Calcium antagonists and chronic cardiac failure.

The treatment of cardiac failure involves a series of steps, which are taken in an order determined by clinical necessity. In some instances there is a treatable cause which may be amenable to appropriate medical or surgical management. In many there are correctable factors exacerbating the situation, for example high blood pressure, anaemia, arrhythmias, high salt intake or drugs such as beta-blockers. More specific treatment includes rest and diuretics, with or without digoxin. If these measures prove insufficient, the next step is to add a vasodilator. There are a number of vasodilators available with only preliminary information on their relative merits (Lipkin & Poole-Wilson, 1985). The calcium antagonists are one group of vasodilators but they have other actions which may make them an attractive choice in a patient with resistant heart failure. Most patients with chronic cardiac failure have either ischaemic heart disease, hypertension or longstanding chest disease with pulmonary hypertension, as the major underlying cause of their heart disease. Calcium antagonists have the potential to ameliorate each of these three underlying disorders. In patients with coronary artery disease calcium antagonists will dilate the coronary arteries (Bourassa et al., 1980), reduce spasm (Antman et al., 1980) and improve flow by their effects on platelets (Dale et al., 1983) and red cells (Waller et al., 1984). Calcium antagonists reduce heart work (Ellrodt et al., 1980) and have an antiarrhythmic effect (Fagbemi & Parratt, 1981). There is ample evidence that these actions are effective since calcium antagonists have repeatedly been shown to help patients with angina (Subramanian et al., 1982; Gerstenblith et al., 1982; Theroux et al., 1982). These drugs have also established a major place in the treatment of systemic hypertension (Hornung et al., 1983; Buhler et al., 1982). Their role in pulmonary hypertension is much less clearly defined but it is possible that they do reduce pressure in the pulmonary vascular bed (Sturani et al., 1984; Packer, 1985). In addition to their effect on the underlying disorder, calcium antagonists correct the disturbed haemodynamic state which occurs in cardiac failure. This state consists of (1) reduced cardiac output, (2) compensatory tachycardia, vasoconstriction and fluid retention and (3) cardiac dilatation and hypertrophy. The body responds to a fall in blood pressure by increasing sympathetic drive which produces the tachycardia, vasoconstriction and renin release. The latter, together with other less well defined processes, causes fluid retention. These responses may help the patient with hypotension due to blood loss but the patient with serious cardiac disease is faced with 3 events which all increase heart work. In addition, tissue perfusion decreases. The cardiac enlargement which occurs may initially have a beneficial effect and improve cardiac output but eventually these structural changes lead to an increase in heart work and exacerbate the problems associated with a defective coronary circulation. The aims of treatment are therefore to improve cardiac output and hopefully to correct the counterproductive responses both functional and structural. Calcium antagonists have 3 major actions which might enable them to achieve the aims of treatment just defined. Firstly, they relax arterial smooth muscle (Katz et al., 1984; Opie, 1984) and thereby dilate arteries and reduce peripheral resistance. Secondly, they reduce myocardial contractility in the same way by modifying the cellular intake of calcium which is a major stimulus to cardiac muscle contraction (Katz et alt, 1984; Opie, 1984). Thirdly, they influence the conducting system in the heart and in particular they delay transmission in the A-V node (Clusin et al., 1982; Opie, 1984). Of these, it is the vasodilatation which is most important but all three may contribute to the twin objectives of achieving increased cardiac output and a reduction in heart work. The output of a pump can be increased by reducing the impedance to flow. In relation to the heart the impedance is predominantly determined by systemic arteriolar tone or resistance but also by blood viscosity and by blood volume. The arterial vasodilatation produced by calcium antagonists is therefore of paramount importance but their effects on red cells which reduce the