Maternal cardiovascular profile is altered in the pre-clinical phase of normotensive early and late fetal growth restriction.

BACKGROUND: Maternal cardiovascular profile of patients developing late fetal growth restriction is yet to be well characterized, although a subclinical impairment of maternal hemodynamics and cardiac function may be present before pregnancy, becoming evident because of the hemodynamic alterations of pregnancy. OBJECTIVES: Our objective was to investigate if maternal hemodynamics and the cardiovascular profile might be different in the preclinical stages (22-24 weeks gestation) 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 22-24 weeks' gestation. The echocardiographic evaluation included morphological parameters (left ventricular mass index and relative wall thickness, left atrial volume index) as well as systolic and diastolic maternal left ventricular function (ejection fraction, left ventricular LV global longitudinal strain, E/A, and E/e'). Patients were followed until the end of pregnancy to note the development of normotensive early or late fetal growth restriction. RESULTS: 1049 patients had no complications, 73 were classified as late fetal growth restriction and 30 as early fetal growth restriction. LEFT VENTRICULAR MORPHOLOGY: Left ventricular end-diastolic diameter was greater in uneventful pregnancies (4.84±0.28 cm) vs late (4.67±0.26 cm) and vs early fetal growth restriction (4.55±0.26 cm) (p<0.001), whereas left ventricular end-systolic diameter was smaller in uneventful pregnancies (2.66±0.39 cm) vs late (2.83±0.40 cm) and early fetal growth restriction (2.82±0.38 cm) (p<0.001). Relative wall thickness was slightly higher in early (0.34±0.05) and late fetal growth restriction (0.35±0.04) vs uneventful pregnancies (0.32±0.05) (p<0.05). SYSTOLIC LEFT VENTRICULAR FUNCTION: At 22-24 weeks' cardiac output was higher in uneventful pregnancies (6.58±1.07 L/min) vs late (5.40±0.97 L/min) and vs early fetal growth restriction (4.76±1.05 L/min) (p<0.001), with the lowest values in the early onset group. Left ventricular global longitudinal strain was lower in AGA (-21.6±2.0%), and progressively higher in late (-20.1±2.2%) and early fetal growth restriction (-18.5±2.3%) (p<0.001). DIASTOLIC LEFT VENTRICULAR FUNCTION: E/e' ratio showed intermediate values in the late fetal growth restriction (7.90±2.73) vs AGA (7.24±2.43) and vs early fetal growth restriction (10.76±3.25) (p<0.001). TOTAL PERIPHERAL VASCULAR RESISTANCE: Total Peripheral Vascular Resistance was also intermediate in the late fetal growth restriction (1300±199 dyne·s·cm-5) vs AGA (993±175 dyne·s·cm-5) and vs early fetal growth restriction (1488±255 dyne·s·cm-5) (p<0.001). CONCLUSIONS: 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 22-24 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 to early onset fetal growth restriction, whereas a milder hypovolemic state seems to favor a development of the disease in the final stages of pregnancy.

Nitric oxide donor increases umbilical vein blood flow and fetal oxygenation in fetal growth restriction. A pilot study.

INTRODUCTION: To evaluate the maternal and fetal hemodynamic effects of treatment with a nitric oxide donor and oral fluid in pregnancies complicated by fetal growth restriction. METHODS: 30 normotensive participants with early fetal growth restriction were enrolled. 15 participants were treated until delivery with transdermal glyceryl trinitrate and oral fluid intake (Treated group), and 15 comprised the untreated group. All women underwent non-invasive assessment of fetal and maternal hemodynamics and repeat evaluation 2 weeks later. RESULTS: In the treated group, maternal hemodynamics improved significantly after two weeks of therapy compared to untreated participants. Fetal hemodynamics in the treated group showed an increase in umbilical vein diameter by 18.87 % (p < 0.01), in umbilical vein blood flow by 48.16 % (p < 0.01) and in umbilical vein blood flow corrected for estimated fetal weight by 30.03 % (p < 0.01). In the untreated group, the characteristics of the umbilical vein were unchanged compared to baseline. At the same time, the cerebro-placental ratio increased in the treated group, while it was reduced in the untreated group, compared to baseline values. The treated group showed a higher birthweight centile (p = 0.03) and a lower preeclampsia rate (p = 0.04) compared to the untreated group. DISCUSSION: The combined therapeutic approach with nitric oxide donor and oral fluid intake in fetal growth restriction improves maternal hemodynamics, which becomes more hyperdynamic (volume-dominant). At the same time, in the fetal circuit, umbilical vein flow increased and fetal brain sparing improved. Although a modest sample size, there was less preeclampsia and a higher birthweight suggesting beneficial maternal and fetal characteristics of treatment.

