Gian Paolo Novelli

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 (≥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/m2; 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).

Fetal subcutaneous tissue thickness (SCTT) in healthy and gestational diabetic pregnancies

To determine reference values of fetal subcutaneous tissue thickness (SCTT) throughout gestation in a healthy population and to compare them with those from a population of pregnant women with gestational diabetes under standard therapy.

Total Vascular Resistance and Left Ventricular Morphology as Screening Tools for Complications in Pregnancy

We evaluated the predictive value of elevated total vascular resistance on the outcome of pregnancy in normotensive high-risk primigravidas with bilateral notching of the uterine artery Doppler. A total of 526 high-risk primigravidas referred to the obstetrics outpatient clinic of Tor Vergata University with bilateral notching of the uterine artery at 20 to 22 weeks’ gestation were submitted to a maternal echocardiographic examination and uterine artery Doppler evaluation at 24 weeks’ gestation. Blood pressure was recorded at the time of the examination, total vascular resistance was calculated, and the geometric pattern of the left ventricle was assessed. Patients were followed until the end of pregnancy to detect fetal/maternal adverse outcomes (gestational hypertension, preeclampsia, abruptio placentae, fetal growth restriction, perinatal death, etc). A total of 111 of the 526 pregnancies showed a bilateral notch at 24 weeks’ gestation, and 97 had an adverse outcome (18.44%). The best independent predictor for maternal and fetal complications was total vascular resistance (odds ratio: 91.25; 95% CI: 39.64 to 210.05; P<0.001). The cutoff value was 1400 dynes · s · cm−5, with a sensitivity and a specificity of 89% and 94%, respectively. A high relative wall thickness of the left ventricle (>0.37; odds ratio: 2.47; 95% CI: 1.12 to 5.44) and a hypertrophized ventricle (left ventricular mass >130 g; odds ratio: 2.52; 95% CI: 1.12 to 5.64) were also independent predictors (P<0.05). Echocardiography might identify at 24 weeks’ gestation patients who subsequently develop maternal and fetal complications through the assessment of maternal hemodynamics and left ventricular geometry.

Maternal Diastolic Dysfunction and Left Ventricular Geometry in Gestational Hypertension

Abstract—The objective of this study was to evaluate diastolic parameters and left ventricular geometry in gestational hypertension. Twenty-one consecutive pregnant women with gestational hypertension and 21 normotensive women matched for age and gestational age were enrolled in the third trimester of gestation. Echocardiographic and uterine color Doppler evaluations were performed. Systolic, diastolic, and mean blood pressure, total vascular resistance (TVR), and uterine resistance index were higher in hypertensive women than in control subjects (P <0.01). Left atrial function and cardiac output were significantly lower in gestational hypertension (P <0.01). Patients with gestational hypertension had longer left ventricular isovolumetric relaxation time (IVRT) (P <0.0001); lower velocity-time integral of the A wave (P <0.05) and of the diastolic pulmonary vein flow (P <0.05); and higher velocity-time integral of the reverse pulmonary vein flow (P <0.05). Systolic fraction of the pulmonary vein flow was higher in women with gestational hypertension than in control subjects (P <0.01); the difference in duration of pulmonary vein flow and A wave was closer to 0 in gestational hypertension (P <0.0001). Altered left ventricular geometry was found in 100% of hypertensive patients and in 19.05% of normotensive patients (P <0.001). IVRT, left ventricular end-systolic volume, atrial function, and uterine resistance index were directly related to TVR (P <0.01); deceleration time of the E wave showed a quadratic correlation with TVR (P <0.01). Gestational hypertension is characterized by an altered cardiac geometric pattern of concentric hypertrophy. The altered geometric pattern assessed during gestational hypertension is associated, in our study, with depressed systolic function, high TVR, altered diastolic function, and left atrial dysfunction. Deceleration time of the E wave, IVRT, and left atrial fractional area change, found in concomitance with the highest TVR, may be useful in the evaluation of cardiac function and hemodynamics present in pregnancy-induced hypertension.

Left ventricular concentric geometry as a risk factor in gestational hypertension.

Abstract—In the past, an adverse prognostic significance of an altered left ventricular geometry in essential hypertension has been demonstrated. There are no data on the prognostic significance of an altered cardiac structure during pregnancy. The present study was designed to evaluate the prognostic impact on the outcome of pregnancy of an altered geometry of the left ventricle in mild gestational hypertension. One hundred forty-eight consecutive, pregnant, mild gestational hypertensive women (systolic and diastolic blood pressure, 140 to 150 mm Hg and 90 to 99 mm Hg, respectively) were included in the study. Patients were monitored until term to detect subsequent fetal and/or maternal adverse outcomes (preeclampsia, preterm delivery, abruptio placentae, other maternal medical problems, fetal distress, neonatal low birth weight, admittance to neonatal intensive care unit). One hundred one gestational hypertensive patients (68.2%) had an uneventful pregnancy; 47 patients (31.8%) showed a subsequent development of maternal and/or fetal complications. Concentric geometry was prevalent among patients with the subsequent development of complicated gestational hypertension (37 out of 47 patients) compared with the uneventful gestational hypertensive patients (31 out of 101 patients; 78.7% versus 30.1%;P =0.0001). The multivariate analysis showed concentric geometry as an independent predictor of adverse outcomes (odds ratio, 3.65; 95% confidence interval, 1.30 to 10.27;P =0.014). In patients with gestational hypertension, blood pressure values alone appear to be insufficient to identify the effective risk of adverse events. Ventricular geometry gives additional prognostic information, possibly improving our clinical ability to follow and eventually treat these patients.

