No abstract

No abstract

suMMARY Treatment with vasodilators in heart failure has not always produced a useful improvement in the haemodynamic responses to exercise, and in many cases early drug tolerance has further limited the potential of this type of treatment. In a study to evaluate the efficacy of felodipine, a new calcium antagonist with selective vasodilator properties, in the management of congestive heart failure 10 patients with congestive heart failure underwent treadmill exercise testing before and during oral treatment with felodipine 30 mg daily. At every level of exercise felodipine lowered the pulmonary capillary wedge pressure, whereas cardiac index and stroke index increased considerably. The haemodynamic improvement was associated with an increase in the duration of exercise to exhaustion. Importantly, these beneficial effects were sustained throughout four weeks of treatment without evidence of drug tolerance. These observations suggest a useful role for felodipine in the long term management of congestive heart failure.In patients with chronic congestive heart failure exercise related fatigue and dyspnoea are the commonest and most troublesome symptoms. The reduced capacity of the failing heart to increase output to meet the metabolic demands of working muscle and the exagerated rise in left atrial pressure largely account for these symptoms. A critical evaluation of specific antifailure treatment must, therefore, examine the influence it has on the haemodynamic responses to exercise. An additional consideration is the long term efficacy of treatment. This is more difficult to assess since the natural history of congestive heart failure involves a variably progressive deterioration in left ventricular function which is not easily distinguished from the development of drug tolerance.Despite

The ability of trimetazidine (2,3,4, trimethoxybenzylpiperazine dihydrochloride, TMZ) to protect the myocardium against anthracycline (ANT)-induced cardiotoxicity during chemotherapy has been evaluated in female patients with breast cancer. A clinical trial was conducted in 61 patients subdivided into three groups: group 1 (n = 15, G1 ) treated with standard ANT protocol and cardioprotection by dexrazoxane (DEX) plus TMZ (60 mg, daily dose); group 2 (n = 22, G2) treated with ANT and cardioprotection by TMZ only; and group 3 (n = 24, G3) scheduled to receive ANT therapy and DEX. All the patients submitted to an echocardiographic evaluation of diastolic function (E wave velocity, A wave velocity, isovolumetric relaxation time [IVRT], deceleration time [DT]) at enrollment (T0), at T1 time, at T2 time, and at T3 time. After a 12-month follow-up period, the patients showed a good conservation of diastolic function both in G1 and G2 groups. No statistically significant difference was observed in E wave and A wave velocity and E/A ratio after ANT treatment. TMZ produced a cardioprotective effect, comparable to DEX protection, against subacute and chronic subclinical cardiotoxicity with no significant changes in diastolic function after 1 year of follow-up.

SUMMARY Felodipine is a new calcium antagonist with a high degree of vascular selectivity. To examine its potential value as an afterload reducing agent in congestive heart failure 11 patients were studied. Substantial increments in cardiac index were associated with a fall in systemic vascular resistance. Left ventricular end diastolic pressure was also significantly reduced. Although left ventricular maximum dP/dt remained unchanged, maximum dP/dt/P increased. Left ventricular unloading was reflected by a reduction in cavity dimensions and a shift in the relation between end systolic pressure and dimension downwards and to the left. The myocardial oxygen supply to demand ratio was also improved: coronary sinus flow increased significantly despite a decline in myocardial oxygen consumption. These beneficial haemodynamic and metabolic effects suggest that felodipine may extend the clinical application of calcium antagonists to include the treatment of congestive heart failure.Calcium antagonists such as nifedipine and verapamil reduce the inward flux of calcium ions across cell membranes by their inhibitory action on the calcium slow channel. ' These drugs are particularly active in the myocardium and vascular smooth muscle, in which the reduction in intracellular calcium ions impairs excitation-contraction coupling thereby inducing negative inotropism and vasodilatation.2 The combination of these separate cardiovascular influences probably underlies the efficacy of calcium antagonists in the treatment of angina and hypertension.3-5The systemic vasodilator effects of calcium antagonists indicate a potential role for this type of treatment in patients with left ventricular failure. A number of acute clinical studies have shown a useful improvement in left ventricular function which-in contrast to the in vitro findings-usually occurs without deterioration in derived indices of contractility.6-9 Other investigators,'0 however, have provided clear evidence of a negative inotropic response to calcium antagonists in patients with severe heart failure, which probably accounts for earlier reports of circulatory collapse and pulmonary oedema during treatment with these compounds. l-14For this reasonRequests for reprints to Dr D E Jewitt,