title: Intracoronary delivery of injectable bioabsorbable scaffold (IK-5001) to treat left ventricular remodeling after ST-elevation myocardial infarction: a first-in-man study.
abstract: BACKGROUND
  We aimed to test, for the first time, the feasibility of intracoronary delivery of an innovative, injectable bioabsorbable scaffold (IK-5001), to prevent or reverse adverse left ventricular remodeling and dysfunction in patients after ST-segment-elevation myocardial infarction.
  
  
  RESULTS
  Patients (n=27) with moderate-to-large ST-segment-elevation myocardial infarctions, after successful revascularization, were enrolled. Two milliliters of IK-5001, a solution of 1% sodium alginate plus 0.3% calcium gluconate, was administered by selective injection through the infarct-related coronary artery within 7 days after myocardial infarction. IK-5001 is assumed to permeate the infarcted tissue, cross-linking into a hydrogel and forming a bioabsorbable cardiac scaffold. Coronary angiography, 3 minutes after injection, confirmed that the injection did not impair coronary flow and myocardial perfusion. Furthermore, IK-5001 deployment was not associated with additional myocardial injury or re-elevation of cardiac biomarkers. Clinical assessments, echocardiographic studies, 12-lead electrocardiograms, 24-hour Holter monitoring, blood tests, and completion of Minnesota Living with Heart Failure Questionnaires were repeated during follow-up visits at 30, 90, and 180 days after treatment. During a 6-month follow-up, these tests confirmed favorable tolerability of the procedure, without device-related adverse events, serious arrhythmias, blood test abnormalities, or death. Serial echocardiographic studies showed preservation of left ventricular indices and left ventricular ejection fraction.
  
  
  CONCLUSIONS
  This first-in-man pilot study shows that intracoronary deployment of an IK-5001 scaffold is feasible and well tolerated. Our results have promoted the initiation of a multicenter, randomized controlled trial to confirm the safety and efficacy of this new approach in high-risk patients after ST-segment-elevation myocardial infarction.
  
  
  BACKGROUND
  http://www.clinicaltrials.gov. Unique identifier: NCT01226563.
authors.affiliation: From the Universitätsklinikum Schleswig-Holstein, Campus Kiel Klinik für Kardiologie und Angiologie, Kiel, Germany (N.F., M.R.); Department of Internal Medicine/Cardiology, University of Leipzig, Heart Center, Leipzig, Germany (A.L.); Medizinische Klinik Kardiologie, Angiologie, Pneumologie Internische Intensivmedizin Hämostasiologie, Mannheim, Germany (T.S.); Department of Internal Medicine III, Heart Center, University of Cologne, Cologne, Germany (J.M.-E.); AZ Middelheim Cardiology, Antwerpen, Belgium (P.V.); UZ Brussel Department of Cardiology, Brussel, Jette, Belgium (D.S.); Medizinische Universitätsklinik (Krehl-Klinik) Abteilung Innere Medizin III, Kardiologie, Angiologie, und Pneumologie, Heidelberg, Germany (F.B.); BioLineRx, Jerusalem, Israel (S.T.); Neufeld Cardiac Research Institute, Tel-Aviv University, Tamman Cardiovascular Research Institute, Regenerative Medicine, Stem Cells and Tissue Engineering Center, Sheba Medical Center, Tel-Hashomer, Israel (J.L.).
authors.forename: Norbert
authors.initials: N
authors.lastname: Frey
authors.affiliation: From the Universitätsklinikum Schleswig-Holstein, Campus Kiel Klinik für Kardiologie und Angiologie, Kiel, Germany (N.F., M.R.); Department of Internal Medicine/Cardiology, University of Leipzig, Heart Center, Leipzig, Germany (A.L.); Medizinische Klinik Kardiologie, Angiologie, Pneumologie Internische Intensivmedizin Hämostasiologie, Mannheim, Germany (T.S.); Department of Internal Medicine III, Heart Center, University of Cologne, Cologne, Germany (J.M.-E.); AZ Middelheim Cardiology, Antwerpen, Belgium (P.V.); UZ Brussel Department of Cardiology, Brussel, Jette, Belgium (D.S.); Medizinische Universitätsklinik (Krehl-Klinik) Abteilung Innere Medizin III, Kardiologie, Angiologie, und Pneumologie, Heidelberg, Germany (F.B.); BioLineRx, Jerusalem, Israel (S.T.); Neufeld Cardiac Research Institute, Tel-Aviv University, Tamman Cardiovascular Research Institute, Regenerative Medicine, Stem Cells and Tissue Engineering Center, Sheba Medical Center, Tel-Hashomer, Israel (J.L.).
