Alcohol septal ablation for obstructive hypertrophic cardiomyopathy Steggerda, Robbert

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1 University of Groningen Alcohol septal ablation for obstructive hypertrophic cardiomyopathy Steggerda, Robbert IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2015 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Steggerda, R. (2015). Alcohol septal ablation for obstructive hypertrophic cardiomyopathy [Groningen]: University of Groningen Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date:

2 ! Chapter 1 General introduction Objectives of the thesis! 9

3 Chapter!1! Obstructive hypertrophic cardiomyopathy Hypertrophic cardiomyopathy (HCM) is characterised by hypertrophy of the left ventricle (LV) in the absence of abnormal loading conditions (pressure overload). It is a genetic disease caused by mutations in genes encoding components of the sarcomere. It is the most common form of cardiomyopathy with a prevalence of 1:500 in the European population (1,2), a figure that is fairly constant worldwide. On the one hand, it is generally a relatively benign disease associated with a good life expectancy, with an overall mortality rate averaging 1%/year (3-5). On the other hand, HCM can be associated with symptoms of heart failure and atrial fibrillation, and selected patient groups have a higher mortality rate averaging 5%/year (3,6). Around a third of all patients with HCM do not have obstruction of the left ventricular outflow tract (LVOT). However, these patients may have symptoms of heart failure due to diastolic dysfunction (seen in 10-20% of this group) or, less commonly, due to end-stage heart failure with systolic dysfunction (3%) (4-8). Around two thirds of patients with HCM do have obstruction of flow in the LVOT, which can also cause symptoms of heart failure and is a predictor of cardiovascular death (9). The obstruction of flow is due to a thickened septum and to systolic anterior motion (SAM) of the mitral valve leaflet. This causes obstruction and a dynamic gradient over the LVOT with a characteristic dagger-shaped Doppler flow pattern (10). Invasive treatment of this particular group of HCM patients with LVOT obstruction was investigated in the present thesis. Obstruction of flow in patients with hypertrophic cardiomyopathy A pressure gradient measured in the LVOT in the absence of a clear anatomic site of obstruction was first recognised in the late 1950s and was attributed to massive left ventricular hypertrophy (11-13). A long debate followed on whether these gradients were actually caused by obstruction or not. The hypothesis put forward by Criley, the main opponent in this debate, was that rapid ejection itself causes the pressure gradients and subsequent SAM of the anterior mitral valve leaflet. The increased ejection fraction and ventricular emptying that is seen in patients with a dynamic gradient was according to Criley very different to that seen in aortic stenosis, where ventricular emptying is hindered and reduced. This increased ejection fraction, rapid ejection and consequent gradient should therefore not be seen as a cause of symptoms of heart failure but as a mere consequence of the diseased hypertrophic myocardium itself. Thus, according to Criley s hypothesis, reducing the gradient using myectomy is not a correct form of treatment, and research should instead focus on the investigation and treatment of the underlying causes of the diseased hypertrophic 10!!

4 ! General!Introduction! myocardium. According to Criley s hypothesis, symptoms of heart failure were merely due to diastolic dysfunction, and the positive effect of beta blockers on symptom improvement were due to improved relaxation and diastolic filling of the left ventricle and not to gradient reduction (14-15). This discussion continued until the mid-1980s (16-17). However, the positive outcomes of surgical myectomy which alleviated symptoms and abolished the gradient together with data from results of echocardiography studies led to the belief that obstruction of flow in hypertrophic cardiomyopathy does by itself lead to symptoms of heart failure. According to current guidelines, the first line of treatment for patients with a symptomatic obstructive hypertrophic cardiomyopathy is medical treatment (18). Indeed, the negative chronotropic and inotropic effects of beta blockers, disopyramide or calcium antagonists have the potential to improve symptoms and reduce outflow tract obstruction. When medical treatment fails to reduce symptoms and outflow tract obstruction, invasive septum reduction therapy is indicated (18). Development of and improvements to surgical myectomy The first surgical myectomy procedures were performed in the 1960s and published by Morrow et al (19). Subsequent results that were presented in the 1980s showed improvement of symptoms in 70% and abolition of the gradient in 98% of the patients, though with a periprocedural mortality rate of % (20,21). Patients undergoing surgical myectomy were operated on during cardiopulmonary bypass under mild hypothermia (30 C). A vertical incision in the aorta was made towards the noncoronary sinus. The left coronary artery was continuously perfused through a cannula supplying oxygenated blood from the arterial return line of the heart-lung machine. The surgeon was thus able to palpate the protruding ventricular mass obstructing the outflow tract via the aortic valve. This palpable mass was then resected using two parallel incisions and a part of the muscle between these lines was then removed. Afterwards, the channel thus obtained was palpated by the surgeon for evaluation of the procedure and for removal of any particulate matter. The aortotomy was closed while the patient s temperature was restored to normal (19,22). Many changes to this procedure have since been introduced, such as improvement of cardiopulmonary bypass, cardioplegia, a more extended resection of the protruding ventricular mass, and the use of periprocedural transesophegal echocardiography (TEE) for the evaluation of the procedure (23). Other improvements are the extended myectomy and the combination with mitral valvular plasty when necessary (24).! 11!

