Atrial Appendage Micrograft Transplants to Assist Heart Repair After Cardiac Surgery

NCT05632432 | Recruiting

• 1 other identifier: AAMS2
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Ischemic heart disease (IHD) leads the global mortality statistics. Atherosclerotic plaques in coronary arteries hallmark IHD, drive hypoxia, and may rupture to result in myocardial infarction (MI) and death of contractile cardiac muscle, which is eventually replaced by a scar. Depending on the extent of the damage, dysbalanced cardiac workload often leads to emergence of heart failure (HF). The atrial appendages, enriched with active endocrine and paracrine cardiac cells, has been characterized to contain cells promising in stimulating cardiac regenerative healing. In this AAMS2 randomized controlled and double-blinded trial, the patient's own tissue from the right atrial appendage (RAA) is for therapy. A piece from the RAA can be safely harvested upon the set-up of the heart and lung machine at the beginning of coronary artery bypass (CABG) surgery. In the AAMS2 trial, a piece of the RAA tissue is processed and utilized as epicardially transplanted atrial appendage micrografts (AAMs) for CABG-support therapy. In our preclinical evaluation, epicardial AAMs transplantation after MI attenuated scarring and improved cardiac function. Proteomics suggested an AAMs-induced glycolytic metabolism, a process associated with an increased regenerative capacity of myocardium. Recently, the safety and feasibility of AAMs therapy was demonstrated in an open-label clinical study. Moreover, as this study suggested increased thickness of the viable myocardium in the scarred area, it also provided the first indication of therapeutic benefit. Based on randomization with estimated enrolment of a total of 50 patients with 1:1 group allocation ratio, the piece of RAA tissue is either perioperatively processed to AAMs or cryostored. The AAMs, embedded in a fibrin matrix gel, are placed on a collaged-based matrix sheet, which is then epicardially sutured in place at the end of CABG surgery. The location is determined by preoperative late gadolinium enhancement cardiac magnetic resonance imaging (LGE-CMRI) to pinpoint the ischemic scar. The controls receive the collagen-based patch, but without the AAMs. Study blood samples, transthoracic echocardiography (TTE), and LGE-CMRI are performed before and at 6-month follow-up after the surgery. The trial's primary endpoints focus on changes in cardiac fibrosis as evaluated by LGE-CMRI and circulating levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP). Secondary endpoints center on other efficacy parameters, as well as both safety and feasibility of the therapy.

Conditions

Ischemic Heart Disease; Ischemic Cardiomyopathy; Heart Failure, Systolic; Heart Failure NYHA Class III; Heart Failure NYHA Class II; Heart Failure NYHA Class IV; Coronary Artery Disease

Keywords

Ischemic heart failure; Ischemic heart disease; Coronary artery disease; Coronary artery bypass grafting; Atrial appendage micrografts; Tissue-engineering; Ischemic cardiomyopathy; Atrial appendage; Micrografts; Cell Therapy; Epitranscriptomics

Outcome Measures

Primary Outcomes (2)

• Change in the amount of myocardial scar tissue

  Measured by LGE-CMRI preoperatively and at the 6-month-follow-up

  6 months

• Change in plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels

  Measured from blood sample at preoperative visit, 3-month, and 6-month follow-ups

  6 months

Secondary Outcomes (20)

• Efficacy: Change in left ventricular wall thickness

  6 months

• Efficacy: Change in viable left ventricular myocardium

  6 months

• Efficacy: Change in movement, systolic or diastolic function of the left ventricle

  6 months

• Efficacy: Change in left ventricular ejection fraction

  6 months

• Efficacy: Change in New York Heart Association (NYHA) class

  6 months

Study Arms (2)

CABG + collaged-based patch arm (control)

ACTIVE COMPARATOR

In total, 25 patients are recruited to form the CABG group. During CABG, RAA tissue is removed as detailed for the AAMs-patch group. However, the tissue is collected as a cryostored sample for later analyses rather than processed to AAMs (Method 4). CABG is performed without epicardial transplantation of AAMs, yet the collagen-based patch material is transplanted onto the epicardium of the scarred myocardium according the same principles as in the AAMs-patch intervention arm.

