- Email: [email protected]
Outcome of Septal Myectomy for Obstructive Hypertrophic Cardiomyopathy in Children and Young Adults
Outcome of Septal Myectomy for Obstructive Hypertrophic Cardiomyopathy in Children and Young Adults
Departments of Surgery-Division of Cardiovascular Surgery, Pediatrics-Division of Pediatric Cardiology, Medicine-Division of Cardiovascular Diseases, Biomedical Statistics and Informatics, and Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota
Background. Obstructive hypertrophic cardiomyopathy (HCM) is an important cause of heart failure in children, but there are limited data addressing outcome of myectomy in children. Our objective was to evaluate the early and late results of septal myectomy in pediatric HCM. Methods. We reviewed 127 consecutive patients (62% male) who underwent transaortic septal myectomy for obstructive HCM from January 1975 to December 2010 at 21 or less years of age. Mean age at operation was 12.9 ⴞ 5.5 years. Preoperatively, mean maximum instantaneous gradient was 89 mm Hg and 95% had significant systolic anterior motion (SAM) with mitral regurgitation (MR). Implantable cardioverter defibrillator (ICD) and permanent pacemaker prior to surgery was present in 21 patients (17%) and 15 (11.7%), respectively. Results. Transaortic extended left ventricular septal myectomy was performed in all patients with no early deaths. Iatrogenic morbidity included new aortic valve regurgitation requiring repair in 7 (5.5%), mitral regurgitation needing repair in 2 (1.5%), ventricular septal defect in 1 (1%), and heart block requiring permanent pacemaker in 1 (1%). An ICD was implanted postoperatively in 8 during the same hospital admission. Mean MIG
decreased from 89 to 6 mm Hg (p < 0.0001). Postoperatively, residual chordal SAM was present in 23% with mild or no MR; moderate MR was detected in 1 patient. Four patients (3%) died late during the mean follow-up period of 8.3 years (maximum, 37 years); 1 death was sudden. Overall survival was 98.6%, 94.9%, 92.4%, and 92.4% at 5, 10, 15, and 20 years, respectively. Freedom from any cardiac reoperation was 91.2%, 87.8%, 78.7%, and 72.7% at 5, 10, 15, and 20 years, respectively. Repeat septal myectomy was performed in 6 patients (5%). At late follow-up, 95% were in New York Heart Association functional class I or II and 25 patients underwent late ICD placement. Conclusions. Septal myectomy is safe and effective in children with obstructive HCM, but limited exposure may increase risk of aortic or mitral valve injury. Late survival is better than the previously published untreated natural history of HCM. Patient selection and surgical expertise remain critical components of septal myectomy, especially before considering a prophylactic myectomy in a seemingly asymptomatic patient.
H
Diversity in symptomatology and clinical presentation varies from asymptomatic disease to severe life limiting symptoms of angina, dyspnea, syncope, or even sudden cardiac death (SCD). Pathophysiologic mechanisms responsible for symptoms in HCM include left ventricular outflow tract (LVOT) obstruction, mitral regurgitation (MR), systolic anterior motion (SAM) of mitral leaflets, ventricular diastolic dysfunction, and ventricular arrhythmias. Children with HCM are usually asymptomatic and the overall annual mortality for pediatric HCM beyond the first year of life is 1%. However, symptomatic HCM and HCM-triggered SCD can occur in childhood [3]. The disease progression with late sequela that may include heart failure is related directly to the dynamic LVOT obstruction, which is the main target of pharmacotherapy
ypertrophic cardiomyopathy (HCM) is viewed generally as an inherited autosomal dominant disorder often caused by mutations in genes that encode critical cardiac myofilaments; mutation positive is often referred to as sarcomeric HCM [1]. Hypertrophic cardiomyopathy occurs in 1 of 500 adults, and is considered to be one of the most common causes of sudden death in young people who are less than 35 years of age [2]. The phenotypic expression of this genetic disorder is characterized by myocardial cellular hypertrophy, which involves primarily the interventricular septum.
Accepted for publication Aug 1, 2012. Presented at the Forty-eighth Annual Meeting of The Society of Thoracic Surgeons, Fort Lauderdale, FL, Jan 28 –Feb 1, 2012. Address correspondence to Dr Dearani, Mayo Clinic, 200 First St SW, Rochester, Minnesota 55905; e-mail: [email protected].
© 2013 by The Society of Thoracic Surgeons Published by Elsevier Inc
(Ann Thorac Surg 2013;95:663–9) © 2013 by The Society of Thoracic Surgeons
0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2012.08.011
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Salah E. Altarabsheh, MD, Joseph A. Dearani, MD, Harold M. Burkhart, MD, Hartzell V. Schaff, MD, Salil V. Deo, MBBS, MS, Benjamin W. Eidem, MD, Steve R. Ommen, MD, Zhuo Li, MS, and Michael J. Ackerman, MD
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Abbreviations and Acronyms HCM ⫽ hypertrophic cardiomyopathy ICD ⫽ implantable cardiac defibrillator LVOT ⫽ left ventricular outflow tract MR ⫽ mitral regurgitation MVR ⫽ mitral valve replacement NYHA ⫽ New York Heart Association PPM ⫽ permanent pacemaker SAM ⫽ systolic anterior motion SCD ⫽ sudden cardiac death TEE ⫽ transesophageal echocardiogram CONGENITAL HEART
and septal reduction therapies [1]. Left ventricular septal myectomy is the standard therapeutic option for patients with LVOT obstruction and associated MR whose symptoms are refractory to pharmacotherapy [1]. While alcohol septal ablation is an alternative septal reduction therapy in selected adults, it is not indicated in children and young adults [1]. Prior published reports showed the effectiveness in the short and intermediate term of septal myectomy in the pediatric age groups [4]. Our objective with the present study was to review our experience with a large number of children and young adults over a long time period.
Patients and Methods The Institutional Review Board approved the study. All patients or parents or guardians gave written consent and were contacted during regular follow-up visits or by telephone to obtain information regarding late reoperation, functional status, and mortality. The medical records of 127 consecutive pediatric and young adult patients (ⱕ21 years of age) who had transaortic left ventricular septal myectomy for obstructive HCM between January 1975 and December 2010 were reviewed. The diagnosis of obstructive HCM was based on echocardiographic studies; however, cardiac catheterization was used early in our series before echocardiography became widely available. Indications for myectomy were the following: (1) patients with resting or provoked LVOT obstruction greater than 50 mm Hg with symptoms despite drug therapy (n ⫽ 104); and (2) patients with severe LVOT obstruction (⬎85 mm Hg) and favorable anatomy who, although reportedly “asymptomatic,” had reduction in functional aerobic capacity on stress testing (n ⫽ 23). Children with biventricular outflow tract obstruction (n ⫽ 14) and those who underwent transapical myectomy (n ⫽ 4) were excluded from the study group. Patient demographics are listed in Table 1. Age at surgery ranged from 2 months to 21 years (mean, 12.9 ⫾ 5.4 years). From the entire cohort, 25 (20%) patients were 18 to 21 years old at the time of surgery. Symptoms included dyspnea in 87 (68%), angina in 47 (37%), and syncope in 39 (30%). Documented ventricular arrhythmias were recorded in 17 (13%) and atrial arrhythmias in 8 (6%). Among the 23 patients (18%) with a so-called
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“prophylactic” myectomy (ie, reportedly asymptomatic but with poor aerobic capacity and severe obstruction), the mean maximum instantaneous gradient was 101 ⫾ 42 mm Hg. One patient had previous alcohol septal ablation. Preoperatively, a dual chamber permanent pacemaker was present in 15 (11.7%) and an implantable cardiac defibrillator (ICD) in 21(16%).
