Recovery of left ventricular systolic function in peripartum cardiomyopathy: an observational study from rural Tanzania.

BACKGROUND: The aim of this study was to evaluate the recovery rate of the left ventricular systolic function of women diagnosed with peripartum cardiomyopathy receiving specialized care in rural Tanzania. METHODS: In this observational study, women diagnosed with peripartum cardiomyopathy at a referral center in rural Tanzania between December 2015 and September 2021 were included. Women diagnosed between February and September 2021 were followed prospectively, those diagnosed between December 2015 and January 2021 were tracked back for a follow-up echocardiography. All participants received a clinical examination, a comprehensive echocardiogram, and a prescription of guideline-directed medical therapy. The primary outcome was recovery of the left ventricular systolic function (left ventricular ejection fraction > 50%). RESULTS: Median age of the 110 participants was 28.5 years (range 17-45). At enrolment, 49 (45%) participants were already on cardiac medication, 50 (45%) had severe eccentric hypertrophy of the left ventricle, and the median left ventricular ejection fraction was 30% (range 15-46). After a median follow-up of 8.98 months (IQR 5.72-29.37), 61 (55%) participants were still on cardiac medication. Full recovery of the left ventricular systolic function was diagnosed in 76 (69%, 95% CI 59.6-77.6%) participants. In the multivariate analysis, a higher left ventricular ejection fraction at baseline was positively associated with full recovery (each 5% increase; OR 1.7, 95% CI 1.10-2.62, p = 0.012), while higher age was inversely associated (each 10 years increase; OR 0.40, 95% CI 0.19-0.82, p = 0.012). CONCLUSION: Left ventricular systolic function recovered completely in 69% of study participants with peripartum cardiomyopathy from rural Tanzania under specialized care.

Pregnancy-related cardiac outcomes among patients with congenital heart disease after formalization of a cardio-obstetrics program.

BACKGROUND: The prevalence of pregnant patients with congenital heart disease (CHD) is increasing, and these patients are at high risk for cardiac morbidity. OBJECTIVE: This study aimed to examine the pregnancy outcomes in patients with congenital heart disease before and after the establishment of formal cardio-obstetrics collaboration between adult congenital heart disease and maternal-fetal medicine programs. STUDY DESIGN: This was a retrospective cohort study of pregnant patients with congenital heart disease from 2002 to 2020 at a single urban academic institution in the United States. This study included patients with a singleton pregnancy who continued a pregnancy beyond 20 weeks of gestation. The primary outcome was a composite adverse maternal cardiac outcome, compared before (2002-2010) and after (2011-2020) the program. The secondary outcomes included gestational age at delivery, mode of delivery, rate of labor induction, use of diuresis after delivery, and a composite maternal morbidity outcome. RESULTS: The number of pregnant patients with congenital heart disease increased after formalization of the cardio-obstetrics program (200 [postprogram group] vs 84 [preprogram group]; 0.48% of all deliveries in the postprogram group vs 0.25% of all deliveries in the preprogram group; P<.001). The postprogram group was more likely to undergo labor induction than the preprogram group (126 [63%] vs 34 [41%], respectively; P<.001). There were fewer patients in the postprogram group than in the preprogram group who were New York Heart Association class II to IV (23 [12%] vs 17 [22%], respectively; P=.04) or with systemic ventricular dysfunction (8 [4%] vs 12 [16%], respectively; P=.001). There was no difference in the primary outcome (38 [19%] in the postprogram group vs 14 [17%] in the preprogram group; P=.64), even after adjusting for confounders, including New York Heart Association class >I and systemic ventricular dysfunction (adjusted odds ratio, 2.3; 95% confidence interval, 0.96-5.4). Patients in the postprogram group were more likely to receive diuresis after delivery than patients in the preprogram group, even in the absence of heart failure or pulmonary edema (9 [4.5%] vs 0 [0.0%], respectively; P=.04). CONCLUSION: In the period after the establishment of a formal cardio-obstetrics program between adult congenital heart disease and maternal-fetal medicine, the number of patients with congenital heart disease delivering at our institution increased significantly. Overall, fewer patients entered pregnancy with advanced-stage heart failure or systemic ventricular dysfunction, possibly suggesting improved prepregnancy cardiac care or improved preconception counseling. Composite maternal cardiac outcomes were similar, but the rates of postpartum diuresis increased significantly, suggesting increased attention to volume status in the postpartum period. Formalized collaboration between congenital heart disease and maternal-fetal medicine may help better optimize patients' care before conception, during pregnancy, and after delivery.