Diagnostic Test: RNA-stabilized whole blood sampling; Diagnostic Test: Plasma sampling; Diagnostic Test: Transthoracic echocardiography; Diagnostic Test: Late-gadolinium enhancement cardiac magnetic resonance imaging (LGE-CMRI); Other: Symptom-scaling; Other: 6-minute walking test (6MWT); Diagnostic Test: Blood sampling (NT-proBNP); Diagnostic Test: Transesophageal echocardiography; Procedure: Epicardial collagen-based patch transplantation

CABG + collagen based patch + AAMs arm (intervention)

EXPERIMENTAL

In total, 25 patients are recruited to the AAMs-patch group. Here, the AAMs are prepared from the RAA tissue sample by mechanical processing in the operating room during the CABG surgery. The RAA tissue piece is removed during right atrial cannulation, a part of the routine setup of cardiopulmonary bypass and mechanically processed to AAMs, which is allowed to gel with fibrinogen and thrombin in cold, covered, and sterile metallic dish until the last stages of CABG surgery. After all the coronary anastomoses are done, to form an AAMs-patch, the AAMs in a fibrin matrix gel are placed onto a collagen based matrix sheet and then epicardially transplanted onto the scar border area identified by preoperative LGE-CMRI to have most suffered from ischemia.

Procedure: Epicardial AAMs-patch transplantation; Diagnostic Test: RNA-stabilized whole blood sampling; Diagnostic Test: Plasma sampling; Diagnostic Test: Transthoracic echocardiography; Diagnostic Test: Late-gadolinium enhancement cardiac magnetic resonance imaging (LGE-CMRI); Other: Symptom-scaling; Other: 6-minute walking test (6MWT); Diagnostic Test: Blood sampling (NT-proBNP); Diagnostic Test: Transesophageal echocardiography

Interventions

Epicardial AAMs-patch transplantation PROCEDURE

Perioperative assembly of an AAMs-patch with epicardial transplantation onto the epicardium of the scarred myocardium at the end of CABG surgery

CABG + collagen based patch + AAMs arm (intervention)

RNA-stabilized whole blood sampling DIAGNOSTIC_TEST

Collection (preoperative and at 6-month-follow-up) of TEMPUS(TM) stabilizing whole blood for epitranscriptomics-oriented measurements

CABG + collaged-based patch arm (control); CABG + collagen based patch + AAMs arm (intervention)

Plasma sampling DIAGNOSTIC_TEST

Collection (preoperative and at 6-month follow-up) of blood-derived both RNA-stabilized and non-stabilized plasma aliquots for epitranscriptomic-oriented and other CVD biomarker oriented measurements, respectively

CABG + collaged-based patch arm (control); CABG + collagen based patch + AAMs arm (intervention)

Transthoracic echocardiography DIAGNOSTIC_TEST

To assess cardiac structure and function both pre- and postoperatively (at both hospital discharge and 3-month follow-up)

Also known as: TTE

CABG + collaged-based patch arm (control); CABG + collagen based patch + AAMs arm (intervention)

Late-gadolinium enhancement cardiac magnetic resonance imaging (LGE-CMRI) DIAGNOSTIC_TEST

To assess detailed cardiac structure (i.e. interstitial fibrosis) and function both preoperatively and at 6-month follow-up postoperatively.

CABG + collaged-based patch arm (control); CABG + collagen based patch + AAMs arm (intervention)

Symptom-scaling OTHER

Standardised evaluation of IHD and HF-related angina pectoris (CCS) and dyspnea (NYHA) and life quality (RAND36) pre- and postoperatively (at both 3- and 6-month follow-up).

CABG + collaged-based patch arm (control); CABG + collagen based patch + AAMs arm (intervention)

6-minute walking test (6MWT) OTHER

Standardised assessment of physcial capacity pre- and postoperatively (at 6-month follow-up)

CABG + collaged-based patch arm (control); CABG + collagen based patch + AAMs arm (intervention)

Blood sampling (NT-proBNP) DIAGNOSTIC_TEST

Collection of a blood sample measurement of NT-proBNP by an accredited hospital laboratory pre- and postoperatively (at both 3- and 6-month follow-up).