Maternal Hemodynamics from Preconception to Delivery: Research and Potential Diagnostic and Therapeutic Implications: Position Statement by Italian Association of Pre-Eclampsia and Italian Society of Perinatal Medicine.

OBJECTIVE: The Italian Association of Preeclampsia (AIPE) and the Italian Society of Perinatal Medicine (SIMP) developed clinical questions on maternal hemodynamics state of the art. STUDY DESIGN: AIPE and SIMP experts were divided in small groups and were invited to propose an overview of the existing literature on specific topics related to the clinical questions proposed, developing, wherever possible, clinical and/or research recommendations based on available evidence, expert opinion, and clinical importance. Draft recommendations with a clinical rationale were submitted to 8th AIPE and SIMP Consensus Expert Panel for consideration and approval, with at least 75% agreement required for individual recommendations to be included in the final version. RESULTS: More and more evidence in literature underlines the relationship between maternal and fetal hemodynamics, as well as the relationship between maternal cardiovascular profile and fetal-maternal adverse outcomes such as fetal growth restriction and hypertensive disorders of pregnancy. Experts agreed on proposing a classification of pregnancy hypertension, complications, and cardiovascular states based on three different hemodynamic profiles depending on total peripheral vascular resistance values: hypodynamic (>1,300 dynes·s·cm-5), normo-dynamic, and hyperdynamic (<800 dynes·s·cm-5) circulation. This differentiation implies different therapeutical strategies, based drugs' characteristics, and maternal cardiovascular profile. Finally, the cardiovascular characteristics of the women may be useful for a rational approach to an appropriate follow-up, due to the increased cardiovascular risk later in life. CONCLUSION: Although the evidence might not be conclusive, given the lack of large randomized trials, maternal hemodynamics might have great importance in helping clinicians in understanding the pathophysiology and chose a rational treatment of patients with or at risk for pregnancy complications. KEY POINTS: · Altered maternal hemodynamics is associated to fetal growth restriction.. · Altered maternal hemodynamics is associated to complicated hypertensive disorders of pregnancy.. · Maternal hemodynamics might help choosing a rational treatment during hypertensive disorders..

NO donors on top of anti-hypertensive therapy reduces complications in chronic hypertensive pregnancies with hypodynamic circulation.

OBJECTIVES: Chronic hypertension is associated with significant adverse maternal and fetal outcomes that appear to be often associated to a hypodynamic circulation. Treatment of hypertensive disorders of pregnancy tailored on maternal hemodynamics might reduce or mitigate these complications. Our purpose was to assess the hemodynamic modifications induced by the addition of NO donors and increased oral fluid intake on top of standard antihypertensive therapy in hypodynamic chronic hypertensive patients. We further evaluated if the possible hemodynamic modification induced by NO donors and increased oral fluid intake might be associated to a reduction of the severity and rate of complications vs. patients on antihypertensive standard treatment. STUDY DESIGN: This was a case-control study of 321 chronic hypertensive patients with a hypodynamic circulation at the echocardiographic evaluation at 24 weeks' gestation. We included 160 controls (standard antihypertensive therapy) and 161 cases (standard therapy + NO donor patches + increased oral fluid intake). Student T test for paired and unpaired data, univariate logistic regression analysis, ROC curve analysis, and Cox Hazards Regression analysis were used as appropriate. RESULTS: At enrollment the hemodynamic parameters were similar between the two groups. After 3-4 weeks stroke volume (77 ± 19 mL vs. 69 ± 19 mL; p < 0.001), and cardiac output (6.2 ± 1.7 L vs. 5.0 ± 1.6 L; p < 0.001) were higher and total peripheral vascular resistance (1465 ± 469 dyne·s·cm-5 vs. 1814 ± 524 dyne·s·cm-5; p < 0.001) was lower in the cases vs controls. Superimposed preeclampsia, preterm delivery before 34 weeks, abruptio placentae, HELLP Syndrome, fetal growth restriction, and perinatal death were more represented in the standard treatment group vs NO treated patients (81% vs 53%; p < 0.001). In particular, the standard treatment group showed 48% fetal growth restriction vs 34% in the NO treated group (p < 0.011). The Cox proportional-hazards regression showed a lower proportion of event-free pregnancies in controls on standard treatment (HR 2.6; 95% CI 2.0-3.5; p < 0.0001), and a prolongation of pregnancies in CH cases complicated by fetal growth restriction taking NO donors (HR 0.29; 95% CI 0.19-0.43; p = 0.0001). CONCLUSIONS: The tailored treatment with NO donors and oral fluids of hypodynamic CH might have positive effects on the reduction or mitigations of adverse outcomes.