Surgical Technique Our technique of left ventricular septal myectomy has evolved from the original myectomydescribed by Morrow and colleagues [5], to include a more extended septal myectomy [6], particularly at the midventricular level. After median sternotomy, direct pressure measurements with needles in the left ventricle and ascending aorta are done prior to cardiopulmonary bypass. Provocation with isoproterenol is performed when the peak-to-peak pressure gradient is less than 20 mm Hg. Intraoperative transesophageal echocardiography (TEE) is used routinely. Standard cardiopulmonary bypass with aortic and right atrial cannulation is utilized. Aortic occlusion with cold blood antegrade cardioplegia and left heart venting through the right superior pulmonary vein is used. An oblique aortotomy toward the mid-noncoronary sinus is performed. A vein retractor is used to reflect and protect the right coronary cusp and a suction catheter is used to retract and protect the mitral valve. The initial incision is slightly rightward of the nadir of the right coronary cusp and extended in a counterclockwise fashion around to the mitral valve. Further resection is done on the apical third of the septum to the right of the coronary cusp incision. The base of the resected area is deepened with a rongeur. The myectomy is wider at the midventricular level and the myectomy trough should mirror the anterior mitral leaflet, chordae, and papillary muscles. Apical extent of the myectomy is the most important technical aspect of the operation. When an abnormal mitral subvalvar apparatus is present, attachments that exist be-
Table 1. Preoperative Demographics Variable Age at surgery (years) Sex (male/female) Family history, HCM, SCD Angina Syncope Dyspnea Atrial arrhythmias Ventricular arrhythmias Preoperative ICD Preoperative PPM Preoperative alcohol septal ablation
Total (n ⫽ 127)
%
13.0 ⫾ 5.4 years 79/48 51 48 39 87 8 17 21 15 1
62 (male) 40 37 31 68.8 6.2 13.3 16.5 11.7 0.8
HCM ⫽ hypertrophic cardiomyopathy; ICD ⫽ implantable cardioverter defibrillator; PPM ⫽ permanent pacemaker; SCD ⫽ sudden cardiac death.
tween the lateral edge of the anterior leaflet and ventricular septum and between the papillary muscle(s) and septum are divided. In addition, the papillary muscle is mobilized (incised) off of the septum down to its base. Extreme care is always given during manipulation or retraction of aortic and mitral leaflets. The smaller the aortic annulus, the greater the difficulty in accomplishing a complete myectomy and the likelihood of valvular injury is higher. The TEE assessment is performed after weaning from the cardiopulmonary bypass, to assess adequacy of the LVOT and valve function. Direct pressure measurements are performed with needles in the aorta and left ventricle. A peak-to-peak gradient of less than10 mm Hg is the goal and generally correlates with the mean gradient obtained by TEE. Indications to resume bypass and perform additional myectomy are a gradient greater than 20 mm Hg, persistent SAM of the anterior leaflet, or evidence of residual LVOT obstruction by TEE. Postoperative medical management includes routine use of beta-blockers. The primary cardiologist directs long-term medical management.
Statistical Analysis Patient data were collected from the Mayo Clinic written and electronic medical records. Follow-up information was obtained from subsequent clinic visits, written correspondence from local physicians, mailed questionnaire, and telephone interviews with patients and families. The rank sum test was used to compare continuous variables. Descriptive statistics for categoric variables are reported as frequency and percentage, and continuous variables are reported as mean (standard deviation) or median (range). The Kaplan-Meier method was used to draw survival curves and calculate 5-, 10-, 15-, and 20-year survival rates and freedom from reoperation rates. The log-rank test was used to explore the association between risk factors and survival, or freedom from reoperation. The Wilcoxon signed rank test was used to compare the change of MR and maximum instantaneous gradient from preoperative to discharge. The McNemar agreement test was performed to compare preoperative and discharge SAM. All statistical tests were two-sided with the alpha level set at 0.05 for statistical significance.
Results Early Results All patients underwent extended left ventricular septal myectomy. Concomitant procedures included division of accessory papillary muscle attachments in 17 patients, mitral repair in 12 (2 for iatrogenic injury and 10 for redundant leaflets), closure of patent foramen ovale or atrial septal defect in 7 patients, and aortic valve repair in 7 (iatrogenic injury). One patient underwent concomitant mitral valve replacement (MVR) after initial attempt at mitral valvuloplasty and myectomy. This patient had congenital mitral stenosis with thickened and dysplastic leaflets, hypertrophied papillary muscles, and foreshort-
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ened chordae. The mean cardiopulmonary bypass and aortic cross-clamp times were 65.2 ⫾ 28.1 and 46.7 ⫾ 19.4 minutes, respectively. Hemodynamic measurements and echocardiographic data were preoperative septal wall thickness was 24.4 ⫾ 9.4 mm and posterior free wall thickness was 13.6 ⫾ 4.4 mm. The LVOT gradients were assessed by preoperative TTE, intraoperative TEE, intraoperative direct pressure measurements premyectomy and postmyectomy, and predischarge echocardiography. The degree of reduction of mean LVOT gradients was significant (mean ⫽ 89.6 ⫾ 28.7 mm Hg preoperative vs 5.9 ⫾ 6.4 mm Hg postoperative, p ⬍ 0.0001). Intraoperative assessment of MR by TEE pre-myectomy and post myectomy demonstrated a concomitant significant reduction of mean echocardiographic grade (mean 2.01 ⫾ 0.95 preoperative vs 1.05 ⫾ 0.40 postoperative, p ⬍ 0.0001). There were no early deaths. One patient required a permanent pacemaker for complete heart block; however, he was in normal sinus rhythm with native atrioventricular conduction at 1-year postoperative. An epicardial ICD was placed at the time of myectomy in 2 patients (1.5%) and 6 additional patients (4.7 %) had an endocardial ICD placed in the early postoperative period during the same hospitalization for the presence of preexisting SCD risk factors.
Late Results Clinical follow-up was achieved with a mean period of 8.3 ⫾ 8.2 (median 5.3, maximum 37 years). Overall survival was 100.0%, 98.6%, 94.9%, 92.4%, and 92.4% at 1, 5, 10, 15, and 20 years, respectively (Fig 1). There were 4 late deaths; one of the late deaths was sudden and occurred 5.9 years after myectomy. That patient had severe hypertrophy but had satisfactory relief of obstruction after myectomy, and at the time of follow-up was doing well clinically. Two patients died from rejection after heart transplantation, which had been performed 3 and 6 years after myectomy due to progressive restrictive physiology and diastolic heart failure. One patient died from unknown causes. At late follow-up, 6 patients underwent repeat septal myectomy for symptoms attributable to LVOT obstruction. Two patients required aortic valve replacement for progressive aortic regurgitation, but neither had undergone aortic valve repair at the time of myectomy. Two patients required MVR during the follow-up period. One had severe mitral stenosis at the time of initial myectomy and underwent mechanical MVR that thrombosed and required redo MVR. The second patient underwent MVR 3 years after initial myectomy and mitral repair for severe mitral dysplasia and recurrent MR. The median duration between the initial myectomy and repeat myectomy was 5.9 years (range 1.8 to 12.4 years). In these 6 patients, the ages at initial myectomy were 1.7, 3.5, 5.2, 8.2, 13.7, and 13.9 years, and the obstruction appeared to be related to mild residual obstruction from the time of initial myectomy because of exposure difficulties and the inability to do a thorough myectomy (as opposed to recurrent obstruction from
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Fig 1. Kaplan-Meier curve demonstrating late survival.
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muscle regrowth). Univariate risk factors for reoperation are shown in Table 2. Freedom from any cardiac reoperation was 91.2%, 87.9%, 78.8% and 72.7 at 5, 10, 15, and 20 years, respectively (Fig 2). At late follow-up, 96% of patients were in New York Heart Association class I or II. One patient had moderate aortic valve regurgitation and is being followed; he had mild aortic regurgitation at hospital discharge after myectomy. An ICD was placed in 25 additional patients during the follow-up period after evaluation and determination of increased risk for SCD. The mean time to late ICD placement was 9.1 ⫾ 9.0 years (median 6.7 years).
