title: Coronary sinus biomarker sampling compared to peripheral venous blood for predicting outcomes in patients with severe heart failure undergoing cardiac resynchronization therapy: the BIOCRT study.
abstract: BACKGROUND
  A significant minority of patients receiving cardiac resynchronization therapy (CRT) remain nonresponsive to this intervention.
  
  
  OBJECTIVE
  This study aimed to determine whether coronary sinus (CS) or baseline peripheral venous (PV) levels of established and emerging heart failure (HF) biomarkers are predictive of CRT outcomes.
  
  
  METHODS
  In 73 patients (aged 68 ± 12 years; 83% men; ejection fraction 27% ± 7%) with CS and PV blood samples drawn simultaneously at the time of CRT device implantation, we measured amino-terminal pro-B-type natriuretic peptide (NT-proBNP), galectin-3 (gal-3), and soluble ST2 (sST2) levels. NT-proBNP concentrations >2000 pg/mL, gal-3 concentrations >25.9 ng/mL, and sST2 concentrations >35 ng/mL were considered positive on the basis of established PV cut points for identifying "high-risk" individuals with HF. CRT response was adjudicated by the HF Clinical Composite Score. A major adverse cardiovascular event (MACE) was defined as the composite end point of death, cardiac transplant, left ventricular assist device, and HF hospitalization at 2 years.
  
  
  RESULTS
  NT-proBNP concentrations were 20% higher in the CS than in the periphery, while gal-3 and sST2 concentrations were 10% higher in the periphery than in the CS (all P < .001). There were 45% CRT nonresponders at 6 months and 16 (22%) patients with MACE. Triple-positive CS values yielded the highest specificity of 95% for predicting CRT nonresponse. Consistently, CS strategies identified patients at higher risk of developing MACE, with >11-fold adjusted increase for triple-positive CS patients compared to triple-negative patients (all P ≤ .04). PV strategies were not predictive of MACE.
  
  
  CONCLUSIONS
  Our findings suggest that CS sampling of HF biomarkers may be better than PV sampling for predicting CRT outcomes. Larger studies are needed to confirm our findings.
authors.affiliation: Dalio Institute of Cardiovascular Imaging, New York-Presbyterian Hospital and Weill Cornell Medical College, New York, New York; Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address: qat9001@med.cornell.edu.
authors.forename: Quynh A
authors.initials: QA
authors.lastname: Truong
authors.affiliation: Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: James L
authors.initials: JL
authors.lastname: Januzzi
authors.affiliation: Massachusetts General Hospital Biostatistics Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Jackie
authors.initials: J
authors.lastname: Szymonifka
authors.affiliation: Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Wai-ee
authors.initials: WE
authors.lastname: Thai
authors.affiliation: Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Bryan
authors.initials: B
authors.lastname: Wai
authors.affiliation: Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Lavender
authors.affiliation: Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Umesh
authors.initials: U
authors.lastname: Sharma
authors.affiliation: Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Sandoval
authors.affiliation: Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Zachary S
authors.initials: ZS
authors.lastname: Grunau
authors.affiliation: Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Basnet
authors.affiliation: Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Adefolakemi
authors.initials: A
authors.lastname: Babatunde
authors.affiliation: University of California Cardiac Arrhythmia Center, Ronald Reagan Medical Center, Los Angeles, California.
authors.forename: Olujimi A
authors.initials: OA
authors.lastname: Ajijola
authors.affiliation: Dalio Institute of Cardiovascular Imaging, New York-Presbyterian Hospital and Weill Cornell Medical College, New York, New York.
authors.forename: James K
authors.initials: JK
authors.lastname: Min
authors.affiliation: Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Cardiac Arrhythmia Service, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Jagmeet P
authors.initials: JP
authors.lastname: Singh
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D001800:Blood Specimen Collection / Q000379:methods*; D058406:Cardiac Resynchronization Therapy / Q000379:methods* / Q000401:mortality; D054326:Coronary Sinus / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D037502:Galectin 3 / Q000097:blood*; D006333:Heart Failure / Q000097:blood / Q000401:mortality* / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D015996:Survival Rate; D016896:Treatment Outcome; D014680:Veins / Q000378:metabolism
chemical_list: D015415:Biomarkers; D037502:Galectin 3; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain
keywords: Biomarker; Cardiac resynchronization therapy; Coronary sinus; Galectin-3; Soluble ST2