Maternal cardiovascular profile is altered in the preclinical phase of normotensive early and late intrauterine growth restriction.

BACKGROUND: The maternal cardiovascular profile of patients who develop late fetal growth restriction has yet to be well characterized, however, a subclinical impairment in maternal hemodynamics and cardiac function may be present before pregnancy and may become evident because of the hemodynamic alterations associated with pregnancy. OBJECTIVE: This study aimed to investigate if maternal hemodynamics and the cardiovascular profile might be different in the preclinical stages (22-24 weeks' gestation) in cases of early and late fetal growth restriction in normotensive patients. STUDY DESIGN: This was a prospective echocardiographic study of 1152 normotensive nulliparous pregnant women at 22 to 24 weeks' gestation. The echocardiographic evaluation included morphologic parameters (left ventricular mass index and relative wall thickness, left atrial volume index) and systolic and diastolic maternal left ventricular function (ejection fraction, left ventricular global longitudinal strain, E/A ratio, and E/e' ratio). Patients were followed until the end of pregnancy to note the development of normotensive early or late fetal growth restriction. RESULTS: Of the study cohort, 1049 patients had no complications, 73 were classified as having late fetal growth restriction, and 30 were classified as having early fetal growth restriction. In terms of left ventricular morphology, the left ventricular end-diastolic diameter was greater in uneventful pregnancies (4.84±0.28 cm) than in late (4.67±0.26 cm) and in early (4.55±0.26 cm) (P<.001) fetal growth restriction cases, whereas left ventricular end-systolic diameter was smaller in uneventful pregnancies (2.66±0.39 cm) than in late (2.83±0.40 cm) and in early (2.82±0.38 cm) (P<.001) fetal growth restriction cases. The relative wall thickness was slightly higher in early (0.34±0.05) and late (0.35±0.04) fetal growth restriction cases than in uneventful pregnancies (0.32±0.05) (P<.05). In terms of systolic left ventricular function, at 22 to 24 weeks' gestation, cardiac output was higher in uneventful pregnancies (6.58±1.07 L/min) than in late (5.40±0.97 L/min) and in early (4.76±1.05 L/min) (P<.001) fetal growth restriction cases with the lowest values in the early-onset group. Left ventricular global longitudinal strain was lower in appropriate for gestational age neonates (-21.6%±2.0%) and progressively higher in late (-20.1%±2.2%) and early (-18.5%±2.3%) (P<.001) fetal growth restriction cases. In terms of diastolic left ventricular function, the E/e' ratio showed intermediate values in the late fetal growth restriction group (7.90±2.73) when compared with the appropriate for gestational age group (7.24±2.43) and with the early fetal growth restriction group (10.76±3.25) (P<.001). The total peripheral vascular resistance was also intermediate in the late fetal growth restriction group (1300±199 dyne·s·cm-5) when compared with the appropriate for gestational age group (993±175 dyne·s·cm-5) and the early fetal growth restriction group (1488±255 dyne.s.cm-5) (P<.001). CONCLUSION: Early and late fetal growth restriction share similar maternal hemodynamic and cardiovascular profiles with a different degree of expression. These features are already present at 22 to 24 weeks' gestation and are characterized by a hypodynamic state. The degree of these cardiovascular changes may influence the timing of the manifestation of the disease; a hypovolemic, high resistance, low cardiac output state might be associated with early-onset fetal growth restriction, whereas a milder hypovolemic state seems to favor the development of the disease in the final stages of pregnancy.

Pregnancy complications in chronic hypertensive patients are linked to pre-pregnancy maternal cardiac function and structure.

