Alcohol Septal Ablation in the <br />
Cath Lab: What is it All About?

Case Presentation A 65-year-old man with hypertension, hypercholesterolemia, benign prostatic hyperplasia and hypertrophic obstructive cardiomyopathy presented to our facility with NYHA class III symptoms of dyspnea and chest tightness with minimal exertion. He denied syncope, lightheadedness or palpitations. Despite aggressive medical treatment with a high-dose beta blocker and calcium channel blocker (metoprolol 300 mg per day and diltiazem 180 mg per day), his symptoms continued to progress. Physical exam revealed a 2/6 systolic ejection murmur at the upper left sternal border, which was accentuated with Valsalva maneuver and diminished with hand-grip. The remainder of his physical exam was unremarkable. Electrocardiogram revealed normal sinus rhythm with right bundle branch block, left ventricular hypertrophy, left atrial enlargement and Q waves in leads II, III and AVF (Figure 1). On echocardiogram, there was asymmetric septal hypertrophy (septal thickness 1.9 cm, posterior wall 0.9 cm), systolic anterior motion (SAM) of the anterior mitral valve leaflet, mild mitral regurgitation, and a provocable subaortic gradient of 120 mmHg (Figure 2). The patient was a good candidate for alcohol septal ablation (ASA) of the hypertrophied septum based on his cardiac anatomy, hemodynamics, and persistent clinical symptomatology, despite maximal medical therapy. Under full heparin anticoagulation and temporary transvenous pacemaker placement, a guide catheter was advanced to the left main coronary artery, and the first septal artery was selected and wired using standard angioplasty technique. A 2.0 X 9 mm over-the-wire angioplasty balloon was advanced and positioned immediately distal to the ostium of the first septal artery, and inflated so as to obstruct blood flow into the artery. After removing the wire, 3 cc of 98% ethanol was infused slowly through the balloon central lumen under vigilant fluoroscopic guidance, with resultant ablation of the septal tissue (Figure 3). Transthoracic echocardiographic guidance was utilized to guide therapy. A successful result was obtained, with >50% immediate reduction in the provocable subaortic gradient, and the procedure was terminated. Over the ensuing six months, the patient reported NYHA class I symptoms of dyspnea only on maximal exertion. Furthermore, he has been able to reduce his medication regimen in half. Discussion Hypertrophic cardiomyopathy (HCM) is defined as hypertrophy of the ventricular myocardium disproportionate to any accompanying hemodynamic load. It is usually asymmetric and most commonly involves the interventricular septum. About 25% of HCM cases are associated with dynamic left ventricular outflow tract (LVOT) obstruction from the hypertrophied septum and opposing systolic anterior motion (SAM), and are termed hypertrophic obstructive cardiomyopathy (HOCM).³² Typically the hypertrophic myocardium is poorly compliant contributing to diastolic dysfunction of the left ventricle. The combination of diastolic dysfunction, LVOT obstruction, mitral regurgitation and eventual secondary pulmonary hypertension results in the characteristic symptoms of dyspnea, chest pain, lightheadedness, and syncope. In addition, patients with HOCM are at increased risk of sudden cardiac death, at a rate of 1-2% per annum.^1,6,19 A genetic disease inherited in autosomal dominant fashion, several echocardiographic studies have estimated the prevalence of HOCM in the general population to be 0.2% or 1 in 500 individuals, regardless of race or ethnicity.² Diagnosis is oftentimes difficult, due to the multiplicity of mutations in any of the 1-10 genes that can be involved, variable phenotypic penetrance, and variable age at presentation, even within a particular family.^1,3-4,17 However, morphology defined by echocardiographic data along with clinical symptoms often leads to a diagnosis of HOCM, regardless of the phenotype. Treatment of HOCM is aimed at alleviating symptoms, preventing disease progression, and reducing the risk of sudden death. The latter is treated primarily by ICD implantation in patients deemed to be at high risk, based on a variety of clinical, genetic, and anatomic factors. In particular, patients with prior resuscitated sudden arrest, a history of syncope, a family history of sudden premature death, extreme hypertrophy (maximal wall thickness >30 mm), evidence for sustained or non-sustained ventricular tachycardia, and/or hypotensive response to exercise may warrant prophylactic ICD implantation.^{1,5-10,13,15-16,18-19} Symptomatic patients are treated with negative chronotropic and inotropic agents like beta blockers (first-line agents) and calcium channel blockers to increase diastolic filling time and myocardial relaxation. Low-dose diuretics can be cautiously used in patients with evidence of significant volume overload. Patients with NYHA class III or IV symptoms refractory to medical management can be offered conventional surgical myectomy or the less invasive ASA of the hypertrophied septum. Younger patients (11,20 ASA can have a more variable effect based on the course of the chosen septal perforator vessel. ASA produces a transmural region of tissue necrosis, usually in the basal septum and extending into the right ventricular portion of the septum at mid ventricular level, which is the usual location of the right bundle branch; thus, it results in a RBBB in about 42–58% patients undergoing ASA.^11,20,22 The frequency of developing complete heart block (CHB) requiring pacing after ASA has varied from 5% to 33%^22-23,28-30 and after surgical myectomy has remained low, 22 However, this may not prove to be a practical solution. Risk factors associated with developing either an intra-procedural or delayed CHB include older age, female gender, a preexisting left or right BBB, first-degree AV block, a prolonged QRS interval (>120 msec) or long HV interval and a post-procedural retrograde AV block, rapid infusion of a large volume of ethanol, and a higher number of septal perforators treated. The positive predictive value of these parameters was low, but they had a negative predictive value of >80%.^22-23,29-30 Given the inherent risk of sudden death in patients with HCM and a somewhat higher risk in patients with significant LVOT obstruction and large septal mass,^5,12-15 there is some concern that alcohol ablation may create a scar in the septum that may be a future nidus for re-entry ventricular tachycardia. However, the limited data available to date has failed to find an increased risk of sudden death or ventricular tachycardia in such patients. Confounding the situation is the background level of sudden death in such patients, whether or not an ablative procedure was performed, making a causal relationship difficult to prove. In one series of EP studies after successful alcohol septal ablation, an increased rate of inducible VT was not found.^24,25 Given the significant benefits of alcohol septal ablation in LVH regression, alleviation of LV outflow obstruction, SAM and mitral regurgitation, resultant improvement in quality of life, and the less invasive nature with the avoidance of cardio-pulmonary bypass, it is likely that alcohol septal ablation procedures will continue to be a valid alternative to surgery in select patients. Whether a similar intracoronary ablative procedure may find its way into the EP lab, as a form of therapy for arrhythmic substrates unapproachable by conventional mapping techniques, remains to be seen.