Blunted beta-adrenoceptor-mediated inotropy in valvular cardiomyopathy: another piece of the puzzle in human aortic valve disease
Standard
Blunted beta-adrenoceptor-mediated inotropy in valvular cardiomyopathy: another piece of the puzzle in human aortic valve disease. / Petersen, Johannes; Kloth, Benjamin; Iqbal, Shahria; Reichenspurner, Hermann; Geelhoed, Bastian; Schnabel, Renate; Eschenhagen, Thomas; Christ, Torsten; Girdauskas, Evaldas.
in: EUR J CARDIO-THORAC, Jahrgang 60, Nr. 1, 14.07.2021, S. 56-63.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Blunted beta-adrenoceptor-mediated inotropy in valvular cardiomyopathy: another piece of the puzzle in human aortic valve disease
AU - Petersen, Johannes
AU - Kloth, Benjamin
AU - Iqbal, Shahria
AU - Reichenspurner, Hermann
AU - Geelhoed, Bastian
AU - Schnabel, Renate
AU - Eschenhagen, Thomas
AU - Christ, Torsten
AU - Girdauskas, Evaldas
N1 - © The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
PY - 2021/7/14
Y1 - 2021/7/14
N2 - OBJECTIVES: Heart failure induced by valvular cardiomyopathy occurs in a substantial proportion of patients undergoing heart valve surgery. We aimed (i) to quantify beta-adrenoceptor (beta-AR) function by measuring the inotropic effect of isoprenaline in left ventricular (LV) tissue and (ii) to correlate beta-AR-mediated inotropy with clinical markers of heart failure.METHODS: A total of 179 LV myocardial samples were obtained from 104 consecutive patients who underwent aortic valve (AV) surgery between 2017 and 2019. Beta-ARs were stimulated by increasing the concentrations of isoprenaline, followed by a single high concentration of forskolin and calcium. Beta-AR sensitivity was estimated as the concentration to achieve half maximum effects (EC50). Maximum effect size was calculated as the relative beta-AR-mediated inotropic response compared to the force in the presence of high calcium [FISO/Ca (%)]. In vitro data were correlated with the clinical indicators of LV disease.RESULTS: FISO/Ca was independent of age and sex and amounted to 79.6 ± 20.5%. In a multivariate regression model, we found a significant inverse association between FISO/Ca and preoperative left ventricular end-diastolic diameter increase per 10 mm (OR -9.24, 95% CI -16.66 to -1.82; P = 0.015). Furthermore, patients with end-stage heart failure showed a strong tendency towards more severe reduction of max beta-AR response, as indicated by reduced FISO/Ca in a multivariate model (OR -29.60, 95% CI -61.92 to 2.72; P = 0.055).CONCLUSIONS: Our study indicates that in vitro myocardial contractility testing can quantify beta-AR dysfunction in patients with AV disease. We found a significant association between reduced beta-AR sensitivity and increased LV diameter, which may indicate a role of beta-AR dysfunction in the development of heart failure in patients with AV disease.
AB - OBJECTIVES: Heart failure induced by valvular cardiomyopathy occurs in a substantial proportion of patients undergoing heart valve surgery. We aimed (i) to quantify beta-adrenoceptor (beta-AR) function by measuring the inotropic effect of isoprenaline in left ventricular (LV) tissue and (ii) to correlate beta-AR-mediated inotropy with clinical markers of heart failure.METHODS: A total of 179 LV myocardial samples were obtained from 104 consecutive patients who underwent aortic valve (AV) surgery between 2017 and 2019. Beta-ARs were stimulated by increasing the concentrations of isoprenaline, followed by a single high concentration of forskolin and calcium. Beta-AR sensitivity was estimated as the concentration to achieve half maximum effects (EC50). Maximum effect size was calculated as the relative beta-AR-mediated inotropic response compared to the force in the presence of high calcium [FISO/Ca (%)]. In vitro data were correlated with the clinical indicators of LV disease.RESULTS: FISO/Ca was independent of age and sex and amounted to 79.6 ± 20.5%. In a multivariate regression model, we found a significant inverse association between FISO/Ca and preoperative left ventricular end-diastolic diameter increase per 10 mm (OR -9.24, 95% CI -16.66 to -1.82; P = 0.015). Furthermore, patients with end-stage heart failure showed a strong tendency towards more severe reduction of max beta-AR response, as indicated by reduced FISO/Ca in a multivariate model (OR -29.60, 95% CI -61.92 to 2.72; P = 0.055).CONCLUSIONS: Our study indicates that in vitro myocardial contractility testing can quantify beta-AR dysfunction in patients with AV disease. We found a significant association between reduced beta-AR sensitivity and increased LV diameter, which may indicate a role of beta-AR dysfunction in the development of heart failure in patients with AV disease.
KW - Aortic Valve/diagnostic imaging
KW - Aortic Valve Disease
KW - Aortic Valve Insufficiency
KW - Cardiomyopathies
KW - Humans
KW - Isoproterenol/pharmacology
KW - Receptors, Adrenergic
U2 - 10.1093/ejcts/ezab004
DO - 10.1093/ejcts/ezab004
M3 - SCORING: Journal article
C2 - 33619556
VL - 60
SP - 56
EP - 63
JO - EUR J CARDIO-THORAC
JF - EUR J CARDIO-THORAC
SN - 1010-7940
IS - 1
ER -
