Intracoronary Myocardial Contrast Echocardiography in a Patient with Drug Refractory Hypertrophic Obstructive Cardiomyopathy Rev

Case Study. A 49-year-old female was investigated for a 2-year history of dyspnea, angina on exertion, and exertional presyncope. Physical examination revealed a 2/6 mid-systolic murmur at rest, increasing in intensity to 3/6 following the Valsalva manoeuvre and assumption of the upright position. The echocardiogram showed asymmetric septal hypertrophy with the basal anterior septum measuring 18 mm with anterolateral wall extension. There was severe systolic anterior mitral valve motion (SAM), significant mitral regurgitation, and her pre-procedure echo showed a resting left ventricular outflow gradient. Left ventricular size and systolic function were normal. Cardiac catheterization demonstrated normal epicardial coronary arteries and a first septal artery that was 2 mm in diameter (Figure 1) and compressed in systole. Despite treatment with atenolol 75 mg daily, the patient remained symptomatic. After considering the different options for treatment she was referred for percutaneous septal ethanol ablation (SEA) in the catheterization laboratory. A 2 x 10 mm over-the-wire balloon was positioned and inflated in the target septal artery. Within 1 minute the LVOTG had decreased from 140 mmHg to 20 mmHg. The procedure was guided with myocardial contrast echocardiography (MCE), injecting 2 cc of contrast (Levovist® at 350 mg/mL) into the target septal artery through the balloon lumen. This revealed an extensive area of myocardium at risk which included the targeted basal septum at the region of the SAM-septal contact but also the basal and mid inferior wall with involvement of the posteromedial papillary muscle (Figure 2). In spite of an anticipated successful reduction in the LVOTG, the alcohol was not administered because of concerns that the resultant infarction would be too extensive with the additional risk of papillary muscle infarction and worsening of the patient’s mitral regurgitation. This case underscores the importance of MCE as a guide during septal ethanol ablation. Of 50 patients who have had SEA performed at our institution, this was the first occasion in which alcohol injection was aborted solely based on the MCE result. In other cases, MCE helped in targeting a different septal branch that was suitable for ablation. There are centers performing SEA without MCE guidance but this case illustrates the potential dangers of such an approach. How Would You Manage This Case? Michael P. Riley, MD, PhD and Joseph R. Carver, MD, FACC Cardiovascular Division of the Abramson Cancer Research Institute University of Pennsylvania, Philadelphia, Pennsylvania Alcohol septal ablation is increasingly used to treat hypertrophic obstructive cardiomyopathy (HCM).1 However, as the case presented demonstrates, this therapy is not uniformly applicable and can expose patients to significant risks. The authors utilized myocardial contrast echocardiography to identify a patient whose first septal perforator supplied an extensive area of myocardium, including a portion of the posteromedial papillary muscle. Inducing an infarction in this particular artery could easily lead to increased morbidity by causing significant papillary muscle dysfunction, exchanging dynamic outflow obstruction with potentially severe mitral regurgitation. We applaud the authors for appreciating the increased risks associated with alcohol septal ablation in this patient, for taking the added time to do pre-procedure contrast echocardiography and for pointing out the necessity of that study prior to injecting alcohol into a septal artery. However, we question whether she had truly reached the point of “medical failure” where this procedure was appropriate. Initial therapy for patients with HCM who have symptoms is pharmacotherapy with beta-blockers, non-dihydropyridine calcium channel blockers and disopyramide.2,3 Often, combinations of these agents are used and many patients require titration to high dosages of multiple agents to achieve symptom relief.3 Such guided pharmacotherapy is successful in alleviating symptoms in 1/3 to 1/2 of all patients.1–3 It is only after these medical therapies have failed to achieve symptom relief that non-pharmacotherapies be attempted. The authors state that the patient continued to have symptoms despite treatment with atenolol 75 mg daily. Clearly, there is substantial room for additional medical therapy that should have been tried prior to any procedure. The mortality rate associated with alcohol septal ablation for HCM ranges between 1–4% depending on the published series and is thought to depend heavily on the experience of the operator.1–3 The mortality risks as well as the published benefits to alcohol septal ablation appear to rival those of surgical myotomy/myomectomy in selected patients. However, the risk of complete heart block appears to be substantially increased with alcohol septal ablation compared with surgery and the risks of inducing a ventricular septal defect or a large anterior myocardial infarction with alcohol septal ablation are currently unknown.1–3 Surgery is required for those patients who need concomitant mitral valve surgery or who have other anatomic abnormalities that can only be approached surgically. Right ventricular pacing, with the goal of inducing asynchronous left ventricular contraction leading to minimization of the outflow tract obstruction, has been an alternative therapy for HCM.2,3 The success of pacing for HCM appears to be modest at best and the therapy should only be considered for patients intolerant of medical therapy who would otherwise require pacing or who are at particularly high risk to undergo surgery or alcohol septal ablation. In addition to therapies to address her outflow tract gradient and resultant symptoms, attention should be devoted to the other significant risk associated with HCM: sudden cardiac death (SCD).2 In terms of this patients risk for SCD, she is in a lower risk cohort by virtue of her age (> 35 years), maximal septal thickness (References 1. Kimmelstiel CD and Maron BJ. Role of percutaneous septal ablation in hypertrophic obstructive cardiomyopathy. Circulation 2004;109:452–456. 