ultima actualización
16 de julio del 2019

10.938.898 visitantes

Pediatric and Congenital Heart Disease
Alcohol septal ablation for hypertrophic obstructive cardiomyopathy: Lower alcohol dose reduces size of infarction and has comparable hemodynamic and clinical outcome

Josef Veselka, MD, PhD *, árka Procházková, MD, Radka Duchoová, MD, Ingrid Bolomová-Homolová, MD, Jana Páleníková, MD, David Tesa, MD, PhD, Pavel ervinka, MD, PhD, Tomá Honk, MD, PhD
Department of Cardiology, University Hospital Motol, Prague, Czech Republic

*Correspondence to Josef Veselka, Department of Cardiology, University Hospital Motol, Vúvalu 84, Prague 5, 15000, Czech Republic

Introduction

Patients with hypertrophic obstructive cardiomyopathy (HOCM) can present with disabling symptoms of dyspnea, angina pectoris, and exertional syncope. Negatively inotropic agents such as -blockers, the calcium channel blockers, and disopyramide have traditionally been administered to symptomatic patients. However, up to 10% of patients with left ventricular outflow pressure gradient (LVOTPG) are unresponsive to medical therapy. Patients in this group are considered to be good candidates for percutaneous transluminal septal myocardial ablation (PTSMA) [[1-11]]. During this procedure, absolute alcohol is introduced into the target septal artery to produce myocardial infarction. On the basis of the results of many recent studies, PTSMA leads to a reduction in basal septal thickness, a substantial decrease in LVOTPG, a decrease in left ventricular filling pressures, an improvement of left ventricular diastolic function and left ventricular performance, and a marked clinical improvement [[1-10][12-14]]. However, PTSMA has not yet been subjected to the scrutiny of randomized or controlled studies.

Several modifications of the ablation technique aim to improve the procedural outcomes. Usually, alcohol ablation has been performed by injection of 2-4 ml of absolute alcohol into target septal branch. The amount of alcohol injected and infarct size, as reflected by the increase in creatine kinase, differ considerably between the studies published so far [[1][2][7]]. Thus, there is ongoing discussion regarding the optimal dose of the injected alcohol and the impact of infarct sizes on the clinical and hemodynamic outcome. Therefore, in this pilot study, we wanted to compare the usually recommended dose (2- 4 ml) and the low dose (1-2 ml) of alcohol used during PTSMA to clinical, electrocardiographic, and echocardiographic outcome.

Materials and methods

Thirty-four patients with symptomatic HOCM receiving maximum medical therapy were enrolled consecutively. The group of patients comprised 20 women and 14 men whose mean age was 55 ± 14 years. All patients suffered from dyspnea and their mean functional class (NYHA) was 2.6 ± 0.7. Thirty patients (88%) suffered from angina pectoris and their mean functional class (CCS) was 2.2 ± 0.9. Thirteen patients (38%) reported episodes of syncope. One patient (3%) has been resuscitated from cardiac arrest prior to procedure with subsequent cardioverter-defibrillator implantation. Seven patients (21%) with a dual-chamber pacing and sensing (DDD) pacemaker implantation that failed to relieve their symptoms were included in this study. The pacing mode has not been changed during the study.

The indication for PTSMA has been restricted to symptomatic patients with maximum LVOTPG greater than 30 mm Hg under basal conditions or greater than 60 mm Hg after isosorbide dinitrate application in a sublingual form. All patients had to have basal septal thickness greater than 15 mm. All patients had the left ventricular outflow obstruction associated with systolic anterior motion and hypertrophy of the basal interventricular septum. Patients with midventricular obstruction or severe mitral regurgitation were not included.

Patients were randomized in a 1:1 ratio into one of the two arms according to dose of injected alcohol (ethanol, 96%) during PTSMA procedure. Seventeen patients (mean age, 57 ± 14 years) were enrolled in group A (alcohol dose during PTSMA procedure, 1-2 ml). Similarly, 17 patients (mean age, 52 ± 11 years) were enrolled into group B (alcohol dose during PTSMA procedure, > 2 ml). All patients provided their written informed consent prior to participation.

