Ablative therapy has been a staple of electrophysiology for years and a major treatment modality for various rhythm disorders. Indeed, the advent of radiofrequency ablative therapy has ushered in a plethora of curative solutions for some of the most complex rhythm disorders, including atrial fibrillation and flutter, AV nodal re-entrant tachycardia, accessory pathway mediated reciprocating tachycardia, and most recently, ventricular tachycardia. Over the past few years, a novel form of ablation that utilizes 98% ethanol has been utilized in the cardiac catheterization laboratory to treat severely symptomatic patients with hypertrophic obstructive cardiomyopathy. Performed by interventional cardiologists, the technique has become an increasingly utilized method to improve quality of life in these debilitated patients.

Figure 1.

The electrocardiogram reveals normal sinus rhythm with left ventricular hypertrophy, left atrial enlargement and Q waves in leads II, III and aVF.

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.

Figure 2.

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.

       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).

Figure 3.

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.

       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.

Ablation of Another Sort

-by Todd J. Cohen, MD As electrophysiologists, we believe we rule the world on ablation — catheter ablation, that is! However, interventionalists such as Dr. Naidu can perform ablations of “another sort.” Any time a doctor destroys, fulgurates, infarcts, and/or kills tissue, they are performing an ablation. In Dr. Naidu’s case report of a patient with hypertrophic cardiomyopathy, ethanol is utilized to infarct the ventricular septum and improve the patient's outflow tract gradient. This approach has some similarities to the percutaneous ablative approach that we electrophysiologists now use routinely for treating arrhythmias. Both ventricular arrhythmias and severe ventricular septal hypertrophy were treated by surgical resection. Percutaneous approaches by both the electrophysiologists and the interventionalists have been refined and are now useful “ablative procedures” in treating arrhythmias and hypertrophic cardiomyopathy, respectively. I hope the readers appreciate this “ablation of another sort” appearing in EP Lab Digest.

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 (<50 years) and those with concomitant cardiac abnormalities (coronary or valvular disease) necessitating cardiac surgery in the near future are preferentially referred for surgery, while older patients and those with significant co-morbidities may opt for the less invasive alcohol ablative procedure. Patient and physician preference along with anatomy of the hypertrophic septum are also taken into account while considering treatment options.
       A study of ASA in 219 HOCM patients by Spencer et al at Baylor College of Medicine and The Medical University of South Carolina showed a marked reduction in their LVOT gradients from 56 mmHg to 7 mmHg to 1 mmHg to 1 mmHg to 0 mmHg at baseline 1, 2, 3 and 4 years, respectively. These patients also demonstrated a significant symptomatic improvement from a NYHA class 2.7 + 0.5 to 0.2 + 0.4 in 3 years, and their mean exercise time (Bruce) increased from 330 seconds at baseline to 420 seconds at two years. This study demonstrated an average decrease of 6% in left ventricular mass after ASA. At long-term follow-up, 88% of patients were asymptomatic, 10% were improved but still symptomatic, and 2% were unimproved.
       From an electrophysiologic standpoint, there are two concerns in patients who receive invasive (surgical or percutaneous) management. First is the development of conduction disease requiring a permanent pacemaker; second is the theoretic potential for pro-arrhythmia from scar tissue in patients who receive the ablative procedure. Both surgical myectomy and alcohol septal ablation affect the conduction system. Using pre- and post-procedure cardiac MR imaging, Valeti et al tried to explain the difference in variability of conduction disease resulting after surgical myectomy/ASA based on the anatomy of the resected/ablated septum. The left bundle branch courses along the anterior inter-ventricular septum. Septal myectomy usually involves the resection of a small portion of the anterior septum (from the endocardium to mid septum) at its region of contact with the anterior mitral valve leaflet. This results in LBBB in about 36–46% of patients undergoing septal myectomy.^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, <1% in the absence of a pre-existing RBBB. Based on a recent study by Lawrenz et al, measuring the changes in intra-cardiac conduction in patients during ASA by simultaneously recording electrophysiological parameters improves the safety of ASA by identifying patients who are at risk to develop CHB after ASA.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.