Case Report and Brief Review

Ethanol Septal Ablation for Refractory Ventricular Tachycardia

Ravi K. Ramana, DO, David J. Wilber, MD, Ferdinand Leya, MD
Ravi K. Ramana, DO, David J. Wilber, MD, Ferdinand Leya, MD

Case Study. A 56-year-old male with severe nonischemic cardiomyopathy and recurrent ventricular tachycardia (VT) presented to our cardiology clinic with complaints of intermittent palpitations and several implantable cardioverter defibrillator (ICD) shocks earlier that same day. He stated that the episodes of palpitations were associated with lightheadedness, but no frank syncope. Interrogation of his pacemaker-defibrillator showed a recording of five episodes of sustained monomorphic VT, with rates near 150 bpm (cycle length 410 msec), which responded to anti-tachycardic pacing (ATP), and two additional episodes which required defibrillation. Therefore, he was admitted for further therapy to attenuate these tachyarrhythymias.
Eight years prior to this admission, this patient was diagnosed with nonischemic cardiomyopathy with sustained VT. At that time, he underwent implantation of a dual-chamber pacemaker-defibrillator. Because of frequent ICD therapies, heunderwent electrophysiologic testing, which localized the tachycardia to a superior mid-septum focus. However, attempts to use radiofrequency ablation (RFA) from both the right and left sides of the septum were unsuccessful.
Because of continued ICD therapies, and despite multiple combinations of anti-arrhythmic medications, including amiodarone, a second ablation procedure was performed 4 months later (6 months prior to this admission). Percutaneous epicardial mapping was performed, which again localized the tachycardia to the superior mid-septum (Figures 1 A and B) between the second and third septal perforator arteries (SP) (noted via a concomitant coronary angiogram). However, epicardial RFA was not successful. We concluded that the central area for maintaining VT was in the deep septum, not amenable to standard endocardial or epicardial radiofrequency ablation. Subsequently, he was referred for evaluation for heart transplantation and was listed for orthotopic heart transplantation after appropriate evaluation.
Over the 3 weeks prior to this admission, the patient had reported increasing fatigue and recurrence of his palpitations and ICD shocks. Otherwise, he had no complaints of recent angina, dyspnea, weight gain, edema or orthopnea. He denied any recent fevers, chills, cough, dysuria or diarrhea. Upon admission to our hospital, physical exam revealed minimal jugular venous
distention and trace pretibial edema. He had a regular cardiac rhythm with a third heart sound but no appreciable murmur. His lungs were clear to auscultation. Hematologic and metabolic laboratory studies were unremarkable. His BNP was 338 pg/mL. A twelve-lead surface electrocardiogram revealed sequential A-V pacing, and a chest radiograph showed no evidence of pulmonary edema, pleural effusion or infiltrate. A transthoracic echocardiogram revealed a dilated left ventricle with severely depressed left ventricular systolic function (ejection fraction 0.20). He was then started on continuous intravenous lidocaine to suppress his arrhythmia.
The patient underwent diagnostic angiography to evaluate his coronary artery system, and multiple septal perforator arteries (SP) were identified. No distal collateral runoff was noted between the SP and the posterior descending artery (PDA). At this time, a Pathfinder mapping catheter (Cardima, Inc., Fremont, California) was advanced into the left anterior descending artery (Figure 2), and pace-mapping was performed. Evaluation of these pace-maps confirmed the patient’s VT focus to lie in the distribution between the 2nd, 3rd and 4th SP. ESA was then performed using a 2 mm PTCA balloon to completely occlude the origin of the 2nd SP in order to inject 1 cc of absolute ethanol to obliterate the vessel. Following the ESA of the 2nd SP, the
patient’s clinical VT still remained easily inducible. Therefore, the 3rd and 4th SP were sequentially isolated and infused with ethanol. The occluding balloon remained inflated for 10 minutes after each ethanol injection. A total of 3 cc of 100% ethanol was slowly injected into the selected vessels. The postprocedural coronary angiogram revealed normal blood flow in the left anterior descending artery, 1st and 5th SP, right coronary artery, and posterior descending arteries. The 2nd, 3rd and 4th SP were totally obliterated (Figure 3). Following the final ethanol infusion, we were unable to reinduce his preprocedural, clinical VT by rapid right ventricular pacing. A postprocedural transthoracic echocardiogram revealed an akinetic and hyperechoic mid-intraventricular septum, findings consistent with ethanol-induced necrosis of the mid-septum.
The first 48 hours following the procedure were uneventful, and only self-terminating, slow, nonsustained VT (105 bpm)
was evident on telemetry (Figure 4). Following the procedure, the patient’s peak CK and troponin were 628 IU/L and 23.1 ng/mL, respectively. On the third postprocedural day, he reported dyspnea and worsening orthopnea with evidence of increasing congestive heart failure. A repeat echocardiogram revealed an ejection fraction of 0.15. On the 5th postprocedural day, a compatible donor heart became available, and the patient underwent orthotopic heart transplantation without any immediate complications. The patient’s postoperative course was uneventful, and he was discharged home in stable condition on standard post-transplantation medication 9 days after the transplantation.
Pathologic and histologic examination of the explanted heart revealed a near-transmural dense infarction, dense infiltration
of polymorphonuclear leukocytes with central necrosis in the anterior to apical intraventricular septum, and a minimal layer of surviving subendocardium (Figures 5 A–D). Also, there was complete disruption of the arterial wall integrity of the SP that was injected (Figures 6A and B).

