Early changes in longitudinal performance predict future improvement in global left ventricular function during long term beta adrenergic blockade

Abstract

Objective: Contraction of longitudinal and subendocardial myocardial muscle fibres is reflected in descent of the atrioventricular (AV) plane. The aim was therefore to determine whether beta blocker treatment with prolongation of diastole might result in improved function as reflected by AV plane movements in patients with chronic heart failure.

Design: Double blind, randomised, placebo controlled and open intervention study.

Setting: University hospital.

Patients: Patients with congestive heart failure: placebo controlled (n = 26) and an open protocol (n = 15).

Interventions: 12 months of metoprolol treatment.

Main outcome measures: Short axis and long axis echocardiography, invasive haemodynamics, radionuclide angiography.

Results: Recovery of systolic and diastolic function during metoprolol treatment was reflected by early changes in mean (SD) AV plane amplitude, from 5.3 (2.0)% to 7.1 (3.2)% and 7.8 (3. 1)% (at 3 and 12 months, respectively; p < 0.05). In a multivariate analysis, only the change in AV plane amplitude by three months was independently associated with improvement in pulmonary capillary wedge pressure by six months (r = 0.80, p = 0.017). Change in AV plane amplitude by three months was also a better predictor of improvement in ejection fraction by 12 months (r = 0.78, p < 0.001) than changes in radionuclide ejection fraction by three months (r = 0.34, p = 0.049).

Conclusions: Improvement in longitudinal contraction was closely associated with a decrease in left ventricular filling pressure during metoprolol treatment. This association was stronger than changes in short axis performance or radionuclide ejection fraction, emphasising the importance of AV plane motion for left ventricular filling and systolic performance in patients with heart failure.

Figure 1

Schematic atrioventricular plane (AVP) curve and delineation of measured periods: (1) start of left ventricular contraction and ejection; (2) end of left ventricular contraction; (3) start of early rapid diastolic filling; (4) end of rapid filling, beginning of the diastasis; (5) end of diastasis, beginning of atrial contraction; (6) end of atrial contraction. (A) Maximum derivative of systolic ejection. (B) Maximum derivative of early rapid filling.

Figure 2

(A) Regional systolic amplitudes in patients on placebo. (B) Regional systolic amplitudes in patients on metoprolol treatment. Empty circles, left lateral atrioventricular plane (AVP); filled circles, septal AVP; empty triangles, posterior wall short axis; filled triangles, interventricular septum short axis. The p values of the analysis of variance test are shown to the right. *p < 0.05 v baseline investigation.

Figure 3

Box plots showing lateral atrioventricular plane (AVP) contraction amplitudes in patients on placebo (all dilated cardiomyopathy, n = 12), in patients with ischaemic cardiomyopathy (IHD, all on open metoprolol, n = 6), and in patients with dilated cardiomyopathy (DCM) treated with metoprolol (open treatment, n = 9; double blind treatment, n = 14). Baseline (white boxes), six months follow up (grey boxes). The boxes encompass the 25th to the 75th centile, and the whiskers the 10th to the 90th centile. Dots denote values outside the 10th and 90th centiles. Solid lines in the boxes denote median values and dotted lines denote mean values.

Figure 4

Linear correlation between systolic fractional shortening in the atrioventricular plane (AVP-FS) v pulmonary capillary wedge pressure (PCWP) in patients treated with metoprolol in the invasive substudy over six months. In a multivariate stepwise regression analysis, the AVP-FS was the only variable that was independently associated with the change in pulmonary capillary wedge pressure. ΔPCW % = −4.35 − 0.96(ΔAVP-FS %), r = 0.90, p = 0.001.

Figure 5

Linear correlation between systolic fractional shortening in the atrioventricular plane (AVP-FS) (over three months) versus change in radionuclide ejection fraction (EF) (over 12 months) in patients treated with metoprolol. In a multivariate stepwise regression analysis, the AVP-FS was the only echocardiographic variable that was independently associated with the future change in EF: ΔEF % = 12.3 + 0.46(ΔAVP-FS %), r = 0.76, p < 0.001.

Figure 6

The atrioventricular plane (AVP) rapid filling time to ejection time ratio, corrected for heart rate by division with Q₁Q₂ interval. There was a significant prolongation of the rapid filling time to ejection time ratio in the metoprolol group, but no change in the placebo group. Filled circles, metoprolol; empty triangles, placebo. *p < 0.05 v baseline.