Left Ventricular Concentric Geometry as a Risk Factor in Gestational Hypertension
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.
Left ventricular adaptation to human essential hypertension is complex and characterized by changes of both left ventricular structure and function.1–4 Since the advent of M-mode echocardiography, the role of left ventricular mass and hypertrophy and the pathophysiologic correlates in essential hypertension have been investigated.1–4 The recent definition of different geometric patterns of the left ventricle3,4 has expanded the interest in the possible prognostic significance of the left ventricular shape4–7 in essential hypertension. Several of these studies have given evidence of an adverse prognostic significance of an altered left ventricular geometry,4–7 with an increasing cardiovascular morbidity and mortality as the cardiac shape worsens from normal geometry to concentric hypertrophy.
The hemodynamic disorders of pregnancy, typically present in gestational hypertension (GH), represent a very interesting model in which a pressure overload develops in a few weeks of time, differing from chronic essential hypertension, which is characterized by a long-lasting pressure overload. Despite the brief period in which these hemodynamic alterations of pregnancy develop, they appear to be associated with an altered left ventricular structure and function.8–12 However, there are no data available on the prognostic significance of an altered cardiac structure and function during pregnancy. The information deriving from the geometric pattern and the maternal hemodynamics might be useful in the decision for the clinical treatment. There is still debate on the appropriate treatment during GH. Nonpharmacologic treatment alone is often suggested for pregnant patients with mild GH, in the absence of maternal and fetal risks factors.13 Although the presence of elevated systolic (SBP) and diastolic blood pressure (DPB) values without proteinuria is linked with a normal evolution of pregnancy, some patients with similar pressure values develop severe complications.
In the past, a complicated evolution of pregnancy has been proposed to be linked to the uterine artery Doppler abnormalities.14,15 For these reasons, the present study was designed to evaluate the prognostic impact on the outcome of pregnancy of different geometric patterns and uterine artery Doppler abnormalities, in a group of nontreated patients with mild GH.
One hundred forty-eight consecutive nulliparous pregnant women, recruited between 27 and 31 weeks of gestation with the following criteria, were entered into the study: (1) the finding of a mild GH, ie, SBP of 140 to 150 mm Hg and DBP of 90 to 99 mm Hg in 2 different measurements 4 to 6 hours apart; (2) absence of proteinuria at the urine analysis at the moment of enrollment; (3) absence of hyperuricemia, thrombocytopenia, elevated liver enzymes, HELLP syndrome, and coagulation abnormalities; (4) an estimated fetal weight >10th percentile; (5) a normal umbilical artery Doppler velocity; and (6) no antihypertensive treatment.
Exclusion criteria included the following: (1) undetermined gestational age, (2) history of chronic hypertension, (3) history of maternal heart disease, (4) tobacco use, and preexisting chronic medical problems (diabetes type 1, lupus erythematosus, antiphospholipid syndrome, gestational diabetes).
Gestational age was determined by last menstrual period and sonographic examination before 20 weeks of gestation.
Blood pressure measurement was performed in the seated position with the arm at the level of the heart and the feet supported or on the ground.16 Korotkoff phase V was used for the determination of DBP.17 GH was diagnosed according to the definition of Davey and MacGillivray: when SBP and DBP were ≥140/90 mm Hg in 2 measurements 4 hours apart.18
Small for gestational age was diagnosed when birth weight was <10th percentile.19
The M-mode, 2D, and Doppler echocardiographic investigation were performed within 24 hours from the diagnosis of mild GH.
The evolution of gestation was followed until term by an investigator, blinded as to the maternal left ventricular geometry, to determine the outcome of pregnancy. Patients who subsequently developed moderate-to-severe hypertension were pharmacologically treated. The instability of the blood pressure values despite an aggressive pharmacological treatment was considered an indication for delivery to the judgment of the referring clinician.
Approval of the university ethics committee was obtained, and written informed consent was collected from all patients.
For all ultrasound examinations, 3.5-MHz sector ultrasound transducer (Esaote AU5) was used with the high-pass filter at 100 Hz.