5 Chapter!1! Development of and improvements to the alcohol septal ablation procedure The concept and development of the alcohol septal ablation procedure was based firstly on the finding of a gradient reduction during temporary balloon occlusion of the first septal branch, and secondly on the idea that injection of alcohol in the first septal branch could cause a scar in the basal septum with a permanent reduction of the gradient. The basal part of the septum would become thinner due to the scar and thus the outflow tract would widen, thereby abolishing both SAM and the obstructive gradient. The extensive experience that had been gained with transcoronary injection of ethanol for treatment of cardiac arrhythmia made the practical development of ASA possible. The first descriptions of ASA were published by Gietzen et al in 1994 (25-27). The procedure was initially performed by cannulating the first septal branch with a guidewire. A balloon was placed in the first septal branch and then inflated in order to induce temporary ischaemia (Figures 1A and 1B). 12!!

6 ! General!Introduction! Figure 1. Coronary angiograns and pressure recordings obtained during alcohol septal ablation. A: Coronary angiogram of the left coronary artery, with the white arrow indicating the first septal branch. B: The same view of the left coronary artery after cannulation and inflation of an over-the-wire balloon in the first septal branch (indicated by the white arrow). Contrast is injected to evaluate complete closure of the septal branch by the balloon. C: Pressure recordings in the left ventricle and aorta before balloon occlusion, showing a gradient of 65 mmhg. D: After balloon occlusion the pressure drops and the gradient disappears.!! A B C D!!! 13!

7 Chapter!1! Simultaneous pressure recording using a catheter in the left ventricle and the aorta was used to observe a reduction of at least 30% of the gradient (Figure 1C and D). In cases where the gradient did not drop, the next septal branch would be cannulated and pressure recordings repeated. When a pressure drop was found, the balloon was left inflated and 96% ethanol (average volume 4-6 ml) would be injected in order to induce a sustained reduction of the gradient. The potential risk of ventricular rhythm disturbances was recognised from the inception of the ASA procedure. An extensive study was published in 1999 by Gietzen et al. that included electrophysiological testing and a pathoanatomical study (28). Early reports of periprocedural mortality after ASA that came from this study were 4% in 62 patients, and permanent pacemaker implantation was necessary in 38% of all patients. However, electrophysiological induction of sustained ventricular tachycardia (VT) occurred only in 2.6% of patients after the ASA procedure. This was much lower than the 20-34% of patients reported to have inducible sustained VT seen after myocardial infarction (29). This gave good hope that the incidence of VT after ASA would be much lower than the incidence of VT seen after myocardial infarction. The pathology results of the deceased patients also showed that the histological pattern of the alcohol-induced scar was different to the histopathology of scarred tissue after myocardial infarction. A well-defined area of circular necrosis around the occluded septal branch with small protrusions, characterised by a homogeneous necrosis with contracted fibres encircled by a sharply demarcated scar was thus seen in deceased ASA patients (29). This was thought to be the reason why patients who have undergone ASA are much less susceptible to the induction of VT. The ASA procedure was improved after the introduction of myocardial contrast echocardiography (MCE) for determining the correct site of myocardial infarction, leading to a reduction in complications and an increase in success rate (30). Other improvements to the technique were the use of decreasing amounts of alcohol over time and slower injection of alcohol instead of a bolus (31,32). Since then, many studies have been published that have shown improved results both in the short and long term. 14!!