BACKGROUND: Chronic hypertension complicates around 3% of all pregnancies and is associated with an increased risk for pregnancy complications such as superimposed preeclampsia, fetal growth restriction, preterm delivery, and stillbirth, reaching a rate of complications of up to 25-28%. OBJECTIVE: We performed an echocardiographic study to evaluate pre-pregnancy cardiac geometry and function, along with the hemodynamic features of treated chronic hypertension patients, searching for a possible correlation with the development of feto-maternal complications and with pre-pregnancy therapy. MATERIALS AND METHODS: This was a prospective observational cohort study of 192 consecutive patients receiving treatment for chronic hypertension (calcium channel blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, ß-blockers, α1-adrenoceptor antagonists, and/or diuretics). Patients underwent echocardiography before pregnancy, assessing left ventricular morphology and function, cardiac output, and total vascular resistance. Pre-pregnancy therapy was noted, patients were shifted to α-methyldopa right before pregnancy, and were followed until delivery, noting major early (<34weeks' gestation) and late (≥34 weeks' gestation) complications. Comparisons among the 3 groups (ie, those with no complications, early complications, and late complications) were performed with 1-way analysis of variance with Student-Newman-Keuls correction for multiple comparisons. The Mann-Whitney U test was used for non-normally distributed data. Comparison of proportions was used as appropriate. Receiver operating characteristic curve analysis was used to identify cutoff values of diastolic dysfunction in this population using the E/e' ratio, and separate cutoff of values for total vascular resistance for the prediction of early and late complications of pregnancy. Binary univariate and multivariate logistic regression as well as Cox proportional hazards regression were used to evaluate the possible correlation among angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and/or calcium channel blocker pre-pregnancy therapy, cardiovascular features, and the risk for subsequent early and late complications of pregnancy. RESULTS: Of 192 patients, 141 had no complications, and 51 had a complicated pregnancy (24 had early complications and 27 had late complications). Concentric geometry was more frequent in those women with early versus late and no complications (50% vs 13.5% and 11.1%, respectively; P < .05), whereas eccentric hypertrophy was more represented in women with late versus early and no complications (32% versus 12.5% and 1.4%, respectively; P < .05). The receiver operating characteristic curve showed an E/e' ratio value >7.65 (sensitivity, 59.6%; specificity, 68.6%) as a predictor of subsequent complications of pregnancy, whereas total vascular resistance <1048 (sensitivity, 83.7%; specificity, 55.6%) was predictive for late complications and total vascular resistance >1498 (sensitivity, 87.5%; specificity, 78.0%) for the early complications of pregnancy. Univariate analysis showed that the following parameters were predictive for complications of pregnancy: altered geometry of the left ventricle (odds ratio, 5.94; 95% confidence interval, 2.90-12.19), diastolic dysfunction (odds ratio, 3.22; 95% confidence interval, 1.63-6.37), altered total vascular resistance (odds ratio, 3.52; 95% confidence interval, 1.78-6.97), and pre-pregnancy therapy without calcium channel blockers/angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (odds ratio, 2.73; 95% confidence interval, 1.37-5.42). These parameters, except for altered total vascular resistance, were independent predictors in the multivariate analysis corrected for body mass index, heart rate, parity, and mean arterial pressure. CONCLUSION: Chronic hypertension patients with pre-pregnancy cardiac remodeling and dysfunction more often develop early and late complications of pregnancy. Pre-pregnancy therapy for chronic hypertension patients with calcium channel blockers and/or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers may positively influence cardiac profiles and the outcome of a future pregnancy with a reduced rate of complications.

Hemodynamic maladaptation and left ventricular dysfunction in chronic hypertensive patients at the beginning of gestation and pregnancy complications: a case control study.

