- Email: [email protected]
Effect of hypnotic sedation during percutaneous transluminal coronary angioplasty on myocardial ischemia and cardiac sympathetic drive
By multivariate analysis, the only variables related to the primary end point were randomization to thrombectomy (odds ratio 3.56, 95% confidence interval 1.11 to 11.42, p ⫽ 0.032), and diabetes mellitus (odds ratio 0.24, 95% confidence interval 0.07 to 0.86, p ⫽ 0.029). •••
This study assessed the efficacy of rheolytic thrombectomy as adjunctive management before routine direct stenting and avoided the confounding effects of procedural variables other than direct stenting, such as conventional balloon angioplasty, conventional stenting before or after dilation, and use or nonuse of abciximab. This feature allowed a correct assessment of the potential of rheolytic thrombectomy for prevention of atheroembolism during PCI. The principal finding from the present trial was that rheolytic thrombectomy before routine direct infarct artery stenting is highly feasible and provides more effective myocardial reperfusion as shown by the more frequent early ST-segment resolution, the lower TIMI frame count values, and smaller infarcts in patients randomized to thrombectomy versus patients randomized to stenting only. After adjustment for differences in clinical, angiographic, and procedural characteristics by multivariate analysis, rheolytic thrombectomy remained independently related to the primary end point. Thus, it is unlikely that the nonsignificant baseline characteristic imbalance between groups affected the primary end point.
1. Topol EJ, Yadav JS. Recognition of the importance of embolization in
atherosclerotic vascular disease. Circulation 2000;101:570 –580. 2. Antoniucci D, Valenti R, Migliorini A, Moschi G, Bolognese L, Cerisano G,
Buonamici P, Santoro GM. Direct infarct artery stenting without predilation and no-reflow in patients with acute myocardial infarction. Am Heart J 2001;142: 684 –690. 3. Loubeyre C, Morice MC, Lefevre T, Pichaud J-F, Louvard Y, Dumas P. A randomized comparison of direct stenting with conventional stent implantation in selected patients with acute myocardial infarction. J Am Coll Cardiol 2002;39: 15–21. 4. Kuntz RE, Baim DS, Cohen DJ, Popma JJ, Carrozza JP, Sharma S, McCormick DJ, Schmidt DA, Lansky AJ, Ho KK, et al. A trial comparing rheolytic thrombectomy with intracoronary urokinase for coronary and vein grafts thrombus (the Vein Graft AngioJet Study). Am J Cardiol 2002;89:326 –330. 5. Silva JA, Ramee SR, Cohen DJ, Carrozza JP, Popma JJ, Lansky AA, Dandreo K, Baim DS, George BS, McCormick DJ, et al. Rheolytic thrombectomy during percutaneous revascularization for acute myocardial infarction; experience with the AngioJet catheter. Am Heart J 2001;141:353–359. 6. Nakagawa Y, Matsuo S, Kimura T, Yokoi H, Tamura T, Hamasaki N, Nosaka H, Nobuyoshi M. Thrombectomy with the AngioJet catheter in native coronary arteries for patients with acute or recent myocardial infarction. Am J Cardiol 1999;83:994 –999. 7. Santoro GM, Antoniucci D, Valenti R, Bolognese L, Buonamici P, Trapani M, Boddi V, Fazzini PF. Rapid reduction of ST-segment elevation after successful direct angioplasty in acute myocardial infarction. Am J Cardiol 1997;80:685–689. 8. TIMI Study Group. The Thrombolysis In Myocardial Infarction (TIMI) trial: phase 1 findings. N Engl J Med 1985;312:932–936. 9. Van der Zwet PMJ, Reiber JHC. A new approach for the quantification of complex lesion morphology: the gradient field transform-basic principles and validation results. J Am Coll Cardiol 1994;24:216 –224. 10. Gibson CM, Cannon CP, Daley WL, Dodge JT Jr, Alexander B Jr, Marble SJ, McCabe CH, Raymond L, Fortin T, Poole WK, Braunwald E. TIMI frame count. A quantitative method of assessing coronary artery flow. Circulation 1996;93: 879 –888. 11. Gibbons RJ, Miller TD, Christian TF. Infarct size measured by single photon emission computed tomographic imaging with 99mTc-sestamibi. A measure of the efficacy of therapy in acute myocardial infarction. Circulation 2000;101:101–108.
Effect of Hypnotic Sedation During Percutaneous Transluminal Coronary Angioplasty on Myocardial Ischemia and Cardiac Sympathetic Drive Roberto Baglini, MD, PhD, Marco Sesana, MD, Cinzia Capuano, MD, Tomaso Gnecchi-Ruscone, MD, Limbruno Ugo, MD, PhD, and Gian Battista Danzi, Forty-six patients were randomized to receive drug (group 1) or hypnotic sedation (group 2) during percutaneous transluminal coronary angioplasty of the left anterior descending coronary artery. Intracoronary and standard electrocardiograms were continuously registered, and heart rate spectral variability was studied. Normalized units of low- and high-frequency components and the ratio of low to high frequency were measured during balloon inflations. The ST segment shifted at the first balloon inflation from 0.02 ⴞ 0.01 to 0.09 ⴞ 0.6 mm in group 1 and from 0.02 ⴞ 0.08 to 0.1 ⴞ 0.6 in group 2 mm (p <0.05). In group 1, the low-frequency band and the ratio of low to high frequency increased significantly during the first balloon From the Department of Invasive Cardiology, Poliambulanza Hospital, Brescia; and the Cardiothoracic Department, University of Pisa, Pisa, Italy. Dr. Baglini’s address is: Catheterisation Laboratory, Poliambulanza Hospital, 25124, Brescia Italy. E-mail: [email protected]. Manuscript received September 8, 2003; revised manuscript received and accepted December 23, 2003. ©2004 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 93 April 15, 2004
MD
inflation (from 59 ⴞ 10 to 75 ⴞ 10 normalized units and from 2.4 ⴞ 1.4 to 7.3 ⴞ 4.7, respectively; p <0.001). The increase of the ratio of low to high frequency was significantly related to ST shift (r ⴝ 0.706; p <0.01). In contrast, no significant variation of spectral parameters was found in group 2. The increase in cardiac sympathetic activity associated with balloon inflation and myocardial ischemia during percutaneous transluminal coronary angioplasty of the left anterior descending coronary artery was selectively eliminated by hypnosis but not by drug sedation. 䊚2004 by Excerpta Medica, Inc. (Am J Cardiol 2004;93:1035–1038)
ercutaneous transluminal coronary angioplasty (PTCA) is used widely in patients with coronary P artery disease. During balloon inflation, brief periods of myocardial ischemia are followed by immediate reperfusion, but few and inconclusive data are available about the influence of these short periods of myocardial ischemia and reperfusion on the cardiac 0002-9149/04/$–see front matter doi:10.1016/j.amjcard.2003.12.058
1035
TABLE 1 Clinical and Procedural Data
Age (yrs) Heart rate Men Stenosis (%) Arterial pressure Inflation time (s) 1st inflation 2nd inflation 3rd inflation Chest pain (%) 1st inflation 2nd inflation 3rd inflation ST shift (mV)* 1st inflation 2nd inflation 3rd inflation
Drug Sedation
Hypnotic Sedation
58 ⫾ 10 88 ⫾ 33 17 82 ⫾ 12 144 ⫾ 67
57 ⫾ 8 79 ⫾ 39 18 80 ⫾ 10 137 ⫾ 72
100 ⫾ 11 108 ⫾ 13 114 ⫾ 9
105 ⫾ 9 114 ⫾ 6 119 ⫾ 5
96% 87% 56%
92% 82% 55%
0.9 ⫾ 0.6 0.5 ⫾ 0.3 0.3 ⫾ 0.2
0.9 ⫾ 0.5 0.3 ⫾ 0.4 0.2 ⫾ 0.3
*ST-segment shift was evaluated by the intracoronary electrocardiographic lead.