Cardiac evaluation in pregnant patients with dyspnea and palpitations.

BACKGROUND: Symptoms of underlying cardiac disease in pregnancy can often be mistaken for common complaints because of normal physiological changes in pregnancy. Echocardiographic evaluation of patients with symptoms of palpitations and dyspnea can detect structural changes and identify high-risk features. OBJECTIVE: This study aimed to examine transthoracic echocardiograms of perinatal individuals completed for palpitations or dyspnea to determine the frequency of identifying structural changes. STUDY DESIGN: This was a retrospective cohort study of all perinatal individuals with a transthoracic echocardiogram at a single academic center between October 1, 2017, and May 1, 2022. The indication for the echocardiogram, demographics, and clinical characteristics were recorded. Transthoracic echocardiograms with any abnormal findings noted in the transthoracic echocardiogram report were reviewed and categorized into findings of congenital heart disease, valvular disease, pericardial effusion, evidence of ischemia or wall motion abnormalities, abnormal diastolic or systolic function, and other. RESULTS: Of 539 transthoracic echocardiograms completed on 478 individuals who were pregnant or in the 12-week postpartum period, 96 (17.8%) had an indication of palpitations, and 32 (5.9%) had an indication of dyspnea. Abnormal findings were seen in 21.9% of patients with palpitations and in 34.4% of patients with dyspnea. In patients with palpitations who had abnormal findings, 33.3% had congenital heart disease; 33.3% had mild valvular disease, including mitral valve prolapse; 19.0% had a pericardial effusion; and 14.3% had evidence of ischemia or wall motion defects. Abnormal transthoracic echocardiogram findings in the dyspnea cohort included ischemia or wall motion defects (27.3%), mild valvular disease or mitral valve prolapse (36.4%), and abnormal systolic or diastolic function (36.4%). CONCLUSION: Many of the transthoracic echocardiograms completed for patients with dyspnea or palpitations identified no structural abnormality; however, in 1 of 3 to 1 of 4 patients, underlying structural heart disease was identified. Although some of these abnormalities were unlikely to change delivery plans, such as mild valvular disease or small effusions, other abnormalities, such as ischemia, congenital abnormalities, and abnormal systolic or diastolic function, were likely to have implications for pregnancy and postpartum management.

Obstetrical and neonatal outcomes in patients with surgically repaired heart disease.

BACKGROUND: Congenital and acquired heart disease complicate 1% to 4% of pregnancies in the United States. Beyond the risks of the underlying maternal congenital heart disease, cardiac surgery and its sequelae, such as surgical scarring resulting in higher rates of arrhythmias and implanted valves altering anticoagulation status, have potential implications that could affect gestation and delivery. OBJECTIVE: This study aimed to investigate whether history of maternal cardiac surgery is associated with adverse obstetrical or neonatal outcomes compared with patients without a history of cardiac disease or surgery, considered "healthy controls." STUDY DESIGN: This is a secondary analysis of retrospective cohort studies performed at a tertiary care facility in the United States comparing obstetrical outcomes in patients with a history of open cardiac surgery who delivered from January 2007 to December 2018 with healthy controls, who delivered from April 2020 to July 2020. There were 74 pregnancies in 61 patients with a history of open cardiac surgery that were compared with pregnancies in healthy controls. Of the 74 pregnancies, 65 were successfully matched based on gestational age to controls at a 1:3 (case-to-control) ratio. The remainder of cases were matched at a 1:2 or 1:1 ratio; therefore, a total of 219 control pregnancies were included in the analysis. Our primary outcome was the incidence of hypertensive disorders of pregnancy, as well as cesarean delivery, in patients with a history of open cardiac surgery compared with healthy controls. Our secondary outcome was the incidence of low-birthweight neonates in patients with a history of open cardiac surgery compared with healthy controls. RESULTS: Patients with a history of cardiac surgery were not more likely to have any hypertensive disorder diagnosed than healthy controls. Patients with a history of cardiac surgery were more likely to have an operative delivery (P<.0001) but equally likely to have a cesarean delivery (P=.528) compared with healthy controls. Birthweight was not statistically different of 2655±808 g in neonates born to patients with a history of cardiac surgery vs 2844±830 g born to healthy controls (P=.092). CONCLUSION: Patients with a history of cardiac surgery may not be at higher risk of hypertensive disorder diagnosis during pregnancy. Similarly, most patients with a history of cardiac surgery are also likely not at higher risk of cesarean delivery or low-birthweight neonates.

