Different responses to dobutamine in the presence of carvedilol or metoprolol in patients with chronic heart failure.

OBJECTIVE: To determine whether patients with congestive heart failure on different beta adrenoreceptor blocking drugs have similar haemodynamic responses to dobutamine. DESIGN: Single centre, single blind, randomised, two period crossover study comparing carvedilol with metoprolol CR/XL. PATIENTS: Ten patients with stable chronic congestive heart failure (ejection fraction < 40%) on chronic treatment with metoprolol CR/XL. METHODS: Patients were treated with carvedilol or metoprolol CR/XL (target dose 50 mg twice daily and 200 mg once daily, respectively) for eight weeks. Stress echocardiography was undertaken at the end of each maintenance period, using dobutamine 5 and 15 microg/kg/min. RESULTS: No significant haemodynamic differences were seen at rest on the two treatments. There was a more pronounced increase in heart rate and cardiac output during dobutamine infusion when the patients were on metoprolol than when they were on carvedilol. Mean arterial pressure increased significantly when the patients were on carvedilol, and cardiac output increased during low dose dobutamine, without further change during high dose dobutamine. During the dobutamine infusion, there was no significant difference in ejection fraction between carvedilol and metoprolol treatment. CONCLUSIONS: Patients with congestive heart failure on a non-selective beta adrenoreceptor blocker or beta1 selective blocker responded differently to the inotropic drug dobutamine: the beta1 blockade caused by metoprolol could be counteracted by dobutamine, whereas with carvedilol a low dose of dobutamine increased cardiac output, and a higher dose of dobutamine caused a pressor effect. These findings may be clinically relevant when choosing an inotropic drug.

Longitudinal myocardial contraction improves early during titration with metoprolol CR/XL in patients with heart failure.

OBJECTIVE: To investigate diastolic and systolic left ventricular recovery during titration with metoprolol CR/XL (controlled release/extended release). DESIGN: Placebo run in, followed by an open study. SETTING: University hospital. PATIENTS: 14 patients with chronic heart failure. INTERVENTIONS: Metoprolol CR/XL titrated from 12.5 mg once daily to 200 mg once daily. MAIN OUTCOME MEASURES: M mode recordings of atrioventricular (AV) plane displacement, Doppler measurement of transmitral flow and pulmonary venous flow, two dimensional ejection fraction, and measurement of venous plasma concentration of noradrenaline. Patients were investigated after 2, 4, 6, and 24 weeks of treatment. RESULTS: A reduction of heart rate was observed on the first dose (12.5 mg once daily), from a mean (SD) of 74 (11) to 67 (11) beats/min, p < 0.05. This was accompanied by prominent effects on AV plane filling parameters, including an increase in early diastolic filling period from 87 (28) to 105 (33) ms (p < 0.05), and in the lateral AV plane fractional shortening from 8.7 (2.7)% to 10.2 (2.8)% (p < 0.05). An early trend towards improvement in global systolic left ventricular function was also seen, although this was not significant until six weeks. Ejection fraction increased from 33 (7.5)% to 38 (11)% (p < 0.05). CONCLUSIONS: First effects of left ventricular recovery during beta blocker treatment were seen in recordings of longitudinal performance, as expressed by AV plane displacement. Doppler flow dynamics as well as global systolic recovery appeared several weeks later, emphasising the importance of longitudinal performance in evaluating left ventricular function.