authors.forename: Axel
authors.initials: A
authors.lastname: Linke
authors.affiliation: From the Universitätsklinikum Schleswig-Holstein, Campus Kiel Klinik für Kardiologie und Angiologie, Kiel, Germany (N.F., M.R.); Department of Internal Medicine/Cardiology, University of Leipzig, Heart Center, Leipzig, Germany (A.L.); Medizinische Klinik Kardiologie, Angiologie, Pneumologie Internische Intensivmedizin Hämostasiologie, Mannheim, Germany (T.S.); Department of Internal Medicine III, Heart Center, University of Cologne, Cologne, Germany (J.M.-E.); AZ Middelheim Cardiology, Antwerpen, Belgium (P.V.); UZ Brussel Department of Cardiology, Brussel, Jette, Belgium (D.S.); Medizinische Universitätsklinik (Krehl-Klinik) Abteilung Innere Medizin III, Kardiologie, Angiologie, und Pneumologie, Heidelberg, Germany (F.B.); BioLineRx, Jerusalem, Israel (S.T.); Neufeld Cardiac Research Institute, Tel-Aviv University, Tamman Cardiovascular Research Institute, Regenerative Medicine, Stem Cells and Tissue Engineering Center, Sheba Medical Center, Tel-Hashomer, Israel (J.L.).
authors.forename: Tim
authors.initials: T
authors.lastname: Süselbeck
authors.affiliation: From the Universitätsklinikum Schleswig-Holstein, Campus Kiel Klinik für Kardiologie und Angiologie, Kiel, Germany (N.F., M.R.); Department of Internal Medicine/Cardiology, University of Leipzig, Heart Center, Leipzig, Germany (A.L.); Medizinische Klinik Kardiologie, Angiologie, Pneumologie Internische Intensivmedizin Hämostasiologie, Mannheim, Germany (T.S.); Department of Internal Medicine III, Heart Center, University of Cologne, Cologne, Germany (J.M.-E.); AZ Middelheim Cardiology, Antwerpen, Belgium (P.V.); UZ Brussel Department of Cardiology, Brussel, Jette, Belgium (D.S.); Medizinische Universitätsklinik (Krehl-Klinik) Abteilung Innere Medizin III, Kardiologie, Angiologie, und Pneumologie, Heidelberg, Germany (F.B.); BioLineRx, Jerusalem, Israel (S.T.); Neufeld Cardiac Research Institute, Tel-Aviv University, Tamman Cardiovascular Research Institute, Regenerative Medicine, Stem Cells and Tissue Engineering Center, Sheba Medical Center, Tel-Hashomer, Israel (J.L.).
authors.forename: Jochen
authors.initials: J
authors.lastname: Müller-Ehmsen
authors.affiliation: From the Universitätsklinikum Schleswig-Holstein, Campus Kiel Klinik für Kardiologie und Angiologie, Kiel, Germany (N.F., M.R.); Department of Internal Medicine/Cardiology, University of Leipzig, Heart Center, Leipzig, Germany (A.L.); Medizinische Klinik Kardiologie, Angiologie, Pneumologie Internische Intensivmedizin Hämostasiologie, Mannheim, Germany (T.S.); Department of Internal Medicine III, Heart Center, University of Cologne, Cologne, Germany (J.M.-E.); AZ Middelheim Cardiology, Antwerpen, Belgium (P.V.); UZ Brussel Department of Cardiology, Brussel, Jette, Belgium (D.S.); Medizinische Universitätsklinik (Krehl-Klinik) Abteilung Innere Medizin III, Kardiologie, Angiologie, und Pneumologie, Heidelberg, Germany (F.B.); BioLineRx, Jerusalem, Israel (S.T.); Neufeld Cardiac Research Institute, Tel-Aviv University, Tamman Cardiovascular Research Institute, Regenerative Medicine, Stem Cells and Tissue Engineering Center, Sheba Medical Center, Tel-Hashomer, Israel (J.L.).