Development and validation of an electrocardiographic artificial intelligence model for detection of peripartum cardiomyopathy.

BACKGROUND: This study used electrocardiogram data in conjunction with artificial intelligence methods as a noninvasive tool for detecting peripartum cardiomyopathy. OBJECTIVE: This study aimed to assess the efficacy of an artificial intelligence-based heart failure detection model for peripartum cardiomyopathy detection. STUDY DESIGN: We first built a deep-learning model for heart failure detection using retrospective data at the University of Tennessee Health Science Center. Cases were adult and nonpregnant female patients with a heart failure diagnosis; controls were adult nonpregnant female patients without heart failure. The model was then tested on an independent cohort of pregnant women at the University of Tennessee Health Science Center with or without peripartum cardiomyopathy. We also tested the model in an external cohort of pregnant women at Atrium Health Wake Forest Baptist. Key outcomes were assessed using the area under the receiver operating characteristic curve. We also repeated our analysis using only lead I electrocardiogram as an input to assess the feasibility of remote monitoring via wearables that can capture single-lead electrocardiogram data. RESULTS: The University of Tennessee Health Science Center heart failure cohort comprised 346,339 electrocardiograms from 142,601 patients. In this cohort, 60% of participants were Black and 37% were White, with an average age (standard deviation) of 53 (19) years. The heart failure detection model achieved an area under the curve of 0.92 on the holdout set. We then tested the ability of the heart failure model to detect peripartum cardiomyopathy in an independent University of Tennessee Health Science Center cohort of pregnant women and an external Atrium Health Wake Forest Baptist cohort of pregnant women. The independent University of Tennessee Health Science Center cohort included 158 electrocardiograms from 115 patients; our deep-learning model achieved an area under the curve of 0.83 (0.77-0.89) for this data set. The external Atrium Health Wake Forest Baptist cohort involved 80 electrocardiograms from 43 patients; our deep-learning model achieved an area under the curve of 0.94 (0.91-0.98) for this data set. For identifying peripartum cardiomyopathy diagnosed ≥10 days after delivery, the model achieved an area under the curve of 0.88 (0.81-0.94) for the University of Tennessee Health Science Center cohort and of 0.96 (0.93-0.99) for the Atrium Health Wake Forest Baptist cohort. When we repeated our analysis by building a heart failure detection model using only lead-I electrocardiograms, we obtained similarly high detection accuracies, with areas under the curve of 0.73 and 0.93 for the University of Tennessee Health Science Center and Atrium Health Wake Forest Baptist cohorts, respectively. CONCLUSION: Artificial intelligence can accurately detect peripartum cardiomyopathy from electrocardiograms alone. A simple electrocardiographic artificial intelligence-based peripartum screening could result in a timelier diagnosis. Given that results with 1-lead electrocardiogram data were similar to those obtained using all 12 leads, future studies will focus on remote screening for peripartum cardiomyopathy using smartwatches that can capture single-lead electrocardiogram data.