Echocardiography

Echocardiograms were performed on either a Vingmed (CFM 800) or a Toshiba (Power Vision 6000) ultrasound imaging system. The echocardiographic data were acquired and analyzed by a single investigator blinded to all data. Parasternal and apical views were acquired. The left ventricular dimension (LVd) was measured in the parasternal long-axis view at both end-diastole and end-systole. Since PTSMA results in an infarction limited to the anteroseptal basal segment, the plain thinning of this segment could induce the false increase of LVd. Therefore, LVd was measured at the level close to the papillary muscles. Ejection fraction (LVEF) was calculated with Teicholz's method. Septal (IVSd) and posterior wall thicknesses were determined from two-dimensional images. The left atrium dimension was measured using M-mode in the parasternal long-axis view. Color-guided continuous-wave Doppler was performed in the apical views to determine the peak LVOT velocity, with care taken to avoid contamination with mitral regurgitation jet. LVOTPG was derived with the modified Bernoulli equation: pressure gradient = 4V2, where V is the maximum velocity recorded in the LVOT.

PTSMA Procedure

All the patients underwent coronary angiography and temporary pacemaker was placed in the apex of the right ventricle except those who already have a permanent pacemaker in place. A multipurpose catheter was advanced into the apex of the left ventricle to measure the pressure gradient between guiding catheter in the aorta and multipurpose catheter in the apex of the left ventricle (PG start). A 6-8 Fr guiding catheter was then engaged in the left main coronary artery. A slightly oversized over-the-wire balloon catheter of 1.5-2.5 mm in diameter was introduced over a coronary wire into the first septal perforator and inflated. A contrast medium was injected through the central balloon lumen to ensure that balloon inflation prevented spillage into the left anterior descending artery. Contrast myocardial echocardiography (concentration, 300 mg/ml; Levovist, Schering, Berlin, Germany) was done to delineate the area to be infarcted. Ethanol (96%) was injected very slowly per fractions (0.5-1 ml/1 min) and finally 2 ml of saline were used to perform a careful flush of the central balloon lumen. The balloon catheter was left in place at least 5 min after the last ethanol injection. The measurement of the final peak-to-peak pressure gradient (PG end) was done by guiding and multipurpose catheters. Finally, the coronary angiography was carried out to confirm the patency of the left anterior descending artery and occlusion of the target branch. If a single large first septal branch was not found or the reduction of pressure gradient was insufficient (< 50%), a second septal branch was ablated. In group A, the maximal amount of alcohol injected was 2 ml. When LVOTPG decreased sufficiently or complete heart block developed, the procedure was stopped at lower dose. In group B, the minimal dose of alcohol was larger than 2 ml and the target dose was 3 ml of alcohol. The total volume of alcohol was based on relief of LVOTPG and development of conduction abnormalities during injection. When LVOTPG was abolished at lower dose than 3 ml or complete heart block developed, the procedure was stopped at lower dose than 3 ml of alcohol.

Patients were observed in the intensive care unit for at least 24 hr; the pacemaker lead was then removed if there was no episode of high-degree atrioventricular block. Blood was withdrawn for MB fraction of creatine kinase (CK-MB) at 6-hr intervals for 2 days.

Follow-Up

Clinical, electrocardiographic, and echocardiographic evaluation was performed by the principal investigator 6 months after the procedure in all patients.

Statistical Analysis

Microsoft Excel was used for the study database. Data are presented as mean ± SD. Paired Student's t-test, chi-square test, and Pearson correlation test were used as appropriate. A P value of 0.05 was considered statistically significant.