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/m2.7 and 30.4±6.8 g/m2.7 versus 24.8±5.0 g/m2.7, 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.

Postpartum cerebellar infarction and haemolysis, elevated liver enzymes, low platelet (HELLP) syndrome.

Pregnancy is considered to be a hypercoagulable state per se with an increased risk for cerebrovascular events, however cerebellar infarction has been rarely described in pregnant women. A nulliparous pre-eclamptic woman at 25 weeks’ gestation was submitted to an echocardiographic exam that showed an impaired cardiac structure and function. After 2 h, the patient underwent caesarean section for diagnosis of haemolysis, elevated liver enzymes, low platelet (HELLP) syndrome. Afterwards her platelet count raised, and eight days later she developed nystagmus, ataxia, dysmetria and motor deficit in the right limbs and sensory impairment in the right side of the face and in the left limbs. Cerebral magnetic resonance imaging (MRI) demonstrated a right cerebellar and median posterior bulbar infarction. Colour-coded sonography of cerebral vessels showed an occlusion of the right vertebral artery. Coagulation pattern analysis evidenced double heterozygosis of the methylenetetrahydrofolate reductase (MTHFR) gene and single mutation of the prothrombin gene. This case report gives evidence of the importance of considering the different risk factors involved in stroke occurrence during pregnancy.

Are Gestational and Essential Hypertension Similar? Left Ventricular Geometry and Diastolic Function

Objective: To evaluate the differences and similarities in diastolic function and left ventricular geometry in gestational and essential hypertension. Methods: Thirty‐nine consecutive gestational hypertensive pregnant women in the third trimester of gestation (GH), 40 nonpregnant essential hypertensive women (EH), and 38 normotensive nonpregnant women (N) matched for age were enrolled into the study and underwent echocardiographic and Doppler evaluations. The GH and EH patients were evaluated prior to the administration of any drug treatment. Results: Left atrial function was similar in GH and N subjects and lower than that in EH patients. Both GH and EH patients had early left ventricular diastolic filling pattern significantly different as compared to N subjects (longer isovolumetric relaxation time, deceleration time of the E wave, and lower E wave velocity in GH and EH vs. N), whereas the late filling properties were similar in GH and N subjects with a lower A velocity, and velocity–time integral vs. EH (p < 0.05). Systolic fraction of the pulmonary vein flow was similar in GH and EH patients and lower in N subjects. Altered left ventricular geometry was more common in GH than in EH, whereas normotensive subjects did not show any alteration of the geometric pattern. Conclusions: Gestational and essential hypertension induce similar early altered diastolic filling of the left ventricle. Essential hypertension is characterized by a compensatory late filling mechanism due to an enhancement of left atrial function. Gestational hypertension is characterized by altered left ventricular geometry, which is far less common during essential hypertension.

C-peptide and insulin levels at 24-30 weeks' gestation: an increased risk of adverse pregnancy outcomes?

OBJECTIVE The hypothesis was that fasting C-peptide and insulin values, during an oral glucose tolerance test (OGTT), might allow an estimation of the increased risk for gestational hypertension (GH) and fetal macrosomia. STUDY DESIGN Two-hundred and six consecutive patients were submitted to an OGTT. Thirty-five developed gestational hypertension and 29 delivered large-for-gestational-age (LGA) newborns. Plasma glucose levels (mg/dl) and insulin levels (microU/ml) were measured fasting and after 60, 120 and 180 min C-peptide fasting levels (ng/ml) were also measured. RESULTS Twenty-five patients were excluded, 181 were enrolled. According to the OGTT, 143 patients were classified as normal, 26 were found affected by gestational diabetes (GD) mellitus, and 12 had impaired gestational glucose tolerance (IGGT). Hypertensive women exhibited higher 60 and 120 min insulin values than the normotensive group (128.3+/-69.9 microU/ml versus 86.2+/-58.3 microU/ml, P<0.05; 104.9+/-66.4 microU/ml versus 78.7+/-56.5 microU/ml, P<0.05).C-peptide cut-off at 2.9 ng/ml resulted predictive for patients delivering large-for-gestational-age newborns (OR=3.42, 95% CI=1.59-7.39). CONCLUSIONS C-peptide and insulin may be used as indicators of risk for the development of complications in late pregnancy.

Fetal growth restriction and maternal cardiac function

Cardiac output rises in pregnancy, and most of this increase occurs in the first trimester. Both heart rate and stroke volume contribute to this increase, which, coupled with a decrease in mean arterial pressure, determines a reduction of maternal total vascular resistance (TVR) in physiological pregnancy. The absence of a ‚correct’ maternal cardiovascular compensatory response (absence of increase in cardiac output, heart rate, stroke volume, left ventricular mass and decrease in maternal TVR), in addition to abnormal trophoblastic invasion, might be one of the factors that could determine a reduced placental perfusion and, eventually, the development of fetal intrauterine growth restriction (IUGR). In fact, pregnancies complicated by IUGR appear to lack the stimulus to induce the hemodynamic changes typically present in physiological pregnancy such as the increase in preload, maternal heart rate, stroke volume, the enlargement of the left atrium and, above all, the reduction of TVR. It is difficult to e...