CABG + collaged-based patch arm (control); CABG + collagen based patch + AAMs arm (intervention)

Transesophageal echocardiography DIAGNOSTIC_TEST

Performed by the perfusion-anesthesiologist at the beginning of the CABG surgery to evaluate both LAA and RAA for blood flow velocities, anatomy, possible sludge and thrombus.

Also known as: TEE

CABG + collaged-based patch arm (control); CABG + collagen based patch + AAMs arm (intervention)

Epicardial collagen-based patch transplantation PROCEDURE

Epicardial transplantation of the collaged-based patch material without the AAMs onto the epicardium of the scarred myocardium at the end of CABG surgery.

CABG + collaged-based patch arm (control)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent obtained
• Left ventricular ejection fraction (LVEF) between ≥ 15% and ≤ 40% at recruitment (transthoracic echocardiography)
• New York Heart Association (NYHA) Class II-IV heart failure symptoms

You may not qualify if:

• Heart failure due to left ventricular outflow tract obstruction
• Acute myocardial infarction (AMI) within last 30 days
• History of life-threatening and possibly repeating ventricular arrhythmias or resuscitation, or an implantable cardioverter-defibrillator
• Stroke or other disabling condition within 3 months before screening
• Severe valve disease or scheduled valve surgery
• Renal dysfunction (GFR \<45 ml/min/1.73m2)
• Other disease limiting life expectancy
• Contraindications for coronary angiogram or LGE-CMRI
• Participation in some other clinical trial
• Screening Failure:
• After optimization of medications, no visible scar or LVEF ≥ 50% in preoperative LGE-CMRI
• Preoperative LGE-CMRI has not been performed prior scheduled CABG

Sponsors & Collaborators

• Hospital District of Helsinki and Uusimaa: lead
• University of Helsinki: collaborator
• Oulu University Hospital: collaborator

Study Sites (1)

Hospital District of Helsinki and Uusimaa, Helsinki University Hospital, Heart and Lung Center & Cardiac Unit

Helsinki, Uusimaa, 00029, Finland

RECRUITING

Related Publications (35)

• GBD 2017 Causes of Death Collaborators. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018 Nov 10;392(10159):1736-1788. doi: 10.1016/S0140-6736(18)32203-7. Epub 2018 Nov 8.

  PMID: 30496103 BACKGROUND

• Timmis A, Townsend N, Gale C, Grobbee R, Maniadakis N, Flather M, Wilkins E, Wright L, Vos R, Bax J, Blum M, Pinto F, Vardas P; ESC Scientific Document Group. European Society of Cardiology: Cardiovascular Disease Statistics 2017. Eur Heart J. 2018 Feb 14;39(7):508-579. doi: 10.1093/eurheartj/ehx628.

  PMID: 29190377 BACKGROUND

• Cohn JN, Ferrari R, Sharpe N. Cardiac remodeling--concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. Behalf of an International Forum on Cardiac Remodeling. J Am Coll Cardiol. 2000 Mar 1;35(3):569-82. doi: 10.1016/s0735-1097(99)00630-0.

  PMID: 10716457 BACKGROUND

• Taylor CJ, Ryan R, Nichols L, Gale N, Hobbs FR, Marshall T. Survival following a diagnosis of heart failure in primary care. Fam Pract. 2017 Apr 1;34(2):161-168. doi: 10.1093/fampra/cmw145.

  PMID: 28137979 BACKGROUND

• Groenewegen A, Rutten FH, Mosterd A, Hoes AW. Epidemiology of heart failure. Eur J Heart Fail. 2020 Aug;22(8):1342-1356. doi: 10.1002/ejhf.1858. Epub 2020 Jun 1.

  PMID: 32483830 BACKGROUND

• van Riet EE, Hoes AW, Wagenaar KP, Limburg A, Landman MA, Rutten FH. Epidemiology of heart failure: the prevalence of heart failure and ventricular dysfunction in older adults over time. A systematic review. Eur J Heart Fail. 2016 Mar;18(3):242-52. doi: 10.1002/ejhf.483. Epub 2016 Jan 4.