The cardiac-fetal-placental unit: fetal umbilical vein flow rate is linked to the maternal cardiac profile in fetal growth restriction.

BACKGROUND: The functional maternal-fetal hemodynamic unit includes fetal umbilical vein flow and maternal peripheral vascular resistance. OBJECTIVE: This study investigated the relationships between maternal and fetal hemodynamics in a population with suspected fetal growth restriction. STUDY DESIGN: This was a prospective study of normotensive pregnancies referred to our outpatient clinic for a suspected fetal growth restriction. Maternal hemodynamics measurement was performed, using a noninvasive device (USCOM-1A) and a fetal ultrasound evaluation to assess fetal biometry and velocimetry Doppler parameters. Comparisons among groups were performed with 1-way analysis of variance with Student-Newman-Keuls correction for multiple comparisons and with Kruskal-Wallis test where appropriate. The Spearman rank coefficient was used to assess the correlation between maternal and fetal hemodynamics. Pregnancies were observed until delivery. RESULTS: A total of 182 normotensive pregnancies were included. After the evaluation, 54 fetuses were classified as growth restricted, 42 as small for gestational age, and 86 as adequate for gestational age. The fetus with fetal growth restriction had significantly lower umbilical vein diameter (P<.0001), umbilical vein velocity (P=.02), umbilical vein flow (P<.0001), and umbilical vein flow corrected for fetal weight (P<.01) than adequate-for-gestational-age and small-for-gestational-age fetuses. The maternal hemodynamic profile in fetal growth restriction was characterized by elevated systemic vascular resistance and reduced cardiac output. The umbilical vein diameter was positively correlated to maternal cardiac output (rs=0.261), whereas there was a negative correlation between maternal systemic vascular resistance (rs=-0.338) and maternal potential energy-to-kinetic energy ratio (rs=-0267). The fetal umbilical vein time averaged max velocity was positively correlated to maternal cardiac output (rs=0.189) and maternal inotropy index (rs=0.162), whereas there was a negative correlation with maternal systemic vascular resistance (rs=-0.264) and maternal potential energy-to-kinetic energy ratio (rs=-0.171). The fetal umbilical vein flow and the flow corrected for estimated fetal weight were positively correlated with maternal cardiac output (rs=0.339 and rs=0.297) and maternal inotropy index (rs=0.217 and r=0.336), whereas there was a negative correlation between maternal systemic vascular resistance (rs=-0.461 and rs=-0.409) and maternal potential energy-to-kinetic energy ratio (rs=-0.336 and rs=-0.408). CONCLUSION: Maternal and fetal hemodynamic parameters were different in the 3 groups of fetuses: fetal growth restriction, small for gestational age, and adequate for gestational age. Maternal hemodynamic parameters were closely and continuously correlated with fetal hemodynamic features. In particular, a maternal hemodynamic profile with high systemic vascular resistance, low cardiac output, reduced inotropism, and hypodynamic circulation was correlated with a reduced umbilical vein flow and increased umbilical artery pulsatility index. The mother, placenta, and fetus should be considered as a single cardiac-fetal-placental unit. The correlations of systemic vascular resistance, cardiac output, and inotropy index with umbilical artery impedance indicate the key role of these 3 parameters in placental vascular tree development. The umbilical vein flow rate and, therefore, the placental perfusion seems to be influenced not only by these three parameters but also by the maternal cardiovascular kinetic energy.

Maternal hemodynamics for the identification of early fetal growth restriction in normotensive pregnancies.

We aimed at testing systemic vascular resistance (SVR) for the correct identification of early fetal growth restriction (FGR). 61 normotensive patients, gestational age 29 + 0-32 + 0, with suspected diagnosis of early FGR, were submitted to USCOM and to an ultrasound evaluation. 24 patients met the criteria of FGR, and 9 patients developed umbilical artery Doppler alterations. SVR>1006 dyn s·cm-5 correctly identified patients with a subsequent diagnosis of FGR, whereas SVR>1222 dyn s·cm-5 was related to FGR with subsequent umbilical artery Doppler alterations. These data might be important to introduce USCOM in the clinical practice to identify and treat FGR.

Systemic vascular resistance may influence the outcome of in vitro fertilization.

