title: Changes in collagen metabolism account for ventricular functional recovery following beta-blocker therapy in patients with chronic heart failure.
abstract: While beta blockade improves left ventricular (LV) function in patients with chronic heart failure (CHF), the mechanisms are not well known. This study aimed to examine whether changes in myocardial collagen metabolism account for LV functional recovery following beta-blocker therapy in 62 CHF patients with reduced ejection fraction (EF). LV function was echocardiographically measured at baseline and 1, 6, and 12 months after bisoprolol therapy along with serum markers of collagen metabolism including C-terminal telopeptide of collagen type I (CITP) and matrix metalloproteinase (MMP)-2. Deceleration time of mitral early velocity (DcT) increased even in the early phase, but LVEF gradually improved throughout the study period. Heart rate (HR) was reduced from the early stage, and CITP gradually decreased. LVEF and DcT increased more so in patients with the larger decreases in CITP (r = -0.33, p < 0.05; r = -0.28, p < 0.05, respectively), and HR (r = -0.31, p < 0.05; r = -0.38, p < 0.05, respectively). In addition, there were greater decreases in CITP, MMP-2 and HR from baseline to 1, 6, or 12 months in patients with above-average improvement in LVEF than in those with below-average improvement in LVEF. Similar results were obtained in terms of DcT. There was no significant correlation between the changes in HR and CITP. In conclusion, improvement in LV systolic/diastolic function was greatest in patients with the larger inhibition of collagen degradation. Changes in myocardial collagen metabolism are closely related to LV functional recovery somewhat independently from HR reduction.
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Fukui
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Goda
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.|Osaka Clinic, Takeda Pharmaceutical Company Limited, Osaka, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Komamura
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Nakabo
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Masaki
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Chikako
authors.initials: C
authors.lastname: Yoshida
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hirotani
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Lee-Kawabata
authors.affiliation: Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Kobe, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tsujino
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Mano
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan. masuyama@hyo-med.ac.jp.
authors.forename: Tohru
authors.initials: T
authors.lastname: Masuyama
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002908:Chronic Disease; D003094:Collagen / Q000378:metabolism*; D024042:Collagen Type I / Q000097:blood; D015150:Echocardiography, Doppler; D005260:Female; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D010455:Peptides / Q000097:blood; D011446:Prospective Studies; D059748:Proteolysis; D020127:Recovery of Function; D013318:Stroke Volume / Q000187:drug effects*; D013997:Time Factors; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects*; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D000319:Adrenergic beta-Antagonists; D015415:Biomarkers; D024042:Collagen Type I; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D003094:Collagen; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: Beta-blocker; Collagen; Heart failure; Heart rate