OBJECTIVE: The aim of this study was to evaluate early pregnancy differences in maternal hemodynamics, cardiac geometry and function, between chronic hypertensive (CH) patients with and without the development of feto-maternal complications later in pregnancy. METHODS: We performed a case-control study on nulliparous CH treated patients. From a group of CH patients referred to our outpatient clinic at 4-6 weeks for a clinical evaluation the first consecutive 30 patients with subsequent complications (superimposed PE, abruptio placentae, uncontrolled severe hypertension with delivery <34 weeks, HELLP syndrome, FGR, perinatal death) were enrolled; the first 2 CH women with uneventful pregnancy referred after the case were enrolled as controls for a total of 60 patients. All patients were shifted to alpha-methyl dopa at the beginning of pregnancy and were submitted to an echocardiographic evaluation to assess the maternal hemodynamics, cardiac geometry, diastolic and systolic function. RESULTS: Patients developing complications had a lower early pregnancy heart rate (73 ± 11 vs. 82 ± 11 bpm), cardiac output (5.23 ± 1.2 vs. 6.5 ± 1.3 L/min, p<.01) and cardiac index (3.0 ± 0.7 vs. 3.6 ± 0.7 L/min/m2, p<.01); higher total vascular resistance (1554 ± 305 vs. 1248 ± 243 d.s.cm-5, p<.01) and total vascular resistance index (2666 ± 519 vs. 2335 ± 431, d.s.cm-5/m2, p<.01); higher left ventricular mass index (42.1 ± 8.6 vs. 36.9 ± 8.3 g/m2, p<.01) and relative wall thickness (0.40 ± 0.05 vs. 0.36 ± 0.05, p<.01) of the left ventricle, resulting in a higher prevalence of altered cardiac geometry vs. uneventful CH controls. Diastolic and systolic dysfunction were also present with a higher E/e' ratio (10.50 ± 3.56 vs. 7.22 ± 1.91, p<.01) and a lower stress corrected midwall mechanics (89 ± 21 vs. 100 ± 22, p=.02) of the left ventricle. CONCLUSION: CH treated patients developing maternal and/or fetal complications show early pregnancy altered cardiac geometry, diastolic and systolic dysfunction, and impaired hemodynamics with a high resistance circulation.

Distinction between SGA and FGR by means of fetal umbilical vein flow and maternal hemodynamics.

OBJECTIVES: To improve identification of fetal growth restriction (FGR) by means of umbilical venous flow (QUV) and maternal hemodynamics, including systemic vascular resistance (SVR) and cardiac output (CO), in order to distinguish between FGR and SGA. METHODS: We enrolled 68 pregnancies (36 SGA, 8 early FGR and 24 late FGR) who underwent a complete fetal hemodynamic examination including QUV and a noninvasive maternal hemodynamics assessment by means of USCOM. RESULTS: In comparison with SGA, QUV and corrected for estimated fetal weight QUV (cQUV) were significantly lower in early and late-FGR. In addition, maternal CO was lower in early and late-FGR, while SVR was lower only in early-onset FGR. According to ROC analysis, cQUV centile (AUC 0.92, 0.72) was the best parameter for the prediction of SGA before and after 32 weeks, followed by SVR and CO. For all parameters, the prediction was always better in the case of early-onset FGR <32 weeks. CONCLUSIONS: UV flow and maternal hemodynamics examination are useful tools to accurately discern between SGA and FGR.

A Five-Year Follow-up of Left Main Coronary Artery Stenting 8 Years After Arterial Switch Operation.

The fate of coronary artery stenting in children several years after implantation is unknown. We previously reported the case of an 8-year-old child undergoing stent implantation for a total left main coronary artery occlusion after arterial switch operation. Six months later, she needed another stent implantation for in-stent restenosis. Here we report the angiographic, intravascular ultrasound and optical coherence tomography findings at 5-year follow-up. Despite nongrowth of the left main coronary artery inherent to the stents, luminal patency, adequate struts apposition, and the absence of in situ complications were confirmed.

On ne sait rien de ce qu'il advient des endoprothèses coronariennes plusieurs années après l'implantation chez les enfants. Nous avons déjà présenté le cas d'une fillette de huit ans chez qui une endoprothèse a été implantée pour corriger une occlusion totale de l'artère coronaire principale gauche après une intervention de détransposition artérielle. Six mois plus tard, la patiente avait besoin d'une autre endoprothèse en raison d'une resténose de l'endoprothèse. Nous rapportons ici les observations effectuées à l'angiographie, à l'échographie intravasculaire et à la tomographie par cohérence optique à l'évaluation de suivi à cinq ans. Malgré l'absence de croissance de l'artère coronaire principale gauche en raison de la présence des endoprothèses, la perméabilité luminale, l'apposition adéquate des entretoises et l'absence de complications in situ ont été confirmées.