Results

Both groups of patients matched in all clinical and echocardiographic data (Table I). In 34 patients, alcohol was injected in 36 septal branches (17 in group A vs. 19 in group B; P = NS). The dose of alcohol injected was 1.6 ± 0.4 in group A and 3.4 ± 0.9 in group B (P < 0.001). All PTSMA procedures were uneventful except for two cases of sustained ventricular tachycardia induced by injection of echocontrast medium into the septal branch and immediate electrical cardioversion was needed. Interventional data are summarized in Table II. The peak of CK-MB was 1.9 kat/L in group A and 3.2 kat/L in group B (P < 0.05). Normal range of CK-MB is up to 0.42 kat/L. For all the patients, there was a correlation between amount of injected alcohol and the peak of CK-MB (r = 0.58; P < 0.01) and there was no significant relationship between the peak of CK-MB and LVOTPG at follow-up (r = 0.16; P = NS). There was no other significant correlation between the dose of injected alcohol and echocardiographic, hemodynamic, or clinical variables.

Table I. Baseline Echocardiographic and Clinical Data

Variable Group A Group B P
Left ventricular ejection fraction, % 81 ± 8 80 ± 6 NS
Septal thickness, mm 21 ± 3 22 ± 3 NS
Posterior wall thickness, mm 12 ± 2 12 ± 2 NS
Left ventricular dimension, mm 44 ± 5 43 ± 6 NS
Left atrial dimension, mm 47 ± 6 44 ± 6 NS
Left ventricular outflow tract gradient, mm Hg 70 ± 35 66 ± 39 NS
Dyspnea, NYHA class 2.7 ± 0.7 2.5 ± 0.6 NS
Angina pectoris, CCS class 2.3 ± 0.9 2.1 ± 0.9 NS
History of syncope, n 6 7 NS
Number of paced patients, n 3 4 NS
Table II. Interventional Data

Variable Group A Group B P
PG start, mm Hg 66 ± 39 56 ± 32 NS
PG end, mm Hg 11 ± 13 14 ± 12 NS
Ethanol injected, ml 1.6 ± 0.4 3.4 ± 0.9 < 0.001
Number of target vessels 1 ± 0 1.1 ± 0.1 NS

In all treated patients, sustained complete heart block after PTSMA occurred in three initially nonpaced patients (11%). Permanent DDD pacemaker implantation was needed in two patients in group A and one patient in group B (P = NS). One patient with concomitant immunosuppressive therapy suffered from a septic shock after the procedure. No patient died during the hospital stay. All patients were discharged and examined at 6-month follow-up.

Follow-Up

At 6-month follow-up, both groups of patients were not significantly different with regard to symptoms and echocardiographic findings. None of the patients reported a further deterioration of symptoms and no patient died during the follow-up. All the patients remained on -blockers or calcium channel blockers (metoprolol, 50-100 mg per day in 10 patients in group A and 13 patients in group B; verapamil, 240 mg per day in 7 patients in group A and 4 patients in group B). One patient in group A was kept on amiodarone 200 mg per day.

Effect of PTSMA on Echocardiographic and Electrocardiographic Parameters

n all the patients, both LVEF and IVSd decreased 6 months after the procedure (81% ± 7% to 75% ± 6%; P < 0.01; 22 ± 3 to 14 ± 4 mm; P < 0.01, respectively). LVd increased significantly (44 ± 6 to 47 ± 5 mm; P < 0.05). The posterior wall thickness and the left atrial dimension remained unchanged. The resting LVOTPG measured by Doppler echocardiography was reduced in all the patients after the procedure (68 ± 37 to 17 ± 15 mm Hg; P < 0.01). The six-month results in both groups are summarized in Table III.

Table III. Echocardiographic and Clinical Data at Follow-Up
Variable Group A Group B P
Left ventricular ejection fraction, % 75 ± 6 75 ± 5 NS
Septal thickness, mm 13 ± 3 14 ± 4 NS
Posterior wall thickness, mm 11 ± 2 11.3 ± 2 NS
Left ventricular dimension, mm 47 ± 4 47 ± 6 NS
Left atrial dimension, mm 46 ± 5 43 ± 5 NS
Left ventricular outflow tract gradient, mm Hg 16 ± 12 17 ± 15 NS
Dyspnea, NYHA class 1.5 ± 0.8 1.2 ± 0.5 NS
Angina pectoris, CCS class 0.9 ± 0.7 0.8 ± 0.7 NS
Number of paced patients, n 5 5 NS

A persistent right bundle branch block was observed in 13 (6 in group A vs. 7 in group B; P = NS) out of 27 nonpaced patients (48%) with previously normal intraventricular conduction. A persistent left bundle branch block occurred in three (1 vs. 2; P = NS) patients (11%). Permanent pacing was initiated in two (1 vs. 1; P = NS) patients (7%) with complete heart block that persisted for 5 days after PTSMA. In one patient, a complete heart block occurred 2 weeks after the procedure, which required subsequent DDD pacemaker implantation.

