title: State of the Art on the Evidence Base in Cardiac Regenerative Therapy: Overview of 41 Systematic Reviews.
abstract: OBJECTIVE
  To provide a comprehensive appraisal of the evidence from secondary research on cardiac regenerative therapy.
  
  
  METHODS
  Overview of systematic reviews of controlled clinical trials concerning stem cell administration or mobilization in patients with cardiovascular disease.
  
  
  RESULTS
  After a systematic database search, we short-listed 41 reviews (660 patients). Twenty-two (54%) reviews focused on acute myocardial infarction (AMI), 19 (46%) on chronic ischemic heart disease (IHD) or heart failure (HF), 29 (71%) on bone marrow-derived stem-cells (BMSC), and 36 (88%) to randomized trials only. Substantial variability among reviews was found for validity (AMSTAR score: median 9 [minimum 3]; 1st quartile 9; 3rd quartile 10; maximum 11), effect estimates (change in ejection fraction from baseline to follow-up: 3.47% [0.02%; 2.90%; 4.22%; 6.11%]), and citations (Web of Science yearly citations: 4.1 [0; 2.2; 6.5; 68.9]). No significant association was found between these three features. However, reviews focusing on BMSC therapy had higher validity scores (P = 0.008) and showed more pronounced effect estimates (P = 0.002). Higher citations were associated with journal impact factor (P = 0.007), corresponding author from North America/Europe (P = 0.022), and inclusion of nonrandomized trials (P = 0.046).
  
  
  CONCLUSIONS
  Substantial heterogeneity is apparent among these reviews in terms of quality and effect estimates.
authors.affiliation: Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Corso della Repubblica 79, 04100 Latina, Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Peruzzi
authors.affiliation: Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Corso della Repubblica 79, 04100 Latina, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: De Falco
authors.affiliation: VCU Pauley Heart Center, Virginia Commonwealth University, 821 West Franklin Street, Richmond, VA 23284, USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Abbate
authors.affiliation: Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Corso della Repubblica 79, 04100 Latina, Italy ; VCU Pauley Heart Center, Virginia Commonwealth University, 821 West Franklin Street, Richmond, VA 23284, USA ; Fondazione Eleonora Lorillard Spencer Cenci, 00185 Roma, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Biondi-Zoccai
authors.affiliation: Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Corso della Repubblica 79, 04100 Latina, Italy.
authors.forename: Isotta
authors.initials: I
authors.lastname: Chimenti
authors.affiliation: Heart Failure and Cardiac Rehabilitation Unit, Columbus Integrated Complex, Via Giuseppe Moscati 31, 00168 Rome, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Lotrionte
authors.affiliation: Oxford Heart Center, Oxford University Hospital, Headley Way, Oxford OX3 9DU, UK.
authors.forename: Umberto
authors.initials: U
authors.lastname: Benedetto
authors.affiliation: Academic Medical Center Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, Netherlands.
authors.forename: Ronak
authors.initials: R
authors.lastname: Delewi
authors.affiliation: Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Corso della Repubblica 79, 04100 Latina, Italy.
authors.forename: Antonino G M
authors.initials: AG
authors.lastname: Marullo
authors.affiliation: Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Corso della Repubblica 79, 04100 Latina, Italy ; Department of AngioCardioNeurology, IRCCS Neuromed, Via Atinense 18, 86077 Pozzilli, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Frati
mesh_terms: D002318:Cardiovascular Diseases / Q000628:therapy*; D064987:Cell- and Tissue-Based Therapy; D006801:Humans; D044968:Regenerative Medicine