Friendly help for clinical use of maternal hemodynamics.

OBJECTIVES: Maternal hemodynamics plays a major role during pregnancy and its evaluation is fundamental to understand obstetric conditions. The modern opinion about maternal hemodynamics assessment is to shift focus from single hemodynamic parameters to the whole hemodynamic profile. Our aim is to create a simple, intuitive, and easily understandable graphing technique to evaluate the main hemodynamic parameters. METHODS: We enrolled 531 pregnant women without maternal or fetal disease. One hundred and forty five in the first trimester of pregnancy, 258 in the second one and 128 in the third one. We performed hemodynamic assessment with ultrasonic cardiac output monitor method. We selected the six main parameters: cardiac output, systemic vascular resistance, heart rate, potential-to-kinetic energy ratio, inotropy index, and stroke volume variation. We chose the radar chart to display the multivariate data of the hemodynamic measurement of the patient in evaluation. RESULTS: We have obtained mean and deviation standard values for the six main hemodynamic parameters in every trimester. They deeply change during the pregnancy, so it is correct to compare a new hemodynamic measurement with the mean values for the specific trimester in order to evaluate any possible alterations. In fact, once a new hemodynamic assessment is performed, we calculate the Z-score in order to fix the positions of the six measured parameters in their specific axis of radar chart. CONCLUSIONS: At the end of a hemodynamic exam, the physician can input the data in the program obtaining a graphic representation. Using this technique, which simultaneously evaluates six hemodynamic parameters, it is possible to easily understand the patient's hemodynamic status. By converting the parameters values in Z-score, it is easier to understand when hemodynamics is altered, even if the physician does not have any experience in maternal hemodynamics.

Genotype-phenotype analysis and natural history of left ventricular hypertrophy in LEOPARD syndrome.

Because it is unclear whether the genotype may influence the clinical course in patients with LEOPARD syndrome (LS), we analyzed clinical and molecular predictors of adverse cardiac events in patients with left ventricular hypertrophy (LVH). A comprehensive cardiovascular evaluation, including baseline electrocardiogram, echocardiography, exercise test and 24 hr Holter monitoring at the time of clinical diagnosis and during follow-up was conducted on 24 patients referred to our departments. Phenotypical examination and diagnosis were performed by expert clinical geneticists. The entire PTPN11 and RAF1 coding regions were screened for mutations by DHPLC analysis, followed by sequencing. Patients without PTPN11 mutations (34%) showed a higher frequency of family history of sudden death (P = 0.007), increased left atrial dimensions (P = 0.05), bradyarrhythmias (P = 0.04), episodes of supraventricular tachycardias (P = 0.06), atrial fibrillation (P = 0.009), and nonsustained ventricular tachycardias (P = 0.05) during Holter monitoring. Six patients (25%) had adverse cardiac events during follow-up (including sudden deaths, resuscitated cardiac arrest, septal myectomy, and heart failure). LVH, New York Heart Association Class, left ventricular outflow tract obstruction, and nonsustained ventricular tachycardias were associated to adverse cardiac events. Of note, three patients with mutations in exon 13 showed a severe obstructive cardiomyopathy, with serious cardiac complications during follow-up (heart failure, septal myectomy, and sudden death). In conclusion, patients with LVH associated with LS seem to carry a relatively high risk of adverse (arrhythmic and nonarrhythmic) events. Further genotype-phenotype studies are warranted to fully elucidate the impact of the genotype on the natural history of patients with LS and LVH.

Foetal heart rate deceleration with combined spinal-epidural analgesia during labour: a maternal haemodynamic cardiac study.