Comment The present study is the largest series of children with obstructive HCM who were treated by septal myectomy over a 35-year period in a single HCM specialty center. Myectomy significantly reduced LVOT obstruction, significantly reduced MR, and significantly decreased HCMrelated symptoms. Although some children with HCM may be asymptomatic, many may have limiting symptoms of angina, syncope, dyspnea, or even SCD [2, 3]. Table 2. Univariate Predictors for Reoperation Variable Age Female Significant MR preop LVMI preop LVEF preop Septal thickness preop NYHA class III/IV preop Chordal SAM postop
HR (95% CI)
p Value
0.90 (0.79–0.95) 3.30 (1.11–9.55) 4.00 (1.41–11.17) 1.00 (1.00–1.01) 0.90 (0.88–1.02) 1.00 (0.89–1.01) 0.90 (0.32–2.42) 1.03 (0.34–3.09)
0.002 0.031 0.009 0.391 0.136 0.085 0.802 0.955
CI ⫽ confidence interval; HR ⫽ hazard ratio; LVEF ⫽ left ventricular ejection fraction; LVMI ⫽ left ventricular mass index; MR ⫽ mitral regurgitation; NYHA ⫽ New York Heart Association; postop ⫽ postoperative; preop ⫽ preoperative; SAM ⫽ systolic anterior motion.
There are numerous mechanisms involved in the symptomatology of HCM, including the dynamic LVOT obstruction, degree of MR, diastolic dysfunction, and cardiac arrhythmias [1]. Pharmacologic therapy, usually beta-blockers and occasionally calcium channel blockers, represents the initial and often only treatment strategy for symptomatic obstructive HCM. Other medications include disopyramide, mexiletine, and amiodarone, depending on the presence of obstruction or arrhythmia. The aim of medical therapy is to abolish the catecholamine-induced effects that may exacerbate LVOT obstruction and to decrease the heart rate, which allows more time for diastolic filling [1]. For patients with obstructive HCM who do not have symptom improvement on medical therapy, septal reduction therapies, including septal myectomy and alcohol septal ablation, are considered next. The late effects of myocardial scar from alcohol septal ablation are unknown and, therefore, are not recommended in children and young adults [1, 7]. Left ventricular septal myectomy was first reported by Cleland in 1963 [8] and Morrow and colleagues [5] subsequently reported good clinical and hemodynamic outcome with myectomy. Since that time, septal myectomy has been considered the gold standard for septal reduction therapy in patients who remain symptomatic despite medical therapy or who are intolerant of medical therapy [1]. Sherrid and colleagues [9] described the mechanism of obstruction in HCM to be related to the effects of flow across the mitral valve that bring the anterior mitral leaflet toward the LVOT and possible abutment against the hypertrophied septum, which is known as SAM of the mitral valve. The mechanism of relief of LVOT obstruction by septal myectomy is physical enlargement of the LVOT. Cooley and colleagues [10] proposed MVR as an alternative method of relieving LVOT obstructive with HCM. Septal myectomy with apical extension to the midventricular level, with or without shaving of the papillary muscles, can eliminate more completely the gradient and SAM-mediated MR [1, 6]. Our study showed a significant reduction in both LVOT obstruction and MR. Because LVOT obstruction is
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Fig 2. Kaplan-Meier curve demonstrating freedom from any reoperation (reop).
considered an independent predictor for development of heart failure and death [11], we believe the relief of obstruction accomplished by septal myectomy may be the main contributing factor for the improvement in survival for the myectomy group compared with the nonoperated patients with LVOT obstruction, as shown in Figure 1 [12]. The technical challenge of transaortic septal myectomy is to remove enough obstructive muscle at the basal and midventricular levels to sufficiently widen the LVOT without creating a ventricular septal defect or heart block, and without injury to the aortic or mitral valves. This approach is more challenging in children because of the small-sized aortic annulus. Inadequate exposure can result in valve injury or inadequate myectomy, and thus residual obstruction [4, 6]. When exposure is difficult, inadequate myectomy is most likely at the midventricle level. Importantly, post myectomy chordal SAM without MR at hospital discharge that might suggest inadequate midventricular myectomy was not a risk factor for needing reoperation in this series (p ⫽ 0.955). When exposure is difficult, the decision to resume bypass for additional myectomy to eliminate a residual gradient must be balanced with the risk of potential valve injury while attempting additional muscular resection. Chordal SAM without MR should be left alone. If significant obstruction persists (anterior leaflet SAM or gradient ⬎20 mm Hg) bypass is resumed and additional transaortic myectomy is performed. If transaortic exposure was difficult, septal myectomy for midventricular obstruction can also be approached by apical ventriculotomy. This should be done cautiously as the papillary muscles and mitral valve are vulnerable to injury, and the ventricular apex is susceptible to aneurysm formation if excessive muscular resection occurs at the ventriculotomy site. Our experience with extended septal myectomy now exceeds 2,000 consecutive patients of all ages with obstructive HCM. Despite this extensive experience, we had iatrogenic injury to the aortic valve in 7 children (6%) and mitral valve in 2 (2%). This rate of aortic valve repair
in our study of 5% is similar to the 4% rate reported by Brown and colleagues [13], where the mean age was 35 years compared with the mean age of 13.6 years in our study. Fortunately, in all 9 cases of aortic or mitral valve injury, valve repair at the time of myectomy was possible. All of the patients who required repeat myectomy had undergone their first myectomy prior to age 14 years and this age cutoff was a risk factor for needing redo myectomy as it was in our previous report [4]. Despite our greater cumulative experience in younger children, it is still important to emphasize that myectomy in smaller children is more difficult and more likely to result in either inadequate relief of obstruction or valve injury because of limited exposure, and both of these problems are more likely with surgeon inexperience. A diversity of mitral valve abnormalities can coexist in patients with HCM [14]. Most are abnormalities of the subvalvar apparatus and can be treated successfully without the need for MVR and without altering the risk of standard myectomy [14, 15]. Treatment of abnormal papillary muscles or chordae is done by division of attachments to the sides of the papillary muscles (fusion to septum or free wall), with preservation of all attachments to the leading edge of the anterior leaflet [15]. Concomitant mitral valve repair is reserved for myxomatous disease (ruptured chordae or severe prolapse). A redundant or elongated mitral leaflet, particularly the anterior leaflet, is not uncommon and was present in 10 patients (8%) in this series. Anterior leaflet plication (n ⫽ 8) or eccentric annuloplasty (n ⫽ 2) was performed in these cases to further reduce or eliminate MR. In general, we do not perform any interventions on the structurally normal mitral valve when the mechanism of regurgitation is SAM, but when there is a structural abnormality (ruptured chordae of prolapsing leaflets), concomitant mitral valve repair is required. While there was no early mortality in this series, it is important to emphasize that there has been an institutional commitment and large experience with myectomy. The literature has also documented that good to excellent
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outcome with septal myectomy is correlated with myectomy volume [1, 16]. While septal myectomy can be performed safely in experienced centers with late survival favorable to an age-matched population without myectomy [11, 12] (Fig 1), it is important to emphasize that although myectomy may exert an antifibrillatory effect [17, 18], surgery does not prevent the risk of SCD entirely. One of our patients died suddenly late after myectomy. That patient was 17 years old; she died suddenly 7 years after myectomy. She had severe left ventricular hypertrophy with wall thickness greater than 25 mm. In 2000, massive hypertrophy (⬎3 cm) was published as a major risk factor for sudden death [19]. However, this patient was evaluated and underwent operation in 1998 when an ICD recommendation generally required the presence of at least 2 major risk factors. Our current practice is to place an ICD when major risk factors are present, irrespective of whether myectomy is performed [19]. The current guideline-based recommendation and indication for septal reduction therapy is obstructive HCM with symptoms attributable to LVOT obstruction despite drug therapy [1]. The role of a so-called “prophylactic” myectomy for seemingly asymptomatic patients is controversial. In addition, the ability to clinically assess symptomatic status in a child is not always straightforward, especially if the symptomatic child has acclimated to his or her condition. In this series, a myectomy was performed on 23 patients (18%) despite the patient and his or her family self-reporting either an asymptomatic state or attenuation of symptoms with drug therapy. Many of these patients had simple fatigue but not the classic angina, dyspnea, or syncope. Nevertheless, these “asymptomatic” patients underwent operation because of severe LVOT obstruction (⬎85 mm Hg); most with documented exercise intolerance on stress testing suggesting unappreciated or unrecognized symptomatic expression of their HCM substrate. In addition, the decision to proceed with operation in these specific cases was motivated further by the presence of severe MR or a positive family history of premature SCD. Finally, in each of these cases, the patient’s septal anatomy was deemed favorable for myectomy; ie, predominant basal septal hypertrophy and a reasonable-sized aortic annulus such that successful transaortic myectomy was felt to be high and operative risk low. Nevertheless, given the overall risk of aortic valve injury in an experienced HCM center to be approximately 5%, we believe myectomy in seemingly asymptomatic children should be advised with caution and should only be considered when the anatomy is ideal and the surgeon is experienced with myectomy. In addition, if the child is old enough for treadmill stress testing, serial stress testing may be helpful to identify the patient with progressive decline in cardiopulmonary fitness despite their annual self-reporting of asymptomatic status. Septal myectomy is safe and effective in children with obstructive HCM, but limited transaortic exposure may increase risk of aortic or mitral valve injury. Late survival is better than the previously published untreated natural
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history of HCM. Patient selection and surgical expertise remain critical components of septal myectomy especially if a prophylactic myectomy is being considered in a seemingly asymptomatic patient.
