies.12-14 Patients with HCM show a prolonged QTc (N 440 milliseconds) and increased QTc dispersion compared with normal subjects. In addition, the degree of left ventricular hypertrophy correlates with maximal QTc. The presence of a prolonged QT with increased regional dispersion may be associated with the occurrence of serious ventricular arrhythmia and sudden death in HCM.15 QT variability is abnormal in patients with HCM and indirectly supports the concept that arrhythmia-related syncope in these patients may be, at least in part, related to an altered control of repolarization.16 The 24-hour QT variability was higher in nonsurvivors than in survivors with HCM. Episodes of nonsustained ventricular tachycardia in untreated patients were more frequent during the nighttime. Twenty-hour QT variability was higher in nonsurvivors than in survivors.17 Although QTd was significantly greater in patients with HCM than in normal controls, its relation to risk factors of sudden death could not be established.18 Increased QT dispersion and JT dispersion are weakly associated with sudden cardiac death in the selected patients with HCM.19 Percutaneous transluminal septal myocardial ablation for HOCM induces significant changes in the resting ECG in most patients, despite the occlusion of a relatively small artery. The changes include new Q waves, new bundle branch block, transient anterior ST-segment elevation, AV block, and transient prolongation of QT interval. JT interval was significantly different from baseline only on the seventh day and at the 6-month followup. These differences were caused by a slightly higher heart rate. JTc interval did not change significantly during followup. No significant changes were found in QT dispersion and QTc dispersion except for QTc-d on the third day. JTcd increased from 73 F 31 milliseconds at baseline to 109 F 39 milliseconds ( P b .05) by the third day. By the ninth day, JTd and JTcd had returned to preablation values.20 Prolongation of QT and QTc intervals has been reported in HOCM, especially in patients with serious ventricular arrhythmias.21,22 QTc prolongation as a result of ablation is at least partly caused by prolongation of the QRS complex. To avoid this influence, we also analyzed the behavior of the JT interval. In contrast to QTc, JTc did not show significant changes. The results of HRV analysis in patients with HCM are conflicting. Most authors think that HRV is reduced in HOCM and well correlated with the degree of subaortic obstruction. Heart rate variability indices are also a sensitive marker of functional status.23 Parasympathetic predominance was shown during autonomic stimulation in patients with HCM. No correlation was found between HRV and echocardiographic measurements under analysis.24 The HRV reduction was more expressed in patients with HCM and family members less than 30 years of age. A significantly reduced SDNN was observed in 54% of patients in the HCM group
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and in 42% of subjects in the members group. Reduced HRV is frequently seen not only in patients with diagnosed HCM, but also in a substantial number of their kindred.25 The values of rMSSD and pNN50 were lower in the patients with HOCM than in the controls before pacing, which were restored to normal levels by the end of the study. Long-term pacing in patients with HOCM restores the sympathovagal balance in the heart by improving vagal activity.26 Our study showed that 1 patient developed complete AV block requiring permanent pacing. The PR interval was significantly prolonged 3 days after ablation, but recovered 3 years postprocedure. Three days after the procedure, all patients developed right bundle branch block, which persisted in 24 patients after 3 years. The QRS duration was significantly prolonged 3 days after ablation and during the 3-year follow-up. There was significant and persistent prolongation of QT interval and transient prolongation of corrected QT dispersion 3 days after ablation and returned to preablation values 3 years postprocedure, but JT interval and corrected JT dispersion were not