  PMID: 26727047 BACKGROUND

• Rihal CS, Raco DL, Gersh BJ, Yusuf S. Indications for coronary artery bypass surgery and percutaneous coronary intervention in chronic stable angina: review of the evidence and methodological considerations. Circulation. 2003 Nov 18;108(20):2439-45. doi: 10.1161/01.CIR.0000094405.21583.7C. No abstract available.

  PMID: 14623791 BACKGROUND

• Eurostat, online material (https://ec.europa.eu/eurostat/web/health/data/database) Accessed 3.4.2022

  BACKGROUND

• Freitas P, Madeira M, Raposo L, Madeira S, Brito J, Brizido C, Gama F, Vale N, Ranchordas S, Magro P, Braga A, Goncalves PA, Gabriel HM, Nolasco T, Boshoff S, Marques M, Bruges L, Calquinha J, Sousa-Uva M, Abecasis M, Almeida M, Neves JP, Mendes M. Coronary Artery Bypass Grafting Versus Percutaneous Coronary Intervention in Patients With Non-ST-Elevation Myocardial Infarction and Left Main or Multivessel Coronary Disease. Am J Cardiol. 2019 Mar 1;123(5):717-724. doi: 10.1016/j.amjcard.2018.11.052. Epub 2018 Dec 3.

  PMID: 30558758 BACKGROUND

• Cutie S, Huang GN. Vertebrate cardiac regeneration: evolutionary and developmental perspectives. Cell Regen. 2021 Mar 1;10(1):6. doi: 10.1186/s13619-020-00068-y.

  PMID: 33644818 BACKGROUND

• Haubner BJ, Schneider J, Schweigmann U, Schuetz T, Dichtl W, Velik-Salchner C, Stein JI, Penninger JM. Functional Recovery of a Human Neonatal Heart After Severe Myocardial Infarction. Circ Res. 2016 Jan 22;118(2):216-21. doi: 10.1161/CIRCRESAHA.115.307017. Epub 2015 Dec 9.

  PMID: 26659640 BACKGROUND

• Cambria E, Pasqualini FS, Wolint P, Gunter J, Steiger J, Bopp A, Hoerstrup SP, Emmert MY. Translational cardiac stem cell therapy: advancing from first-generation to next-generation cell types. NPJ Regen Med. 2017 Jun 13;2:17. doi: 10.1038/s41536-017-0024-1. eCollection 2017.

  PMID: 29302353 BACKGROUND

• Koninckx R, Daniels A, Windmolders S, Mees U, Macianskiene R, Mubagwa K, Steels P, Jamaer L, Dubois J, Robic B, Hendrikx M, Rummens JL, Hensen K. The cardiac atrial appendage stem cell: a new and promising candidate for myocardial repair. Cardiovasc Res. 2013 Mar 1;97(3):413-23. doi: 10.1093/cvr/cvs427. Epub 2012 Dec 19.

  PMID: 23257022 BACKGROUND

• Detert S, Stamm C, Beez C, Diedrichs F, Ringe J, Van Linthout S, Seifert M, Tschope C, Sittinger M, Haag M. The atrial appendage as a suitable source to generate cardiac-derived adherent proliferating cells for regenerative cell-based therapies. J Tissue Eng Regen Med. 2018 Mar;12(3):e1404-e1417. doi: 10.1002/term.2528. Epub 2017 Nov 21.

  PMID: 28752609 BACKGROUND

• Evens L, Belien H, D'Haese S, Haesen S, Verboven M, Rummens JL, Bronckaers A, Hendrikx M, Deluyker D, Bito V. Combinational Therapy of Cardiac Atrial Appendage Stem Cells and Pyridoxamine: The Road to Cardiac Repair? Int J Mol Sci. 2021 Aug 27;22(17):9266. doi: 10.3390/ijms22179266.