Introduction: The number of pregnancies obtained through in vitro fertilization (IVF) techniques are increasing, and only few studies have investigated hemodynamic variations in women undergoing IVF techniques. The aim of this study was to evaluate the hemodynamic parameters in women undergoing IVF, to assess a possible correlation between hemodynamics and embryo implantation.Methods: 45 normotensive non-obese women, age ≤ 43 years, with idiopathic or tubal infertility, referred to the Reproductive Physiopathology and Andrology Unit, Sandro Pertini Hospital, Rome, during the period 2020/2021, underwent IVF techniques. All women were evaluated with Ultra Sonic Cardiac Output Monitor (USCOM) to detect hemodynamic parameters at two different stages: at the mid-luteal phase, before the beginning of IVF, and at the day of embryo transfer (dET). All demographics and hormonal parameters in both groups were comparable. The hemodynamic parameters were compared between women with a positive ß-HCG test vs. those testing negative.Results: 11 out of 45 (24,5%) women obtained positive ß-HCG test. All demographics and hormonal parameters were comparable in both groups. Women with a positive ß-HCG test showed statistically lower systemic vascular resistance (SVR) at mid-luteal phase (868.61 ± 100.1 vs. 1009 ± 168.4) and dET (818,9 ± 104.5 vs 1038.52 ± 150.82 dynes × s/cm5).Conclusions: Hemodynamic assessment can identify a more favorable pre-pregnancy cardiovascular adaptation. Embryo implantation might be positively influenced by the hemodynamic parameters, e.g. lower SVR, before the beginning of IVF techniques, and during the window of implantation.

Hemodynamic assessment in patients with preterm premature rupture of the membranes (pPROM).

OBJECTIVE: The aim of this study was to assess the hemodynamic differences in women with pPROM versus physiological pregnancies. STUDY DESIGN: This was a prospective case control study of 15 patients with pPROM and 45 controls. Patients and controls were submitted at enrollment to a non-invasive hemodynamic evaluation with UltraSonic Cardiac Output Monitor (USCOM), and to blood tests to check white blood cells count and C-reactive protein (CRP) levels. We followed pPROM patients until delivery noting fetal/neonatal and maternal unfavorable outcomes (maternal fever, APGAR 1' and 5'< 7, stillbirth). RESULTS: Patients with pPROM showed higher values of cardiac output (9.1 ± 2.3 vs 7.1 ± 0.85, p < 0.01), lower systemic vascular resistances (792.1 ± 162 vs 1006.2 ± 110.7, p < 0.01), higher minute distance (32.3 ± 7.8 vs 25 ± 2.8, p < 0.01), lower Potential to Kinetic Energy Ratio (16.5 ± 5.3 vs 22.4 ± 6.8, p < 0.01), higher heart rate (97.5 ± 15.4 vs 82.4 ± 12, p < 0.01) and higher oxygen delivery (1313.2 ± 325.8 vs 1080.7 ± 151.8, p < 0.01) vs. controls. Six out of 15 pPROM patients had an unfavorable outcome. There were no significant differences in CRP levels and WBC count at admission in the two pPROM subgroups, whereas maternal hemodynamics was characterized by lower SVR (718 ± 72 vs 863 ± 123, p = 0.02) in subsequently complicated patients. CONCLUSIONS: Maternal hemodynamics is altered in pPROM patients, with a lower Systemic Vascular Resistance and higher Cardiac Output vs. controls. This hyperdynamic circulation appears to anticipates the changes of serum markers of inflammation (CRP, WBC count) and seems to be more pronounced at admission in pPROM patients developing unfavorable outcomes.

Maternal peripheral vascular resistance at mid gestation in chronic hypertension as a predictor of fetal growth restriction.

We aimed at analyzing the relationship between maternal hemodynamics as expressed by Peripheral Vascular Resistance (PVR) at mid gestation and fetal growth at delivery in chronic hypertension. 152 chronic hypertensive patients were submitted to echocardiography noting PVR at 22-24 weeks' gestation and were followed until delivery noting birthweight centile and the diagnosis of fetal growth restriction (FGR). The logarithmic correlation analysis showed that PVR at mid gestation was strongly related to birthweight at delivery (r = -0.72; p < .001). Moreover, PVR was predictive of both a birthweight <10th centile (PVR >1466 Sensitivity 75.0%, Specificity 93.4%, AUC 0.83, p < .001) and FGR (PVR > 1355 Sensitivity 84.2%, Specificity 93.2%, AUC 0.88, p < .001). This study highlights the importance of maternal hemodynamics as expressed by PVR at mid gestation for the identification of chronic hypertensive patients at risk for developing fetal growth restriction. This observation might open new areas of intervention to treat patients with altered hemodynamics (PVR > 1355 dyne s cm-5).

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.

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.

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.

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.

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.

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).