Pre-eclampsia: does cardiac function differ in HIV-positive and -negative women?

This review aimed to establish the impact of pre-eclampsia and HIV infection on cardiac function. Cardiovascular diseases have been reported to affect pregnancies complicated by both HIV and pre-eclampsia. Pre-eclampsia has been found to be associated with both systolic and diastolic dysfunction. Currently it has been found that there may be a dual, bidirectional pathophysiology, where placenta-mediated factors can influence cardiac function, or pre-existing cardiovascular disease can predispose to pre-eclampsia. Cardiovascular disease, HIV and pre-eclampsia are major health challenges individually and are interrelated with regard to pathophysiology. It has been found that both pre-eclampsia and HIV contribute to cardiac dysfunction as does the impact of antiretroviral therapy. Further research is needed to investigate the link between these diseases for the development of novel therapeutic interventions.

Cardiac Doppler in poorly controlled gestational diabetics and its link to markers of intra-uterine hypoxia and adverse outcome.

The aim of the study was to investigate foetal cardiac function using the modified myocardial performance index (Mod-MPI) in poorly controlled gestational diabetics and its link with intrauterine markers for hypoxia and to an adverse outcome. In a prospective, cross sectional study, 44 consecutive women with severe or poorly controlled gestational diabetic pregnancies in their third trimester on insulin therapy were recruited and matched with 44 women with normal pregnancies which served as the control group. Using Doppler echocardiography the foetal Mod-MPI was calculated. The foetal Mod-MPI was significantly higher in the diabetic group compared to the controls indicating significant myocardial dysfunction. The Mod-MPI served as an excellent marker of adverse outcomes. Foetal myocardial function was significantly impaired in poorly controlled gestational diabetics and there was a significant link of Mod-MPI to intrauterine markers of hypoxia, as well as to an adverse outcome. Mod-MPI has the potential to improve foetal surveillance in gestational diabetes.IMPACT STATEMENTWhat is already known on this subject? Abnormal foetal cardiac function, as reflected in the modified myocardial performance index, has been reported to be significantly increased in foetuses of poorly controlled diabetics managed on insulin.What do the results of this study add? There is a significant link between abnormal foetal cardiac function to intrauterine markers of hypoxia, as well as to an adverse outcome; and that development of myocardial dysfunction could be one of the main mechanisms, inducing foetal compromise in poorly controlled gestational diabetes.What are the implications of these findings for clinical practice and/or further research? This study explores an interesting concept of foetal pathophysiology in gestational diabetes, namely the concept of "pseudo-hypoxia" in a foetus of a gestational diabetic mother, and this intrauterine "hypoxic stress" in turn leading to myocardial dysfunction. The Mod-MPI, a clinical marker for cardiac dysfunction, can therefore be used in the clinical setting to track a deteriorating metabolic state.

Assessment of the Fetal Myocardial Performance Index in Well-Controlled Gestational Diabetics and to Determine Whether It Is Predictive of Adverse Perinatal Outcome.

This study was aimed at determining if the myocardial performance index (MPI) is altered in well-controlled gestational diabetics and if so whether it is predictive of adverse perinatal outcome. In a prospective cross-sectional study, 54 consecutive women with well-controlled gestational diabetes controlled on insulin or metformin in the third trimester were recruited and matched with 54 women with normal pregnancies (control group). Using Doppler echocardiography, the MPI was calculated. Sonographic biophysical and placental resistance Doppler markers in both groups were also determined. An abnormal outcome was defined as any of the following: stillbirth; neonatal death; neonatal intensive care admissions; tachypnea with pulmonary edema; neonatal cord pH < 7.15; 5-min Apgar score < 7, polycythemia; and nucleated red blood cells > 10/100 white blood cell counts, hypoglycemia. The MPI was significantly higher in the diabetic group compared to controls (p < 0.0001). Rate of adverse outcome was 22% in the diabetic group. The diabetic group with adverse outcomes had significantly elevated MPI values compared to the diabetic group with normal outcomes. There were 26 diabetics controlled on metformin and 28 controlled on insulin. The adverse outcome rate was slightly higher in the IDDM group compared to the non-insulin-dependent group but was not statistically significant. The main adverse outcomes were low Apgars (18%), hypoglycemia (22%), polycythemia (13%) and low pH in 7%. All control births had normal outcomes. MPI served as an independent predictor of adverse outcome. The MPI z-score had a good diagnostic accuracy as evidenced by the area under the ROC curve of 0.83. An MPI z-score exceeding 4.55 conferred a 90% sensitivity and 74% specificity, with 77% of outcomes correctly classified with a likelihood ratio of 3.5. The MPI is impaired in fetuses in well-controlled gestational diabetes, with fetuses with an adverse outcome having significantly higher MPI values compared to the fetuses with normal outcome in the diabetic group. MPI has the potential to improve fetal surveillance in gestational diabetes.