  PMID: 34502175 BACKGROUND

• Madonna R, Van Laake LW, Botker HE, Davidson SM, De Caterina R, Engel FB, Eschenhagen T, Fernandez-Aviles F, Hausenloy DJ, Hulot JS, Lecour S, Leor J, Menasche P, Pesce M, Perrino C, Prunier F, Van Linthout S, Ytrehus K, Zimmermann WH, Ferdinandy P, Sluijter JPG. ESC Working Group on Cellular Biology of the Heart: position paper for Cardiovascular Research: tissue engineering strategies combined with cell therapies for cardiac repair in ischaemic heart disease and heart failure. Cardiovasc Res. 2019 Mar 1;115(3):488-500. doi: 10.1093/cvr/cvz010.

  PMID: 30657875 BACKGROUND

• Lampinen M, Nummi A, Nieminen T, Harjula A, Kankuri E; AADC Consortium. Intraoperative processing and epicardial transplantation of autologous atrial tissue for cardiac repair. J Heart Lung Transplant. 2017 Sep;36(9):1020-1022. doi: 10.1016/j.healun.2017.06.002. Epub 2017 Jun 10. No abstract available.

  PMID: 28668192 BACKGROUND

• Nummi A, Nieminen T, Patila T, Lampinen M, Lehtinen ML, Kivisto S, Holmstrom M, Wilkman E, Teittinen K, Laine M, Sinisalo J, Kupari M, Kankuri E, Juvonen T, Vento A, Suojaranta R, Harjula A; AADC consortium. Epicardial delivery of autologous atrial appendage micrografts during coronary artery bypass surgery-safety and feasibility study. Pilot Feasibility Stud. 2017 Dec 20;3:74. doi: 10.1186/s40814-017-0217-9. eCollection 2017.

  PMID: 29276625 BACKGROUND

• Nummi A, Mulari S, Stewart JA, Kivisto S, Teittinen K, Nieminen T, Lampinen M, Patila T, Sintonen H, Juvonen T, Kupari M, Suojaranta R, Kankuri E, Harjula A, Vento A; AADC consortium. Epicardial Transplantation of Autologous Cardiac Micrografts During Coronary Artery Bypass Surgery. Front Cardiovasc Med. 2021 Sep 14;8:726889. doi: 10.3389/fcvm.2021.726889. eCollection 2021.

  PMID: 34595223 BACKGROUND

• Xie Y, Lampinen M, Takala J, Sikorski V, Soliymani R, Tarkia M, Lalowski M, Mervaala E, Kupari M, Zheng Z, Hu S, Harjula A, Kankuri E; AADC consortium. Epicardial transplantation of atrial appendage micrograft patch salvages myocardium after infarction. J Heart Lung Transplant. 2020 Jul;39(7):707-718. doi: 10.1016/j.healun.2020.03.023. Epub 2020 Apr 7.

  PMID: 32334944 BACKGROUND

• Lalowski MM, Bjork S, Finckenberg P, Soliymani R, Tarkia M, Calza G, Blokhina D, Tulokas S, Kankainen M, Lakkisto P, Baumann M, Kankuri E, Mervaala E. Characterizing the Key Metabolic Pathways of the Neonatal Mouse Heart Using a Quantitative Combinatorial Omics Approach. Front Physiol. 2018 Apr 11;9:365. doi: 10.3389/fphys.2018.00365. eCollection 2018.

  PMID: 29695975 BACKGROUND

• Nakada Y, Canseco DC, Thet S, Abdisalaam S, Asaithamby A, Santos CX, Shah AM, Zhang H, Faber JE, Kinter MT, Szweda LI, Xing C, Hu Z, Deberardinis RJ, Schiattarella G, Hill JA, Oz O, Lu Z, Zhang CC, Kimura W, Sadek HA. Hypoxia induces heart regeneration in adult mice. Nature. 2017 Jan 12;541(7636):222-227. doi: 10.1038/nature20173. Epub 2016 Oct 31.

  PMID: 27798600 BACKGROUND

• Kimura W, Xiao F, Canseco DC, Muralidhar S, Thet S, Zhang HM, Abderrahman Y, Chen R, Garcia JA, Shelton JM, Richardson JA, Ashour AM, Asaithamby A, Liang H, Xing C, Lu Z, Zhang CC, Sadek HA. Hypoxia fate mapping identifies cycling cardiomyocytes in the adult heart. Nature. 2015 Jul 9;523(7559):226-30. doi: 10.1038/nature14582. Epub 2015 Jun 22.

