Cardiology in the Young 2015; Page 1 of 4
© Cambridge University Press, 2015
doi:10.1017/S104795111500013X
Brief Report Septal myectomy for hypertrophic obstructive cardiomyopathy in Friedreich’s ataxia Heather N. Anderson,1 Harold M. Burkhart,2 Jonathan N. Johnson3 1
Department of Pediatric and Adolescent Medicine; 2Division of Cardiovascular Surgery; 3Department of Pediatrics, Division of Pediatric Cardiology, Mayo Clinic, Rochester, Minnesota, United States of America Abstract Hypertrophic cardiomyopathy associated with Friedreich’s ataxia is progressive, and there are few, if any, effective treatments available at present. This case report describes a Friedreich’s ataxia patient who had a septal myectomy for the management of hypertrophic cardiomyopathy with improved symptoms over a 7-year period. This suggests that septal myectomy may be a viable option to relieve symptoms and interrupt progression of heart disease in appropriately selected Friedreich’s ataxia patients. Keywords: Friedreich’s ataxia; hypertrophic cardiomyopathy; septal myectomy Received: 5 October 2014; Accepted: 17 January 2015
RIEDREICH’S ATAXIA IS AN AUTOSOMAL RECESSIVE
F
disorder characterised by progressive nervous system damage and ataxia. Other manifestations of Friedreich’s ataxia include cardiomyopathy, scoliosis, and diabetes.1,2 More than 60% of patients with Friedreich’s ataxia may develop hypertrophic cardiomyopathy.3,4 Attempts to identify treatments to prevent and manage hypertrophic cardiomyopathy in these patients have been limited.5,7 This article details the first reported case of Friedreich’s ataxiaassociated hypertrophic cardiomyopathy successfully managed with septal myectomy.
Case report Our patient was diagnosed with Friedreich’s ataxia at 4 years of age following a period of progressive ataxia. As part of the initial workup, an echocardiogram was performed, which demonstrated hypertrophic cardiomyopathy. Follow-up echocardiograms showed worsening left ventricular outflow tract obstruction, and he was referred to our centre. His echocardiogram at that time demonstrated a peak left ventricular Correspondence to: Dr J. N. Johnson, MD, FACC, FASE, FAAP, Department of Medicine, Division of Cardiovascular Disease, Mayo Clinic, Gonda 6-138SW, First Street SW, Rochester, MN 55905, United States of America. Tel: 507 266 0676; Fax: 507 284 3968; E-mail: [email protected]
outflow tract gradient of 80 mmHg and moderate septal wall hypertrophy. During the time of this evaluation, the patient was treated with propranolol (0.7 mg/day). Following presentation to our institution, preoperative echocardiography showed severe hypertrophic cardiomyopathy (septal thickness of 16 mm) with a peak left ventricular outflow tract gradient of 104 mmHg and mitral valve systolic anterior motion. In addition, moderate mitral valve regurgitation and borderline left atrial enlargement were observed. The right ventricle had normal size and systolic function. The following day, an extended left ventricular septal myectomy was performed with resection of an accessory mitral chord. The mitral papillary muscles were noted to be highly hypertrophied (up to 1.5 cm in diameter). The septal myectomy was performed starting at the nadir of the right coronary cusp and extending leftward towards the free wall. There was a large and thickened accessory cord from the papillary muscle of the mitral valve to the posterior edge of the free wall and this was resected. The myectomy was then extended towards the edge of the mitral valve. The cross-clamp time for this procedure was 83 minutes, and total bypass time was 91 minutes. Postoperative trans-oesophageal echocardiography demonstrated no evidence of left ventricular outflow tract obstruction
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Cardiology in the Young
2015
Figure 1. Still-frame images from the patient’s preoperative (a–c) and postoperative (d–f) echocardiograms. (a) Preoperative four-chamber view demonstrating prominent septal hypertrophy. (b) Systolic anterior motion of the anterior mitral leaflet into the left ventricular outflow tract (arrow). (c) Doppler imaging demonstrating increased velocity through the left ventricular outflow tract (peak gradient 80 mmHg). (d) Postoperative four-chamber view showing the site of the septal myectomy and a widely patent left ventricular outflow tract. (e) Doppler imaging demonstrating decreased flow acceleration through the left ventricular outflow tract and mild dynamic mid-ventricular obstruction at the level of the papillary muscles (arrow). (f) Parasternal long-axis view showing a widely patent left ventricular outflow tract. LA = left atrium; LV = left ventricle; LVOT = left ventricular outflow tract; RA = right atrium; RV = right ventricle; *ventricular septum.