To understand the mechanisms those are involved in the appearance of foetal heart rate decelerations (FHR) after the combined epidural analgesia in labour. Observational study done at University Hospital for 86-term singleton pregnant women with spontaneous labour. Serial bedside measurement of the main cardiac maternal parameters with USCOM technique; stroke volume (SV), heart rate (HR), cardiac output (CO) and total vascular resistances (TVR) inputting systolic and diastolic blood pressure before combined epidural analgesia and after 5', 10', 15' and 20 min. FHR was continuously recorded though cardiotocography before and after the procedure. Correlation between the appearance of foetal heart rate decelerations and the modification of maternal haemodynamic parameters. Fourteen out of 86 foetuses showed decelerations after the combined spino epidural procedure. No decelerations occurred in the women with low TVR (<1000 dyne/s/cm(-5)) at the basal evaluation. FHR abnormalities were concentrated in 39 women who presented elevated TVR values at the basal evaluation (>1200 dyne/s/cm(-5)). Soon after the epidural procedure, the absence of increase in SV and CO was observed in these women. No variations in systolic and diastolic blood pressure values were found. The level of TVR before combined epidural analgesia in labour may indicate the risk of FHR abnormalities after the procedure. Low TVR (<1000 dyne/s/cm(-5)) showed a reduced risk of FHR abnormalities. FHR decelerations seem to occur in women without the ability to upregulate SV and CO in response to the initial effects of analgesia.

Persistent Maternal Cardiac Dysfunction After Preeclampsia Identifies Patients at Risk for Recurrent Preeclampsia.

The purpose of our study was to assess cardiac function in nonpregnant women with previous early preeclampsia before a second pregnancy to highlight the cardiovascular pattern, which may take a risk for recurrent preeclampsia. Seventy-five normotensive patients with previous preeclampsia and 147 controls with a previous uneventful pregnancy were enrolled in a case-control study and submitted to echocardiographic examination in the nonpregnant state 12 to 18 months after the first delivery. All patients included in the study had pregnancy within 24 months from the echocardiographic examination and were followed until term. Twenty-two (29%) of the 75 patients developed recurrent preeclampsia. In the nonpregnant state, patients with recurrent preeclampsia compared with controls and nonrecurrent preeclampsia had lower stroke volume (63 ± 14 mL versus 73 ± 12 mL and 70 ± 11 mL, P<0.05), cardiac output (4.6 ± 1.2 L versus 5.3 ± 0.9 L and 5.2 ± 1.0 L, P<0.05), higher E/E' ratio (11.02 ± 3.43 versus 7.34 ± 2.11 versus 9.03 ± 3.43, P<0.05), and higher total vascular resistance (1638 ± 261 dyne · s(-1) · cm(-5) versus 1341 ± 270 dyne · s(-1) · cm(-5) and 1383 ± 261 dyne · s(-1) · cm(-5), P<0.05). Left ventricular mass index was higher in both recurrent and nonrecurrent preeclampsia compared with controls (30.0 ± 6.3 g/m(2.7) and 30.4 ± 6.8 g/m(2.7) versus 24.8 ± 5.0 g/m(2.7), P<0.05). Signs of diastolic dysfunction and different left ventricular characteristics are present in the nonpregnant state before a second pregnancy with recurrent preeclampsia. Previous preeclamptic patients with nonrecurrent preeclampsia show left ventricular structural and functional features intermediate with respect to controls and recurrent preeclampsia.

Orthotopic heart transplantation for congenital heart disease: an alternative for high-risk fontan candidates?