Effect of PTSMA on Symptoms

All the patients reported improvement in symptoms at follow-up. At 6-month evaluation, both the mean NYHA class and the mean CCS class decreased significantly in both groups (P < 0.001). There were no significant differences in subjective evaluation of angina pectoris and dyspnea between both groups of patients (P = NS). In both groups, the number of patients who reported episodes of syncope decreased. Data are summarized in Table III.

Discussion

In the randomized fashion, we studied two groups of patients who underwent the same PTSMA procedure using low dose or standard dose of alcohol injected during the procedure into target septal branch. Both groups of patients were comparable in the baseline characteristics. The most important result of this study is that the small infarctions localized primarily by myocardial contrast echocardiography are sufficient to reduce LVOTPG to a similar extent as larger infarctions induced by higher dose of alcohol. In both groups, the only significant difference was the size of myocardial necrosis expressed as the peak of CK-MB. Similarly, Boekstegers et al. [[1]] in their observational study restricted the amount of the alcohol injected to a maximum of 2 ml per septal branch and subsequently found a close correlation between the amount of alcohol injected and the maximum rise in CK levels as an estimate of infarct size. Also, they did not confirm that a higher CK level was associated with a greater reduction in the LVOT gradient.

Apart from the amount of alcohol injected, this study confirmed that PTSMA using selective septal perforator injection of absolute alcohol is a safe, rational, and effective therapy for symptomatic patients with HOCM. This treatment substantially reduced LVOTPG and symptoms.

There are two implications for clinical practice from this study. First, it is of interest to minimize the extent of myocardial necrosis during PTSMA. The use of low dose of alcohol may be suited to achieve this goal and this approach might have positive consequences in the long-term follow-up. Moreover, Lawrenz et al. [[15]] documented that injection of a minimum amount of ethanol (0.1-0.3 ml) into septal branch resulted in a marked increase of ethanol concentration in the coronary sinus (0.13-0.62%). Therefore, we believe that lower doses of alcohol should be used in the near future. Second, good outcomes have been achieved in both groups of patients, with high rates of abolition of the left ventricular obstruction and the left ventricular remodeling. Thus, as described previously, PTSMA is an effective therapy for symptomatic patients with HOCM.

There are several study limitations. Although our randomized study is the largest reported so far, it included relatively modest number of patients. Clearly, more prospective data are needed to determine the ultimate value of the low dose of alcohol injected. In this sense, it is also necessary to bear in mind that all patients in this study had the septum thickness < 30 mm. Hence, an important clinical question is whether the effectiveness of low dose of alcohol would be comparable in patients with the septum thickness > 30 mm. Also, the reliability of our data may be limited since we followed up our patients just for a 6-month period. Therefore, this finding requires further investigation over longer period of observation.

The observed positive changes in symptoms, LVOTPG reduction, and the left ventricular remodeling confirm the safety and efficacy of PTSMA in the treatment of highly symptomatic patients with HOCM. The present study suggests that the low dose (1-2 ml) of alcohol injected into target septal branch is probably as efficacious as the usually used doses (2-4 ml) and reduces the size of myocardial necrosis. Hence, to avoid unnecessarily large areas of myocardial necrosis with potential induction of the left ventricular dysfunction and an arrhytmogenic substrate, the application of alcohol should be restricted to a maximum of 2 ml during a single ablation procedure.

