Objective-To study the effects of adding a salicylate to the angiotensin converting enzyme inhibitor enalapril in patients with heart failure due to coronary artery disease. Design-Double blind, crossover study for three days in hospital followed by an extended similar study outside hospital over two months of once daily enalapril plus salicylate and enalapril plus placebo. Setting-Tertiary referral centre. Patients-20 patients with heart failure due to myocardial infarction (New York Heart Association class II or III) and an ejection fraction less than 040. Twelve patients completed the two parts ofthe study. Main outcome measures-Blood pressure, plasma converting enzyme activity; plasma angiotensin II and noradrenaline concentrations; excretion of metabolites of renal and systemic prostanoids. Results-The unloading effect of first and second dose of enalapril in the morning lasted only during the day; in the extended study it lasted 24 hours because of the drug's accumulation. Converting enzyme inhibitors attenuate the breakdown of bradykinin and therefore enhance prostaglandin E, synthesis mediated by bradykinin. Evidence was found of such a prostaglandin E2 mediated contribution to ventricular unloading by enalapril, which was blocked by salicylate. The contribution, however, was small and variable, and salicylate addition had on average no significant de-unloading effect during the day. Unloading was abolished in only three of the 20 patients in the short term study and in one of the 12 in the extended study. At night, when other effects of enalapril on blood pressure had waned and the bradykinin induced effect persisted, salicylate significantly reduced the remaining small unloading effect. No effect was seen of salicylate addition on reversal of remodelling. Enalapril reduced angiotensin II induced synthesis of systemic and renal prostaglandin I2 and thromboxane A2, initially only during the day, but later also at night. It thereby masked suppression of thromboxane A2 synthesis by salicylate, which is the effect to which reinfarct prevention by salicylate is attributed. Conclusion-The risk is low that salicylate will substantially reduce the benefit of enalapril in patients with heart failure by de-unloading the ventricle. Like other effects induced by bradykinin significant de-unloading occurs in only a minority of the patients. In the presence of enalapril, however, salicylate will probably not be as effective as expected in reducing reinfarction risk, because enalapril already reduces thromboxane A, synthesis effectively in patients with heart failure and no further reduction by salicylate was found. (Br HeartJa 1995;73:227-236)

After myocardial infarction, left ventricular volume and ejection fraction can be assessed by echocardiography, magnetic resonance imaging and radionuclide angiography to guide therapy and determine prognosis. Whether a measured parameter gives the same results irrespective of the method used and the observer who performs the analysis is only partly known. Intra-observer and inter-observer variability were determined for echo and magnetic resonance imaging. Left ventricular ejection fraction measured by these techniques was related to radionuclide angiograms performed in the same period. Intra-observer variability for both echo and MRI was low and in most instances below 5%. Inter-observer variability for the echo and MRI measurements were substantially higher than intra-observer variability. Comparison of the three imaging modalities revealed systematic differences. Therefore, in clinical studies, left ventricular volume and function parameters have to be measured with the same technique and by the same observer in qualified core laboratories.

Regional curvature analysis correctly identifies the geometric changes induced by myocardial infarction. Apical systolic curvature can distinguish those patients that are at risk for left ventricular remodelling from those who are not at risk.

Eleven patients with coronary artery disease and chronic heart failure were studied before and three months after the angiotensin converting enzyme inhibitor enalapril was added to their frusemide medication. The following were measured: left ventricular pressure and volume with transient occlusion of the inferior vena cava, radionuclide angiography, and hormone concentrations in plasma. As in other reported studies, the clinical condition of the patients improved and their exercise tolerance increased moderately. Addition of enalapril reduced end diastolic and systolic pressure, reduced ventricular volume, and concomitantly increased the ejection fraction. The end systolic pressure-volume relation shifted to the left as it did in a similar animal study. In the animal study unloading by a vasodilator did not induce a leftward shift, so it can be inferred that in the present study unloading combined with a decrease in the angiotensin concentration was instrumental in remodelling the heart. Though unloading was expected to have a beneficial effect on the oxygen supply/demand ratio of the heart, the patients still showed the same drop in the ejection fraction during exercise as they did before treatment with enalapril, and early diastolic filling did not improve. Normally, regression of cardiac dilatation is only found if pump function improves; the present study showed that unloading in combination with angiotensin converting enzyme inhibition reshapes the ventricle without improving intrinsic pump function.