autonomic balance.1– 4 The aim of this study was to assess the effect of hypnosis on myocardial ischemia and cardiac autonomic balance in patients undergoing PTCA of the left anterior descending coronary artery stenosis. •••
During January 1998, 153 patients with objective evidence of myocardial ischemia underwent elective PTCA for 1-vessel coronary artery stenosis involving the proximal part of the left anterior descending coronary artery. Only patients with the following inclusion criteria were enrolled in the study: stable angina, no previous myocardial infarction, no significant valve disease, normal left ventricular function, absence of rhythm disturbances other than sporadic ectopic beats, absence of hypertension, diabetes, and therapy with  or ␣ blockers, digoxin, or antiarrhythmic drugs. Fifty-one eligible patients were evaluated further to test their sensitivity to hypnosis. A first hypnotic induction was attempted the day before the procedure; 5 patients were judged as poor responders5 and not included in the study. Thus, 46 patients were randomized to receive PTCA with or without hypnotic sedation. The study was approved by the ethical committee of Poliambulanza Hospital. Written informed consent was obtained from each patient. Beginning on the day before the PTCA procedure, all patients received aspirin 250 to 500 mg/day and 250 mg of ticlopidine twice daily. Heparin was administered as a bolus dose of 10,000 U at the start of the procedure. All interventions were performed with conventional balloon PTCA; stent use was limited to abrupt or threatened vessel occlusion. At least 3 inflations lasting 90 to 120 seconds were performed in each subject. Isosorbide dinitrate was administered intravenously at a constant infusion rate of 4 mg/hour throughout the intervention. Atropine was not used in any patient. Moreover, patients were instructed to breathe at a constant rate, to avoid unnecessary talking, and to signal chest pain by a hand movement. Dye 1036 THE AMERICAN JOURNAL OF CARDIOLOGY姞
VOL. 93
injections were avoided during data acquisition, and patients were unaware of the timing of the balloon inflation. Continuous recording of ST-segment shift was obtained by using an intracoronary lead through the PTCA balloon wire. Arterial pressure was registered continuously from the beginning to the end of the PTCA procedure. Successful PTCA was defined as the presence of residual stenosis ⬍50% by on-line quantitative coronary angiography without the occurrence of any clinical complication, such as death, myocardial infarction, or emergency bypass surgery. We randomized 23 patients (group 1) to receive drug sedation and 23 (group 2) to receive hypnotic sedation during PTCA. Drug sedation was obtained by oral administration of 10 mg of diazepam 30 minutes before starting the procedure. Hypnosis was performed by the same PTCA operator according to Erickson’s indirect methods.6 Fifteen minutes before the procedure, a new induction was performed and hypnosis was deepened as usual. Every effort was made to produce a “neutral” state of hypnosis, in which only ideas of relaxation and wellness were suggested to the patients, during the procedure. Patients were connected to a standard electrocardiographic recorder with chest electrodes. Respiratory activity was monitored by a nose-tip thermistor. Arterial blood pressure was measured directly from the guide catheter. Electrocardiograms were digitized with an analog-to-digital converter and stored in a microcomputer. After reviewing the electrocardiograms on the computer display, sequences of about 250 consecutive RR intervals of stationary sinus rhythm were selected. Two time periods of the same length were analyzed in our protocol: (1) baseline conditions, that is, starting 3 minutes before balloon positioning through the stenosis, to obtain a sufficient resolution of the electrocardiographic sample; and (2) a second period, starting 20 seconds after the beginning of arterial occlusion and lasting 3 minutes, was used for the analysis of the autonomic changes during myocardial ischemia and reperfusion. An autoregressive model was used to estimate the power spectrum of the heart rate variability. The autoregressive coefficients were automatically calculated by the computer program, and the model order was chosen as the one that minimized Akaike’s final prediction error figure of merit.7,8 Each spectral component was then identified by the center frequency and quantified by its power as normalized units to facilitate the comparison of spectra with large differences in total variances.7–13 Only components with a patient power ⬎5% of the total power were considered to be significant: those at 0.04 to 0.15 Hz were defined as low-frequency components and those at 0.15 to 0.40 Hz were defined as high-frequency components. Low frequency has been shown to reflect sympathetic cardiac function, whereas high frequency seems to provide an index of vagal modulation of the heart.10 The RR-interval variance and the low- to high-frequency ratio, as an index of sympathovagal cardiac balance, were also calculated. Spectral analysis of heart rate variability was APRIL 15, 2004
TABLE 2 Heart Rate Variability During Percutaneous Transluminal Coronary Angioplasty* Without Hypnosis Basal Variance LF band NU HF band NU LF/HF
2,041 726 59 359 30 2.4
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
1st 1 70 10 38 11 1.4
2,085 919 75 210 14 7.3
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
With Hypnosis
2nd 1 65 10 26 7† 4.7*
1,750 527 64 238 25 2.9
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
3rd 9 38 9† 21 8 1.5
2,062 547 59 277 30 2.1
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
Basal 1 52 7 24 6 0.7
2,111 744 61 366 33 2.5
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
1st 1 68 9 32 9 1.3
2,021 784 64 336 30 2.7
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
2nd 1 66 5 26 8 1.5
1,882 446 58 374 36 1.9
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
3rd 9 36 8 31 6 0.6
1,949 422 50 388 39 2.0
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
8 28 6 29 4 0.9
Data are presented as means ⫾ SD. *p ⬍0.01; †p ⬍0.05. HF ⫽ high frequency; LF ⫽ low frequency; NU ⫽ normalized units.