  PMID: 26098368 BACKGROUND

• Puente BN, Kimura W, Muralidhar SA, Moon J, Amatruda JF, Phelps KL, Grinsfelder D, Rothermel BA, Chen R, Garcia JA, Santos CX, Thet S, Mori E, Kinter MT, Rindler PM, Zacchigna S, Mukherjee S, Chen DJ, Mahmoud AI, Giacca M, Rabinovitch PS, Aroumougame A, Shah AM, Szweda LI, Sadek HA. The oxygen-rich postnatal environment induces cardiomyocyte cell-cycle arrest through DNA damage response. Cell. 2014 Apr 24;157(3):565-79. doi: 10.1016/j.cell.2014.03.032.

  PMID: 24766806 BACKGROUND

• World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013 Nov 27;310(20):2191-4. doi: 10.1001/jama.2013.281053. No abstract available.

  PMID: 24141714 BACKGROUND

• Sikorski V, Karjalainen P, Blokhina D, Oksaharju K, Khan J, Katayama S, Rajala H, Suihko S, Tuohinen S, Teittinen K, Nummi A, Nykanen A, Eskin A, Stark C, Biancari F, Kiss J, Simpanen J, Ropponen J, Lemstrom K, Savinainen K, Lalowski M, Kaarne M, Jormalainen M, Elomaa O, Koivisto P, Raivio P, Backstrom P, Dahlbacka S, Syrjala S, Vainikka T, Vahasilta T, Tuncbag N, Karelson M, Mervaala E, Juvonen T, Laine M, Laurikka J, Vento A, Kankuri E. Epitranscriptomics of Ischemic Heart Disease-The IHD-EPITRAN Study Design and Objectives. Int J Mol Sci. 2021 Jun 21;22(12):6630. doi: 10.3390/ijms22126630.

  PMID: 34205699 BACKGROUND

• Qin Y, Li L, Luo E, Hou J, Yan G, Wang D, Qiao Y, Tang C. Role of m6A RNA methylation in cardiovascular disease (Review). Int J Mol Med. 2020 Dec;46(6):1958-1972. doi: 10.3892/ijmm.2020.4746. Epub 2020 Oct 6.

  PMID: 33125109 BACKGROUND

• McKie PM, Burnett JC Jr. NT-proBNP: The Gold Standard Biomarker in Heart Failure. J Am Coll Cardiol. 2016 Dec 6;68(22):2437-2439. doi: 10.1016/j.jacc.2016.10.001. No abstract available.

  PMID: 27908348 BACKGROUND

• Schulz-Menger J, Bluemke DA, Bremerich J, Flamm SD, Fogel MA, Friedrich MG, Kim RJ, von Knobelsdorff-Brenkenhoff F, Kramer CM, Pennell DJ, Plein S, Nagel E. Standardized image interpretation and post-processing in cardiovascular magnetic resonance - 2020 update : Society for Cardiovascular Magnetic Resonance (SCMR): Board of Trustees Task Force on Standardized Post-Processing. J Cardiovasc Magn Reson. 2020 Mar 12;22(1):19. doi: 10.1186/s12968-020-00610-6.

  PMID: 32160925 BACKGROUND

• Hays RD, Morales LS. The RAND-36 measure of health-related quality of life. Ann Med. 2001 Jul;33(5):350-7. doi: 10.3109/07853890109002089.

  PMID: 11491194 BACKGROUND

• Campeau L. Letter: Grading of angina pectoris. Circulation. 1976 Sep;54(3):522-3. No abstract available.

  PMID: 947585 BACKGROUND

• Russell SD, Saval MA, Robbins JL, Ellestad MH, Gottlieb SS, Handberg EM, Zhou Y, Chandler B; HF-ACTION Investigators. New York Heart Association functional class predicts exercise parameters in the current era. Am Heart J. 2009 Oct;158(4 Suppl):S24-30. doi: 10.1016/j.ahj.2009.07.017.