Limitations of Study Late echocardiography data were not included because of wide variability of reporting from outside echo laboratories, and quantitative and qualitative measurements were often incomplete (eg, wall thickness and LV mass measurements, degrees of MR, “mean” or “maximum instantaneous” gradients, resting or provoked, etc). These inconsistencies and variability precluded a meaningful echocardiographic analysis. While it was also our goal to also obtain information about ICD discharge rates, device interrogation data (eg, cumulative shocks, appropriate versus inappropriate shocks, etc) were not always available and therefore were not included. We acknowledge with appreciation Judy Lenoch for assistance with data collection and analysis, and Rhonda Brincks for secretarial support.
References 1. Gersh BJ, Maron BJ, Bonow RO, et al. 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2011;124:2761–96. 2. Yetman AT, McCrindle BW. Management of pediatric hypertrophic cardiomyopathy. Curr Opin Cardiol 2005;20:80 –3. 3. Colan SD, Lipshultz SE, Lowe AM, et al. Epidemiology and cause-specific outcome of hypertrophic cardiomyopathy in children: findings from the Pediatric Cardiomyopathy Registry. Circulation 2007;115:773– 81. 4. Minakata K, Dearani JA, O’Leary PW, Danielson GK. Septal myectomy for obstructive hypertrophic cardiomyopathy in pediatric patients: early and late results. Ann Thorac Surg 2005;80:1424 –30. 5. Morrow AG, Fogarty TJ, Hannah H, Braunwald E. Operative treatment in idiopathic hypertrophic subaortic stenosis.Techniques, and the results of preoperative and postoperative clinical and hemodynamic assessments. Circulation 1968;37:589 –96. 6. Dearani JA, Danielson GK. Septal myectomy for obstructive hypertrophic cardiomyopathy. Semin Thorac Cardiovasc Surg Ped Card Surg Ann 2005:86 –91. 7. Agarwal S, Tuzcu EM, Desai MY, et al. Updated metaanalysis of septal alcohol ablation versus myectomy for hypertrophic cardiomyopathy. J Am Coll Cardiol 2010;55: 823–34. 8. Cleland WP. The surgical management of obstructive cardiomyopathy. J Cardiovasc Surg (Torino)1963;4:489 –91. 9. Sherrid MV, Gunsburg DZ, Moldenhauer S, Pearle G. Systolic anterior motion begins at low left ventricular outflow tract velocity in obstructive hypertrophic cardiomyopathy. J Am Coll Cardiol 2000;36:1344 –54. 10. Cooley DA, Leachman RD, Hallman GL, Gerami S, Hall RJ. Idiopathic hypertrophic subaortic stenosis. Surgical treatment including mitral valve replacement. Arch Surg 1971; 103:606 –9. 11. Maron MS, Olivotto I, Betocchi S, et al. Effect of left ventricular outflow tract obstruction on clinical outcome in hypertrophic cardiomyopathy.N Engl J Med 2003;348:295–303.
12. Ommen SR, Maron BJ, Olivotto I, et al. Long-term effects of surgical septal myectomy on survival in patients with obstructive hypertrophic cardiomyopathy. J Am Coll Cardiol 2005;46:470 – 6. 13. Brown PS Jr, Roberts CS, McIntosh CL, Clark RE. Aortic regurgitation after left ventricular myotomy and myectomy. Ann Thorac Surg 1991;51:585–92. 14. Maron MS, Olivotto I, Harrigan C, et al. Mitral valve abnormalities identified by cardiovascular magnetic resonance represent a primary phenotypic expression of hypertrophic cardiomyopathy. Circulation 2011;124:40 –7. 15. Minakata K, Dearani JA, Nishimura RA, Maron BJ, Danielson GK. Extended septal myectomy for hypertrophic obstructive cardiomyopathy with anomalous mitral papillary muscles or chordae. J Thorac Cardiovasc Surg 2004;127: 481–9.
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16. Smedira NG, Lytle BW, Lever HM, et al. Current effectiveness and risks of isolated septal myectomy for hypertrophic obstructive cardiomyopathy. Ann Thorac Surg 2008;85:127–33. 17. McLeod CJ, Ommen SR, Ackerman MJ, et al. Surgical septal myectomy decreases the risk for appropriate implantable cardioverter defibrillator discharge in obstructive hypertrophic cardiomyopathy. Eur Heart J 2007;28:2583– 8. 18. Spirito P, Bellone P, Harris KM, Bernabo P, Bruzzi P, Maron BJ. Magnitude of left ventricular hypertrophy and risk of sudden death in hypertrophic cardiomyopathy. N Engl J Med 2000;342:1778 – 85. 19. Maron BJ, Shen WK, Link MS, et al. Efficacy of implantable cardioverter-defibrillators for the prevention of sudden death in patients with hypertrophic cardiomyopathy. N Engl J Med 2000;342:365–73.
DISCUSSION DR HITENDU DAVE (Zurich, Switzerland): Really very impressive results. My question is, I probably missed it, what are the indications of putting a simultaneous intracardiac defibrillator? Because as I understand, these patients in spite of relief of obstruction still have a risk of sudden death. So what are your indications, and if you have put an ICD [implantable cardiac defibrillator], where is the place where you put your ventricular electrodes? DR ALTARABSHEH: Thank you. That is a good question, and I would like an input from Dr Dearani on this subject. DR JOSEPH A. DEARANI (Rochester, MN): The indications for placement of ICD: Ventricular septal thickness 30 mm or greater,
positive family history of sudden death, a history of syncope felt to be related to arrhythmia and not obstruction, which requires an analysis by a cardiologist experienced with HCM [hypertrophic cardiomyopathy]. Our technique of defibrillator implantation is as follows: if they are big enough, they get an endocardial system. In a younger child, we use an endocardial system that is placed epicardially at the time of surgery. The endocardial lead is placed through the transverse sinus and it is fixed to the pericardium over the anterolateral wall of the left ventricle, and the generator is placed in the right upper quadrant of the abdomen. This results in the vector through the heart from the right upper quadrant of the abdomen to the left shoulder. Thank you.