Discussion. Patients with severe cardiomyopathy have an increased risk of ventricular arrhythmias and sudden death. Over the past 10 years, there have been considerable advancements in the treatment of preventing these arrhythmias with anti-arrhythmic medications including beta-blockers, amiodarone, sotalol and dofetilide. Acute life-saving therapy for hemodynamically significant ventricular tachycardia, ventricular fibrillation or sudden cardiac death can be provided by an ICD. Lastly, patients with refractory VT can undergo radiofrequency catheter ablation techniques in attempts to extinguish the foci. However, in a small subset of patients, these medications, devices and procedures are not sufficient to maintain survival and an adequate quality of life. Therefore, more extreme therapeutic measures need be taken, including possible alcohol ablation techniques.
The feasibility to ablate ventricular tachycardia foci via myocardial necrosis induced by chemical agents injected into selected arteries was first demonstrated in 1987. Inoue et al injected aconitine solution in the left ventricular wall to induce localized ventricular tachycardia in 59 anesthetized dogs. Subsequently, phenol or ethyl alcohol was injected into the coronary artery that supplied that area of myocardium. In over three-fourths of the subjects, the VT was eliminated. Histologic evaluation revealed transmural myocardial necrosis (85% of subjects), with occasional intra-arterial fibrin deposition and adventitial hemorrhage.1
Following initial animal model studies, studies involving human patients with refractory VT demonstrated that persistent VTs could be terminated by transient occlusion of the blood flow supplying the arrhythmogenic area2 or via intracoronary administration of an antiarrhythmic medication to the site of origin of VT.3 In 1989, Brugada et al clearly demonstrated that it was possible to identify, catheterize and infuse sterile ethanol into small coronary arteries and therefore ablate the myocardium, including the site of origin of incessant VT, in post-myocardial infarction patients.4 Two additional studies demonstrated similar efficacy with infusing ethanol into targeted coronary arteries in 23 patients with paroxysmal VT.5,6
Although the data suggest promising immediate results, other studies report a 20% recurrence rate of inducible VT in patients who underwent ESA.5,7 Complications from ESA include complete AV block, reflux of ethanol into another coronary artery8 causing diffuse myocardial necrosis, variable lesion infarct size, a possible heterogenous necrotic lesion leading to new arrhythmogenicity, progressive congestive heart failure or cardiogenic shock due to the “therapeutic infarction”.8,9 Further studies investigating the possible role of chemical ablation in arrhythmogenic patients have been completed, including assessing its efficacy for AV nodal ablation,10 using the coronary veins as the conduit for the chemical agents (as opposed to the coronary arteries),11 and the feasibility of infusing lidocaine to reversibly stun possible ablation target foci, followed by ESA to create permanent lesions.12
In our case, it seems that ESA was successful in terminating the patient’s clinical VT, which had required ATP and defibrillation. However, the loss of the septum’s contribution to systolic function likely resulted in a further decline in left ventricular function and decompensated heart failure. Fortunately, the patient underwent successful heart transplantation soon thereafter.
In addition, the explanted heart has given us interesting insight into the acute pathologic and histologic consequences of ESA. Despite the growing depth of literature regarding ESA for refractory VT, there is very little pathologic information directly available from human studies: one case report described the pathologic and histologic postmortem findings 5 days following the procedure.5 In comparison, our patient’s native heart was examined after heart transplantation 5 days following the ESA procedure. Based on a review of the literature, ours is only the second case (first case that is not postmortem) that reveals the acute pathologic and histologic effects of ESA for the treatment of refractory VT. Similar findings of near-transmural infarction and necrosis were identified in both specimens.
In conclusion, ESA is a possible “final” therapeutic option for patients with VT resistant to standard medical, pacemaker and VTRFA techniques. However, ESA for the treatment of refractory VT, should be performed only at medical institutions with highly skilled interventional cardiologists, electrophysiologists, heart failure specialists and on-site surgical backup (for possible ventricular assist device insertion).

Acknowledgment. We would like to thank Drs. Brian Long, Pranab Das and Adam Shapira for their assistance and review of this manuscript, and Dr. Horea Baila for the preparation of the pathologic slides for this manuscript.

 

 

 

 

 

 

 

 

References

References

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