All patients underwent uterine artery color Doppler examination with the calculation of the resistance index (RI) according to the following formula: RI=(A−B)/A, where A was the highest and B the lowest velocity measured from the waveform. A mean RI of both uterine arteries >0.6 was considered abnormal.
Fetal Doppler measurements were obtained from umbilical artery (UA) and middle cerebral artery (MCA) with the calculation of pulsatility indices (PI) according to the following formula: PI=(A−B)/M, where A was the highest and B the lowest and M the mean velocity measured from the waveform. A PI of the UA >95th percentile and a PI of the MCA less than the fifth percentile for gestational age were considered abnormal.
Fetal biometry and estimated fetal weight were assessed according to the local reference values.19
The M-Mode, 2D, and Doppler echocardiographic evaluations were performed with the patient in lateral position with a 1.8- to 3.6-MHz transducer in harmonic imaging interfaced with a commercially available echocardiographic machine (Acuson Sequoia 256). All data were recorded on SVHS videotape.
Left ventricular end-diastolic and end-systolic diameters, and interventricular septum and posterior wall diastolic thickness were detected in the parasternal long-axis view during M-mode tracing, according to the recommendation of the American Society of Echocardiography.20 Left ventricular mass (LVM) in grams was calculated by the Devereux formula.21 Left atrial dimension and function were detected as previously described.8
Left Ventricular Geometric Pattern
LVM index (LVMi) was then calculated as follows: LVMi=LVM/m2.7, where m was the height of the patient in meters.3
Relative wall thickness (RWT) was calculated as the ratio [(interventricular septum diameter+posterior wall diastolic thickness)/left ventricular end-diastolic diameter]. Left ventricular geometric pattern was considered normal if LVMi≤50 g/m2.7 and RWT≤0.44. Concentric remodeling was diagnosed when LVMi≤50 g/m2.7 and RWT>0.44; concentric hypertrophy was defined as a LVMi>50 g/m2.7 and a RWT>0.44; eccentric hypertrophy was diagnosed when LVMi>50 g/m2.7 and RWT≤0.44.3,4,6,8
Left ventricular end-diastolic and end-systolic volumes were calculated according to the Teicohholz formula.22 Stroke volume was calculated as the difference between end-diastolic and end-systolic volumes. Cardiac output was calculated as the product of stroke volume and heart rate derived from electrocardiographic monitoring. Ejection fraction was also calculated.
Total Vascular Resistance
At the end of maternal echocardiographic examination, blood pressure was measured from the brachial artery with a manual cuff. Mean arterial pressure was calculated. Total vascular resistance (TVR) was calculated in dynes · sec · cm−5 according to the following formula: TVR=mean arterial pressure [mm Hg]/cardiac output [L/min])×80.
Selected Adverse Outcomes
All patients were longitudinally monitored with the evaluation of maternal and feto-neonatal outcomes. Adverse maternal and feto-neonatal outcomes were considered: (1) the occurrence of proteinuria (>300 mg/24 hours) (preeclampsia), (2) induced preterm delivery before 34 weeks for maternal conditions (patients successively treated and not responding to pharmacological treatment), (3) abruptio placentae, (4) medical problems related to pregnancy (ie, occurrence of thrombocytopenia, elevated liver enzymes, HELLP syndrome, and coagulation abnormalities), (5) birth weight <10th percentile for gestational age of the reference population,19 (6) fetal distress in labor; and (7) admittance to neonatal intensive care unit.
Patients were classified as either uneventful or complicated at the follow-up. Values were expressed as mean±SD. The Student t test for unpaired data was used for normally distributed parameters, whereas Mann-Whitney U test was used for nonparametric data. Differences among more than 2 groups were tested by one-way ANOVA followed by the Newman-Keuls pot-hoc test.
The outcomes of GH pregnancies were classified as uneventful, and complicated GH. The variables for the prediction of complicated GH were as follows: (1) the geometric pattern divided into normal geometry, concentric remodeling, eccentric hypertrophy, and concentric hypertrophy; (2) the presence or absence of concentric geometry (concentric remodeling and concentric hypertrophy); and (3) the presence or absence of uterine artery Doppler abnormalities.