Stretch-induced compliance mechanism in pregnancy-induced cardiac hypertrophy and the impact of cardiovascular risk factors.

Pressure overload-induced hypertrophy compromises cardiac stretch-induced compliance (SIC) after acute volume overload (AVO). We hypothesized that SIC could be enhanced by physiological hypertrophy induced by pregnancy's chronic volume overload. This study evaluated SIC-cardiac adaptation in pregnant women with or without cardiovascular risk (CVR) factors. Thirty-seven women (1st trimester, 1stT) and a separate group of 31 (3rd trimester, 3rdT) women [healthy or with CVR factors (obesity and/or hypertension and/or with gestational diabetes)] underwent echocardiography determination of left ventricular end-diastolic volume (LVEDV) and E/e' before (T0), immediately after (T1), and 15 min after (T2; SIC) AVO induced by passive leg elevation. Blood samples for NT-proBNP quantification were collected before and after the AVO. Acute leg elevation significantly increased inferior vena cava diameter and stroke volume from T0 to T1 in both 1stT and 3rdT, confirming AVO. LVEDV and E/e' also increased immediately after AVO (T1) in both 1stT and 3rdT. SIC adaptation (T2, 15 min after AVO) significantly decreased E/e' in both trimesters, with additional expansion of LVEDV only in the 1stT. NT-pro-BNP increased slightly after AVO but only in the 1stT. CVR factors, but not parity or age, significantly impacted SIC cardiac adaptation. A distinct functional response to SIC was observed between 1stT and 3rdT, which was influenced by CVR factors. The LV of 3rdT pregnant women was hypertrophied, showing a structural limitation to dilate with AVO, whereas the lower LV filling pressure values suggest increased diastolic compliance.NEW & NOTEWORTHY The sudden increase of volume overload triggers an acute myocardial stretch characterized by an immediate rise in contractility by the Frank-Starling mechanism, followed by a progressive increase known as the slow force response. The present study is the first to characterize echocardiographically the stretch-induced compliance (SIC) mechanism in the context of physiological hypertrophy induced by pregnancy. A distinct functional adaptation to SIC was observed between first and third trimesters, which was influenced by cardiovascular risk factors.

Disease features and management of cardiomyopathies in women.

Over the last years, there has been a growing interest in the clinical manifestations and outcomes of cardiomyopathies in women. Peripartum cardiomyopathy is the only women-specific cardiomyopathy. In cardiomyopathies with X-linked transmission, women are not simply healthy carriers of the disorder, but can show a wide spectrum of clinical manifestations ranging from mild to severe manifestations because of heterogeneous patterns of X-chromosome inactivation. In mitochondrial disorders with a matrilinear transmission, cardiomyopathy is part of a systemic disorder affecting both men and women. Even some inherited cardiomyopathies with autosomal transmission display phenotypic and prognostic differences between men and women. Notably, female hormones seem to exert a protective role in hypertrophic cardiomyopathy (HCM) and variant transthyretin amyloidosis until the menopausal period. Women with cardiomyopathies holding high-risk features should be referred to a third-level center and evaluated on an individual basis. Cardiomyopathies can have a detrimental impact on pregnancy and childbirth because of the associated hemodynamic derangements. Genetic counselling and a tailored cardiological evaluation are essential to evaluate the likelihood of transmitting the disease to the children and the possibility of a prenatal or early post-natal diagnosis, as well as to estimate the risk associated with pregnancy and delivery, and the optimal management strategies.

Arrhythmias in Female Patients: Incidence, Presentation and Management.

There is a growing appreciation for differences in epidemiology, treatment, and outcomes of cardiovascular conditions by sex. Historically, cardiovascular clinical trials have under-represented females, but findings have nonetheless been applied to clinical care in a sex-agnostic manner. Thus, much of the collective knowledge about sex-specific cardiovascular outcomes result from post hoc and secondary analyses. In some cases, these investigations have revealed important sex-based differences with implications for optimizing care for female patients with arrhythmias. This review explores the available evidence related to cardiac arrhythmia care among females, with emphasis on areas in which important sex differences are known or suggested. Considerations related to improving female enrollment in clinical trials as a way to establish more robust clinical evidence for the treatment of females are discussed. Areas of remaining evidence gaps are provided, and recommendations for areas of future research and specific action items are suggested. The overarching goal is to improve appreciation for sex-based differences in cardiac arrhythmia care as 1 component of a comprehensive plan to optimize arrhythmia care for all patients.