2. Braunwald E, Seidman CE, Sigwart U. Contemporary evaluation and management of hypertrophic cardiomyopathy. Circulation 2002;106:1312–1316. 3. Nishimura RA and Holmes DR Jr. Hypertrophic obstructive cardiomyopathy. N Engl J Med 2004;350:1320–1327. Kul Aggarwal, MD, MRCP (UK), FACC and Erskine A. James, MD University of Missouri-Columbia and Harry S. Truman Veterans Hospital Columbia, Missouri The case report by Monakier et al. describes the use of myocardial contrast echocardiography (MCE) to guide the treatment for septal ablation; in this case, aborting the procedure. The authors should be commended on the use of MCE to predict the potentially adverse outcome of the proposed procedure. This case helps elucidate the importance of MCE during septal ablations, as other work has also shown. Alcohol septal ablation was first described by Dr. Ulrich Sigwart.1 At that time, the occlusion balloon was used to determine the proper septals to target for ablation. The use of MCE has enabled more accurate targeting of the proper septal segment2 and improved assessment of the point of mitral valve contact and maximal flow acceleration. Two alternate approaches in this case would have been to (a) angiographically assess the size of the proposed septal branch to be ablated. As is evident from the angiographic image accompanying this case, there is an unusually large septal perforator coming off the left anterior descending coronary artery without any septal perforator of similar size, suggesting that this septal is supplying a large amount of myocardium; and (b) echocardiographically assess the acute effects of temporary balloon occlusion of the septal branch. In this case, it would have likely shown the extensive wall motion abnormality and probably also worsening of the mitral regurgitation with balloon occlusion. There is a large amount of individual variation in the size and myocardial distribution of the first septal perforator artery.3 We would have probably used a combination of the above two methods in decision making. The main consequence of alcohol septal ablation is myocardial injury and if the extent of such injury is extensive, the results could conceivably be deleterious. One of the main complications from alcohol septal ablation is the need for a permanent pacemaker post-procedure. While studies prior to MCE reported rates of pacemaker implantation of 17–38%, other studies reported reduction to less than 10% with the use of MCE4.5 In addition, MCE is able to identify the correct septal more readily which has decreased the number of septals that need to be injected with alcohol as well as the amount of alcohol injected.6 However, a recent report does suggest that a larger “infarct” is associated with improved therapeutic outcome.7 In conclusion, we agree that the use of MCE is a safe and effective way to aid in the procedure of alcohol septal ablations. Dr. Monakier and colleagues have re-emphasized this point by their description of an aborted procedure through the guidance of myocardial contrast echocardiography. Shahid Aziz, MRCP and David R. Ramsdale, MD The Cardiothoracic Centre Liverpool, United Kingdom This case illustrates the importance of using myocardial contrast echocardiography to localise the target area during percutaneous alcohol septal ablation. In the majority of cases, the first septal perforator artery is selectively infused with 100% alcohol resulting in a controlled infarction of the basal septum. Subsequent thinning and remodeling of the basal septum leads to a decrease in the left ventricular outflow tract gradient. The anatomical course and distribution of the septal perforator arteries is highly variable and up to 20% of patients may not have a septal artery that is suitable for alcohol ablation. The coronary anatomy demonstrated in this case is unusual with a septal artery supplying the inferior wall and the posteromedial papillary muscle. This region is normally supplied by the posterior descending artery, which in 85% of cases is a branch of the right coronary artery and in 15% of cases branches from the left circumflex artery. The posteromedial papillary muscle is vulnerable to ischaemia during inferior myocardial infarction and may undergo rupture resulting in severe mitral regurgitation. The anterolateral papillary muscle is more resistant to ischaemia having a dual blood supply from both the left anterior descending and the left circumflex arteries. However, even if the posteromedial papillary muscle was found to have a dual blood supply, since alcohol ablation acts by causing direct cell death, the safer option would be surgical septal myectomy.

1. Sigwart U. Non-surgical myocardial reduction for hypertrophic obstructive cardiomyopathy. Lancet 1995;346:211–214. 2. Martin WA and Sigwart U. Who and how to treat with non-surgical myocardial reduction therapy in hypertrophic cardiomyopathy: Long-term outcomes. Heart Fail Monit 2002;3:15–27. 3. Singh M, Edwards WD, Holmes DR Jr, et al. Anatomy of the first septal perforating artery: A study with implications for ablation therapy for hypertrophic cardiomyopathy. Mayo Clin Proc 2001;76:799–802. 4. Faber L, Ziemssen P, Seggewiss H. Targeting percutaneous transluminal septal ablation for hypertrophic obstructive cardiomyopathy by intraprocedural echocardiographic monitoring. J Am Soc Echo 2000;13:1074–1079. 5. Faber L, Seggewiss H, Gleichmann U. Percutaneous transluminal septal myocardial ablation in hypertrophic obstructive cardiomyopathy: Results with respect to intraprocedural myocardial contrast echocardiography. Circulation 1998;98:2415–2421. 6. Lakkis NM, Nagueh SF, Kleiman NS, et al. Echocardiography-guided ethanol septal reduction for hypertrophic obstructive cardiomyopathy. Circulation 1998;98:17501755. 7. Chang SM, Lakkis NM, Franklin J, et al. Predictors of outcome after alcohol septal ablation therapy in patients with hypertrophic obstructive cardiomyopathy. Circulation 2004;109:824–827.