OBJECTIVE: Evaluation of incremental risk factors for early mortality in children undergoing orthotopic heart transplantation (OHT) for congenital heart disease. METHODS: Between 1988 and 2002, 43 patients (mean age 9.1+/-7.2 years) underwent 44 OHT for complex TGA (6), DORV (4), single ventricle (21), and other end-stage structural heart disease (11). Two discernible ventricular chambers were present in 18 pts (41.8%). Previous reconstructive or palliative procedures had been previously accomplished in 35 pts (83.3%), including atrial switch (5), systemic-to-pulmonary shunts (10), cavopulmonary anastomosis (9), Fontan completion (6), and others (5). RESULTS: 30-day survival for the 2-ventricle subgroup was 94.4+/-5.4% compared with 67.2+/-9.5% for the single ventricle subgroup (P=0.04) (overall 78.6%+/-3.3%). OHT following single ventricle staging to bi-directional cavopulmonary anastomosis exhibited 100% early survival, as opposed to 62.5+/-17.1% for OHT after systemic-to-pulmonary shunts, and 33.3+/-19.2% for OHT following failing Fontan (P=0.010). HLHS diagnosis (0.0085) and failing Fontan (P=0.003) were identified as independent predictors of early mortality by regression logistic modeling, while Fontan stage represented the only predictor of overall mortality by Cox proportional hazard. Overall 10-year survival was 54.3+/-11%. CONCLUSIONS: OHT for structural congenital heart disease with single ventricle physiology entails substantial early mortality and bi-directional cavopulmonary anastomosis enables the best transition to heart transplant. OHT should be considered in the decision making process as an alternative to Fontan completion in high-risk candidates, since rescue-OHT after failing Fontan seems unwarranted.

Percutaneous recanalization of a chronic total left main coronary artery occlusion in an 8-year-old child after arterial switch surgery.

How and when to treat patients with coronary occlusion after arterial switch surgery is still under debate. We report the case of a child who underwent arterial switch surgery a few weeks after birth. At the age of 8 years, coronary angiography showed a total occlusion of the left main coronary artery, successfully treated using percutaneous coronary intervention. Percutaneous coronary recanalization of chronic total occlusions might be considered the first treatment strategy in children who undergo complex surgical procedures.

PP065. Assessment of total vascular resistance and total body water in normotensive women during the first trimester of pregnancy in order to predict hypertensive complications.

INTRODUCTION: In pregnancy there is an increase in maternal cardiac output (CO) and a reduction in total vascular resistance (TVR). Abnormalities of this adaptive mechanisms lead to numerous disorders of pregnancy. Moreover the mother's body water composition undergoes important modifications in total body water (TBW), extracellular and intracellular body water (EBW, IBW). OBJECTIVES: Aim of the study is to identify a group of patients at high risk of developing hypertensive complications of pregnancy in frist trimester. METHOD: To investigate hemodynamic changes and distribution of body water during the frist trimester of pregnancy, we conducted an observational study. We evaluated CO, TVR and Time Flow Corrected (TFc) with the USCOM system, a non invasive method. Patients were, also, subjected to BIA (Body Impedance Assessment). RESULTS: We enrolled 120 healthy pregnant women. 20 patients, were excluded for bad signal. Absolute values of haemodynamic and body impedance measures are shown in Fig. 1. Patients were divided in two groups:Group A with TVR>1200 dyne and Group B with TVR<1200 dyne. CO values were higher in group B. There wasn't significant differences in TBW, haematocrit, TFc and WBI (water balance index: TBW/Hct) between the two groups. CONCLUSION: Our results show that at costant values of TBW, Hct and WBI,we can find difference in term of TVR and CO in the first trimester of pregnancy. These parameters may improve the accuracy of screening in clinical practice.

PP064. Total vascular resistances in early pregnancy: A key to understand abnormal cardiovascular adaptation associated with spontaneous abortion.

INTRODUCTION: From early pregnancy, maternal hemodynamic profile begins to change. The absence of these changes leads to increased risk of complication during the gestation. OBJECTIVES: Aim of this study is to understand in early pregnancy the behaviour of total vascular resistances (TVR) as a sign of maternal cardiovascular adaptation to pregnancy. METHOD: A cross section study was conducted. We followed 160 healthy women with singleton pregnancy during the first trimester of gestation. We evaluated cardiac output (CO) and TVR at 7, 9 and 11 weeks of gestation. We obtained the following haemodynamic measurements with the USCOM system, a non invasive method: heart rate (HR), systolic and diastolic blood pressure (SBP, DBP), CO and TVR. RESULTS: 160 healthy pregnant women were selected, 8 patients, were excluded for a bad signal. Absolute values of the haemodynamic measures are shown in Fig. 1. 41 patients underwent spontaneous embryonic demise. This last group of patients showed in 54% (group A) TVR values within the normal limits (TVR<1200), while 46% patients (group B) showed TVR values well above the normal limits (TVR>1200) and CO values below the normal adaptation to pregnancy. Table 1 shows hemodynamic measures for the group A and group B; we found differences in term of CO, TVR and PAS between the two groups. CONCLUSION: Elevated TVR might indicate an abnormal vascular adaptation already in first weeks of pregnancy. Moreover, in women who undergo to abortion, elevated TVR could be use to distinguish genetic or environmental causes of miscarriage.