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Departments of Surgery-Division of Cardiovascular Surgery, Pediatrics-Division of Pediatric Cardiology, Medicine-Division of Cardiovascular Diseases, Biomedical Statistics and Informatics, and Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota
Background. Obstructive hypertrophic cardiomyopathy (HCM) is an important cause of heart failure in children, but there are limited data addressing outcome of myectomy in children. Our objective was to evaluate the early and late results of septal myectomy in pediatric HCM. Methods. We reviewed 127 consecutive patients (62% male) who underwent transaortic septal myectomy for obstructive HCM from January 1975 to December 2010 at 21 or less years of age. Mean age at operation was 12.9 ⴞ 5.5 years. Preoperatively, mean maximum instantaneous gradient was 89 mm Hg and 95% had significant systolic anterior motion (SAM) with mitral regurgitation (MR). Implantable cardioverter defibrillator (ICD) and permanent pacemaker prior to surgery was present in 21 patients (17%) and 15 (11.7%), respectively. Results. Transaortic extended left ventricular septal myectomy was performed in all patients with no early deaths. Iatrogenic morbidity included new aortic valve regurgitation requiring repair in 7 (5.5%), mitral regurgitation needing repair in 2 (1.5%), ventricular septal defect in 1 (1%), and heart block requiring permanent pacemaker in 1 (1%). An ICD was implanted postoperatively in 8 during the same hospital admission. Mean MIG
decreased from 89 to 6 mm Hg (p < 0.0001). Postoperatively, residual chordal SAM was present in 23% with mild or no MR; moderate MR was detected in 1 patient. Four patients (3%) died late during the mean follow-up period of 8.3 years (maximum, 37 years); 1 death was sudden. Overall survival was 98.6%, 94.9%, 92.4%, and 92.4% at 5, 10, 15, and 20 years, respectively. Freedom from any cardiac reoperation was 91.2%, 87.8%, 78.7%, and 72.7% at 5, 10, 15, and 20 years, respectively. Repeat septal myectomy was performed in 6 patients (5%). At late follow-up, 95% were in New York Heart Association functional class I or II and 25 patients underwent late ICD placement. Conclusions. Septal myectomy is safe and effective in children with obstructive HCM, but limited exposure may increase risk of aortic or mitral valve injury. Late survival is better than the previously published untreated natural history of HCM. Patient selection and surgical expertise remain critical components of septal myectomy, especially before considering a prophylactic myectomy in a seemingly asymptomatic patient.
H
Diversity in symptomatology and clinical presentation varies from asymptomatic disease to severe life limiting symptoms of angina, dyspnea, syncope, or even sudden cardiac death (SCD). Pathophysiologic mechanisms responsible for symptoms in HCM include left ventricular outflow tract (LVOT) obstruction, mitral regurgitation (MR), systolic anterior motion (SAM) of mitral leaflets, ventricular diastolic dysfunction, and ventricular arrhythmias. Children with HCM are usually asymptomatic and the overall annual mortality for pediatric HCM beyond the first year of life is 1%. However, symptomatic HCM and HCM-triggered SCD can occur in childhood [3]. The disease progression with late sequela that may include heart failure is related directly to the dynamic LVOT obstruction, which is the main target of pharmacotherapy
ypertrophic cardiomyopathy (HCM) is viewed generally as an inherited autosomal dominant disorder often caused by mutations in genes that encode critical cardiac myofilaments; mutation positive is often referred to as sarcomeric HCM [1]. Hypertrophic cardiomyopathy occurs in 1 of 500 adults, and is considered to be one of the most common causes of sudden death in young people who are less than 35 years of age [2]. The phenotypic expression of this genetic disorder is characterized by myocardial cellular hypertrophy, which involves primarily the interventricular septum.
Accepted for publication Aug 1, 2012. Presented at the Forty-eighth Annual Meeting of The Society of Thoracic Surgeons, Fort Lauderdale, FL, Jan 28 –Feb 1, 2012. Address correspondence to Dr Dearani, Mayo Clinic, 200 First St SW, Rochester, Minnesota 55905; e-mail: [email protected].
© 2013 by The Society of Thoracic Surgeons Published by Elsevier Inc
(Ann Thorac Surg 2013;95:663–9) © 2013 by The Society of Thoracic Surgeons
0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2012.08.011
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Salah E. Altarabsheh, MD, Joseph A. Dearani, MD, Harold M. Burkhart, MD, Hartzell V. Schaff, MD, Salil V. Deo, MBBS, MS, Benjamin W. Eidem, MD, Steve R. Ommen, MD, Zhuo Li, MS, and Michael J. Ackerman, MD
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Abbreviations and Acronyms HCM ⫽ hypertrophic cardiomyopathy ICD ⫽ implantable cardiac defibrillator LVOT ⫽ left ventricular outflow tract MR ⫽ mitral regurgitation MVR ⫽ mitral valve replacement NYHA ⫽ New York Heart Association PPM ⫽ permanent pacemaker SAM ⫽ systolic anterior motion SCD ⫽ sudden cardiac death TEE ⫽ transesophageal echocardiogram CONGENITAL HEART
and septal reduction therapies [1]. Left ventricular septal myectomy is the standard therapeutic option for patients with LVOT obstruction and associated MR whose symptoms are refractory to pharmacotherapy [1]. While alcohol septal ablation is an alternative septal reduction therapy in selected adults, it is not indicated in children and young adults [1]. Prior published reports showed the effectiveness in the short and intermediate term of septal myectomy in the pediatric age groups [4]. Our objective with the present study was to review our experience with a large number of children and young adults over a long time period.
Patients and Methods The Institutional Review Board approved the study. All patients or parents or guardians gave written consent and were contacted during regular follow-up visits or by telephone to obtain information regarding late reoperation, functional status, and mortality. The medical records of 127 consecutive pediatric and young adult patients (ⱕ21 years of age) who had transaortic left ventricular septal myectomy for obstructive HCM between January 1975 and December 2010 were reviewed. The diagnosis of obstructive HCM was based on echocardiographic studies; however, cardiac catheterization was used early in our series before echocardiography became widely available. Indications for myectomy were the following: (1) patients with resting or provoked LVOT obstruction greater than 50 mm Hg with symptoms despite drug therapy (n ⫽ 104); and (2) patients with severe LVOT obstruction (⬎85 mm Hg) and favorable anatomy who, although reportedly “asymptomatic,” had reduction in functional aerobic capacity on stress testing (n ⫽ 23). Children with biventricular outflow tract obstruction (n ⫽ 14) and those who underwent transapical myectomy (n ⫽ 4) were excluded from the study group. Patient demographics are listed in Table 1. Age at surgery ranged from 2 months to 21 years (mean, 12.9 ⫾ 5.4 years). From the entire cohort, 25 (20%) patients were 18 to 21 years old at the time of surgery. Symptoms included dyspnea in 87 (68%), angina in 47 (37%), and syncope in 39 (30%). Documented ventricular arrhythmias were recorded in 17 (13%) and atrial arrhythmias in 8 (6%). Among the 23 patients (18%) with a so-called
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“prophylactic” myectomy (ie, reportedly asymptomatic but with poor aerobic capacity and severe obstruction), the mean maximum instantaneous gradient was 101 ⫾ 42 mm Hg. One patient had previous alcohol septal ablation. Preoperatively, a dual chamber permanent pacemaker was present in 15 (11.7%) and an implantable cardiac defibrillator (ICD) in 21(16%).
