Surgical Septal Myectomy vs Percutaneous Transluminal Alcohol Septal Ablation in Patients With Hypertrophic Obstructive Cardiomyopathy

Hypertrophic Cardiomyopathy Clinical Trial

— AMARONE  

Official title:

Surgical Septal Myectomy Versus Percutaneous Transluminal Alcohol Septal Ablation in Patients With Hypertrophic Obstructive Cardiomyopathy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04684290
• Other study ID #: NL73176.100.20
• Status: Recruiting
• Phase: N/A
• Start date: June 30, 2021
• Est. completion date: May 1, 2026

Study information

• Verified date: September 2021
• Source: St. Antonius Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this randomized trial is to compare the improvement in exercise capacity among patients with highly symptomatic hypertrophic obstructive cardiomyopathy despite optimal medical treatment who undergo alcohol septal ablation (ASA) or surgical septal myectomy (SSM).

Description:

This is a prospective, multicentre, open label, randomized controlled, non-inferiority trial (RCT) with a 1:1 randomization to alcohol septal ablation or surgical septal myectomy in patients with hypertrophic obstructive cardiomyopathy (HOCM) between 40-75 year of age with symptoms and/or syncope due to HOCM despite medical therapy. A total of 100 patients will be included. All patients will be evaluated with bicycle ergometry exercise test, MRI and 2D-echo before and 1 year after invasive treatment. Follow-up will be at 1,3 and 5 years.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: May 1, 2026
• Est. primary completion date: May 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Age between 40-75 years including 40 and 75 years of age

2. HOCM eligible for both SSM and ASA by a heart team (multidisciplinary team) and core lab.

3. Left ventricle outflow tract (LVOT) obstruction > 30mmHg at rest or during physiological provocation by transthoracic echocardiogram

4. Symptomatic (New York Heart Association classification (NYHA) >1 or Canadian Cardiovascular Society (CCS) class >1) and/or syncope due to HOCM

Exclusion Criteria:

1. Unable to give informed consent

2. A life expectancy of less than 1 year

3. Concomitant (structural valve disease, aorta, rhythm, CABG) surgery during the same session

4. Not able to perform bicycle ergometry exercise test

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy, Hypertrophic
• Hypertrophic Cardiomyopathy
• Hypertrophy

Intervention

Procedure:
• Alcohol Septal Ablation
Participants will be treated with alcohol septal ablation.
• Surgical Septal Myectomy
Participants will be treated with surgical septal myectomy.

Locations

Country	Name	City	State
Netherlands	St. Antonius Hospital	Nieuwegein	Utrecht

Sponsors (2)

Lead Sponsor	Collaborator
St. Antonius Hospital	Erasmus Medical Center

Country where clinical trial is conducted

Netherlands, 

References & Publications (16)

Arslan F, Akdim F, Ten Berg JM. Reverse remodeling after percutaneous transluminal septal myocardial ablation in severe but asymptomatic LVOT obstruction (RASTA) study: Rationale and design of transcatheter septal reduction in asymptomatic patients with severe hypertrophic obstructive cardiomyopathy. Catheter Cardiovasc Interv. 2021 Feb 15;97(3):488-492. doi: 10.1002/ccd.29178. Epub 2020 Aug 18. — View Citation

Authors/Task Force members, Elliott PM, Anastasakis A, Borger MA, Borggrefe M, Cecchi F, Charron P, Hagege AA, Lafont A, Limongelli G, Mahrholdt H, McKenna WJ, Mogensen J, Nihoyannopoulos P, Nistri S, Pieper PG, Pieske B, Rapezzi C, Rutten FH, Tillmanns C, Watkins H. 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). Eur Heart J. 2014 Oct 14;35(39):2733-79. doi: 10.1093/eurheartj/ehu284. Epub 2014 Aug 29. — View Citation

Gersh BJ, Maron BJ, Bonow RO, Dearani JA, Fifer MA, Link MS, Naidu SS, Nishimura RA, Ommen SR, Rakowski H, Seidman CE, Towbin JA, Udelson JE, Yancy CW; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines; American Association for Thoracic Surgery; American Society of Echocardiography; American Society of Nuclear Cardiology; Heart Failure Society of America; Heart Rhythm Society; Society for Cardiovascular Angiography and Interventions; Society of Thoracic Surgeons. 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 Dec 13;124(24):e783-831. doi: 10.1161/CIR.0b013e318223e2bd. Epub 2011 Nov 8. — View Citation