performed by an operator not participating in this study. Data were expressed as mean ⫾ SD. The significance of differences between baseline and occlusion spectral values was tested by Student’s paired t test. Linear regression analysis was also performed between spectral parameters and ST-segment shift. A p value ⬍0.05 was considered statistically significant. Clinical and procedural data did not differ significantly between groups 1 and 2 (Table 1). All procedures were angiographically successful, and stent implantation was never required. No difference was encountered with regard to inflation time, incidence of chest pain, and the entity of ST shift as measured by intracoronary electrocardiography between the 2 groups. No difference was encountered in terms of mean arterial pressure values between the 2 groups (Table 1). Table 2 lists the main spectral parameters in basal conditions and during balloon inflations in groups 1 and 2. The ST segment shifted from baseline values at the first balloon inflation from 0.02 ⫾ 0.01 to 0.9 ⫾ 0.6 mm (p ⬍0.01) in group 1 and from 0.02 ⫾ 0.08 to 0.9 ⫾ 0.5 mm (p ⬍0.01) in group 2 (Table 1). STsegment shift decreased significantly (p ⬍0.05) from the first to the third inflations in the 2 groups (Table 1). In group 1, the low-frequency component (band) and the low- to high-frequency ratio increased significantly compared with baseline during the first balloon inflation only (from 59 ⫾ 10 to 75 ⫾ 10 normalized units and from 2.4 ⫾ 1.4 to 7.3 ⫾ 4.7, respectively; p ⬍0.001; Table 2). Moreover, the increase of the lowto high-frequency ratio was significantly related to the entity of electrocardiographic ST-segment shift (r ⫽ 0.706; p ⬍0.01). In contrast, no significant variation of spectral parameters from basal values during balloon inflation was found in group 2 (Table 2). •••
The selective influence of hypnosis on cardiac neurovegetative tone is well known.14 In this study only patients with a high level of responsiveness to hypnosis were chosen to accelerate the procedure in the catheterization laboratory. The data of this study showed a selective influence of hypnosis on the mechanisms that regulate the sympathetic drive during PTCA, in particular, a selective inhibition on central autonomic nervous pathways. Our findings agree with
those of recent studies reporting that hypnosis decreases the central signaling of nociceptive stimuli at different levels15; moreover, cortical and subcortical correlates of autonomic activation have been found.16 –18 In particular, inhibition of serotoninergic neurons during animal hypnosis has been demonstrated, and this kind of neuron, whose activation accompanies sympathoexcitation, has been found in spinal cord and brainstem regions known to be involved in autonomic regulation.17,18 Conversely, benzodiazepines did not influence the increase of sympathetic drive during balloon occlusion of the left anterior descending coronary artery. These drugs are known to act predominantly on cortical prefrontal areas and can inhibit sympathetic drive only by weakening emotional and perceptive mechanisms.19,20 Our data differ from those obtained by Airakseinen et al,4 who found that coronary artery occlusion during PTCA leads to divergent and unpredictable changes in heart rate variability. These results may have been biased by the inclusion in the study population of patients with multiple vessel disease (8%), previous myocardial infarction (24%), and treatment with -blocker drugs (75%). Moreover, the RR-interval sequence used to calculate the heart rate variability was very short (60 seconds) and probably not sufficient to provide a reliable resolution, especially in the range of the low-frequency components. In the present study, a longer RR-interval sequence (3 minutes) was chosen to provide a sufficient resolution in the frequency domain, including the early reperfusion period and a possible “phase lag” in the autonomic response. The lack of sympathetic activation during PTCA of the left anterior descending coronary artery in hypnotically sedated patients seems to be in accordance with the hypothesis of a selective subcortical inhibitory influence of hypnosis on the sympathetic coronary reflex arch during balloon occlusion of the left anterior descending coronary artery. Further studies are needed to elucidate the central nervous localization of this pathway. The number of patients included in this study was relatively small, depending on the strict criteria used for enlisting. No instrumental grading of the hypnotic status was performed. Systemic catecholamine levels BRIEF REPORTS