Categoric variables were analyzed by univariate binary logistic analysis and multivariate binary logistic regression analysis, adjusting the odds ratio for total vascular resistance and LVMi. The first model of multivariate analysis was focused on the geometric pattern and uterine artery Doppler, whereas the second model considered the presence of concentric geometry and the uterine artery Doppler.
To test intraobserver and interobserver variability, 2 independent observers measured data on videotape recordings from 20 randomly selected patients. The same data were than remeasured on tape after 1 month by one of the 2 observers.
Blood pressure values of the 148 women at 21±2-week gestation were SBP 121±9 mm Hg and DBP 69±7 mm Hg. Data were collected for all 148 consecutive patients, and there were no drop-outs during follow-up. Out of 148 pregnancies reviewed, 101 GH patients (68.2%) had an uneventful pregnancy (subsequent uneventful GH group), 47 patients (31.8%) showed a subsequent development of maternal and/or fetal complications (subsequent complicated GH group). The main maternal and fetal/neonatal complications are shown in Table 1. Out of 148 patients, 16 developed moderate to severe hypertension, 9 responded to pharmacological treatment and delivered at-term-gestation fetuses of normal weight, and 7 did not respond and were induced deliver before 34 weeks. The latter are the patients referred to as induced delivery before 34 weeks for maternal conditions.
Postpartum Blood Pressure Values
Blood pressure values at 1-month postpartum were SBP 128±7 mm Hg, DBP 74±9 mm Hg, and MBP 92±7 mm Hg. According to the geometric pattern, patients with normal geometry (1) showed SBP 125±7 mm Hg, DBP 71±8 mm Hg, and MBP 89±6 mm Hg. Those with concentric remodeling (2) had SBP 128±6 mm Hg, DBP 79±7 mm Hg, and MBP 95±5 mm Hg. Women with eccentric hypertrophy (3) showed postpartum SBP 128±6 mm Hg, DBP 69±7 mm Hg, and MBP 88±5 mm Hg. Patients with concentric hypertrophy (4) had SBP 134±4 mm Hg, DBP 78±9 mm Hg, and MBP 97±6 mm Hg. ANOVA with correction for multiple comparisons showed a significant difference in SBP (P<0.001 4 versus 1, 2, and 3), DBP (P<0.001 2 versus 1 and 3; 4 versus 1 and 3), and mean arterial pressure (P<0.001 2 versus 1 and 3; 4 versus 1 and 3) among the groups.
The baseline features at the moment of the diagnosis of GH of the 2 selected groups are shown in Table 2. Age, height, prepregnancy body mass index, heart rate, SBP, DBP, and mean arterial pressure were similar in the 2 groups. TVR resulted higher in the subsequent complicated GH respect to the uneventful hypertensive group (P=0.002).
Uterine artery Doppler abnormalities were more prevalent in GH patients who developed complications compared with patients with uneventful GH (P=0.001).
The complicated GH group gave birth earlier to newborns of lower birthweight and weight percentile compared with the patients with uneventful GH.
M-Mode and 2D-Derived Parameters
The main hemodynamic parameters of the 2 groups at the moment of the diagnosis of GH are shown in Table 3. Left atrial diameter, end-diastolic volume, and left atrial maximal area were not statistically different between the 2 groups, whereas patients with the subsequent complications showed a larger left atrial minimal area (P=0.008) and a lower left atrial fractional area change (LA FAC%; P<0.0001) than those of the hypertensive women with uneventful pregnancy. RWT, interventricular septum diameter, and posterior wall diastolic thickness, as well as LVM and LVMi, resulted higher in the complicated compare to the uneventful hypertensive group (Table 3). ESV was larger and ejection fraction percentage was lower than those in the uneventful hypertensive group. Stroke volume and cardiac output were lower in patients with complicated GH compare to the uneventful pregnancies.
Geometric Pattern of the Left Ventricle
A normal geometric pattern was found in 68 out of 148 (45,95%) GH patients, 60 were uneventful, and 8 were complicated GH. Eighty patients (54,05%) showed an abnormal geometric pattern: (1) 31 patients showed a concentric remodeling (16 had an uneventful pregnancy, and 15 had a complicated GH); (2) 12 had an eccentric hypertrophy (10 with uneventful and 2 complicated GH); and (3) 37 showed a concentric hypertrophy (15 with uneventful and 22 with complicated GH).