Jensen MK, Faber L, Liebregts M, Januska J, Krejci J, Bartel T, Cooper RM, Dabrowski M, Hansen PR, Almaas VM, Seggewiss H, Horstkotte D, Adlova R, Berg JT, Bundgaard H, Veselka J. Effect of impaired cardiac conduction after alcohol septal ablation on clinical outcomes: insights from the Euro-ASA registry. Eur Heart J Qual Care Clin Outcomes. 2019 Jul 1;5(3):252-258. doi: 10.1093/ehjqcco/qcy049. — View Citation

Liebregts M, Faber L, Jensen MK, Vriesendorp PA, Januska J, Krejci J, Hansen PR, Seggewiss H, Horstkotte D, Adlova R, Bundgaard H, Ten Berg JM, Veselka J. Outcomes of Alcohol Septal Ablation in Younger Patients With Obstructive Hypertrophic Cardiomyopathy. JACC Cardiovasc Interv. 2017 Jun 12;10(11):1134-1143. doi: 10.1016/j.jcin.2017.03.030. — View Citation

Liebregts M, Steggerda RC, Vriesendorp PA, van Velzen H, Schinkel AF, Willems R, van Cleemput J, van den Berg MP, Michels M, ten Berg JM. Long-Term Outcome of Alcohol Septal Ablation for Obstructive Hypertrophic Cardiomyopathy in the Young and the Elderly. JACC Cardiovasc Interv. 2016 Mar 14;9(5):463-9. doi: 10.1016/j.jcin.2015.11.036. — View Citation

Liebregts M, Vriesendorp PA, Mahmoodi BK, Schinkel AF, Michels M, ten Berg JM. A Systematic Review and Meta-Analysis of Long-Term Outcomes After Septal Reduction Therapy in Patients With Hypertrophic Cardiomyopathy. JACC Heart Fail. 2015 Nov;3(11):896-905. doi: 10.1016/j.jchf.2015.06.011. Epub 2015 Oct 7. Review. — View Citation

Liebregts M, Vriesendorp PA, Steggerda RC, Schinkel AF, Balt JC, Ten Cate FJ, Michels M, Ten Berg JM. Effect of alcohol dosage on long-term outcomes after alcohol septal ablation in patients with hypertrophic cardiomyopathy. Catheter Cardiovasc Interv. 2016 Nov 15;88(6):945-952. doi: 10.1002/ccd.26448. Epub 2016 Mar 4. — View Citation

Sherrid MV, Wever-Pinzon O, Shah A, Chaudhry FA. Reflections of inflections in hypertrophic cardiomyopathy. J Am Coll Cardiol. 2009 Jul 14;54(3):212-9. doi: 10.1016/j.jacc.2009.03.052. Review. — View Citation

Veselka J, Faber L, Liebregts M, Cooper R, Januska J, Krejci J, Bartel T, Dabrowski M, Hansen PR, Almaas VM, Seggewiss H, Horstkotte D, Adlova R, Bundgaard H, Ten Berg J, Stables RH, Jensen MK. Outcome of Alcohol Septal Ablation in Mildly Symptomatic Patients With Hypertrophic Obstructive Cardiomyopathy: A Long-Term Follow-Up Study Based on the Euro-Alcohol Septal Ablation Registry. J Am Heart Assoc. 2017 May 16;6(5). pii: e005735. doi: 10.1161/JAHA.117.005735. — View Citation

Veselka J, Faber L, Liebregts M, Cooper R, Januska J, Krejci J, Dabrowski M, Hansen PR, Seggewiss H, Horstkotte D, Hansvenclova E, Bundgaard H, Ten Berg J, Jensen MK. Long-term outcome of repeated septal reduction therapy after alcohol septal ablation for hypertrophic obstructive cardiomyopathy: insight from the Euro-ASA registry. Arch Med Sci. 2020 Aug 10;16(5):1239-1242. doi: 10.5114/aoms.2020.97969. eCollection 2020. — View Citation

Veselka J, Jensen M, Liebregts M, Cooper RM, Januska J, Kashtanov M, Dabrowski M, Hansen PR, Seggewiss H, Hansvenclova E, Bundgaard H, Ten Berg J, Hilton Stables R, Faber L. Alcohol septal ablation in patients with severe septal hypertrophy. Heart. 2020 Mar;106(6):462-466. doi: 10.1136/heartjnl-2019-315422. Epub 2019 Aug 30. — View Citation

Veselka J, Jensen MK, Liebregts M, Januska J, Krejci J, Bartel T, Dabrowski M, Hansen PR, Almaas VM, Seggewiss H, Horstkotte D, Tomasov P, Adlova R, Bundgaard H, Steggerda R, Ten Berg J, Faber L. Long-term clinical outcome after alcohol septal ablation for obstructive hypertrophic cardiomyopathy: results from the Euro-ASA registry. Eur Heart J. 2016 May 14;37(19):1517-23. doi: 10.1093/eurheartj/ehv693. Epub 2016 Jan 7. — View Citation

