© Med Sci Monit, 2007; 13(4): RA62-68 PMID: 17392660
Received: 2006.08.29 Accepted: 2007.01.02 Published: 2007.03.30
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Review Article
Alcohol septal ablation for hypertrophic obstructive cardiomyopathy: A review of the literature Josef Veselka Cardiovascular Center, University Hospital Motol, Prague, Czech Republic Source of support: Grant of Ministry of Health of Czech Republic No. 00064203
Summary Hypertrophic obstructive cardiomyopathy (HOCM) is a common inheritable cardiac disorder that can lead to symptoms of dyspnea, angina pectoris, and syncope. Symptomatic patients are usually treated with negatively inotropic agents, such as beta-blockers, calcium channel blockers, or disopyramide. However, up to 10% of patients with outflow pressure gradient are unresponsive to medical therapy. Until the early 1990s, surgical myectomy represented the standard treatment for patients with HOCM and drug-refractory symptoms. More than one decade ago, alcohol septal ablation (ASA) was introduced as a less invasive alternative therapy for symptomatic HCM patients with obstruction. ASA is performed through a percutaneous approach, in which 1–3 ml of absolute alcohol is introduced into the septal branch to create a controlled septal infarction of the basal interventricular septum. This procedure results in relief of symptoms, a decrease in the pressure gradient, and improvement in left ventricular diastolic function. A randomized controlled trial is needed to compare ASA and surgical myectomy in order to determine which technique provides maximal benefit.
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alcohol ablation • ethanol • hypertrophic cardiomyopathy • obstruction
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J. Veselka, MD, Ph.D, FESC, FSCAI, CardioVascular Center, University Hospital Motol, V úvalu 84, Prague 5, 150 00, Czech Republic, e-mail:
[email protected]
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Med Sci Monit, 2007; 13(4): RA62-68
BACKGROUND Hypertrophic obstructive cardiomyopathy (HOCM) is a complex cardiac disease with unique pathophysiological characteristics and a great diversity of morphologic, functional, and clinical features. HOCM is defined as a primary myocardial hypertrophy, with dynamic left ventricular outflow tract obstruction and diastolic dysfunction of the left ventricle. Typical symptoms are dyspnea, angina pectoris, and syncope [1]. Recent observations suggest that the prevalence of hypertrophic cardiomyopathy (HCM) is higher (1 in 500) than previously thought. More than 25% of patients with HCM have evidence of obstruction of the left ventricular outflow tract (LVOT). The condition therefore seems to be a common genetic malformation of the heart [1]. However, up to now the clinical implications of various genetic abnormalities have not been determined. The clinical course varies markedly. Some patients remain asymptomatic throughout their whole lives, some have severe symptomatology of heart failure or angina pectoris, and others die suddenly even in the absence of previous symptoms. The annual mortality rate varies in different studies. In unselected populations it is reported to be about 1% [1–3]. These observations suggest that a substantial proportion of patients with HCM has a more favorable course than previously believed. With respect to the various clinical courses, it seems impossible to define precise guidelines for management. As in many diseases, it is often necessary to individualize the therapy. Unfortunately, some of the conventionally treated patients are unresponsive to medical therapy. Nevertheless, during the past few years, technological developments in non-surgical treatment have provided new therapeutic options for patients with this disease. Since 1995, alcohol septal ablation (ASA) by selective ethanol injection into the target septal branch has been used as a therapeutic measure for HOCM [4]. Current clinical studies have demonstrated the therapeutic efficacy with ASA, but there is an ongoing debate about the long-term impact of the resultant myocardial scar and comparison with surgical therapy of HOCM (myectomy).
INDICATIONS The accepted patient selection criteria for ASA, as outlined in the recent ACC/ASC consensus document about hypertrophic cardiomyopathy [1], are as follows: 1) anatomic findings of marked septal hypertrophy which projects from the left ventricular outflow tract (LVOT), 2) dynamic obstruction of LVOT, and 3) unresponsiveness to medical therapy (Table 1). There are no sufficient data available to confirm the exact hemodynamic (pressure gradient >50 mmHg), anatomic (septum thickness >18 mm), or clinical (dyspnea with NYHA class III or IV) criteria that resulted in a certain relaxation of indications in clinical practice. Patients with moderate symptoms are treated if they have high gradients and additional findings, such as recurrent exercise-induced syncope, markedly abnormal blood pressure response at exercise, paroxysmal atrial fibrillation, or extremely high pressure gradient after provocative maneuvers (the Valsalva maneuver or use of nitrates) [5]. It is a very important question in clinical practice whether the increased risk of sudden car-
Veselka J et al – Alcohol septal ablation for hypertrophic obstructive…
Table 1. Indications for ASA. Clinical indication Symptoms, functional class III or IV Severe side effects of medical treatment Hemodynamic indication LVOT pressure gradient (maximum gradient) >30 (50) mmHg Provokable LVOT pressure gradient (maximum gradient) >50 (100) mmHg Morphologic indication Systolic anterior motion related obstruction Mid-cavitary obstruction (?) Septal thickness >15 (18) mm Suitable septal branch
diac death associated with LVOT obstruction justifies the use of ASA in slightly symptomatic or completely asymptomatic patients. At present there are not sufficient data to answer this question. However, a relatively low risk of sudden death in asymptomatic patients with obstruction and none of the recognized risk factors for sudden death (1. ventricular tachycardia, 2. abnormal exercise blood pressure response, 3. family history of premature death, 4. unexplained syncope, and 5. severe left ventricular hypertrophy in any myocardial segment >30 mm) suggests that aggressive interventions are unjustified in this group [6]. The situation in asymptomatic patients with obstruction and additional risk factors is less clear. The approach must be individualized. It seems to be reasonable to implant an AV-sequential ICD to try atrio-ventricular sequential pacing to reduce obstruction for six months, and then to perform ASA if it needed. Nevertheless, ASA as the primary treatment is still unjustified in this group of patients, given the potential mortality and morbidity associated with this procedure. Patient preference should, of course, be considered in such discussion, and surgical myectomy should be mentioned as a gold standard in majority of western countries [1].