Complications in Patients With and Without Concentric Geometry
Concentric geometry (concentric remodeling and concentric hypertrophy) was prevalent among patients with the subsequent development of complicated GH (37 out of 47, 78.72%) respective to the uneventful GH patients (31 out of 101, 30.69%; P=0.0001). The number of total complications and for each adverse outcome in patients with and without concentric geometry are shown in Table 4. Patients with concentric geometry had a significantly higher incidence of complications in the follow-up (P<0.0001), mainly represented by maternal disorders (occurrence of proteinuria and medical problems related to GH); no statistical difference was found in fetal complications between the 2 groups.
Prediction of Adverse Outcomes
In the univariate analysis, the altered geometric pattern (concentric remodeling and concentric hypertrophy), concentric geometry, and abnormal uterine artery Doppler were all predictive of the adverse outcome (Table 5). The multivariate binary logistic regression analysis adjusted for LVMi and TVR showed concentric remodeling in the first model (P=0.038) and concentric geometry in the second model as independent predictors of adverse outcomes (P=0.014) (Table 5).
Sensitivity and specificity of concentric geometry in the prediction of adverse outcomes were 78.7% and 69.3%, respectively; positive and negative predictive values were 54.4% and 87.5%, respectively.
Table 6 shows the differences in hemodynamic characteristics among patients with different geometric patterns.
Intra- and Interobserver Variability
Intra- and interobserver variability in terms of coefficient of variation (CV) and regression coefficient are reported. For interventricular septum thickness CV were 8.5%(r=0.97) and 9.1% (r=0.95), respectively; for posterior wall thickness, 8.4% (r=0.98) and 8.7% (r=0.96), respectively; for left ventricular diastolic diameter, 5.3% (r=0.96) and 8.4% (0.95), respectively; for left ventricular systolic diameter, 7.9% (r=0.96) and 9.5% (r=0.94); and for left ventricular mass, 9.1% (r=0.95) and 10.1% (r=0.94).
Previous reports have suggested that echocardiography plays a key role in cardiovascular risk stratification in essential hypertension. In particular, the assessment of left ventricular structure with the evidence of an altered geometry may provide important prognostic information.5,7 Recent data have shown that GH is characterized by an altered left ventricular geometry,8–10 although no data are present to our knowledge on the possible prognostic implication of these structural alterations. Our main interest was to evaluate if the presence of an altered left ventricular geometric pattern in the early stages of nontreated mild GH might be predictive of maternal and fetal future complications. Our results show that in GH an altered geometry is, indeed, related to an adverse outcome of pregnancy, and that concentric geometry is an independent predictor of adverse maternal events.
The benefit of treatment of mild hypertension has been clearly established for the general population, whereas in pregnancy it remains an area of controversy, and there is still debate on the opportunity of a pharmacological treatment. In fact, general guidelines do not suggest antihypertensive treatment in case of mild GH.13,16 In our study, a concentric geometry of the left ventricle is present in ≈46% (68 of 148) of the GH patients, despite the mildly increased pressure regimen and the normal general maternal conditions.
Although blood pressure values were similar between the uneventful and complicated GH groups, those patients who subsequently developed an adverse outcome showed not only a higher prevalence of concentric geometry but also some functional differences compared with uneventful patients, such as a reduced left atrial and ventricular function, higher TVR, and higher prevalence of abnormal uterine artery Doppler. These results are in accordance with other investigators that have reported in patients with chronic essential hypertension and concentric geometry, the presence of elevated peripheral resistance and a lower cardiac function, as if the central hemodynamics followed the ventricular geometric pattern.2,23 In this view, in GH patients, blood pressure values alone appear to be insufficient to identify the effective risk of adverse events; therefore, central and peripheral adaptation to pregnancy might interact the evolution of the hypertensive disease, influencing its clinical manifestations. Hence, the decision for a pharmacological treatment in GH patients shouldn’t be based only on the levels of blood pressure values, but might also take into consideration the features of cardiac function and structure.