Veselka J, Tomašov P, Zemánek D. Long-term effects of varying alcohol dosing in percutaneous septal ablation for obstructive hypertrophic cardiomyopathy: a randomized study with a follow-up up to 11 years. Can J Cardiol. 2011 Nov-Dec;27(6):763-7. doi: 10.1016/j.cjca.2011.09.001. Epub 2011 Oct 14. — View Citation

Wigle ED, Sasson Z, Henderson MA, Ruddy TD, Fulop J, Rakowski H, Williams WG. Hypertrophic cardiomyopathy. The importance of the site and the extent of hypertrophy. A review. Prog Cardiovasc Dis. 1985 Jul-Aug;28(1):1-83. Review. — View Citation

Wigle ED. Cardiomyopathy: The diagnosis of hypertrophic cardiomyopathy. Heart. 2001 Dec;86(6):709-14. Review. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Metabolic Equivalent (METs) assessed with a bicycle ergometry exercise test	The primary endpoint is the improvement of the exercise capacity in the form of Metabolic Equivalent (METs) which will be assessed with a bicycle ergometry exercise test (difference in exercise capacity in Metabolic Equivalents) performed before and 1 year after invasive treatment.	1 year after the invasive treatment
Secondary	Number of participants with all-cause mortality		Follow up will be 1,3 and 5 years
Secondary	Number of participants with cardiovascular mortality		Follow up will be 1,3 and 5 years
Secondary	Number of participants with transient Ischemic Attack		Follow up will be 1,3 and 5 years
Secondary	Number of participants with hospital Readmittance		Follow up will be 1,3 and 5 years
Secondary	Number of participants with with occurrence of atrial fibrillation		Follow up will be 1,3 and 5 years
Secondary	Number of participants with ventricular arrhythmias		Follow up will be 1,3 and 5 years
Secondary	Number of participants with with complete heart block requiring permanent pacemaker implantation		Follow up will be 1,3 and 5 years
Secondary	Number of participants with major bleeding	Bleeding rate will be analysed using Bleeding Academic Research Consortium (type 3,4 or 5), TIMI major and VARC major criteria.	First 30 days
Secondary	Number of participants with re-intervention	One more time need for Alcohol septal ablation or surgical septal myectomy	Follow up will be 1,3 and 5 years
Secondary	Blood sample results	Troponin T (in ug/l)	Follow up will be 1,3 and 5 years
Secondary	Blood sample results	N-terminal prohormone of brain natriuretic peptide (NT-pro-BNP in pg/ml)	Follow up will be 1,3 and 5 years
Secondary	Blood sample results	Creatine-kinase (CK in U/l)	Follow up will be 1,3 and 5 years
Secondary	Quality of life evaluation using the The Kansas City Cardiomyopathy Questionnaire (KCCQ)	In the KCCQ, an overall summary score can be derived from the physical function, symptom (frequency and severity), social function and quality of life domains. For each domain, the validity, reproducibility, responsiveness and interpretability have been independently established. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. For brevity, only the performance characteristics of the overall summary score are presented in this discussion.	Follow up will be 1,3 and 5 years
Secondary	Cardiac Magnetic Resonance Imaging (CMR) parameters	Interventricular septal thickness (mm), atrial diameter (mm) , left and right ventricular diameter (mm), left ventricle end diastolic volume (ml), left ventricle systolic volume (ml)	Follow up will be 1,3 and 5 years
Secondary	Cardiac Magnetic Resonance Imaging (CMR) parameters	Left ventricle end diastolic volume (ml), left ventricle systolic volume (ml)	Follow up will be 1,3 and 5 years
Secondary	Transthoracic echocardiogram	Left ventricle ejection fraction (%)	Follow up will be 1,3 and 5 years
Secondary	Transthoracic echocardiogram	Left ventricle outflow tract gradient (mmHg)	Follow up will be 1,3 and 5 years
Secondary	Transthoracic echocardiogram	Left ventricular internal systolic and diastolic dimension (cm)	Follow up will be 1,3 and 5 years
Secondary	Transthoracic echocardiogram	Atrial diameter (ml/m2)	Follow up will be 1,3 and 5 years
Secondary	Transthoracic echocardiogram	Valvular function	Follow up will be 1,3 and 5 years
Secondary	Transthoracic echocardiogram	Right ventricular systolic pressure (mmHg)	Follow up will be 1,3 and 5 years
Secondary	Transthoracic echocardiogram	Interventricular septal thickness (mm)	Follow up will be 1,3 and 5 years