Surgical Technique Our technique of left ventricular septal myectomy has evolved from the original myectomydescribed by Morrow and colleagues [5], to include a more extended septal myectomy [6], particularly at the midventricular level. After median sternotomy, direct pressure measurements with needles in the left ventricle and ascending aorta are done prior to cardiopulmonary bypass. Provocation with isoproterenol is performed when the peak-to-peak pressure gradient is less than 20 mm Hg. Intraoperative transesophageal echocardiography (TEE) is used routinely. Standard cardiopulmonary bypass with aortic and right atrial cannulation is utilized. Aortic occlusion with cold blood antegrade cardioplegia and left heart venting through the right superior pulmonary vein is used. An oblique aortotomy toward the mid-noncoronary sinus is performed. A vein retractor is used to reflect and protect the right coronary cusp and a suction catheter is used to retract and protect the mitral valve. The initial incision is slightly rightward of the nadir of the right coronary cusp and extended in a counterclockwise fashion around to the mitral valve. Further resection is done on the apical third of the septum to the right of the coronary cusp incision. The base of the resected area is deepened with a rongeur. The myectomy is wider at the midventricular level and the myectomy trough should mirror the anterior mitral leaflet, chordae, and papillary muscles. Apical extent of the myectomy is the most important technical aspect of the operation. When an abnormal mitral subvalvar apparatus is present, attachments that exist be-
Table 1. Preoperative Demographics Variable Age at surgery (years) Sex (male/female) Family history, HCM, SCD Angina Syncope Dyspnea Atrial arrhythmias Ventricular arrhythmias Preoperative ICD Preoperative PPM Preoperative alcohol septal ablation
Total (n ⫽ 127)
%
13.0 ⫾ 5.4 years 79/48 51 48 39 87 8 17 21 15 1
62 (male) 40 37 31 68.8 6.2 13.3 16.5 11.7 0.8
HCM ⫽ hypertrophic cardiomyopathy; ICD ⫽ implantable cardioverter defibrillator; PPM ⫽ permanent pacemaker; SCD ⫽ sudden cardiac death.
tween the lateral edge of the anterior leaflet and ventricular septum and between the papillary muscle(s) and septum are divided. In addition, the papillary muscle is mobilized (incised) off of the septum down to its base. Extreme care is always given during manipulation or retraction of aortic and mitral leaflets. The smaller the aortic annulus, the greater the difficulty in accomplishing a complete myectomy and the likelihood of valvular injury is higher. The TEE assessment is performed after weaning from the cardiopulmonary bypass, to assess adequacy of the LVOT and valve function. Direct pressure measurements are performed with needles in the aorta and left ventricle. A peak-to-peak gradient of less than10 mm Hg is the goal and generally correlates with the mean gradient obtained by TEE. Indications to resume bypass and perform additional myectomy are a gradient greater than 20 mm Hg, persistent SAM of the anterior leaflet, or evidence of residual LVOT obstruction by TEE. Postoperative medical management includes routine use of beta-blockers. The primary cardiologist directs long-term medical management.
Statistical Analysis Patient data were collected from the Mayo Clinic written and electronic medical records. Follow-up information was obtained from subsequent clinic visits, written correspondence from local physicians, mailed questionnaire, and telephone interviews with patients and families. The rank sum test was used to compare continuous variables. Descriptive statistics for categoric variables are reported as frequency and percentage, and continuous variables are reported as mean (standard deviation) or median (range). The Kaplan-Meier method was used to draw survival curves and calculate 5-, 10-, 15-, and 20-year survival rates and freedom from reoperation rates. The log-rank test was used to explore the association between risk factors and survival, or freedom from reoperation. The Wilcoxon signed rank test was used to compare the change of MR and maximum instantaneous gradient from preoperative to discharge. The McNemar agreement test was performed to compare preoperative and discharge SAM. All statistical tests were two-sided with the alpha level set at 0.05 for statistical significance.
Results Early Results All patients underwent extended left ventricular septal myectomy. Concomitant procedures included division of accessory papillary muscle attachments in 17 patients, mitral repair in 12 (2 for iatrogenic injury and 10 for redundant leaflets), closure of patent foramen ovale or atrial septal defect in 7 patients, and aortic valve repair in 7 (iatrogenic injury). One patient underwent concomitant mitral valve replacement (MVR) after initial attempt at mitral valvuloplasty and myectomy. This patient had congenital mitral stenosis with thickened and dysplastic leaflets, hypertrophied papillary muscles, and foreshort-
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ened chordae. The mean cardiopulmonary bypass and aortic cross-clamp times were 65.2 ⫾ 28.1 and 46.7 ⫾ 19.4 minutes, respectively. Hemodynamic measurements and echocardiographic data were preoperative septal wall thickness was 24.4 ⫾ 9.4 mm and posterior free wall thickness was 13.6 ⫾ 4.4 mm. The LVOT gradients were assessed by preoperative TTE, intraoperative TEE, intraoperative direct pressure measurements premyectomy and postmyectomy, and predischarge echocardiography. The degree of reduction of mean LVOT gradients was significant (mean ⫽ 89.6 ⫾ 28.7 mm Hg preoperative vs 5.9 ⫾ 6.4 mm Hg postoperative, p ⬍ 0.0001). Intraoperative assessment of MR by TEE pre-myectomy and post myectomy demonstrated a concomitant significant reduction of mean echocardiographic grade (mean 2.01 ⫾ 0.95 preoperative vs 1.05 ⫾ 0.40 postoperative, p ⬍ 0.0001). There were no early deaths. One patient required a permanent pacemaker for complete heart block; however, he was in normal sinus rhythm with native atrioventricular conduction at 1-year postoperative. An epicardial ICD was placed at the time of myectomy in 2 patients (1.5%) and 6 additional patients (4.7 %) had an endocardial ICD placed in the early postoperative period during the same hospitalization for the presence of preexisting SCD risk factors.
Late Results Clinical follow-up was achieved with a mean period of 8.3 ⫾ 8.2 (median 5.3, maximum 37 years). Overall survival was 100.0%, 98.6%, 94.9%, 92.4%, and 92.4% at 1, 5, 10, 15, and 20 years, respectively (Fig 1). There were 4 late deaths; one of the late deaths was sudden and occurred 5.9 years after myectomy. That patient had severe hypertrophy but had satisfactory relief of obstruction after myectomy, and at the time of follow-up was doing well clinically. Two patients died from rejection after heart transplantation, which had been performed 3 and 6 years after myectomy due to progressive restrictive physiology and diastolic heart failure. One patient died from unknown causes. At late follow-up, 6 patients underwent repeat septal myectomy for symptoms attributable to LVOT obstruction. Two patients required aortic valve replacement for progressive aortic regurgitation, but neither had undergone aortic valve repair at the time of myectomy. Two patients required MVR during the follow-up period. One had severe mitral stenosis at the time of initial myectomy and underwent mechanical MVR that thrombosed and required redo MVR. The second patient underwent MVR 3 years after initial myectomy and mitral repair for severe mitral dysplasia and recurrent MR. The median duration between the initial myectomy and repeat myectomy was 5.9 years (range 1.8 to 12.4 years). In these 6 patients, the ages at initial myectomy were 1.7, 3.5, 5.2, 8.2, 13.7, and 13.9 years, and the obstruction appeared to be related to mild residual obstruction from the time of initial myectomy because of exposure difficulties and the inability to do a thorough myectomy (as opposed to recurrent obstruction from
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Fig 1. Kaplan-Meier curve demonstrating late survival.
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muscle regrowth). Univariate risk factors for reoperation are shown in Table 2. Freedom from any cardiac reoperation was 91.2%, 87.9%, 78.8% and 72.7 at 5, 10, 15, and 20 years, respectively (Fig 2). At late follow-up, 96% of patients were in New York Heart Association class I or II. One patient had moderate aortic valve regurgitation and is being followed; he had mild aortic regurgitation at hospital discharge after myectomy. An ICD was placed in 25 additional patients during the follow-up period after evaluation and determination of increased risk for SCD. The mean time to late ICD placement was 9.1 ⫾ 9.0 years (median 6.7 years).