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were not determined, and no information on peripheral autonomic tone was available. 1. Griffin B, Timmis AD, Crick JCP, Sowton E. The evolution of myocardial ischemia during percutaneous transluminal coronary angioplasty. Eur Heart J 1987;8:347–353. 2. Collins MN, Billman GE. Autonomic response to coronary occlusion in animals susceptible to ventricular fibrillation. Am J Physiol 1989;26:1886 –1894. 3. Bigger JT, Hoover CA, Steinman RC, Rolnitzky LM, Fleiss JL. Autonomic nervous system activity during myocardial ischaemia in man estimated by power spectral analysis of heart period variability. Am J Cardiol 1990;66:497–498. 4. Airaksinen KJ, Ikaheimo MJ, Huikuri HV, Linnaluoto MK, Takkunen JT. Responses of heart rate variability to coronary occlusion during coronary angioplasty. Am J Cardiol 1993;72:1026 –1030. 5. Wetzenhofer AM. Hypnotic susceptibility: a personal and historical note regarding the development and naming of the Stanford Scale. Int J Clin Exp Hypn 1997;45:126 –143. 6. Fourie DP. Indirect suggestion in hypnosis: theoretical and experimental issues. Psychol Rep 1997;80:1255–1266. 7. Baselli G, Cerrutti S, Civardi S, Liberati D, Lombardi F, Malliani A, Pagani M. Spectral and cross-spectral analysis of heart rate and arterial blood pressure variability signals. Comp Biomed Res 1986;19:520 –534. 8. Pagani M, Lombardi F, Guzzetti S, Rimoldi O, Furlan R, Pizzinelli P, Sandrone G, Malfatto G, Dell’Orto S, Piccaluga E, et al. Power spectral analysis of heart rate and arterial pressure variabilities as a marker of sympathovagal interaction in man and conscious dog. Circ Res 1986;59:178 –193. 9. Kay SM, Marple SM. Spectrum analysis: a modern perspective. Proc IEEE 1981;69:1380 –1384. 10. Malliani G, Pagani M, Lombardi F, Cerutti S. Cardiovascular and neural regulation explored in the frequency domain. Circulation 1991;84:482–492. 11. Akselrod S, Gordon D, Ubel FA, Shannon DC, Barger AC, Cohen RJ. Power
spectrum analysis of heart rate fluctuation: a quantitative probe of beat to beat cardiovascular control. Science 1981;213:220 –222. 12. Hayano J, Yamada M, Fujinami T, Yokoyama K, Watanabe Y, Takata K. Autonomic nervous function and spectral components of heart rate variability. Biophysics 1988;28:32–36. 13. Pomeranz B, Macaulay RJB, Caudill MA, Kutz I, Adam D, Gordon D, Kilborn KM, Barger AC, Shannon DC, Cohen RJ, Benson H. Assessment of autonomic function in humans by heart rate spectral analysis. Am J Physiol 1985;248:151–153. 14. Hippel CV, Hole G, Kaschka WP. Autonomic profile under hypnosis as assessed by heart rate variability and spectral analysis. Pharmacopsychiatry 2001;34:111–113. 15. Faymonville ME, Laureys S, Degueldre C, DelFiore G, Luxen A, Franck G, Lamy M, Maquet P. Neural mechanisms of antinociceptive effects of hypnosis. Anesthesiology 2000;92:1257–1267. 16. Critchley HD, Corfield DR, Chandler MP, Mathias CJ, Dolan RJ. Cerebral correlates of autonomic cardiovascular arousal: a functional neuroimaging investigation in humans. J Physiol 2000;523:259 –270. 17. Hisamitsu T, Fujishita M, Asamoto S, Nakamura A, Takeshige C. Serotoninergic neurons in the brainstem modulate animal hypnosis. Brain Res Bull 1992; 29:141–145. 18. Passerin AM, Henley WN. Activation of spinal cord serotoninergic neurons accompanies cold-induced sympathoexcitation. Can J Physiol Pharmacol 1994; 72:884 –892. 19. Brambilla P, Stanley JA, Nicoletti M, Harenski K, Wells KF, Mallinger AG, Keshavan MS, Soares JC. 1H MRS brain measures and acute lorazepam administration in healthy human subjects. Neuropsychopharmacology 2002;26:546 – 551. 20. Northoff G, Witzel G, Richter A, Gessner M, Schlagenhauf F, Fell J, Baumgart F, Kaulisch T, Tempelmann C, Heinzel A, et al. GABA-ergic modulation of prefrontal spatio-temporal activation pattern during emotional processing: a combined fMRI/MEG study with placebo and lorazepam. J Cogn Neurosci 2002;14:348 –370.
Analysis of Nonintervention Strategy for In-Stent Restenosis in Pauci- or Asymptomatic Patients He´ le`ne Eltchaninoff, Carlos Sanchez-Giron,
MD,
Raphae¨lle Carlot, MD, Christophe Tron, MD, MD, Laurent Sebagh, MD, Carla Agatiello, MD, and Alain Cribier, MD
Between January 1996 and May 2000, we retrospectively identified 66 patients (61 ⴞ 11 years) with in-stent restenosis who did not undergo percutaneous coronary intervention and/or bypass surgery and were maintained on medical treatment alone. In-stent restenosis was diffuse or proliferative in 86% of these patients. At 33 ⴞ 11 months, 2 patients died, none developed myocardial infarction, and 6 (9%) had target lesion revascularization only (repeat percutaneous transluminal coronary angioplasty). Medical treatment alone was associated with a good longterm clinical follow-up in selected patients with significant documented in-stent restenosis. 䊚2004 by Excerpta Medica, Inc. (Am J Cardiol 2004;93:1038 –1040)
oronary stenting is the procedure of choice in most percutaneous coronary interventions. However, C angiographic and clinical in-stent restenosis (ISR) will From the Charles Nicolle Hospital, University of Rouen, Rouen, France. Dr. Eltchaninoff’s address is: Hoˆ pital Charles Nicolle, 1, rue de Germont, 76031 Rouen Cedex, France. E-mail: helene.eltchaninoff@ chu-rouen.fr. Manuscript received September 5, 2003; revised manuscript received January 3, 2004 and accepted January 5, 2004.