and trivial mitral regurgitation. Mild dynamic midventricular obstruction was noted at the level of the mid-papillary muscles with a maximum gradient of 40 mmHg; this was secondary to the hypertrophied papillary muscles and did not cause outlet obstruction. Postoperatively, the patient required an esmolol infusion for heart rate and blood pressure control. Transthoracic echocardiography was performed on day 11, which demonstrated no evidence of left ventricular outflow tract obstruction. The patient was discharged on postoperative day 11. His hospitalisation was prolonged due to pleural effusion requiring chest tube placement on postoperative day 2. The chest tube was subsequently removed on postoperative day 9. The patient had close outpatient surveillance following surgery. It is now 7 years since the surgery, and serial echocardiograms of the patient continue to demonstrate no significant outflow tract obstruction
and only trivial mitral regurgitation (Fig 1). He currently takes no cardiac medications.
Discussion This case report is the first to describe the use of septal myectomy in the management of hypertrophic cardiomyopathy with left ventricular outflow tract obstruction in Friedreich’s ataxia. Kipps et al4 in 2009 sought to describe the natural progression of cardiomyopathy in patients with Friedreich’s ataxia. In this study, patients initially demonstrated left ventricular hypertrophy on echocardiogram, with a portion then progressing to systolic dysfunction at an average age of 22 years. In all, 12 of the 23 patients (52%) with Friedreich’s ataxia and hypertrophic cardiomyopathy developed systolic dysfunction. A portion of the patients in this
Anderson et al: Friedreich’s ataxia-associated hypertrophic cardiomyopathy
study received coenzyme Q or idebenone during their follow-up, with some demonstrating improvement or at least stabilisation of their disease; however, this was not a targeted outcome evaluated in this study. Despite early promising evidence,5 a recent study published on the use of idebenone did not show clinically relevant improvement in left ventricular hypertrophy or systolic function over a 6-month follow-up period.6 At present, there are other anti-oxidant treatments that are undergoing evaluation of their use in patients with Friedreich’s ataxia; however, a recent Cochrane review identified no other treatments that have shown significant benefits for patients with Friedreich’s ataxiaassociated hypertrophic cardiomyopathy.7 The use of septal myectomy as a technique for the management of patients with hypertrophic cardiomyopathy and left ventricular outflow tract obstruction has been in practice for almost 50 years.8 This procedure reliably relieves outflow tract obstruction, thereby normalising left ventricular pressures and decreasing the risk of progressive heart failure.9 It is generally indicated in patients with significant symptoms due to left ventricular outflow tract obstruction, such as fatigue, exertional chest pain, and palpitations, which are refractory to pharmacologic therapy. Usually the maximal instantaneous gradient is at least 50 mmHg across the left ventricular outflow tract.10 Our patient had symptoms of fatigue and palpitations before surgery with a preoperative left ventricular outflow tract gradient of 104 mmHg secondary to systolic anterior motion of the mitral valve. Despite treatment with propranolol, symptoms and echocardiographic findings did not improve. Therefore, he met the outlined criteria to undergo a septal myectomy, which provided relief of obstruction and improvement in symptoms. Given the progressive nature of cardiomyopathy in Friedreich’s ataxia, it might be a concern that the hypertrophy and obstruction would recur; however, this patient did not demonstrate any recurrence over a 7-year follow-up period. In addition, this patient has not developed systolic dysfunction during this follow-up period. This suggests that myectomy may be a viable option for the management of select Friedreich’s ataxia patients who would otherwise meet the standard criteria for septal myectomy. Myectomy should not be withheld if standard hypertrophic cardiomyopathy indications are present in patients with Friedreich’s ataxia. It should be noted that there has been sustained improvement in the degree of mitral regurgitation following septal myectomy. Although speculative, it is possible that an increasing degree of mitral regurgitation related to left ventricular outflow tract
3
obstruction, over time, could have accelerated his degree of systolic dysfunction and symptomatology related to his hypertrophic cardiomyopathy. Preventing ventricular dysfunction related to mitral regurgitation or residual obstruction may have specific importance to patients with Friedreich’s ataxia.
Conclusion This case report suggests that septal myectomy may be an effective and appropriate choice of intervention in specifically selected patients with Friedreich’s ataxia and hypertrophic cardiomyopathy, who also demonstrate left ventricular outflow tract obstruction. Further research is needed to describe the longterm outcomes for patients who undergo this procedure. Acknowledgements The authors thank Dr. Ralitza Garvilova and Dr. Frank Cetta for reviewing this manuscript before publication. Financial Support This research received no specific grant from any funding agency, commercial or not-for-profit sectors. Conflicts of Interest None. Ethical Standards The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national guidelines on human experimentation in the United States of America and with the Helsinki Declaration of 1975, as revised in 2008, and has been approved by the institutional committees of Mayo Clinic.