An integrated model of materno-foetal cardiac dysfunction in severe pre-eclampsia.

Maternal cardiovascular deterioration in severe pre-eclampsia is due to a combination of factors in the setting of severe trophoblastic ischaemia and the outpouring of maternal cathecolamines, leading to increased left ventricular afterload and increasing ventricular volumes, resulting in increased left ventricular stroke work and demand myocardial ischaemia. This is the substrate for ventricular arrhythmias. Foetal cardiac dysfunction is most likely on the basis of the increased afterload, consequent upon widespread vasoconstriction, due to angiogenic imbalances. In this integrated model, chronic trophoblastic ischaemia is the central role player by releasing vasoactive substances that induce haemodynamic alterations in the maternofoetal complex, augmented and modified by 'latent' maternal cardiovascular dysfunction and increased maternal cathecolamine secretion on the one hand, and altered foetal signalling mechanisms on the other, all three components of the materno-placental-foetal complex being in constant interaction with each other. This unified hypothesis may explain the development of both maternal and foetal morbidity and/or mortality on a unitary basis in severe, complicated preeclampsia.

Pre-eclampsia and the foetus: a cardiovascular perspective.

Pre-eclampsia is the leading cause of perinatal morbidity and mortality. A full understanding of the pathogenesis of this enigmatic condition is essential if we are to develop new prophylactic and therapeutic interventions. Central to our understanding of the pathogenesis of early-onset preeclampsia is absolute utero-placental ischaemia, which is lack of placental vascular transformation in early pregnancy. By contrast, relative utero-placental ischaemia, due to a mismatch between utero-placental blood flow and increased demand for nutrients occurring later in pregnancy, may be central to the development of late-onset pre-eclampsia. These pathogenic mechanisms have advanced our understanding of this condition, leading to better prediction, screening and intervention modalities. Screening for pre-eclampsia in the first and second trimesters by investigating the maternoplacental circulation and placental hormones could identify a high-risk subgroup. The advantage of screening in the first trimester is that a prophylactic intervention is available in the form of low-dose aspirin, if started before 16 weeks' gestation in the high-risk group, resulting in a substantial reduction in severe early-onset pre-eclampsia, while identification of a high-risk group in the second trimester will lead to focused management in this group. Using a combination of cardiac Doppler, multi-vessel Doppler assessment of the foetal circulation and biomarkers in established pre-eclampsia in the third trimester could predict adverse outcomes and guide clinicians to timeous delivery. Hopefully, advances in our understanding of this enigmatic disease will lead to further prophylactic and new therapeutic interventions.

Determination of the fetal myocardial performance index in women with gestational impaired glucose tolerance and to assess whether this parameter is a possible prognostic indicator of adverse fetal outcome.