Hypertension in pregnancy and endothelial activation: An emerging risk factor for cardiovascular disease.

OBJECTIVE: There is emerging evidence suggesting that women who develop hypertensive disorders of pregnancy should be considered at risk for cardiovascular disease (CVD). Our objective was to determine whether persistent endothelial activation, which represents the earliest step in atherogenesis, is present after delivery in women with a history of hypertensive pregnancies compared to women with normal pregnancies. STUDY DESIGN: Two matched case-control studies were conducted. In the first study, endothelial activation was assessed by the measurement of soluble intercellular adhesion molecules, namely, intercellular adhesion molecules-1 (ICAM-1), vascular cellular adhesion molecules-1 (V-CAM-1), E-selectin and P-selectin in 25 women with hypertensive pregnancies and in a matched control group with an uncomplicated pregnancy one month and three months after delivery. In the second study, adhesion molecules were measured in 20 patients with a history of HELLP syndrome several years after pregnancy and in 20 matched controls. RESULTS: Increased levels of soluble adhesion molecules were found in women with hypertensive complications compared to women with uncomplicated pregnancies shortly after delivery. Significant differences were still present, several years after delivery comparing levels of adhesion molecules in women with a history of HELLP syndrome with those found in control patients. CONCLUSIONS: Patients with hypertensive pregnancies showed an abnormal activation of the endothelium which persists after pregnancy. This activation was particularly marked in patients experiencing HELLP syndrome. These observations may represent an explanation to the increased risk of CVD later in life in patients experiencing hypertensive pregnancies, especially in women with a history of HELLP syndrome.

Early and late preeclampsia: two different maternal hemodynamic states in the latent phase of the disease.

Because early and late preeclampsia (PE) are thought to be different disease entities, we compared maternal cardiac function at 24 weeks gestation in a group of normotensive asymptomatic patients with subsequent development of early (<34 weeks gestation) and late (>or=34 weeks gestation) PE (blood pressure >140/90+proteinuria >300 mg/dL) to detect possible early differences in the hemodynamic state. A group of 1345 nulliparous normotensive asymptomatic women underwent at 24 weeks gestation uterine artery Doppler evaluation and maternal echocardiography calculating total vascular resistance. In the subsequent follow-up 107 patients showed PE: 32 patients had late and 75 had early PE. Five of 32 patients with late PE and 45 of 75 patients with early PE had bilateral notching of the uterine artery at 24 weeks (15.6% versus 60.0%; P<0.05). Total vascular resistance was 1605+/-248 versus 739+/-244 dyn . s . cm(-5), and cardiac output was 4.49+/-1.09 versus 8.96+/-1.83 L in early versus late PE (P<0.001). Prepregnancy body mass index was higher in late versus early PE (28+/-6 versus 24+/-2 kg/m(2); P<0.001). Early and late PE appear to develop from different hemodynamic states. Late PE appears to be more frequent in patients with high body mass index and low total vascular resistance; earlier forms of PE appear to be more frequent in patients with lower BMI and with bilateral notching of the uterine artery. These findings support the hypothesis of different hemodynamics and origins for early PE (placental mediated, linked to defective trophoblast invasion with high percentage of altered uterine artery Doppler) and late PE (linked to constitutional factors such as high body mass index).