References

  1. Boekstegers P, Steinbigler P, Molnar A, et al. Pressure-guided nonsurgical myocardial reduction induced by small septal infarctions in hypertrophic obstructive cardiomyopathy. J Am Coll Cardiol 2001; 38: 846-853.
  2. Lakkis N, Nagueh S, Killip D, Torre G, Roberts R, Spencer W III. Nonsurgical septal reduction for symptomatic hypertrophic obstructive cardiomyopathy: the Baylor experience. J Interv Cardiol 2000; 13: 157-159.
  3. Mazur W, Nagueh SF, Lakkis NM, et al. Regression of left ventricular hypertrophy after nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy. Circulation 2001; 103: 1492-1496.
  4. Nagueh S, Lakkis NM, Middleton K, et al. Changes in left ventricular filling and left atrial function six months after nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy. J Am Coll Cardiol 1999; 34: 1123-1128.
  5. Nagueh SF, Lakkis NM, Middleton KJ, et al. Changes in left ventricular diastolic function 6 months after nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy. Circulation 1999; 99: 344-347.
  6. Rovner A, Sitges M, Smith R, et al. Improvement in diastolic suction in patients with hypertrophic obstructive cardiomyopathy after septal ablation. J Am Coll Cardiol 2002; 39(Suppl A): 451A.
  7. Ruzyllo W, Chojnowska L, Demkow M, et al. Left ventricular outflow tract gradient decrease with non-surgical myocardial reduction improves exercise capacity in patients with hypertrophic obstructive cardiomyopathy. Eur Heart J 2000; 21: 770-777.
  8. Seggewiss H, Faber L, Gleichmann U. Percutaneous transluminal septal ablation in hypertrophic obstructive cardiomyopathy. Thorac Cardiovasc Surg 1999; 47: 94-100.
  9. Sigwart U. Non-surgical myocardial reduction for patients with hypertrophic obstructive cardiomyopathy. Eur Heart J 2001; 3(Suppl L): L38-L42.
  10. Sigwart U. Non-surgical myocardial reduction for hypertrophic obstructive cardiomyopathy. Lancet 1995; 346: 211-214.
  11. Veselka J, Honk T. The management of hypertrophic obstructive cardiomyopathy: the role of percutaneous transluminal septal myocardial ablation. Cardiol 2000; 9: 327-332.
  12. Faber L, Seggewiss H, Kuhn H, et al. Catheter interventional septal ablation for hypertrophic obstructive cardiomyopathy: an analysis of the follow-up data from the Registry of the German Society of Cardiology. J Am Coll Cardiol 2002; 39(Suppl A): 3A.
  13. Faber L, Welge D, Ziemssen P, Seggewiss H, Fassbender D, Horstkotte D. Septal ablation for symptomatic hypertrophic obstructive cardiomyopathy: an analysis of the patients with dissatisfactory intervention results. J Am Coll Cardiol 2003; 41(Suppl A): 145A.
  14. Veselka J, Honk T. Early remodeling of left ventricle and improvement of myocardial performance in patients after percutaneous transluminal septal myocardial ablation for hypertrophic obstructive cardiomyopathy. Int J Cardiol 2003; 88: 27-32.
  15. Lawrenz T, Lieder F, Leuner C, et al. Transcoronary ablation of septal hypertrophy for hypertrophic obstructive cardiomyopathy: studies of infarction markers and alcohol spill over. Eur Heart J 2003; 24(Suppl): 556.

Autor: Josef Veselka, MD, PhD, árka Procházková, MD, Radka Duchoová, MD, Ingrid Bolomová-Homolová, MD, Jana Páleníková, MD, David Tesa, MD, PhD, Pavel ervinka, MD, PhD, Tomá Honk, MD, PhD

Fuente: Catheterization and Cardiovascular Interventions. Volume 63, Issue 2, Pages 231 - 235

Ultima actualizacion: 2 DE OCTUBRE DE 2004

© hemodinamiadelsur.com.ar es desarrollado y mantenido por ASAP Web | Consultoria de sistemas
Acuerdo con los usuarios
Get Adobe Reader Get Adobe Flash Player