TECHNIQUE The idea of inducing a septal infarction by catheter techniques was suggested by the observation that myocardial function of selected areas of the left ventricle can be suppressed by balloon occlusion of the supplying artery during angioplasty. Outflow pressure gradient in HOCM decreased significantly when the first septal artery was temporarily occluded by an angioplasty balloon catheter. This new concept was also supported by observations that the outflow pressure gradient decreased after the anterior myocardial infarction in HOCM patients. As the first, Sigwart published his experience with “non-surgical myocardial reduction” in three patients with HOCM in 1995 [4]. The original technique of ASA has undergone several modifications with the intention to improve both the identification of the target septal branch and hemodynamic efficacy, to decrease the risk of
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Figure 3. LVOT pressure gradient at baseline and after ASA. Figure 1. Transthoracic echocardiography, apical four-chamber view with optimal opacification of the basal interventricular septum by echocontrast medium. A
B
Figure 2. Coronary angiography of the left coronary artery before (A) and after (B) the procedure. Two proximal septal branches were occluded during ASA. major acute complications (heart block, arrhythmias, alcohol spillage), and the long-term impact of resultant myocardial scar [4,5,7–13].
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The following course of ASA is usually recommended: A temporary pacemaker is placed in the apex of the right ventricle in all patients except those who already have a permanent dual-chamber pacemaker in place. However, fluctuation of the pacing threshold has to be anticipated if the lead is directed towards the septum, i.e. with the tip in proximity to the ablation lesion. A multipurpose catheter is advanced through the aortic valve into the apex of the left ventricle, and the intraventricular gradient is measured by a pull-back technique. A 6 or 7F guiding catheter is then engaged into the ostium of the left coronary artery. Initial angiography is performed to localize the origin of the septal arteries. Over-the-wire balloon catheter is introduced over a coronary wire into one of the major and proximal septal perforators and inflated. Contrast medium is injected through the central balloon lumen to delineate the area supplied by the septal branch and to ensure that balloon inflation prevented spillage into the left anterior descending artery. Contrast myocardial echocardiography is done to delineate the area to be infarcted (Figure 1) and to exclude contrast (and subsequently alcohol) deposition in remote myocardial regions such as the left ventricular posterior wall or papillary muscles. The optimal septal branch is identified by opacification of the area in the basal septum which is adjacent to the zone of maximal acceleration of the outflow jet and includes the point of coaptation between septum and anterior mitral leaflet. Usually, the target septal branch originates from the proximal segment of the left anterior descending artery. However, in exceptional cases it originates from diagonal or intermediate branches of the left coronary artery. Depending on the septal artery’s size and septal thickness, 1–3 ml of absolute ethanol are very slowly (2–5 minutes) instilled through the lumen of the inflated balloon catheter and left in place for 5 minutes [14]. After balloon deflation and removal, angiography is done to confirm the patency of the left anterior descending artery and occlusion of the target septal branch (Figure 2). Measurement of the intraventricular gradient is usually performed by a multipurpose catheter and a guiding catheter and/or Doppler echocardiography. Of course, an invasively measured pressure gradient (peak-topeak pressure gradient) is always lower than the maximal pressure gradient measured by Doppler echocardiography. The gradient should decrease at least to one half (Figure 3). A temporary pacemaker is sutured in place. The patient is observed in the coronary care unit for at least 48 hours. If there is no high-degree atrioventricular block, the pacemaker lead is then removed.
Med Sci Monit, 2007; 13(4): RA62-68
COMPLICATIONS
Veselka J et al – Alcohol septal ablation for hypertrophic obstructive…
Table 2. Major procedural and post-procedural complications of ASA.
In-hospital death, the most significant complication, is rare; nevertheless, it ranges in the literature from 1 to 4%. However, some observations suggest that in skilled hands, the mortality rate can be less than 1% [15–17].
In-hospital death (1–4%)
Complete heart block is a frequent complication in clinical practice. Initially, its rate was reported as up to 50% of procedures, although its occurrence varied substantially. In most cases, complete heart blocks were only transitory, and after the introduction of more recent procedural technique (myocardial contrast echocardiography, lower ethanol dose, and slower ethanol injection), the number of required permanent pacemaker implantations was reduced to 5–15% of cases. Furthermore, multivariate analyses documented that the most important risk factors predicting complete heart block were rapid ethanol injection, baseline duration of QRS, and initial left bundle branch block (50% of ASA patients with left bundle branch block at baseline require permanent pacemaker implantation) [8–12,15–21]. It is of note that patients with complete heart block derive a similar clinical and hemodynamic benefit over patients who do not require permanent pacing.
Non-therapeutic myocardial infarction (