Another interesting finding of the present study is the linkage between cardiac structural alteration and the subsequent development of proteinuria (preeclampsia). Recent reports have evidenced that in essential hypertension, patients with high-normal albuminuria had a greater RWT and more frequent concentric left ventricular hypertrophy,24 and that the prevalence of concentric left ventricular hypertrophy was significantly higher in microalbuminuric compared with normoalbuminuric subjects.25 Our data suggest that concentric geometry in mild GH women might be linked to the occurrence of proteinuria, because 12 out of the 14 patients with preeclampsia had a concentric geometry before its appearance.
The finding of a concentric geometry in the early stages of GH might be associated to the subsequent development of target organ damage other than the kidney (eg, liver, placenta), justifying the broad clinical spectrum of the disease (eg, HELLP syndrome, thrombocytopenia, growth restriction). This finding on GH women is in line with other reports showing that in chronic essential hypertension extracardiac target organ damage is consistently more frequent in patients with concentric hypertrophy than in those with eccentric hypertrophy.23 Different outcomes, however, could be related to different cardiac structural and functional features: In the future, this hypothetic linkage should be investigated.
An interesting aspect is the absence of correlation between eccentric hypertrophy and unfavorable outcomes. This result might be explained by the different hemodynamic characteristics associated to eccentric hypertrophy compared with concentric geometry. In fact, stroke volume and cardiac output are higher and TVR is lower in GH patients with eccentric hypertrophy compared with patients with concentric geometry (Table 6). This hemodynamic feature has been already reported in essential hypertension by Ganau et al.2 Furthermore, in the past a progressive eccentric left ventricular enlargement with a decreased ratio between posterior wall thickness and left ventricular end-diastolic diameter was reported in normal pregnancy.26 Normal geometry and eccentric hypertrophy probably represent the adequate cardiac adaptation in GH pregnancies in response to a plasma volume expansion. Patients with concentric geometry are those with pressure overload and volume underload, as they show the highest TVR and the lowest stroke volume.
Another interesting result is related to the higher 1-month postpartum blood pressure values, within the normal range, in those patients showing concentric geometry (remodeling and hypertrophy) and eccentric hypertrophy during pregnancy. This datum appears not to exclude a possible pregestational predisposition to pregnancy complications. This hypothesis should be confirmed by large longitudinal studies, including a long postpartum follow-up.
Our study confirms the important role of the altered uterine resistances and abnormal uterine artery Doppler waveforms in established GH as previously reported.14,15 Although the uterine vascular bed has a specific and well-established role in the physiological adaptation of the whole maternal peripheral vasculature,27,28 and in the genesis of hemodynamic alterations in pregnancy, this parameter does not appear to be an independent predictor when analyzed together with the cardiac parameters. In our model, concentric geometry results were the strongest independent predictor of adverse outcomes. These data should be collected and analyzed on larger numbers of GH patients to design adequate protocols of investigation and eventual medical intervention.
Our finding support the concept that the hypertensive disease induced by pregnancy is an event with multiple and different aspects. Although the absence of proteinuria indicates a minor degree of clinical severity and end-organ damage, maternal cardiac adaptation appears to play an important role despite the increased blood pressure levels found. An abnormal geometric cardiac pattern is found in these patients and correlates with the elevated incidence of pregnancy complications. The knowledge of the maternal cardiac function and structure in nonproteinuric GH patients might help in the future to evaluate the degree of central response in the elevated blood pressure regimen. For research purposes, this will bring the collection of different patients with homogeneous patterns of cardiovascular response, reducing the elevated variability of results found in this field. For clinical purposes, the knowledge of the central cardiac status and performance might increase the ability to select the ideal treatment to evaluate the blood pressure, the peripheral resistances, and the cardiac parameters. The longitudinal evolution of pregnancy and the response to antihypertensive therapy could be monitored with these parameters with a greater rate of success versus the simple measurement of the peripheral blood pressure. Eventually, the presence of a cardiac abnormal geometry in GH should be an indication for a complete and prolonged cardiological postpartum follow-up.
- Received September 13, 2002.
- Revision received October 9, 2002.
- Accepted January 15, 2003.
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