  PMID: 19782785 BACKGROUND

• Bittner V, Weiner DH, Yusuf S, Rogers WJ, McIntyre KM, Bangdiwala SI, Kronenberg MW, Kostis JB, Kohn RM, Guillotte M, et al. Prediction of mortality and morbidity with a 6-minute walk test in patients with left ventricular dysfunction. SOLVD Investigators. JAMA. 1993 Oct 13;270(14):1702-7.

  PMID: 8411500 BACKGROUND

• Sikorski V, Vento A, Kankuri E; IHD-EPITRAN Consortium. Emerging roles of the RNA modifications N6-methyladenosine and adenosine-to-inosine in cardiovascular diseases. Mol Ther Nucleic Acids. 2022 Jul 20;29:426-461. doi: 10.1016/j.omtn.2022.07.018. eCollection 2022 Sep 13.

  PMID: 35991314 BACKGROUND

• Sikorski V, Nummi A, Kuuva A, Wilkman E, Rajala H, Stewart J, Junttila J, Lindgren K, Kervinen K, Teittinen K, Kohonen K, Oksaharju K, Okkonen M, Holmstrom M, Lehtinen M, Mulari S, Taskinen P, Simonen P, Karvonen P, Kastell P, Karja-Koskenkari P, Kandolin R, Kesavuori R, Kaarlenkaski S, Vaara S, Dahlbacka S, Syrjala S, Syvaranta S, Juvonen T, Erkinaro T, Makela T, Karjalainen P, Kankuri E, Vento A, Nykanen A. Autologous atrial appendage micrografts transplanted during coronary artery bypass surgery: design of the AAMS2 randomized, double-blinded, and placebo-controlled trial. Trials. 2026 Jan 2;27(1):97. doi: 10.1186/s13063-025-09379-4.

  PMID: 41485016 DERIVED

MeSH Terms

Conditions

Myocardial Ischemia; Heart Failure, Systolic; Coronary Artery Disease

Interventions

Echocardiography; Blood Specimen Collection; Echocardiography, Transesophageal

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Heart Failure; Coronary Disease; Arteriosclerosis; Arterial Occlusive Diseases

Intervention Hierarchy (Ancestors)

Cardiac Imaging Techniques; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Ultrasonography; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Specimen Handling; Clinical Laboratory Techniques; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Antti Nykänen, Docent

  Hospital District of Helsinki and Uusimaa

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Antti Nykänen, Docent

CONTACT

050 427 0625; antti.nykanen@hus.fi

Antti E Vento, Professor

CONTACT

050 427 0629; antti.vento@hus.fi

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Patients are randomized to CABG or AAMs groups using block randomization via the online tool at www.sealedenvelope.com with block sizes 2 and 4, and stratification to sex (female, male). Randomization is carried out by the study nurse, who texts the Sealed Envelope service phone number 'AAMS2' and a command 'randomise', and the participant pseudonym. The allocation is received by a text message. The study nurse oversees the allocation in a double-blinded manner, where the patient and the evaluating cardiologist and radiologists remain blinded. Given the nature of the treatment (AAMs-processing vs. no processing) it is impossible to blind the operating surgeon or the study nurse to the allocations intraoperatively. However, the surgeon is blinded when planning the anastomoses. All LGE-CMRI and TTE measurements as well as laboratory analyses are done by those blinded to the allocations.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Docent Antti Nykänen, MD PhD

Model Details: The trial enrolls 50 patients in a 1:1 group allocation ratio to the two study groups: 1.) collagen-based patch + AAMs + CABG (treatment arm) and 2.) collagen-based patch + CABG (control arm). Autologous RAA tissue is harvested from the RAA during CABG from all participants. Based on randomization, the piece of RAA tissue is either processed to AAMs perioperatively or stored for biochemical analyses. The AAMs, embedded in fibrin matrix gel, are placed on an collagen-based patch sheet, which is epicardially adhered in place. The epicardial transplantation site is pinpointed to ischemic scar area by preoperative LGE-CMRI.

Study Record Dates

• First Submitted: October 27, 2022
• First Posted: November 30, 2022
• Study Start: April 1, 2024
• Primary Completion: January 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 19, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: Openly by 31.12.2027 as (a) peer-reviewed academic publication(s).
• Access Criteria: Open access for academic publications.

Locations

FI (1)