8 ! General!Introduction! Objectives of the current thesis Since the introduction of ASA as an alternative to surgical myectomy, the question has arisen regarding which treatment option is the preferred treatment. Does ASA yield the same results as myectomy in terms of gradient reduction, symptomatic improvement, risk of complications and long-term results? In the current thesis, ASA was therefore investigated in depth and compared with myectomy. Chapter 2 describes the aetiology, pathophysiology, genetics, and clinical course and management of hypertrophic cardiomyopathy. Chapter 3.1 describes how septal coronary anatomy can limit the interventional cardiologist to perform a successful procedure. In Chapter 3.2 the characteristics of septal coronary anatomy and its relation to residual gradients after the infarction is investigated. In Chapter 4, the relationship between the size and location of the septal infarction after ASA is investigated using cardiac magnetic resonance imaging (CMR). In Chapter 5, the effect of a larger-sized infarction and larger amounts of alcohol on outcome and increased risk of ventricular arrhythmia after ASA are investigated. The ASA procedure is considered by some as being less safe than surgical myectomy. Chapter 6 therefore focuses on periprocedural complications and long-term outcome in a single-centre study. Survival, cardiac death, symptomatic improvement and gradients are also investigated in Chapter 7, which describes a multi-centre study that compared myectomy and ASA. American guidelines state that ASA is mainly an option for the elderly. This notion is addressed in Chapter 8, which compares periprocedural complications and long-term outcome between younger and older age groups. Using data from the European database for ASA which contains data from ten European centres Chapter 9 further investigates complications and survival, including the effect of residual obstruction on survival. Finally, the data are discussed (Chapter 10) and summarised (Chapter 11). In particular, the practical implications in terms of the technical aspects of the procedure and the potential impact on the current guidelines are discussed.! 15!

9 Chapter!1! Reference list: 1. Richard P, Charron P, Carrier L et al. Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy. Circulation 2003; 107: Elliott PM, Gimeno B jr, Mahon NG et al. Relation between severity of left ventricular hypertrophy and prognosis in patients with hypertrophic cardiomyopathy. 3.Maron BJ, Maron MS. Hypertrophic cardiomyoptahy. Lancet 2013; 381: Maron BJ, Casey SA, Hauser RG, Aeppli DM. Clinical course of hypertrophic cardiomyopathy with survival to advanced age. J Am Coll Cardiol 2003; 42: Wigle ED, Rakowski H, Kimball BP, Williams WG. Hypertrophic cardiomyopathy: clinical spectrum and treatment. Circulation 1995; 92: Elliott PM, Poloniecki J, Dickie S, et al. Sudden death in hypertrophic cardiomyopathy: identification of high risk patients. J Am Coll Cardiol 2000; 36: !Olivotto I1, Maron MS, Adabag AS, Casey SA, Vargiu D, Link MS, Udelson JE, Cecchi F, Maron BJ. Gender realted differences in the clinical presentation and outcome of hypertrophic cardiomyoapthy. J Am Coll Cardiol 2005; 46: Spirito P, Seidman CE, McKenna WJ, Maron BJ. The management of hypertrophic of hypertrophic cardiomyopathy. N Engl J Med 1997;336: Harris KM, Spirito P, Maron MS et al. Prevalence, clinical profile, and significance of left ventricular remodeling in the end-stage phase of hypertrophic cardiomyopathy. Circulation 2006; 114: !Maron MS, Olivotto I, Betocchi S, Casey SA, Lesser JR, Losi MA, Cecchi F, Maron BJ. Effect of left ventricular outflow tract obstruction on clinical outcome in hypertrophic cardiomyopathy. N Engl J Med Jan 23;348(4): ten Berg J, Robbert C Steggerda!RC, Siebelink!HMJ. Myocardial disease: the patient with hypertrophic cardiomyopathy. Heart 2010; 96: Brock RC. Functional obstruction of the left ventricle (aquired aortic subvalvular stenosis). Guys Hosp Rep 1957; 106: Teare D. Asymmetrical hypertrophy of the heart in young adults. R Heart J 1958; 20: Morrow AG, Braunwald E. Functional aortic stenosis. A malformation characterized by resistance to left ventricular outflow tract obstruction. Circulation 1959; 20: Criley JM, Kenneth BL, White RI, Ross RS. Pressure gradient without stenosis. a new concept of Hypertrophic subaortic stenosis. Circulation 1965; 32: !!