References 1. Harding AE. Friedreich's ataxia: a clinical and genetic study of 90 families with an analysis of early diagnostic criteria and intrafamilial clustering of clinical features. Brain: J Neurol 1981; 104: 589–620. 2. Schulz JB, Boesch S, Bürk K, et al. Diagnosis and treatment of Friedreich ataxia: a European perspective. Nature reviews Neurology 2009; 5: 222–234. 3. Durr A, Cossee M, Agid Y, et al. Clinical and genetic abnormalities in patients with Friedreich’s ataxia. N Engl J Med 1996; 335: 1169–1175. 4. Kipps A, Alexander M, Colan SD, et al. The longitudinal course of cardiomyopathy in Friedreich's ataxia during childhood. Pediatr Cardiol 2009; 30: 306–310. 5. Hausse AO, Aggoun Y, Bonnet D, et al. Idebenone and reduced cardiac hypertrophy in Friedreich's ataxia. Heart 2002; 87: 346–349.
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6. Lagedrost SJ, Sutton MSJ, Cohen MS, et al. Idebenone in Friedreich ataxia cardiomyopathy-results from a 6-month phase III study (IONIA). Am Heart J 2011; 161: 639.e1–645.e1. 7. Kearney M, Orrell RW, Fahey M, et al. Antioxidants and other pharmacological treatments for Friedreich ataxia. Cochrane Database Syst Rev 2012; 4: CD007791. 8. Maron BJ, Maron MS. Hypertrophic cardiomyopathy. Lancet 2013; 381: 242–255. 9. Maron BJ, McKenna WJ, Danielson GK, et al. American College of Cardiology/European Society of Cardiology clinical expert
2015
consensus document on hypertrophic cardiomyopathy. A report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the European Society of Cardiology Committee for Practice Guidelines. J Am Coll Cardiol 2003; 42: 1687–1713. 10. Gersh BJ, Maron BJ, Bonow RO, et al. 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: a report of the American College of Cardiology Foundation/ American Heart Association Task Force on Practice Guidelines. Circulation 2011; 124: e783–e831.
© Cambridge University Press, 2015
doi:10.1017/S104795111500013X
Brief Report Septal myectomy for hypertrophic obstructive cardiomyopathy in Friedreich’s ataxia Heather N. Anderson,1 Harold M. Burkhart,2 Jonathan N. Johnson3 1
Department of Pediatric and Adolescent Medicine; 2Division of Cardiovascular Surgery; 3Department of Pediatrics, Division of Pediatric Cardiology, Mayo Clinic, Rochester, Minnesota, United States of America Abstract Hypertrophic cardiomyopathy associated with Friedreich’s ataxia is progressive, and there are few, if any, effective treatments available at present. This case report describes a Friedreich’s ataxia patient who had a septal myectomy for the management of hypertrophic cardiomyopathy with improved symptoms over a 7-year period. This suggests that septal myectomy may be a viable option to relieve symptoms and interrupt progression of heart disease in appropriately selected Friedreich’s ataxia patients. Keywords: Friedreich’s ataxia; hypertrophic cardiomyopathy; septal myectomy Received: 5 October 2014; Accepted: 17 January 2015
RIEDREICH’S ATAXIA IS AN AUTOSOMAL RECESSIVE
F
disorder characterised by progressive nervous system damage and ataxia. Other manifestations of Friedreich’s ataxia include cardiomyopathy, scoliosis, and diabetes.1,2 More than 60% of patients with Friedreich’s ataxia may develop hypertrophic cardiomyopathy.3,4 Attempts to identify treatments to prevent and manage hypertrophic cardiomyopathy in these patients have been limited.5,7 This article details the first reported case of Friedreich’s ataxiaassociated hypertrophic cardiomyopathy successfully managed with septal myectomy.
