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There is accumulating evidence that β blockers improve symptoms and prognosis in patients with ischaemic heart disease (IHD).1 Impaired filling of the left ventricle is often found in association with IHD.2 Improvement in diastolic left ventricular function may be an important mechanism of action of β blockers. This study investigated the effect of β adrenergic blockade on diastolic filling in patients with IHD.
We carried out a retrospective analysis of left ventricular filling in 265 consecutive patients attending our department for routine clinical evaluation of chest pain. All patients underwent our standard imaging protocol of thallium-201 myocardial perfusion imaging and list mode radionuclide ventriculography (RNVG). Left ventricular filling was assessed using RNVG, which has been previously validated for the assessment of cardiac diastolic function.3 4 It has also been extensively used in the assessment of left ventricular filling in various conditions.4
Background corrected left ventricular activity–time curves were generated using a fixed left ventricular and background region of interest. Left ventricular ejection fraction (LVEF) was calculated in the usual manner. The normal lower limit of LVEF with this technique is 40% in our institution. The percentage of left ventricular filling in the first third of the diastolic period was defined as the first third filling fraction (1/3FF), expressed as a percentage of the stroke volume. The previously described heart rate adjusted first third filling fraction index (which is equal to 1/3FF/R-R interval) was also used.5
Values are expressed as mean (SD). Spearman's correlation coefficient (r s) was used for correlation between variables. Non-parametric Kruskal-Wallis statistic was used for data comparison between three groups. Individual pairs of parameters were further compared by Dunn's formula. A probability value of p < 0.05 was considered significant.
All patients were in sinus rhythm; valve incompetence was ruled out on the grounds of history, physical examination, and echocardiography. According to patients' medication and the results of the radionuclide tests the following three groups of patients were formed: (1) a control group of 32 individuals receiving no systematic cardioactive medication and with normal myocardial perfusion and normal left ventricular function; (2) a group of 148 patients receiving no systematic cardioactive medication and with abnormal perfusion; (3) a group of 85 patients on β blockers and with abnormal perfusion. Seventy one of these patients were receiving atenolol, six were on propranolol, four on metoprolol, and four on bisoprolol.
There was no significant difference in age, and resting diastolic and systolic blood pressure between the groups of patients studied. LVEF was not correlated to either the first third filling fraction or the heart rate adjusting first third filling fraction. LVEF was significantly lower in patients with IHD, as assessed by thallium scintigraphy, receiving no medication (38.9 (11.0) compared to the control group (44.8 (6.3), p < 0.001). In patients on β blockers the LVEF (38.1 (9.5)) was also significantly reduced in comparison with the control group (p < 0.001). No significant difference in LVEF was found between the two groups of patients with IHD. Finally, the R-R interval (in ms) was significantly prolonged in patients with IHD on β blockers (972 (143)) compared to the control group (853 (125), p < 0.005) and the patients with IHD receiving no cardioactive medication (819 (136), p < 0.001); no significant difference in the R-R interval was found between the latter two groups of patients.
The first third filling fraction was significantly reduced in patients with IHD receiving no medication (41.1 (14.9)) in comparison to the control group (49.4 (14.5), p < 0.05) and to patients with IHD on β blockers (56.5 (15.2), p < 0.001); no significant difference was found between the latter two groups. Figure 1 shows the comparison of the first third filling fraction in the three groups of patients.
The heart rate adjusted first third filling fraction index was also significantly reduced in patients with IHD receiving no medication (49.7 (15.3)) in comparison to the control group (57.6 (13.3), p < 0.02) and to patients with IHD on β blockers (58.0 (13.8), p < 0.001); no significant difference was found between the latter two groups. These findings imply that the early filling enhancement that β blockers exert in patients with IHD may not be a function of suppressed heart rate alone.
Apart from LVEF, no other variables that may influence diastolic indices were significantly different between the control group and those patients with IHD receiving no systematic cardioactive medication. However, the first third filling fraction did not depend on LVEF. R-R interval was significantly prolonged in the group of patients with IHD on β blockers compared to both the control group and the patients with IHD receiving no medication. Again, the heart rate adjusted first third filling fraction radionuclide ventriculography index allowed for the adjustment of the heart rate effect on left ventricular filling.
The present study suggests that in patients with IHD on β blocker treatment resting diastolic function is restored to normal levels, and is significantly above that of a group of patients with IHD receiving no cardioactive medication. A decrease in the myocardial oxygen requirement, and hence prevention of myocardial ischaemia, may be the most important mechanism involved. A reduction in systemic blood pressure might also be expected to improve diastolic function. However, only 17.5% of patients included in the β blocker group gave a history of hypertension, and no significant difference in blood pressure was found between the groups of patients studied.
This study is consistent with other work suggesting that diastolic dysfunction is associated with ischaemic heart disease. A limitation of this present paper is that coronary angiography was not carried out on all patients; however thallium scintigraphy was used to carry out a functional assessment of the extent of ischaemic heart disease. Moreover, it suggests that this significant resting filling impairment can be restored to normal levels using β blockade.