Cardiac muscle contraction is under the regulatory control of the ANS. The interaction of a catecholamine with its membrane-bound β1‑adrenergic receptor activates the enzyme adenylate cyclase. The resultant increase in intracellular cyclic adenosine monophosphate (c-AMP) facilitates transmembrane calcium flux. In cardiac muscle, the β1‑adrenergic pathway can therefore be characterized as a series of events that begins with the interaction of a β1‑adrenergic receptor agonist with its receptor and concludes with an increase in muscle contraction.
Heart failure (HF) is a chronic contractile dysfunction characterized by myocyte loss and increased interstitial collagen deposits associated with organic cardiac diseases. Cardiac output is decreased resulting in reduced renal perfusion leading to increased renin-angiotensin-aldosterone synthesis. Decreased hepatic perfusion leads to decreased aldosterone clearance. Increased aldosterone concentrations lead to coronary and renovascular fibrosis, endothelial cell and baroreceptor dysfunction, and decreased myocardial norepinephrine uptake.
The most common cause of HF is left ventricular (LV) systolic dysfunction. Most cases are a result of CAD, previous MI, or a chronically under-perfused myocardium.28 Other common causes are cardiomyopathy, valvular disease, and HTN. Right-ventricular (RV) systolic dysfunction is usually a consequence of LV systolic dysfunction.28 Other causes include right-ventricular infarction, pulmonary hypertension, chronic severe tricuspid regurgitation, or arrhythmogenic right-ventricular dysplasia.
When the heart is no longer able to pump an adequate supply of blood to meet metabolic demand for oxygen, the patient develops heart failure. To improve myocardial contractility, the patient is prescribed a cardiac glycoside; to reduce workload, the patient may be prescribed a diuretic, an ACE inhibitor, an AT II-receptor antagonist, or a β1‑adrenergic receptor antagonist. Non-pharmacological strategies include heart transplantation. Key recommendations for practice are presented in Table 14.