Case report Our patient was diagnosed with Friedreich’s ataxia at 4 years of age following a period of progressive ataxia. As part of the initial workup, an echocardiogram was performed, which demonstrated hypertrophic cardiomyopathy. Follow-up echocardiograms showed worsening left ventricular outflow tract obstruction, and he was referred to our centre. His echocardiogram at that time demonstrated a peak left ventricular Correspondence to: Dr J. N. Johnson, MD, FACC, FASE, FAAP, Department of Medicine, Division of Cardiovascular Disease, Mayo Clinic, Gonda 6-138SW, First Street SW, Rochester, MN 55905, United States of America. Tel: 507 266 0676; Fax: 507 284 3968; E-mail: [email protected]
outflow tract gradient of 80 mmHg and moderate septal wall hypertrophy. During the time of this evaluation, the patient was treated with propranolol (0.7 mg/day). Following presentation to our institution, preoperative echocardiography showed severe hypertrophic cardiomyopathy (septal thickness of 16 mm) with a peak left ventricular outflow tract gradient of 104 mmHg and mitral valve systolic anterior motion. In addition, moderate mitral valve regurgitation and borderline left atrial enlargement were observed. The right ventricle had normal size and systolic function. The following day, an extended left ventricular septal myectomy was performed with resection of an accessory mitral chord. The mitral papillary muscles were noted to be highly hypertrophied (up to 1.5 cm in diameter). The septal myectomy was performed starting at the nadir of the right coronary cusp and extending leftward towards the free wall. There was a large and thickened accessory cord from the papillary muscle of the mitral valve to the posterior edge of the free wall and this was resected. The myectomy was then extended towards the edge of the mitral valve. The cross-clamp time for this procedure was 83 minutes, and total bypass time was 91 minutes. Postoperative trans-oesophageal echocardiography demonstrated no evidence of left ventricular outflow tract obstruction
2
Cardiology in the Young
2015
Figure 1. Still-frame images from the patient’s preoperative (a–c) and postoperative (d–f) echocardiograms. (a) Preoperative four-chamber view demonstrating prominent septal hypertrophy. (b) Systolic anterior motion of the anterior mitral leaflet into the left ventricular outflow tract (arrow). (c) Doppler imaging demonstrating increased velocity through the left ventricular outflow tract (peak gradient 80 mmHg). (d) Postoperative four-chamber view showing the site of the septal myectomy and a widely patent left ventricular outflow tract. (e) Doppler imaging demonstrating decreased flow acceleration through the left ventricular outflow tract and mild dynamic mid-ventricular obstruction at the level of the papillary muscles (arrow). (f) Parasternal long-axis view showing a widely patent left ventricular outflow tract. LA = left atrium; LV = left ventricle; LVOT = left ventricular outflow tract; RA = right atrium; RV = right ventricle; *ventricular septum.
and trivial mitral regurgitation. Mild dynamic midventricular obstruction was noted at the level of the mid-papillary muscles with a maximum gradient of 40 mmHg; this was secondary to the hypertrophied papillary muscles and did not cause outlet obstruction. Postoperatively, the patient required an esmolol infusion for heart rate and blood pressure control. Transthoracic echocardiography was performed on day 11, which demonstrated no evidence of left ventricular outflow tract obstruction. The patient was discharged on postoperative day 11. His hospitalisation was prolonged due to pleural effusion requiring chest tube placement on postoperative day 2. The chest tube was subsequently removed on postoperative day 9. The patient had close outpatient surveillance following surgery. It is now 7 years since the surgery, and serial echocardiograms of the patient continue to demonstrate no significant outflow tract obstruction
and only trivial mitral regurgitation (Fig 1). He currently takes no cardiac medications.
Discussion This case report is the first to describe the use of septal myectomy in the management of hypertrophic cardiomyopathy with left ventricular outflow tract obstruction in Friedreich’s ataxia. Kipps et al4 in 2009 sought to describe the natural progression of cardiomyopathy in patients with Friedreich’s ataxia. In this study, patients initially demonstrated left ventricular hypertrophy on echocardiogram, with a portion then progressing to systolic dysfunction at an average age of 22 years. In all, 12 of the 23 patients (52%) with Friedreich’s ataxia and hypertrophic cardiomyopathy developed systolic dysfunction. A portion of the patients in this
Anderson et al: Friedreich’s ataxia-associated hypertrophic cardiomyopathy