authors.forename: Paul
authors.initials: P
authors.lastname: Vermeersch
authors.affiliation: From the Universitätsklinikum Schleswig-Holstein, Campus Kiel Klinik für Kardiologie und Angiologie, Kiel, Germany (N.F., M.R.); Department of Internal Medicine/Cardiology, University of Leipzig, Heart Center, Leipzig, Germany (A.L.); Medizinische Klinik Kardiologie, Angiologie, Pneumologie Internische Intensivmedizin Hämostasiologie, Mannheim, Germany (T.S.); Department of Internal Medicine III, Heart Center, University of Cologne, Cologne, Germany (J.M.-E.); AZ Middelheim Cardiology, Antwerpen, Belgium (P.V.); UZ Brussel Department of Cardiology, Brussel, Jette, Belgium (D.S.); Medizinische Universitätsklinik (Krehl-Klinik) Abteilung Innere Medizin III, Kardiologie, Angiologie, und Pneumologie, Heidelberg, Germany (F.B.); BioLineRx, Jerusalem, Israel (S.T.); Neufeld Cardiac Research Institute, Tel-Aviv University, Tamman Cardiovascular Research Institute, Regenerative Medicine, Stem Cells and Tissue Engineering Center, Sheba Medical Center, Tel-Hashomer, Israel (J.L.).
authors.forename: Danny
authors.initials: D
authors.lastname: Schoors
authors.affiliation: From the Universitätsklinikum Schleswig-Holstein, Campus Kiel Klinik für Kardiologie und Angiologie, Kiel, Germany (N.F., M.R.); Department of Internal Medicine/Cardiology, University of Leipzig, Heart Center, Leipzig, Germany (A.L.); Medizinische Klinik Kardiologie, Angiologie, Pneumologie Internische Intensivmedizin Hämostasiologie, Mannheim, Germany (T.S.); Department of Internal Medicine III, Heart Center, University of Cologne, Cologne, Germany (J.M.-E.); AZ Middelheim Cardiology, Antwerpen, Belgium (P.V.); UZ Brussel Department of Cardiology, Brussel, Jette, Belgium (D.S.); Medizinische Universitätsklinik (Krehl-Klinik) Abteilung Innere Medizin III, Kardiologie, Angiologie, und Pneumologie, Heidelberg, Germany (F.B.); BioLineRx, Jerusalem, Israel (S.T.); Neufeld Cardiac Research Institute, Tel-Aviv University, Tamman Cardiovascular Research Institute, Regenerative Medicine, Stem Cells and Tissue Engineering Center, Sheba Medical Center, Tel-Hashomer, Israel (J.L.).
authors.forename: Mark
authors.initials: M
authors.lastname: Rosenberg
authors.affiliation: From the Universitätsklinikum Schleswig-Holstein, Campus Kiel Klinik für Kardiologie und Angiologie, Kiel, Germany (N.F., M.R.); Department of Internal Medicine/Cardiology, University of Leipzig, Heart Center, Leipzig, Germany (A.L.); Medizinische Klinik Kardiologie, Angiologie, Pneumologie Internische Intensivmedizin Hämostasiologie, Mannheim, Germany (T.S.); Department of Internal Medicine III, Heart Center, University of Cologne, Cologne, Germany (J.M.-E.); AZ Middelheim Cardiology, Antwerpen, Belgium (P.V.); UZ Brussel Department of Cardiology, Brussel, Jette, Belgium (D.S.); Medizinische Universitätsklinik (Krehl-Klinik) Abteilung Innere Medizin III, Kardiologie, Angiologie, und Pneumologie, Heidelberg, Germany (F.B.); BioLineRx, Jerusalem, Israel (S.T.); Neufeld Cardiac Research Institute, Tel-Aviv University, Tamman Cardiovascular Research Institute, Regenerative Medicine, Stem Cells and Tissue Engineering Center, Sheba Medical Center, Tel-Hashomer, Israel (J.L.).