Comment The present study is the largest series of children with obstructive HCM who were treated by septal myectomy over a 35-year period in a single HCM specialty center. Myectomy significantly reduced LVOT obstruction, significantly reduced MR, and significantly decreased HCMrelated symptoms. Although some children with HCM may be asymptomatic, many may have limiting symptoms of angina, syncope, dyspnea, or even SCD [2, 3]. Table 2. Univariate Predictors for Reoperation Variable Age Female Significant MR preop LVMI preop LVEF preop Septal thickness preop NYHA class III/IV preop Chordal SAM postop
HR (95% CI)
p Value
0.90 (0.79–0.95) 3.30 (1.11–9.55) 4.00 (1.41–11.17) 1.00 (1.00–1.01) 0.90 (0.88–1.02) 1.00 (0.89–1.01) 0.90 (0.32–2.42) 1.03 (0.34–3.09)
0.002 0.031 0.009 0.391 0.136 0.085 0.802 0.955
CI ⫽ confidence interval; HR ⫽ hazard ratio; LVEF ⫽ left ventricular ejection fraction; LVMI ⫽ left ventricular mass index; MR ⫽ mitral regurgitation; NYHA ⫽ New York Heart Association; postop ⫽ postoperative; preop ⫽ preoperative; SAM ⫽ systolic anterior motion.
There are numerous mechanisms involved in the symptomatology of HCM, including the dynamic LVOT obstruction, degree of MR, diastolic dysfunction, and cardiac arrhythmias [1]. Pharmacologic therapy, usually beta-blockers and occasionally calcium channel blockers, represents the initial and often only treatment strategy for symptomatic obstructive HCM. Other medications include disopyramide, mexiletine, and amiodarone, depending on the presence of obstruction or arrhythmia. The aim of medical therapy is to abolish the catecholamine-induced effects that may exacerbate LVOT obstruction and to decrease the heart rate, which allows more time for diastolic filling [1]. For patients with obstructive HCM who do not have symptom improvement on medical therapy, septal reduction therapies, including septal myectomy and alcohol septal ablation, are considered next. The late effects of myocardial scar from alcohol septal ablation are unknown and, therefore, are not recommended in children and young adults [1, 7]. Left ventricular septal myectomy was first reported by Cleland in 1963 [8] and Morrow and colleagues [5] subsequently reported good clinical and hemodynamic outcome with myectomy. Since that time, septal myectomy has been considered the gold standard for septal reduction therapy in patients who remain symptomatic despite medical therapy or who are intolerant of medical therapy [1]. Sherrid and colleagues [9] described the mechanism of obstruction in HCM to be related to the effects of flow across the mitral valve that bring the anterior mitral leaflet toward the LVOT and possible abutment against the hypertrophied septum, which is known as SAM of the mitral valve. The mechanism of relief of LVOT obstruction by septal myectomy is physical enlargement of the LVOT. Cooley and colleagues [10] proposed MVR as an alternative method of relieving LVOT obstructive with HCM. Septal myectomy with apical extension to the midventricular level, with or without shaving of the papillary muscles, can eliminate more completely the gradient and SAM-mediated MR [1, 6]. Our study showed a significant reduction in both LVOT obstruction and MR. Because LVOT obstruction is
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Fig 2. Kaplan-Meier curve demonstrating freedom from any reoperation (reop).
considered an independent predictor for development of heart failure and death [11], we believe the relief of obstruction accomplished by septal myectomy may be the main contributing factor for the improvement in survival for the myectomy group compared with the nonoperated patients with LVOT obstruction, as shown in Figure 1 [12]. The technical challenge of transaortic septal myectomy is to remove enough obstructive muscle at the basal and midventricular levels to sufficiently widen the LVOT without creating a ventricular septal defect or heart block, and without injury to the aortic or mitral valves. This approach is more challenging in children because of the small-sized aortic annulus. Inadequate exposure can result in valve injury or inadequate myectomy, and thus residual obstruction [4, 6]. When exposure is difficult, inadequate myectomy is most likely at the midventricle level. Importantly, post myectomy chordal SAM without MR at hospital discharge that might suggest inadequate midventricular myectomy was not a risk factor for needing reoperation in this series (p ⫽ 0.955). When exposure is difficult, the decision to resume bypass for additional myectomy to eliminate a residual gradient must be balanced with the risk of potential valve injury while attempting additional muscular resection. Chordal SAM without MR should be left alone. If significant obstruction persists (anterior leaflet SAM or gradient ⬎20 mm Hg) bypass is resumed and additional transaortic myectomy is performed. If transaortic exposure was difficult, septal myectomy for midventricular obstruction can also be approached by apical ventriculotomy. This should be done cautiously as the papillary muscles and mitral valve are vulnerable to injury, and the ventricular apex is susceptible to aneurysm formation if excessive muscular resection occurs at the ventriculotomy site. Our experience with extended septal myectomy now exceeds 2,000 consecutive patients of all ages with obstructive HCM. Despite this extensive experience, we had iatrogenic injury to the aortic valve in 7 children (6%) and mitral valve in 2 (2%). This rate of aortic valve repair
in our study of 5% is similar to the 4% rate reported by Brown and colleagues [13], where the mean age was 35 years compared with the mean age of 13.6 years in our study. Fortunately, in all 9 cases of aortic or mitral valve injury, valve repair at the time of myectomy was possible. All of the patients who required repeat myectomy had undergone their first myectomy prior to age 14 years and this age cutoff was a risk factor for needing redo myectomy as it was in our previous report [4]. Despite our greater cumulative experience in younger children, it is still important to emphasize that myectomy in smaller children is more difficult and more likely to result in either inadequate relief of obstruction or valve injury because of limited exposure, and both of these problems are more likely with surgeon inexperience. A diversity of mitral valve abnormalities can coexist in patients with HCM [14]. Most are abnormalities of the subvalvar apparatus and can be treated successfully without the need for MVR and without altering the risk of standard myectomy [14, 15]. Treatment of abnormal papillary muscles or chordae is done by division of attachments to the sides of the papillary muscles (fusion to septum or free wall), with preservation of all attachments to the leading edge of the anterior leaflet [15]. Concomitant mitral valve repair is reserved for myxomatous disease (ruptured chordae or severe prolapse). A redundant or elongated mitral leaflet, particularly the anterior leaflet, is not uncommon and was present in 10 patients (8%) in this series. Anterior leaflet plication (n ⫽ 8) or eccentric annuloplasty (n ⫽ 2) was performed in these cases to further reduce or eliminate MR. In general, we do not perform any interventions on the structurally normal mitral valve when the mechanism of regurgitation is SAM, but when there is a structural abnormality (ruptured chordae of prolapsing leaflets), concomitant mitral valve repair is required. While there was no early mortality in this series, it is important to emphasize that there has been an institutional commitment and large experience with myectomy. The literature has also documented that good to excellent
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outcome with septal myectomy is correlated with myectomy volume [1, 16]. While septal myectomy can be performed safely in experienced centers with late survival favorable to an age-matched population without myectomy [11, 12] (Fig 1), it is important to emphasize that although myectomy may exert an antifibrillatory effect [17, 18], surgery does not prevent the risk of SCD entirely. One of our patients died suddenly late after myectomy. That patient was 17 years old; she died suddenly 7 years after myectomy. She had severe left ventricular hypertrophy with wall thickness greater than 25 mm. In 2000, massive hypertrophy (⬎3 cm) was published as a major risk factor for sudden death [19]. However, this patient was evaluated and underwent operation in 1998 when an ICD recommendation generally required the presence of at least 2 major risk factors. Our current practice is to place an ICD when major risk factors are present, irrespective of whether myectomy is performed [19]. The current guideline-based recommendation and indication for septal reduction therapy is obstructive HCM with symptoms attributable to LVOT obstruction despite drug therapy [1]. The role of a so-called “prophylactic” myectomy for seemingly asymptomatic patients is controversial. In addition, the ability to clinically assess symptomatic status in a child is not always straightforward, especially if the symptomatic child has acclimated to his or her condition. In this series, a myectomy was performed on 23 patients (18%) despite the patient and his or her family self-reporting either an asymptomatic state or attenuation of symptoms with drug therapy. Many of these patients had simple fatigue but not the classic angina, dyspnea, or syncope. Nevertheless, these “asymptomatic” patients underwent operation because of severe LVOT obstruction (⬎85 mm Hg); most with documented exercise intolerance on stress testing suggesting unappreciated or unrecognized symptomatic expression of their HCM substrate. In addition, the decision to proceed with operation in these specific cases was motivated further by the presence of severe MR or a positive family history of premature SCD. Finally, in each of these cases, the patient’s septal anatomy was deemed favorable for myectomy; ie, predominant basal septal hypertrophy and a reasonable-sized aortic annulus such that successful transaortic myectomy was felt to be high and operative risk low. Nevertheless, given the overall risk of aortic valve injury in an experienced HCM center to be approximately 5%, we believe myectomy in seemingly asymptomatic children should be advised with caution and should only be considered when the anatomy is ideal and the surgeon is experienced with myectomy. In addition, if the child is old enough for treadmill stress testing, serial stress testing may be helpful to identify the patient with progressive decline in cardiopulmonary fitness despite their annual self-reporting of asymptomatic status. Septal myectomy is safe and effective in children with obstructive HCM, but limited transaortic exposure may increase risk of aortic or mitral valve injury. Late survival is better than the previously published untreated natural
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history of HCM. Patient selection and surgical expertise remain critical components of septal myectomy especially if a prophylactic myectomy is being considered in a seemingly asymptomatic patient.