study received coenzyme Q or idebenone during their follow-up, with some demonstrating improvement or at least stabilisation of their disease; however, this was not a targeted outcome evaluated in this study. Despite early promising evidence,5 a recent study published on the use of idebenone did not show clinically relevant improvement in left ventricular hypertrophy or systolic function over a 6-month follow-up period.6 At present, there are other anti-oxidant treatments that are undergoing evaluation of their use in patients with Friedreich’s ataxia; however, a recent Cochrane review identified no other treatments that have shown significant benefits for patients with Friedreich’s ataxiaassociated hypertrophic cardiomyopathy.7 The use of septal myectomy as a technique for the management of patients with hypertrophic cardiomyopathy and left ventricular outflow tract obstruction has been in practice for almost 50 years.8 This procedure reliably relieves outflow tract obstruction, thereby normalising left ventricular pressures and decreasing the risk of progressive heart failure.9 It is generally indicated in patients with significant symptoms due to left ventricular outflow tract obstruction, such as fatigue, exertional chest pain, and palpitations, which are refractory to pharmacologic therapy. Usually the maximal instantaneous gradient is at least 50 mmHg across the left ventricular outflow tract.10 Our patient had symptoms of fatigue and palpitations before surgery with a preoperative left ventricular outflow tract gradient of 104 mmHg secondary to systolic anterior motion of the mitral valve. Despite treatment with propranolol, symptoms and echocardiographic findings did not improve. Therefore, he met the outlined criteria to undergo a septal myectomy, which provided relief of obstruction and improvement in symptoms. Given the progressive nature of cardiomyopathy in Friedreich’s ataxia, it might be a concern that the hypertrophy and obstruction would recur; however, this patient did not demonstrate any recurrence over a 7-year follow-up period. In addition, this patient has not developed systolic dysfunction during this follow-up period. This suggests that myectomy may be a viable option for the management of select Friedreich’s ataxia patients who would otherwise meet the standard criteria for septal myectomy. Myectomy should not be withheld if standard hypertrophic cardiomyopathy indications are present in patients with Friedreich’s ataxia. It should be noted that there has been sustained improvement in the degree of mitral regurgitation following septal myectomy. Although speculative, it is possible that an increasing degree of mitral regurgitation related to left ventricular outflow tract
3
obstruction, over time, could have accelerated his degree of systolic dysfunction and symptomatology related to his hypertrophic cardiomyopathy. Preventing ventricular dysfunction related to mitral regurgitation or residual obstruction may have specific importance to patients with Friedreich’s ataxia.
Conclusion This case report suggests that septal myectomy may be an effective and appropriate choice of intervention in specifically selected patients with Friedreich’s ataxia and hypertrophic cardiomyopathy, who also demonstrate left ventricular outflow tract obstruction. Further research is needed to describe the longterm outcomes for patients who undergo this procedure. Acknowledgements The authors thank Dr. Ralitza Garvilova and Dr. Frank Cetta for reviewing this manuscript before publication. Financial Support This research received no specific grant from any funding agency, commercial or not-for-profit sectors. Conflicts of Interest None. Ethical Standards The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national guidelines on human experimentation in the United States of America and with the Helsinki Declaration of 1975, as revised in 2008, and has been approved by the institutional committees of Mayo Clinic.
References 1. Harding AE. Friedreich's ataxia: a clinical and genetic study of 90 families with an analysis of early diagnostic criteria and intrafamilial clustering of clinical features. Brain: J Neurol 1981; 104: 589–620. 2. Schulz JB, Boesch S, Bürk K, et al. Diagnosis and treatment of Friedreich ataxia: a European perspective. Nature reviews Neurology 2009; 5: 222–234. 3. Durr A, Cossee M, Agid Y, et al. Clinical and genetic abnormalities in patients with Friedreich’s ataxia. N Engl J Med 1996; 335: 1169–1175. 4. Kipps A, Alexander M, Colan SD, et al. The longitudinal course of cardiomyopathy in Friedreich's ataxia during childhood. Pediatr Cardiol 2009; 30: 306–310. 5. Hausse AO, Aggoun Y, Bonnet D, et al. Idebenone and reduced cardiac hypertrophy in Friedreich's ataxia. Heart 2002; 87: 346–349.
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Cardiology in the Young
6. Lagedrost SJ, Sutton MSJ, Cohen MS, et al. Idebenone in Friedreich ataxia cardiomyopathy-results from a 6-month phase III study (IONIA). Am Heart J 2011; 161: 639.e1–645.e1. 7. Kearney M, Orrell RW, Fahey M, et al. Antioxidants and other pharmacological treatments for Friedreich ataxia. Cochrane Database Syst Rev 2012; 4: CD007791. 8. Maron BJ, Maron MS. Hypertrophic cardiomyopathy. Lancet 2013; 381: 242–255. 9. Maron BJ, McKenna WJ, Danielson GK, et al. American College of Cardiology/European Society of Cardiology clinical expert
2015
consensus document on hypertrophic cardiomyopathy. A report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the European Society of Cardiology Committee for Practice Guidelines. J Am Coll Cardiol 2003; 42: 1687–1713. 10. Gersh BJ, Maron BJ, Bonow RO, et al. 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: a report of the American College of Cardiology Foundation/ American Heart Association Task Force on Practice Guidelines. Circulation 2011; 124: e783–e831.
