PMID- 35714178
OWN - NLM
STAT- MEDLINE
DCOM- 20220711
LR  - 20230703
IS  - 1522-1539 (Electronic)
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 323
IP  - 1
DP  - 2022 Jul 1
TI  - Nonplatelet thromboxane generation is associated with impaired cardiovascular 
      performance and mortality in heart failure.
PG  - H248-H255
LID - 10.1152/ajpheart.00212.2022 [doi]
AB  - Nonplatelet thromboxane generation, stimulated largely by oxidative stress, is a 
      novel mortality risk factor in individuals with coronary artery disease. Though 
      inversely associated with left ventricular ejection fraction (LVEF), a potential 
      role in the pathobiology of heart failure (HF) remains poorly defined. 
      Nonplatelet thromboxane generation and oxidative stress were assessed by 
      measuring urine thromboxane-B(2) metabolites (TXB(2)-M) and 8-isoPGF(2alpha) by ELISA 
      in 105 subjects taking aspirin and undergoing right heart catheterization for 
      evaluation of HF, valve disease, or after transplantation. Multivariable logistic 
      regression and survival analyses were used to define associations of TXB(2)-M to 
      invasive measures of cardiovascular performance and 4-year clinical outcomes. 
      TXB(2)-M was elevated (>1,500 pg/mg creatinine) in 46% of subjects and correlated 
      with HF severity by New York Heart Association (NYHA) functional class and brain 
      natriuretic peptide level, modestly with LVEF, but not with HF etiology. There 
      was no association of oxidative stress to HF type or etiology but a trend with 
      NYHA functional class. Multiple invasive hemodynamic parameters independently 
      associated with TXB(2)-M after adjustment for oxidative stress, age, sex, and 
      race with pulmonary effective arterial elastance (E(a pulmonary)), reflective of 
      right ventricular afterload, being the most robust on hierarchical analysis. 
      Similar to E(a pulmonary), elevated urinary TXB(2)-M is associated with increased 
      risk of death (adjusted HR = 2.15, P = 0.037) and a combination of death, 
      transplant, or mechanical support initiation (adjusted HR = 2.0, P = 0.042). 
      Nonplatelet TXA(2) thromboxane generation is independently associated with HF 
      severity reflected by invasive measures of cardiovascular performance, 
      particularly right ventricular afterload, and independently predicted long-term 
      mortality risk.NEW & NOTEWORTHY Nonplatelet thromboxane generation in heart 
      failure is independently associated with risk of death, transplant, or need for 
      mechanical support. Measurement of urine thromboxane metabolites using a 
      clinically available assay may be a useful surrogate for invasive measurement of 
      cardiovascular hemodynamics and performance that could provide prognostic 
      information and facilitate tailoring of therapy in patients with heart failure. 
      Inhibiting thromboxane generation or its biological effects is a potential 
      strategy for improving cardiovascular performance and outcomes in heart failure.
FAU - Hariri, Essa
AU  - Hariri E
AD  - Division of Cardiovascular Medicine, Department of Medicine, University of 
      Massachusetts Chan Medical School, Worcester, Massachusetts.
AD  - Department of Medicine, Cleveland Clinic Foundation, Cleveland, Ohio.
FAU - Kakouros, Nikolaos
AU  - Kakouros N
AD  - Division of Cardiovascular Medicine, Department of Medicine, University of 
      Massachusetts Chan Medical School, Worcester, Massachusetts.
FAU - Bunsick, David A
AU  - Bunsick DA
AUID- ORCID: 0000-0002-7050-5042
AD  - Division of Cardiovascular Medicine, Department of Medicine, University of 
      Massachusetts Chan Medical School, Worcester, Massachusetts.
FAU - Russell, Stuart D
AU  - Russell SD
AUID- ORCID: 0000-0003-1115-0349
AD  - Division of Cardiology, Department of Medicine, Johns Hopkins School of Medicine, 
      Baltimore, Maryland.
FAU - Mudd, James O
AU  - Mudd JO
AD  - Division of Cardiology, Department of Medicine, Johns Hopkins School of Medicine, 
      Baltimore, Maryland.
FAU - Laws, Katherine
AU  - Laws K
AD  - Division of Cardiology, Department of Medicine, Johns Hopkins School of Medicine, 
      Baltimore, Maryland.
FAU - Lake, Mikhailia W
AU  - Lake MW
AD  - Division of Cardiology, Department of Medicine, Johns Hopkins School of Medicine, 
      Baltimore, Maryland.
FAU - Rade, Jeffrey J
AU  - Rade JJ
AUID- ORCID: 0000-0001-8607-4569
AD  - Division of Cardiovascular Medicine, Department of Medicine, University of 
      Massachusetts Chan Medical School, Worcester, Massachusetts.
AD  - Division of Cardiology, Department of Medicine, Johns Hopkins School of Medicine, 
      Baltimore, Maryland.
LA  - eng
SI  - figshare/10.6084/m9.figshare.20052125.v1
GR  - TL1 TR001454/TR/NCATS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20220617
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Thromboxanes)
RN  - 54397-85-2 (Thromboxane B2)
SB  - IM
MH  - *Heart Failure/diagnosis
MH  - Humans
MH  - Stroke Volume
MH  - Thromboxane B2/urine
MH  - Thromboxanes
MH  - *Ventricular Function, Left
PMC - PMC9273282
OTO - NOTNLM
OT  - heart failure
OT  - hemodynamics
OT  - outcome
OT  - thromboxane
COIS- No conflicts of interest, financial or otherwise, are declared by the authors.
EDAT- 2022/06/18 06:00
MHDA- 2022/07/12 06:00
PMCR- 2023/07/01
CRDT- 2022/06/17 14:04
PHST- 2022/06/18 06:00 [pubmed]
PHST- 2022/07/12 06:00 [medline]
PHST- 2022/06/17 14:04 [entrez]
PHST- 2023/07/01 00:00 [pmc-release]
AID - H-00212-2022 [pii]
AID - 10.1152/ajpheart.00212.2022 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2022 Jul 1;323(1):H248-H255. doi: 
      10.1152/ajpheart.00212.2022. Epub 2022 Jun 17.