Time course of improvement in left ventricular function, mass and geometry in patients with congestive heart failure treated with beta-adrenergic blockade

Abstract

Patients with heart failure treated with metoprolol do not demonstrate an improvement in systolic performance until after 1 month of therapy and may have a mild reduction in function initially. Long-term therapy with metoprolol results in a reversal of maladaptive remodeling with reduction in left ventricular volumes, regression of left ventricular mass and improved ventricular geometry by 18 months.

Myocardial Contractile Reserve by Dobutamine Stress Echocardiography Predicts Improvement in Ejection Fraction With β-Blockade in Patients With Heart Failure

“…␤-Blockade improves LVEF by biologically augmenting myocyte and chamber contractility. [1][2][3][4] This improvement does not occur immediately but rather between 1 and 3 months of therapy. 3 A partial explanation of biological improvement in LVEF may be upregulation of sarcoplasmic reticulum calcium ATPase (SERCA2), a protein that controls calcium sequestration, and an increase in the relative amount of ␣-myosin heavy chain.…”

“…[1][2][3][4] This improvement does not occur immediately but rather between 1 and 3 months of therapy. 3 A partial explanation of biological improvement in LVEF may be upregulation of sarcoplasmic reticulum calcium ATPase (SERCA2), a protein that controls calcium sequestration, and an increase in the relative amount of ␣-myosin heavy chain. 16 In the absence of contractile reserve (ie, when myocytes have been supplanted by replacement fibrosis because of cell death and interstitial remodeling 1,17 ), ventricular function cannot improve by this biological mechanism because there are not enough contractile units.…”

“…[1][2][3][4] This results in improved ventricular function, an increase in myocardial chamber efficiency, and a reversal in the pathological remodeling process. [1][2][3][4] In many cases, this translates into a survival benefit, [5][6][7][8] but in the BEST study, there was no clear survival benefit, despite an improvement in left ventricular ejection fraction (LVEF) with bucindolol. 9 However, not all patients have improved LVEF with ␤-blocker therapy.…”

“…8 This phenomenon may occur because ␤-blockers have 2 effects: pharmacological withdrawal of adrenergic support that tends to reduce LVEF and biological improvement in myocyte and chamber function that tends to improve LVEF. 1,3 If there is little contractile reserve, the negative inotropic effects of pharmacological adrenergic withdrawal may predominate, and LVEF may fall. Conversely, in patients with contractile reserve, the biological improvement in myocyte and chamber function predominates over the negative inotropic (pharmacological) effect of ␤-blockade.…”

β 2 -Adrenoceptor signaling is required for the development of an asthma phenotype in a murine model

“…In CHF, drugs classified as ␤-blockers (␤-AR antagonists and inverse agonists) were once contraindicated because acute administration decreased cardiac output and produced other negative inotropic effects (8). However, large clinical trials have shown that chronic administration of certain ␤-blockers improves cardiac output and decreases mortality (9,10). Presently, ␤-blockers are contraindicated in asthma because their acute administration may cause airway narrowing (11,12).…”