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

Abstract

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 β 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.

Abnormal left ventricular function occurs on exercise in well-treated hypertensive subjects with normal resting echocardiography

“…Borges et al 24 found acute treatment with captopril had no significant effect on either Sm or Em in subjects with hypertension with or without LVH. In heart failure subjects Andersson et al 28 found that treatment with metoprolol CR/XL led to an increase in atrioventricular plane displacement after 6 weeks. In patients with heart failure and normal ejection fraction diuretics combined with irbesartan or ramipril led to a small but significant improvement in longitudinal velocities 29.…”

Abnormal regional left ventricular mechanics in treated hypertensive patients with ‘normal left ventricular function’

“…More interestingly, the recovery of long axis function actually precedes that of short axis [16]. We feel, therefore, that our findings are clinically relevant.…”

The function of left ventricular basal segments is most important for long-term recovery

“…We have previously shown that basal LV function is important for long-term recovery, and that metoprolol treatment exerts effects in these segments early after institution of therapy [8]. The cellular mechanism behind the ability of metoprolol treatment to recruit contractility in the basal segments is not known.…”

“…Each segment contained 16 chords except segments 6, 7, 10, 12, 13 and 16 that contained 17 chords. LV regional function was evaluated in three sections of the left ventricle: the basal segments (segments 2, 4, 7, 10, 13, 16); mid segments (segments 1, 3, 6, 9, 12, 15); and apical segments (segments 5,8,11,14) as shown in Fig. 1.…”

“…We have previously shown that the basal part of the left ventricle responds early during selective beta 1 -blockade treatment preceding global improvement and that changes in longitudinal performance predict future global improvement [8,9]. Originating from an earlier observation that metoprolol treatment exerted heterogeneous regional improvement [10], this study was conducted to increase our knowledge about beta-blocker effects and regional recovery.…”