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. 1999 Apr;81(4):336–341. doi: 10.1136/hrt.81.4.336

Potential interests of heart rate lowering drugs

T Laperche 1, D Logeart 1, A Cohen-Solal 1, R Gourgon 1
PMCID: PMC1729002  PMID: 10092556

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Figure 1  .

Figure 1  

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Relation between heart rate and percentage diastole. Because of the non-linearity of the relation, a small decrease in heart rate results, at lower heart rates especially, in a dramatic increase in the diastolic part of the cardiac cycle. (Reproduced from Boudoulas H, Rittgers SE, Lewis RP, et al. Circulation 1979;60:164-9, with permission of American Heart Association.)

Figure 2  .

Figure 2  

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(Left) Work efficiency in normal subjects. Ees represents the slope of the left ventricular end systolic pressure−volume relation, and Ea the slope of the arterial end systolic pressure−stroke volume relation. External work (EW) (area in grey), the mechanical cardiac work, represents the area bounded by the pressure−volume trajectory of one beat. Pressure−volume area (PVA) represents the area bounded by the end systolic pressure−volume relation, the end diastolic pressure−volume relation, and the systolic pressure−volume trajectory of the contraction. Potential energy (PE) is the difference between PVA and EW. EW/PVA represents the work efficiency. ESV, end systolic volume; EDV, end diastolic volume; V0 is the volume axis intercept of the end systolic pressure−volume relation. (Right) Effect of a heart rate lowering drug on work efficiency in patients with heart failure. In comparison with basal conditions (solid lines and white area), negative chronotropic effect (dashed lines and grey area) considerably reduces Ea and Ees to a lower extent, resulting in a fall in the Ea/Ees ratio, so that EW/PVA significantly increases, meaning an increase in work efficiency. (Adapted from Yamakawa H, Takeuchi M, Takaoka H, et al. Circulation 1996;94:340-5, with permission of American Heart Association.)

Figure 3  .

Figure 3  

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Force−frequency relation in human hearts. The figure displays the force−frequency relation developed by papillary muscles of six normal subjects and six patients with heart failure (cardiomyopathy) in response to a progressive increase in stimulation frequency. Force increases with the increase in stimulation frequency in normal subjects (open symbols), up to a critical frequency above which it decreases. In heart failure (filled symbols), the force−frequency slope is considerably decreased. Increasing the stimulation frequency does not produce a meaningful increase of force; furthermore, the point of inflexion occurs at a low frequency. This explains why, at high heart rates, the force of contraction of cardiac fibres of patients with heart failure is not increased, and may even be decreased. Negative chronotropic agents shift the operating frequencies during exercise to the left part of the axis, which may in part explain their beneficial effect on cardiac function. (Reproduced from Mulieri LA, Hasenfuss G, Leavitt B, et al. Circulation 1992;85:1743-50, with permission of American Heart Association.)

Figure 4  .

Figure 4  

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Effects of heart rate increase on left ventricular filling (the same model applies for the three parts of the figure). Top of figure: pressure−volume relation (ESV, end systolic volume; ESPVR, end systolic pressure−volume relation; EDV, end diastolic volume; EDVPR, end diastolic pressure−volume relation; SV, stroke volume). Bottom of figure: left ventricular volume changes (expressed in percentage end diastolic volume (EDV)) during one cardiac cycle. Vertical lines summarise the consequences of heart rate (HR) variations on left ventricular filling volume. Depending on the context, various increases in heart rate (leftward displacement of arrow) result in modifications of left ventricular volume filling. In normal subjects (left part of the figure) with normal pressure−volume relation (dashed line loop), modifications of heart rate mainly affect diastasis. Volume changes during this period are minor, with most of the filling occurring in early and late diastole, so that tachycardia, up to a critical limit, does not significantly affect ventricular volume. In patients with impaired relaxation (middle part of the figure), because of the delayed early diastolic rapid filling phase (solid line loop in the top of the figure), diastasis is shortened or abolished and atrial systolic filling is increased in compensation for the reduced contribution of rapid filling. So, inappropriate tachycardia will significantly reduce ventricular filling. This explains the benefit of heart rate lowering drugs in patients with impaired relaxation and heart failure caused by inappropriate tachycardia. Finally, in patients with increased chamber stiffness (right part of the figure), stroke volume is reduced (solid line loop in the top of the figure) and there is a leftward and upward displacement of the end diastolic pressure−volume relation (arrow). So, tachycardia represents a compensatory response to reduced systolic ejection volume. In these patients, a heart rate lowering drug may have a deleterious effect, by creating an important increase of pressure levels even with small volume variations, caused by the steep end diastolic pressure−volume relation.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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