1038
©2004 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 93 April 15, 2004
develop in 15% to 45% of cases. Therefore, the management of ISR has become an important clinical problem. Balloon angioplasty alone for the treatment of ISR has been associated with a high recurrence rate of restenosis,1 reaching 85% in angiographic studies.2,3 Several alternative percutaneous techniques have been evaluated in this setting: repeat stenting,4,5 rotational atherectomy,6 laser angioplasty,7 and use of a cutting balloon.8 None of these9 has demonstrated any advantage over plain balloon angioplasty. Intracoronary radiation therapy10,11 has been evaluated and appears promising, but its use is limited by cost and availability. Despite very limited series and preliminary results, the use of drug-coated stents also appears encouraging.12–14 However, few data are available on the long-term outcome of patients maintained on medical therapy alone.15 Thus, the goal of our study was to evaluate the long-term outcome of patients with angiographically proved ISR who received medical treatment alone without percutaneous or surgical revascularization. •••
Review of consecutive patients who underwent cardiac catheterization at the Charles Nicolle Hospital in Rouen, France, between January 1996 and May 0002-9149/04/$–see front matter doi:10.1016/j.amjcard.2004.01.012
This study assessed the efficacy of rheolytic thrombectomy as adjunctive management before routine direct stenting and avoided the confounding effects of procedural variables other than direct stenting, such as conventional balloon angioplasty, conventional stenting before or after dilation, and use or nonuse of abciximab. This feature allowed a correct assessment of the potential of rheolytic thrombectomy for prevention of atheroembolism during PCI. The principal finding from the present trial was that rheolytic thrombectomy before routine direct infarct artery stenting is highly feasible and provides more effective myocardial reperfusion as shown by the more frequent early ST-segment resolution, the lower TIMI frame count values, and smaller infarcts in patients randomized to thrombectomy versus patients randomized to stenting only. After adjustment for differences in clinical, angiographic, and procedural characteristics by multivariate analysis, rheolytic thrombectomy remained independently related to the primary end point. Thus, it is unlikely that the nonsignificant baseline characteristic imbalance between groups affected the primary end point.
1. Topol EJ, Yadav JS. Recognition of the importance of embolization in
atherosclerotic vascular disease. Circulation 2000;101:570 –580. 2. Antoniucci D, Valenti R, Migliorini A, Moschi G, Bolognese L, Cerisano G,
Buonamici P, Santoro GM. Direct infarct artery stenting without predilation and no-reflow in patients with acute myocardial infarction. Am Heart J 2001;142: 684 –690. 3. Loubeyre C, Morice MC, Lefevre T, Pichaud J-F, Louvard Y, Dumas P. A randomized comparison of direct stenting with conventional stent implantation in selected patients with acute myocardial infarction. J Am Coll Cardiol 2002;39: 15–21. 4. Kuntz RE, Baim DS, Cohen DJ, Popma JJ, Carrozza JP, Sharma S, McCormick DJ, Schmidt DA, Lansky AJ, Ho KK, et al. A trial comparing rheolytic thrombectomy with intracoronary urokinase for coronary and vein grafts thrombus (the Vein Graft AngioJet Study). Am J Cardiol 2002;89:326 –330. 5. Silva JA, Ramee SR, Cohen DJ, Carrozza JP, Popma JJ, Lansky AA, Dandreo K, Baim DS, George BS, McCormick DJ, et al. Rheolytic thrombectomy during percutaneous revascularization for acute myocardial infarction; experience with the AngioJet catheter. Am Heart J 2001;141:353–359. 6. Nakagawa Y, Matsuo S, Kimura T, Yokoi H, Tamura T, Hamasaki N, Nosaka H, Nobuyoshi M. Thrombectomy with the AngioJet catheter in native coronary arteries for patients with acute or recent myocardial infarction. Am J Cardiol 1999;83:994 –999. 7. Santoro GM, Antoniucci D, Valenti R, Bolognese L, Buonamici P, Trapani M, Boddi V, Fazzini PF. Rapid reduction of ST-segment elevation after successful direct angioplasty in acute myocardial infarction. Am J Cardiol 1997;80:685–689. 8. TIMI Study Group. The Thrombolysis In Myocardial Infarction (TIMI) trial: phase 1 findings. N Engl J Med 1985;312:932–936. 9. Van der Zwet PMJ, Reiber JHC. A new approach for the quantification of complex lesion morphology: the gradient field transform-basic principles and validation results. J Am Coll Cardiol 1994;24:216 –224. 10. Gibson CM, Cannon CP, Daley WL, Dodge JT Jr, Alexander B Jr, Marble SJ, McCabe CH, Raymond L, Fortin T, Poole WK, Braunwald E. TIMI frame count. A quantitative method of assessing coronary artery flow. Circulation 1996;93: 879 –888. 11. Gibbons RJ, Miller TD, Christian TF. Infarct size measured by single photon emission computed tomographic imaging with 99mTc-sestamibi. A measure of the efficacy of therapy in acute myocardial infarction. Circulation 2000;101:101–108.
Effect of Hypnotic Sedation During Percutaneous Transluminal Coronary Angioplasty on Myocardial Ischemia and Cardiac Sympathetic Drive Roberto Baglini, MD, PhD, Marco Sesana, MD, Cinzia Capuano, MD, Tomaso Gnecchi-Ruscone, MD, Limbruno Ugo, MD, PhD, and Gian Battista Danzi, Forty-six patients were randomized to receive drug (group 1) or hypnotic sedation (group 2) during percutaneous transluminal coronary angioplasty of the left anterior descending coronary artery. Intracoronary and standard electrocardiograms were continuously registered, and heart rate spectral variability was studied. Normalized units of low- and high-frequency components and the ratio of low to high frequency were measured during balloon inflations. The ST segment shifted at the first balloon inflation from 0.02 ⴞ 0.01 to 0.09 ⴞ 0.6 mm in group 1 and from 0.02 ⴞ 0.08 to 0.1 ⴞ 0.6 in group 2 mm (p <0.05). In group 1, the low-frequency band and the ratio of low to high frequency increased significantly during the first balloon From the Department of Invasive Cardiology, Poliambulanza Hospital, Brescia; and the Cardiothoracic Department, University of Pisa, Pisa, Italy. Dr. Baglini’s address is: Catheterisation Laboratory, Poliambulanza Hospital, 25124, Brescia Italy. E-mail: [email protected]. Manuscript received September 8, 2003; revised manuscript received and accepted December 23, 2003. ©2004 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 93 April 15, 2004
MD
inflation (from 59 ⴞ 10 to 75 ⴞ 10 normalized units and from 2.4 ⴞ 1.4 to 7.3 ⴞ 4.7, respectively; p <0.001). The increase of the ratio of low to high frequency was significantly related to ST shift (r ⴝ 0.706; p <0.01). In contrast, no significant variation of spectral parameters was found in group 2. The increase in cardiac sympathetic activity associated with balloon inflation and myocardial ischemia during percutaneous transluminal coronary angioplasty of the left anterior descending coronary artery was selectively eliminated by hypnosis but not by drug sedation. 䊚2004 by Excerpta Medica, Inc. (Am J Cardiol 2004;93:1035–1038)
ercutaneous transluminal coronary angioplasty (PTCA) is used widely in patients with coronary P artery disease. During balloon inflation, brief periods of myocardial ischemia are followed by immediate reperfusion, but few and inconclusive data are available about the influence of these short periods of myocardial ischemia and reperfusion on the cardiac 0002-9149/04/$–see front matter doi:10.1016/j.amjcard.2003.12.058
1035
TABLE 1 Clinical and Procedural Data
Age (yrs) Heart rate Men Stenosis (%) Arterial pressure Inflation time (s) 1st inflation 2nd inflation 3rd inflation Chest pain (%) 1st inflation 2nd inflation 3rd inflation ST shift (mV)* 1st inflation 2nd inflation 3rd inflation
Drug Sedation
Hypnotic Sedation
58 ⫾ 10 88 ⫾ 33 17 82 ⫾ 12 144 ⫾ 67
57 ⫾ 8 79 ⫾ 39 18 80 ⫾ 10 137 ⫾ 72
100 ⫾ 11 108 ⫾ 13 114 ⫾ 9
105 ⫾ 9 114 ⫾ 6 119 ⫾ 5
96% 87% 56%
92% 82% 55%
0.9 ⫾ 0.6 0.5 ⫾ 0.3 0.3 ⫾ 0.2
0.9 ⫾ 0.5 0.3 ⫾ 0.4 0.2 ⫾ 0.3
*ST-segment shift was evaluated by the intracoronary electrocardiographic lead.