AIM: The aim of this study was to investigate if the myocardial performance index (MPI) is altered in fetuses in women with gestational impaired glucose tolerance (GIGT), controlled on diet and whether this parameter is also predictive of adverse outcome in this group, as in poorly controlled gestational diabetes. METHODS: In a prospective cross-sectional study, 32 women with GIGT on diet in the 3rd trimester were recruited and matched with 32 women with normal pregnancies (control group). Using Doppler echocardiography, the MPI was calculated. Placental resistance Doppler markers in both groups were also determined. An abnormal outcome was defined as any of the following: stillbirth, neonatal death, neonatal intensive care unit (NICU) admissions, tachypnea with pulmonary oedema, neonatal cord pH <7.15, five minute Apgar score <7, and cardiomyopathy. RESULTS: The cases had a significantly higher median MPI compared to controls, p value <.0001. There were eight abnormal outcomes recorded in the 32 fetuses in the study group, corresponding to an adverse outcome rate of 25%. Fetuses with an adverse outcome had significantly higher MPI measurements compared to the GIGT fetuses with normal outcome. The MPI served as an excellent predictor of adverse outcome in the GIGT fetuses, with a total area under the ROC curve of 0.96. An MPI z-score greater than 4.0 conferred a sensitivity of 100% and specificity of 80%. No abnormal outcomes were noted in the control group. CONCLUSIONS: The MPI is impaired in fetuses in GIGT women, with fetuses with an adverse outcome having significantly higher MPI measurements compared to the fetuses with normal outcome in the GIGT group. MPI has the potential to improve fetal surveillance in gestational diabetes.

Use of the myocardial performance index as a prognostic indicator of adverse fetal outcome in poorly controlled gestational diabetic pregnancies.

OBJECTIVE: The aim of this study was to determine whether there are any changes in cardiac function in fetuses of poorly controlled gestational diabetics and whether these changes influence perinatal outcome. METHODS: Twenty-nine pregnant women with severe gestational diabetes on insulin therapy in the third trimester of pregnancy were recruited and matched with 29 women with normal pregnancies (control group). Using Doppler echocardiography, the modified myocardial performance index (Mod-MPI) and E wave/A wave peak velocities (E/A) ratios were determined. Placental resistance Doppler markers were also determined in both groups. Adverse perinatal outcome was defined as perinatal death, admission to the neonatal intensive care unit, cord pH <7.15, 5-min Apgar score <7 and presence of cardiomyopathy. RESULTS: The median Mod-MPI was increased (0.59 vs 0.38; p < 0.0001) and the E/A ratio was decreased (0.65 vs 0.76; p < 0.0001) in fetuses of diabetic mothers compared with controls. An MPI >0.52 had a sensitivity of 100% [95% confidence interval (CI) 85-100%] and specificity of 92% (95% CI 70-92%) for prediction of adverse perinatal outcome, including one stillbirth and one neonatal death. No abnormal outcomes occurred in the control group. CONCLUSIONS: There is significant impairment of cardiac function in fetuses of poorly controlled gestational diabetics. Mod-MPI and E/A ratio have the potential to improve fetal surveillance in diabetic pregnancies.

Gestational age-adjusted trends and reference intervals of the Modified Myocardial Performance Index (Mod-MPI) and its components, with its interpretation in the context of established cardiac physiological principles.

OBJECTIVE: The objective of this study is to establish gestational age-adjusted reference intervals and trends of the modified myocardial performance index (Mod-MPI), isovolumetric contraction time (ICT), isovolumetric relaxation time (IRT), and ejection time (ET) in pregnancy METHODS: A cross-sectional study using Doppler echocardiography to determine the Mod-MPI was performed on 419 fetuses from 20 to 38 weeks of gestation. Doppler signals of the opening and closing of the mitral and aortic valves were used as landmarks to determine the ICT, IRT, and ET. The Mod-MPI was modeled using fractional polynomials and the exponential-normal model. RESULTS: The Mod-MPI was relatively constant from 20 to 26 weeks and thereafter steadily decreased with advancing gestational age. ICT and ET remained constant, whereas IRT decreased with advancing gestation similar to the Mod-MPI. CONCLUSION: Reference intervals of the Mod-MPI evaluating fetal cardiac function have been established. Maturational and developmental alterations in the myocardial performance in utero resulting in better ventricular compliance is most likely responsible for the decreasing trend of the Mod-MPI noted with advancing gestation.