10 ! General!Introduction! 15.Criley JM, Siegel RJ. Has obstruction hindered our understanding of hypertrophic cardiomyopathy? 1985; 72(6): Murgo JP, Alter BR, Dorethy JF, Altobelli SA, McGranahan GM Jr. Dynamics of left ventricular ejection in obstructive and non-obstructive hypertrophic cardiomyopathy. J Clin Invest 1980; 66: Jenni R, Ruffmann K, Vieli A, Anliker M, Krayenbuchl HP. Dynamics of aortic flow in hypertrophic cardiomyopathy. Eur Heart J 1985; 6: Elliott PM, Anastasakis A, Borger MA, et al ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy. European Heart J 2014; 35: Morrow AG, Lambrew CT, Braunwald E. Idiopathic hypertrophic subaortic stenosis II. Operative treatment and the results of pre- and postoperative hemodynamic evaluations. Circulation 1964; 29:supl4: Maron BJ, Epstein SE, Morrow AG. Symptomatic status and prognosis of patients after operation for hypertrophic obstructive cardiomyopathy: efficacy of ventricular septal myotomy and myectomy. European Heart J 1983; supplf: Bircks W, Schulte HD. Surgical treatment of hypertrophic obstructive cardiomyopathy with special reference to complications and to atypical hypertrophic obstructive cardiomyopathy. Eur Heart J 1983; supplf: Morrow AG, Fogarty TJ, Hannah III H, Braunwald E. Operative treatment in idiopathic hypertrophic subaortic stenosis. Circulation 1968; 38: Schoendube FA, Klues HG, Reith S, Flachskampf FA, Hanrath P, Messmer BJ. Long-term Clinical and echocardiographic follow-up after surgical correction of hypertrophic obstructive cardiomyopathy with extended myectomy and reconstruction of the subvalvular mitral apparatus. Circulation 1995; 95: Swistel DG, Balaram SK. Surgical myectomy for hypertrophic cardiomyopathy in the 21st century, the evloution of the RPR repair: resection, plication and release. Progress in cardiovascular disease 2012; 54: Gietzen F, Leuner Ch, Gerenkamp T, Kuhn H. Relief of obstruction in hypertrophic cardiomyopathy by transient occlusion of the first septal branch of the left coronary artery. Eur Heart J 1994; 15: Kuhn H, Gietzen F, Leuner Ch, Gerenkamp T. Induction of subaortic septal ischemia to reduce obstruction in hypertrophic obstructive cardiomyopathy. Studies to develop a new cathter-based concept of tretmant. Eur Heart J 1997; 18: ! 17!

11 Chapter!1! 27.Kay GN, Epstein AE, Bubien RS et al. Intracoronary ethanol ablation for the treatment of recurrent sustained ventricular tachycardia. J Am Coll Cardiol 1992; 19: Gietzen FH, Leuner CJ, Raute-Kreinsen U, Dellman A, Hegselmann J, Strunk-Mueller C, Kuhn HJ. Acute and long-term results after transcoronary ablation of septal hypertrophy (TASH). catheter interventional treatment for hypertrophic obstructive cardiomyopathy. Eur. Heart J 1999; 20: Denniss AR, Richard DA, Cody DV et al. Prognostic significance of ventricular tachycardia and fibrillation induced at programmed stimulation and delayed potentials detected on the signal-averaged electrocardiograms of survivors of acute myocardial infarction. Circulation 1986; 74: Faber L, Seggewiss H, Welge D, Fassbender D, Schmidt HK, Gleichmann U, Horstkotte D. Echo-guided percutaneous septal ablation for symptomatic hypertrophic obstructive cardiomyopathy: 7 years of experience. Eur J Echocardiography 2004; 5: Veselka J, Tomašov P, Zemánek D. Long-term effects of varying alcohol dosing in percutaneous septal ablation for obstructive hypertrophic cardiomyopathy: A randomised study with a follow-up up to 11 years. Can J Cardiology 2011; 27: Su Min Chang, MD, Sherif F. Nagueh, MD, William H. Spencer, III, MD, Nasser M. Lakkis, MD. Complete Heart Block: Determinants and Clinical Impact in Patients With Hypertrophic Obstructive Cardiomyopathy Undergoing Nonsurgical Septal Reduction Therapy J Am Coll Cardiol 2003;42: !!