autonomic balance.1– 4 The aim of this study was to assess the effect of hypnosis on myocardial ischemia and cardiac autonomic balance in patients undergoing PTCA of the left anterior descending coronary artery stenosis. •••
During January 1998, 153 patients with objective evidence of myocardial ischemia underwent elective PTCA for 1-vessel coronary artery stenosis involving the proximal part of the left anterior descending coronary artery. Only patients with the following inclusion criteria were enrolled in the study: stable angina, no previous myocardial infarction, no significant valve disease, normal left ventricular function, absence of rhythm disturbances other than sporadic ectopic beats, absence of hypertension, diabetes, and therapy with  or ␣ blockers, digoxin, or antiarrhythmic drugs. Fifty-one eligible patients were evaluated further to test their sensitivity to hypnosis. A first hypnotic induction was attempted the day before the procedure; 5 patients were judged as poor responders5 and not included in the study. Thus, 46 patients were randomized to receive PTCA with or without hypnotic sedation. The study was approved by the ethical committee of Poliambulanza Hospital. Written informed consent was obtained from each patient. Beginning on the day before the PTCA procedure, all patients received aspirin 250 to 500 mg/day and 250 mg of ticlopidine twice daily. Heparin was administered as a bolus dose of 10,000 U at the start of the procedure. All interventions were performed with conventional balloon PTCA; stent use was limited to abrupt or threatened vessel occlusion. At least 3 inflations lasting 90 to 120 seconds were performed in each subject. Isosorbide dinitrate was administered intravenously at a constant infusion rate of 4 mg/hour throughout the intervention. Atropine was not used in any patient. Moreover, patients were instructed to breathe at a constant rate, to avoid unnecessary talking, and to signal chest pain by a hand movement. Dye 1036 THE AMERICAN JOURNAL OF CARDIOLOGY姞
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injections were avoided during data acquisition, and patients were unaware of the timing of the balloon inflation. Continuous recording of ST-segment shift was obtained by using an intracoronary lead through the PTCA balloon wire. Arterial pressure was registered continuously from the beginning to the end of the PTCA procedure. Successful PTCA was defined as the presence of residual stenosis ⬍50% by on-line quantitative coronary angiography without the occurrence of any clinical complication, such as death, myocardial infarction, or emergency bypass surgery. We randomized 23 patients (group 1) to receive drug sedation and 23 (group 2) to receive hypnotic sedation during PTCA. Drug sedation was obtained by oral administration of 10 mg of diazepam 30 minutes before starting the procedure. Hypnosis was performed by the same PTCA operator according to Erickson’s indirect methods.6 Fifteen minutes before the procedure, a new induction was performed and hypnosis was deepened as usual. Every effort was made to produce a “neutral” state of hypnosis, in which only ideas of relaxation and wellness were suggested to the patients, during the procedure. Patients were connected to a standard electrocardiographic recorder with chest electrodes. Respiratory activity was monitored by a nose-tip thermistor. Arterial blood pressure was measured directly from the guide catheter. Electrocardiograms were digitized with an analog-to-digital converter and stored in a microcomputer. After reviewing the electrocardiograms on the computer display, sequences of about 250 consecutive RR intervals of stationary sinus rhythm were selected. Two time periods of the same length were analyzed in our protocol: (1) baseline conditions, that is, starting 3 minutes before balloon positioning through the stenosis, to obtain a sufficient resolution of the electrocardiographic sample; and (2) a second period, starting 20 seconds after the beginning of arterial occlusion and lasting 3 minutes, was used for the analysis of the autonomic changes during myocardial ischemia and reperfusion. An autoregressive model was used to estimate the power spectrum of the heart rate variability. The autoregressive coefficients were automatically calculated by the computer program, and the model order was chosen as the one that minimized Akaike’s final prediction error figure of merit.7,8 Each spectral component was then identified by the center frequency and quantified by its power as normalized units to facilitate the comparison of spectra with large differences in total variances.7–13 Only components with a patient power ⬎5% of the total power were considered to be significant: those at 0.04 to 0.15 Hz were defined as low-frequency components and those at 0.15 to 0.40 Hz were defined as high-frequency components. Low frequency has been shown to reflect sympathetic cardiac function, whereas high frequency seems to provide an index of vagal modulation of the heart.10 The RR-interval variance and the low- to high-frequency ratio, as an index of sympathovagal cardiac balance, were also calculated. Spectral analysis of heart rate variability was APRIL 15, 2004
TABLE 2 Heart Rate Variability During Percutaneous Transluminal Coronary Angioplasty* Without Hypnosis Basal Variance LF band NU HF band NU LF/HF
2,041 726 59 359 30 2.4
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
1st 1 70 10 38 11 1.4
2,085 919 75 210 14 7.3
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
With Hypnosis
2nd 1 65 10 26 7† 4.7*
1,750 527 64 238 25 2.9
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
3rd 9 38 9† 21 8 1.5
2,062 547 59 277 30 2.1
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
Basal 1 52 7 24 6 0.7
2,111 744 61 366 33 2.5
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
1st 1 68 9 32 9 1.3
2,021 784 64 336 30 2.7
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
2nd 1 66 5 26 8 1.5
1,882 446 58 374 36 1.9
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
3rd 9 36 8 31 6 0.6
1,949 422 50 388 39 2.0
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
8 28 6 29 4 0.9
Data are presented as means ⫾ SD. *p ⬍0.01; †p ⬍0.05. HF ⫽ high frequency; LF ⫽ low frequency; NU ⫽ normalized units.