significantly changed after PTSMA. Heart rate variability data (time domain and frequency domain) 3 days and 3 years after PTSMA, including LF, HF, rMSSD, and PNN50, significantly increased compared to that before the procedure. Low frequency/HF, SDNN, and SDANN were not significantly changed after PTSMA. Left ventricular outflow tract gradient was greatly decreased in patients with HOCM undergoing a PTSMA procedure, and their symptoms were greatly improved without cardiac complications during the 3-year follow-up. Possible complications include different degree of heart block including trifascicular blocks, requiring temporary pacemaker implantation. Percutaneous transluminal septal myocardial ablation is a promising nonsurgical method for the treatment of symptomatic patients with HOCM. Percutaneous transluminal septal myocardial ablation for HOCM induces significant delayed electrocardiographic changes in most patients. The changes include QRS duration, right bundle branch block, QT interval, corrected QT dispersion, and HRV data. Electrocardiographic longterm follow-up of a larger series of patients is required to determine the conclusive therapeutic significance. References 1. Gleichmann U, Seggewiss H. Clinical picture and therapy of hypertrophic cardiomyopathy. Med Klin 1998;93:260. 2. Meisel E, Rauwolf T, Burghardt M, et al. Pacemaker therapy of hypertrophic obstructive cardiomyopathy. PIC (Pacing in Cardiomyopathy) Study Group. Herz 2000;25:461. 3. Qin JX, Shiota T, Lever HM, et al. Outcome of patients with hypertrophic obstructive cardiomyopathy after percutaneous transluminal septal myocardial ablation and septal myectomy surgery. J Am Coll Cardiol 2001;38:1994. 4. Seggewiss H. Current status of alcohol septal ablation for patients with hypertrophic cardiomyopathy. Curr Cardiol Rep 2001;3:160. 5. Guo H, Wang J, Chen J, et al. Percutaneous transluminal septal myocardial ablation in hypertrophic obstructive cardiomyopathy: acute results and three-year noninvasive follow-up in 18 patients. Can J Cardiol 2004;20:779. 6. Airoldi F, Di Mario C, Catanoso A, et al. Progressive decrease of outflow gradient and septum thickness after percutaneous alcohol-
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17. Goktekin O, Ritsushi K, Matsumoto K, et al. The relationship between QT dispersion and risk factors of sudden death in hypertrophic cardiomyopathy. Anadolu Kardiyol Derg 2002;2:226. 18. Baranowski R, Chojnowska L, Michalak E, et al. Analysis of the corrected QT before the onset of nonsustained ventricular tachycardia in patients with hypertrophic cardiomyopathy. Pacing Clin Electrophysiol 2003;26:387. 19. Yi G, Poloniecki J, Dickie S, et al. Is QT dispersion associated with sudden cardiac death in patients with hypertrophic cardiomyopathy? Ann Noninvasive Electrocardiol 2001;6:209. 20. Kazmierczak J, Kornacewicz-Jach Z, Kisly M, et al. Electrocardiographic changes after alcohol septal ablation in hypertrophic obstructive cardiomyopathy. Heart 1998;80:257. 21. Dritsas A, Sbarouni E, Gilligan D, et al. QT interval abnormalities in hypertrophic cardiomyopathy. Clin Cardiol 1992;15:739. 22. Fei L, Slade A, Grace A, et al. Ambulatory assessment of the QT interval in patients with hypertrophic cardiomyopathy: risk stratification and effect of low dose amiodarone. Pacing Clin Electrophysiol 1994;17:2222. 23. Doven O, Sayin T, Guldal M, et al. Heart rate variability in hypertrophic obstructive cardiomyopathy: association with functional classification and left ventricular outflow gradients. Int J Cardiol 2001; 77:281. 24. Bittencourt MI, Barbosa PR, Drumond Neto C, et al. Assessing autonomic function in hypertrophic cardiomyopathy [Portuguese]. Arq Bras Cardiol 2005;85:388. 25. Sosnowski M, Kozakiewicz K, Korzeniowska B, et al. Heart rate variability in patients with hypertrophic cardiomyopathy and in their close relatives. Wiad Lek 2002;55:561 [Polish]. 26. Simantirakis EN, Kochiadakis GE, Kanakaraki MK, et al. Impact of chronic DDD pacing on time-domain indexes of heart rate variability in patients with hypertrophic obstructive cardiomyopathy. Pacing Clin Electrophysiol 1999;22:1808.