authors.forename: Florian
authors.initials: F
authors.lastname: Bea
authors.affiliation: From the Universitätsklinikum Schleswig-Holstein, Campus Kiel Klinik für Kardiologie und Angiologie, Kiel, Germany (N.F., M.R.); Department of Internal Medicine/Cardiology, University of Leipzig, Heart Center, Leipzig, Germany (A.L.); Medizinische Klinik Kardiologie, Angiologie, Pneumologie Internische Intensivmedizin Hämostasiologie, Mannheim, Germany (T.S.); Department of Internal Medicine III, Heart Center, University of Cologne, Cologne, Germany (J.M.-E.); AZ Middelheim Cardiology, Antwerpen, Belgium (P.V.); UZ Brussel Department of Cardiology, Brussel, Jette, Belgium (D.S.); Medizinische Universitätsklinik (Krehl-Klinik) Abteilung Innere Medizin III, Kardiologie, Angiologie, und Pneumologie, Heidelberg, Germany (F.B.); BioLineRx, Jerusalem, Israel (S.T.); Neufeld Cardiac Research Institute, Tel-Aviv University, Tamman Cardiovascular Research Institute, Regenerative Medicine, Stem Cells and Tissue Engineering Center, Sheba Medical Center, Tel-Hashomer, Israel (J.L.).
authors.forename: Shmuel
authors.initials: S
authors.lastname: Tuvia
authors.affiliation: From the Universitätsklinikum Schleswig-Holstein, Campus Kiel Klinik für Kardiologie und Angiologie, Kiel, Germany (N.F., M.R.); Department of Internal Medicine/Cardiology, University of Leipzig, Heart Center, Leipzig, Germany (A.L.); Medizinische Klinik Kardiologie, Angiologie, Pneumologie Internische Intensivmedizin Hämostasiologie, Mannheim, Germany (T.S.); Department of Internal Medicine III, Heart Center, University of Cologne, Cologne, Germany (J.M.-E.); AZ Middelheim Cardiology, Antwerpen, Belgium (P.V.); UZ Brussel Department of Cardiology, Brussel, Jette, Belgium (D.S.); Medizinische Universitätsklinik (Krehl-Klinik) Abteilung Innere Medizin III, Kardiologie, Angiologie, und Pneumologie, Heidelberg, Germany (F.B.); BioLineRx, Jerusalem, Israel (S.T.); Neufeld Cardiac Research Institute, Tel-Aviv University, Tamman Cardiovascular Research Institute, Regenerative Medicine, Stem Cells and Tissue Engineering Center, Sheba Medical Center, Tel-Hashomer, Israel (J.L.). leorj@post.tau.ac.il.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Leor
mesh_terms: D020341:Absorbable Implants / Q000009:adverse effects; D000328:Adult; D000368:Aged; D000464:Alginates / Q000008:administration & dosage* / Q000009:adverse effects; D001530:Belgium; D002125:Calcium Gluconate / Q000008:administration & dosage* / Q000009:adverse effects; D005240:Feasibility Studies; D005260:Female; D005858:Germany; D020723:Glucuronic Acid / Q000008:administration & dosage / Q000009:adverse effects; D006334:Heart Function Tests; D006603:Hexuronic Acids / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D020100:Hydrogels; D007269:Injections, Intra-Arterial; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D010865:Pilot Projects; D011237:Predictive Value of Tests; D044968:Regenerative Medicine / Q000379:methods*; D011795:Surveys and Questionnaires; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000009:adverse effects; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D020100:Hydrogels; D020723:Glucuronic Acid; D002125:Calcium Gluconate
keywords: coronary disease; heart failure; myocardial infarction; ventricular remodeling