performed by an operator not participating in this study. Data were expressed as mean ⫾ SD. The significance of differences between baseline and occlusion spectral values was tested by Student’s paired t test. Linear regression analysis was also performed between spectral parameters and ST-segment shift. A p value ⬍0.05 was considered statistically significant. Clinical and procedural data did not differ significantly between groups 1 and 2 (Table 1). All procedures were angiographically successful, and stent implantation was never required. No difference was encountered with regard to inflation time, incidence of chest pain, and the entity of ST shift as measured by intracoronary electrocardiography between the 2 groups. No difference was encountered in terms of mean arterial pressure values between the 2 groups (Table 1). Table 2 lists the main spectral parameters in basal conditions and during balloon inflations in groups 1 and 2. The ST segment shifted from baseline values at the first balloon inflation from 0.02 ⫾ 0.01 to 0.9 ⫾ 0.6 mm (p ⬍0.01) in group 1 and from 0.02 ⫾ 0.08 to 0.9 ⫾ 0.5 mm (p ⬍0.01) in group 2 (Table 1). STsegment shift decreased significantly (p ⬍0.05) from the first to the third inflations in the 2 groups (Table 1). In group 1, the low-frequency component (band) and the low- to high-frequency ratio increased significantly compared with baseline during the first balloon inflation only (from 59 ⫾ 10 to 75 ⫾ 10 normalized units and from 2.4 ⫾ 1.4 to 7.3 ⫾ 4.7, respectively; p ⬍0.001; Table 2). Moreover, the increase of the lowto high-frequency ratio was significantly related to the entity of electrocardiographic ST-segment shift (r ⫽ 0.706; p ⬍0.01). In contrast, no significant variation of spectral parameters from basal values during balloon inflation was found in group 2 (Table 2). •••
The selective influence of hypnosis on cardiac neurovegetative tone is well known.14 In this study only patients with a high level of responsiveness to hypnosis were chosen to accelerate the procedure in the catheterization laboratory. The data of this study showed a selective influence of hypnosis on the mechanisms that regulate the sympathetic drive during PTCA, in particular, a selective inhibition on central autonomic nervous pathways. Our findings agree with
those of recent studies reporting that hypnosis decreases the central signaling of nociceptive stimuli at different levels15; moreover, cortical and subcortical correlates of autonomic activation have been found.16 –18 In particular, inhibition of serotoninergic neurons during animal hypnosis has been demonstrated, and this kind of neuron, whose activation accompanies sympathoexcitation, has been found in spinal cord and brainstem regions known to be involved in autonomic regulation.17,18 Conversely, benzodiazepines did not influence the increase of sympathetic drive during balloon occlusion of the left anterior descending coronary artery. These drugs are known to act predominantly on cortical prefrontal areas and can inhibit sympathetic drive only by weakening emotional and perceptive mechanisms.19,20 Our data differ from those obtained by Airakseinen et al,4 who found that coronary artery occlusion during PTCA leads to divergent and unpredictable changes in heart rate variability. These results may have been biased by the inclusion in the study population of patients with multiple vessel disease (8%), previous myocardial infarction (24%), and treatment with -blocker drugs (75%). Moreover, the RR-interval sequence used to calculate the heart rate variability was very short (60 seconds) and probably not sufficient to provide a reliable resolution, especially in the range of the low-frequency components. In the present study, a longer RR-interval sequence (3 minutes) was chosen to provide a sufficient resolution in the frequency domain, including the early reperfusion period and a possible “phase lag” in the autonomic response. The lack of sympathetic activation during PTCA of the left anterior descending coronary artery in hypnotically sedated patients seems to be in accordance with the hypothesis of a selective subcortical inhibitory influence of hypnosis on the sympathetic coronary reflex arch during balloon occlusion of the left anterior descending coronary artery. Further studies are needed to elucidate the central nervous localization of this pathway. The number of patients included in this study was relatively small, depending on the strict criteria used for enlisting. No instrumental grading of the hypnotic status was performed. Systemic catecholamine levels BRIEF REPORTS
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were not determined, and no information on peripheral autonomic tone was available. 1. Griffin B, Timmis AD, Crick JCP, Sowton E. The evolution of myocardial ischemia during percutaneous transluminal coronary angioplasty. Eur Heart J 1987;8:347–353. 2. Collins MN, Billman GE. Autonomic response to coronary occlusion in animals susceptible to ventricular fibrillation. Am J Physiol 1989;26:1886 –1894. 3. Bigger JT, Hoover CA, Steinman RC, Rolnitzky LM, Fleiss JL. Autonomic nervous system activity during myocardial ischaemia in man estimated by power spectral analysis of heart period variability. Am J Cardiol 1990;66:497–498. 4. Airaksinen KJ, Ikaheimo MJ, Huikuri HV, Linnaluoto MK, Takkunen JT. Responses of heart rate variability to coronary occlusion during coronary angioplasty. Am J Cardiol 1993;72:1026 –1030. 5. Wetzenhofer AM. Hypnotic susceptibility: a personal and historical note regarding the development and naming of the Stanford Scale. Int J Clin Exp Hypn 1997;45:126 –143. 