Limitations of Study Late echocardiography data were not included because of wide variability of reporting from outside echo laboratories, and quantitative and qualitative measurements were often incomplete (eg, wall thickness and LV mass measurements, degrees of MR, “mean” or “maximum instantaneous” gradients, resting or provoked, etc). These inconsistencies and variability precluded a meaningful echocardiographic analysis. While it was also our goal to also obtain information about ICD discharge rates, device interrogation data (eg, cumulative shocks, appropriate versus inappropriate shocks, etc) were not always available and therefore were not included. We acknowledge with appreciation Judy Lenoch for assistance with data collection and analysis, and Rhonda Brincks for secretarial support.
References 1. Gersh BJ, Maron BJ, Bonow RO, et al. 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2011;124:2761–96. 2. Yetman AT, McCrindle BW. Management of pediatric hypertrophic cardiomyopathy. Curr Opin Cardiol 2005;20:80 –3. 3. Colan SD, Lipshultz SE, Lowe AM, et al. Epidemiology and cause-specific outcome of hypertrophic cardiomyopathy in children: findings from the Pediatric Cardiomyopathy Registry. Circulation 2007;115:773– 81. 4. Minakata K, Dearani JA, O’Leary PW, Danielson GK. Septal myectomy for obstructive hypertrophic cardiomyopathy in pediatric patients: early and late results. Ann Thorac Surg 2005;80:1424 –30. 5. Morrow AG, Fogarty TJ, Hannah H, Braunwald E. Operative treatment in idiopathic hypertrophic subaortic stenosis.Techniques, and the results of preoperative and postoperative clinical and hemodynamic assessments. Circulation 1968;37:589 –96. 6. Dearani JA, Danielson GK. Septal myectomy for obstructive hypertrophic cardiomyopathy. Semin Thorac Cardiovasc Surg Ped Card Surg Ann 2005:86 –91. 7. Agarwal S, Tuzcu EM, Desai MY, et al. Updated metaanalysis of septal alcohol ablation versus myectomy for hypertrophic cardiomyopathy. J Am Coll Cardiol 2010;55: 823–34. 8. Cleland WP. The surgical management of obstructive cardiomyopathy. J Cardiovasc Surg (Torino)1963;4:489 –91. 9. Sherrid MV, Gunsburg DZ, Moldenhauer S, Pearle G. Systolic anterior motion begins at low left ventricular outflow tract velocity in obstructive hypertrophic cardiomyopathy. J Am Coll Cardiol 2000;36:1344 –54. 10. Cooley DA, Leachman RD, Hallman GL, Gerami S, Hall RJ. Idiopathic hypertrophic subaortic stenosis. Surgical treatment including mitral valve replacement. Arch Surg 1971; 103:606 –9. 11. Maron MS, Olivotto I, Betocchi S, et al. Effect of left ventricular outflow tract obstruction on clinical outcome in hypertrophic cardiomyopathy.N Engl J Med 2003;348:295–303.
12. Ommen SR, Maron BJ, Olivotto I, et al. Long-term effects of surgical septal myectomy on survival in patients with obstructive hypertrophic cardiomyopathy. J Am Coll Cardiol 2005;46:470 – 6. 13. Brown PS Jr, Roberts CS, McIntosh CL, Clark RE. Aortic regurgitation after left ventricular myotomy and myectomy. Ann Thorac Surg 1991;51:585–92. 14. Maron MS, Olivotto I, Harrigan C, et al. Mitral valve abnormalities identified by cardiovascular magnetic resonance represent a primary phenotypic expression of hypertrophic cardiomyopathy. Circulation 2011;124:40 –7. 15. Minakata K, Dearani JA, Nishimura RA, Maron BJ, Danielson GK. Extended septal myectomy for hypertrophic obstructive cardiomyopathy with anomalous mitral papillary muscles or chordae. J Thorac Cardiovasc Surg 2004;127: 481–9.
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16. Smedira NG, Lytle BW, Lever HM, et al. Current effectiveness and risks of isolated septal myectomy for hypertrophic obstructive cardiomyopathy. Ann Thorac Surg 2008;85:127–33. 17. McLeod CJ, Ommen SR, Ackerman MJ, et al. Surgical septal myectomy decreases the risk for appropriate implantable cardioverter defibrillator discharge in obstructive hypertrophic cardiomyopathy. Eur Heart J 2007;28:2583– 8. 18. Spirito P, Bellone P, Harris KM, Bernabo P, Bruzzi P, Maron BJ. Magnitude of left ventricular hypertrophy and risk of sudden death in hypertrophic cardiomyopathy. N Engl J Med 2000;342:1778 – 85. 19. Maron BJ, Shen WK, Link MS, et al. Efficacy of implantable cardioverter-defibrillators for the prevention of sudden death in patients with hypertrophic cardiomyopathy. N Engl J Med 2000;342:365–73.
DISCUSSION DR HITENDU DAVE (Zurich, Switzerland): Really very impressive results. My question is, I probably missed it, what are the indications of putting a simultaneous intracardiac defibrillator? Because as I understand, these patients in spite of relief of obstruction still have a risk of sudden death. So what are your indications, and if you have put an ICD [implantable cardiac defibrillator], where is the place where you put your ventricular electrodes? DR ALTARABSHEH: Thank you. That is a good question, and I would like an input from Dr Dearani on this subject. DR JOSEPH A. DEARANI (Rochester, MN): The indications for placement of ICD: Ventricular septal thickness 30 mm or greater,
positive family history of sudden death, a history of syncope felt to be related to arrhythmia and not obstruction, which requires an analysis by a cardiologist experienced with HCM [hypertrophic cardiomyopathy]. Our technique of defibrillator implantation is as follows: if they are big enough, they get an endocardial system. In a younger child, we use an endocardial system that is placed epicardially at the time of surgery. The endocardial lead is placed through the transverse sinus and it is fixed to the pericardium over the anterolateral wall of the left ventricle, and the generator is placed in the right upper quadrant of the abdomen. This results in the vector through the heart from the right upper quadrant of the abdomen to the left shoulder. Thank you.
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