DISCUSSION
8.2 Prognostic value of haemodynamic studies
8.2.3 Clinical limitations: effects of treatment and maternal body habitus Other factors that limit a precise evaluation of hemodynamics in hypertensive
8.2.3 Clinical limitations: effects of treatment and maternal body habitus
We also describe an elevated cardiac output in gestational hypertensive participants compared to normotensives pregnant women, but these differences were not evident when cardiac output was standardized for body surface area. These findings imply that the elevated cardiac output reported early in pregnancy as a marker for
subsequent development of hypertensive disease (Easterling et al (1999) and Bosio et al (1999) may in fact be recognising the risk related to obesity. Despite shortcomings
when applied to pregnant women, it still remains necessary and logical to standardize maternal hemodynamic parameters for differences in body surface area or height;
otherwise the effects of obesity would be obscured (de Simone et al, (1997).
Our study is limited by baseline differences in maternal body size and clinical severity of the disease as well as the treatment effect medication prior to measurement on hemodynamic parameters. Early invasive hemodynamic studies (Cotton et al, (1988)) showed that most pre-eclamptic participants had a hyperdynamic circulation with an elevated cardiac index. However, in addition to the inclusion of chronic hypertensives the pre-eclamptic women in Cotton's study received magnesium infusion prior to baseline measurements, introducing significant heterogenicity in the study groups.
The other large invasive hemodynamic study of Mabie et al, (1989) also demonstrated a hyperdynamic circulation with an elevated cardiac index in majority of their pre- eclamptic participants similar to the Cotton study. These findings were also complicated by effects of treatment, since approximately a third of the participants had received hydralazine and almost half were in early labour, factors that likely
affected hemodynamic measurements. In both studies, intravenous fluid was also administered. This differed from the invasive study of Visser et al, (1991) in which intravenous fluid was not administered. Visser et al, (1991) pointed out that the marked disparity in haemodynamic studies in pre-eclamptic women, erroneously attributed to a variable hemodynamic expression of the disease, may in fact be related to administration of anti-hypertensive medication and/or intravenous fluids.
Such effects of treatment on maternal hemodynamics were reported in a study by Hung et al, (2000) who showed that preeclamptic women given methyl-dopa for five days had a significant reduction in retinal artery vascular resistance. In a small study assessing treatment effects in preeclamptic women, Scardo et al, (1999) reported a significant increase in cardiac index measured by thoracic electric bioimpedence in the group given non-dihydropyradine calcium antagonist, nifedipine, but no change in the group that was administered combined alpha-beta adrenergic blocking agent, labetalol. These differences in cardiac index occurred despite similar reductions in blood pressure, and, in part, were due to differences in heart rate; (an increase with nifedipine and a decrease with labetalol.
The contribution of heart rate to cardiac output was reported by Bolte et al, (1998) who attributed the increase in cardiac index to an increased heart rate in hypertensive pregnant women given dihydrallazine compared to group given the selective serotonin receptor blocker, ketanserin. Similarly, in their echocardiographic hemodynamic study of predominantly obese hypertensive pregnant women, Easterling et al (1990) attributed an elevated cardiac output to an increased heart rate. In another study of hemodynamics measured by thoracic electric bioimpedence in severe preeclamptics,
Scardo et al, (1996) also observed an increased heart rate but without any change in cardiac output. The authors therefore stated that the increased heart rate in their preeclamptics cohort prevented the expected fall in cardiac output.
Our study clearly demonstrates a significant lower heart rate in untreated
preeclamptics with severe proteinuria compared to untreated gestational aproteinuric hypertensives (60 ± 11 versus 84 ± 9; p=0.001). Untreated preeclamptics with mild to moderate proteinuria had an intermediate heart rate of 72 ± 8. This lower heart rate was associated with a significantly higher stroke index resulting in little change in cardiac index. This is an important observation as pre-eclampsia has been described as a state of relative hypovolemia or failure of an adequate expansion of plasma volume and with some resultant hemoconcentration. However, the compensatory increase in stroke volume and preserved cardiac index and left ventricular systolic function indicate that there is probably an adequate preload reserve to allow for a compensatory increase in stroke volume, thereby maintaining maternal cardiac output.
This reduced heart rate in untreated pre-eclamptic women in our study supports early observations made by Kuzniar et al, (1982) in a M-mode echocardiography study of pre-eclamptic women and in the important invasive hemodynamic study of Visser et al, (1991). At variance to our study, however Kuzniar et al, (1982) also showed a
reduced stroke volume that was measured by the less accurate and unvalidated technique of M-mode echocardiography.
Differences of heart rate in pre-eclamptic women observed between studies can also be attributable to significant disease heterogenecity and maternal body size. For
instance, the Easterling study (1990) included women who were hypertensive prior to 20 weeks gestation and also included a milder category of hypertensive pregnant women defined by an increase in diastolic blood pressure of 15mmHg above baseline.
It is unlikely variations in levels of aerobic conditioning as described in the non- pregnant setting could account for differences in heart rate. Wolfe et al, (1999) recently reported that aerobic conditioning had minimal effects on cardiovascular parameters in normotensive pregnant women. These effects are probably obscured by more powerful hemodynamics effects of pregnancy in the resting state.
Haemodynamic changes secondary to pharmacologic therapy may be an important determinant of cardiac index. In the setting of bradycardia, cardiac index is the normal pregnant state usually maintained by a compensatory increase in stroke index.
In severe pre-eclampsia a significantly contracted plasma volume may attenuate this compensatory increase in stroke volume with a resultant fall in the cardiac index. It is worth nothing that treatment with B-adrenergic blocking agents may significantly lower heart rate to an extent whereby the compensatory increase in stroke volume may be inadequate to maintain a satisfactory cardiac output. This scenario explains the reduced cardiac output and associated fetal growth restriction in hypertensive women prescribed atenolol in the study by Easterling et al, (1999). This observation was further supported by the recent meta-analysis of Easterling et al, (2001) in which atenolol associated with a reduced incidence of pre-eclampsia but with fetal growth restriction that was attributed to inappropriate reduction in cardiac output with the drug. Similar observations were made by von Dadelszen et al, (2000) in a meta- analysis of randomised controlled trials evaluating pharmacological lowering of blood
pressure during pregnancy and feto-neonatal outcome. They concluded that treatment induced falls in maternal blood pressure could adversely affect fetal growth.