6. Fourie DP. Indirect suggestion in hypnosis: theoretical and experimental issues. Psychol Rep 1997;80:1255–1266. 7. Baselli G, Cerrutti S, Civardi S, Liberati D, Lombardi F, Malliani A, Pagani M. Spectral and cross-spectral analysis of heart rate and arterial blood pressure variability signals. Comp Biomed Res 1986;19:520 –534. 8. Pagani M, Lombardi F, Guzzetti S, Rimoldi O, Furlan R, Pizzinelli P, Sandrone G, Malfatto G, Dell’Orto S, Piccaluga E, et al. Power spectral analysis of heart rate and arterial pressure variabilities as a marker of sympathovagal interaction in man and conscious dog. Circ Res 1986;59:178 –193. 9. Kay SM, Marple SM. Spectrum analysis: a modern perspective. Proc IEEE 1981;69:1380 –1384. 10. Malliani G, Pagani M, Lombardi F, Cerutti S. Cardiovascular and neural regulation explored in the frequency domain. Circulation 1991;84:482–492. 11. Akselrod S, Gordon D, Ubel FA, Shannon DC, Barger AC, Cohen RJ. Power
spectrum analysis of heart rate fluctuation: a quantitative probe of beat to beat cardiovascular control. Science 1981;213:220 –222. 12. Hayano J, Yamada M, Fujinami T, Yokoyama K, Watanabe Y, Takata K. Autonomic nervous function and spectral components of heart rate variability. Biophysics 1988;28:32–36. 13. Pomeranz B, Macaulay RJB, Caudill MA, Kutz I, Adam D, Gordon D, Kilborn KM, Barger AC, Shannon DC, Cohen RJ, Benson H. Assessment of autonomic function in humans by heart rate spectral analysis. Am J Physiol 1985;248:151–153. 14. Hippel CV, Hole G, Kaschka WP. Autonomic profile under hypnosis as assessed by heart rate variability and spectral analysis. Pharmacopsychiatry 2001;34:111–113. 15. Faymonville ME, Laureys S, Degueldre C, DelFiore G, Luxen A, Franck G, Lamy M, Maquet P. Neural mechanisms of antinociceptive effects of hypnosis. Anesthesiology 2000;92:1257–1267. 16. Critchley HD, Corfield DR, Chandler MP, Mathias CJ, Dolan RJ. Cerebral correlates of autonomic cardiovascular arousal: a functional neuroimaging investigation in humans. J Physiol 2000;523:259 –270. 17. Hisamitsu T, Fujishita M, Asamoto S, Nakamura A, Takeshige C. Serotoninergic neurons in the brainstem modulate animal hypnosis. Brain Res Bull 1992; 29:141–145. 18. Passerin AM, Henley WN. Activation of spinal cord serotoninergic neurons accompanies cold-induced sympathoexcitation. Can J Physiol Pharmacol 1994; 72:884 –892. 19. Brambilla P, Stanley JA, Nicoletti M, Harenski K, Wells KF, Mallinger AG, Keshavan MS, Soares JC. 1H MRS brain measures and acute lorazepam administration in healthy human subjects. Neuropsychopharmacology 2002;26:546 – 551. 20. Northoff G, Witzel G, Richter A, Gessner M, Schlagenhauf F, Fell J, Baumgart F, Kaulisch T, Tempelmann C, Heinzel A, et al. GABA-ergic modulation of prefrontal spatio-temporal activation pattern during emotional processing: a combined fMRI/MEG study with placebo and lorazepam. J Cogn Neurosci 2002;14:348 –370.
Analysis of Nonintervention Strategy for In-Stent Restenosis in Pauci- or Asymptomatic Patients He´ le`ne Eltchaninoff, Carlos Sanchez-Giron,
MD,
Raphae¨lle Carlot, MD, Christophe Tron, MD, MD, Laurent Sebagh, MD, Carla Agatiello, MD, and Alain Cribier, MD
Between January 1996 and May 2000, we retrospectively identified 66 patients (61 ⴞ 11 years) with in-stent restenosis who did not undergo percutaneous coronary intervention and/or bypass surgery and were maintained on medical treatment alone. In-stent restenosis was diffuse or proliferative in 86% of these patients. At 33 ⴞ 11 months, 2 patients died, none developed myocardial infarction, and 6 (9%) had target lesion revascularization only (repeat percutaneous transluminal coronary angioplasty). Medical treatment alone was associated with a good longterm clinical follow-up in selected patients with significant documented in-stent restenosis. 䊚2004 by Excerpta Medica, Inc. (Am J Cardiol 2004;93:1038 –1040)
oronary stenting is the procedure of choice in most percutaneous coronary interventions. However, C angiographic and clinical in-stent restenosis (ISR) will From the Charles Nicolle Hospital, University of Rouen, Rouen, France. Dr. Eltchaninoff’s address is: Hoˆ pital Charles Nicolle, 1, rue de Germont, 76031 Rouen Cedex, France. E-mail: helene.eltchaninoff@ chu-rouen.fr. Manuscript received September 5, 2003; revised manuscript received January 3, 2004 and accepted January 5, 2004.
1038
©2004 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 93 April 15, 2004
develop in 15% to 45% of cases. Therefore, the management of ISR has become an important clinical problem. Balloon angioplasty alone for the treatment of ISR has been associated with a high recurrence rate of restenosis,1 reaching 85% in angiographic studies.2,3 Several alternative percutaneous techniques have been evaluated in this setting: repeat stenting,4,5 rotational atherectomy,6 laser angioplasty,7 and use of a cutting balloon.8 None of these9 has demonstrated any advantage over plain balloon angioplasty. Intracoronary radiation therapy10,11 has been evaluated and appears promising, but its use is limited by cost and availability. Despite very limited series and preliminary results, the use of drug-coated stents also appears encouraging.12–14 However, few data are available on the long-term outcome of patients maintained on medical therapy alone.15 Thus, the goal of our study was to evaluate the long-term outcome of patients with angiographically proved ISR who received medical treatment alone without percutaneous or surgical revascularization. •••
Review of consecutive patients who underwent cardiac catheterization at the Charles Nicolle Hospital in Rouen, France, between January 1996 and May 0002-9149/04/$–see front matter doi:10.1016/j.amjcard.2004.01.012