Pregnancy and Reproductive Risk Factors for Cardiovascular Disease in Women.

Beyond conventional risk factors for cardiovascular disease, women face an additional burden of sex-specific risk factors. Key stages of a woman's reproductive history may influence or reveal short- and long-term cardiometabolic and cardiovascular trajectories. Early and late menarche, polycystic ovary syndrome, infertility, adverse pregnancy outcomes (eg, hypertensive disorders of pregnancy, gestational diabetes, preterm delivery, and intrauterine growth restriction), and absence of breastfeeding are all associated with increased future cardiovascular disease risk. The menopause transition additionally represents a period of accelerated cardiovascular disease risk, with timing (eg, premature menopause), mechanism, and symptoms of menopause, as well as treatment of menopause symptoms, each contributing to this risk. Differences in conventional cardiovascular disease risk factors appear to explain some, but not all, of the observed associations between reproductive history and later-life cardiovascular disease; further research is needed to elucidate hormonal effects and unique sex-specific disease mechanisms. A history of reproductive risk factors represents an opportunity for comprehensive risk factor screening, refinement of cardiovascular disease risk assessment, and implementation of primordial and primary prevention to optimize long-term cardiometabolic health in women.

Sex Differences and Similarities in Valvular Heart Disease.

As populations age worldwide, the burden of valvular heart disease has grown exponentially, and so has the proportion of affected women. Although rheumatic valve disease is declining in high-income countries, degenerative age-related causes are rising. Calcific aortic stenosis and degenerative mitral regurgitation affect a significant proportion of elderly women, particularly those with comorbidities. Women with valvular heart disease have been underrepresented in many of the landmark studies which form the basis for guideline recommendations. As a consequence, surgical referrals in women have often been delayed, with worse postoperative outcomes compared with men. As described in this review, a more recent effort to include women in research studies and clinical trials has increased our knowledge about sex-based differences in epidemiology, pathophysiology, diagnostic criteria, treatment options, outcomes, and prognosis.

Cardiovascular Disease Screening in Women: Leveraging Artificial Intelligence and Digital Tools.

Cardiovascular disease remains the leading cause of death in women. Given accumulating evidence on sex- and gender-based differences in cardiovascular disease development and outcomes, the need for more effective approaches to screening for risk factors and phenotypes in women is ever urgent. Public health surveillance and health care delivery systems now continuously generate massive amounts of data that could be leveraged to enable both screening of cardiovascular risk and implementation of tailored preventive interventions across a woman's life span. However, health care providers, clinical guidelines committees, and health policy experts are not yet sufficiently equipped to optimize the collection of data on women, use or interpret these data, or develop approaches to targeting interventions. Therefore, we provide a broad overview of the key opportunities for cardiovascular screening in women while highlighting the potential applications of artificial intelligence along with digital technologies and tools.

The Impact of Sex and Gender on Stroke.

Women face a disproportionate burden of stroke mortality and disability. Biologic sex and sociocultural gender both contribute to differences in stroke risk factors, assessment, treatment, and outcomes. There are substantial differences in the strength of association of stroke risk factors, as well as female-specific risk factors. Moreover, there are differences in presentation, response to treatment, and stroke outcomes in women. This review outlines current knowledge of impact of sex and gender on stroke, as well as delineates research gaps and areas for future inquiry.

Evaluation of Cardiac Function of Pregnant Women with High Blood Pressure during Gestation Period and Coupling of Hearts with Peripheral Vessels by Ultrasonic Cardiogram under Artificial Intelligence Algorithm.

The research was aimed at analyzing the value of the optimized eXtreme Gradient Boosting (XGBoost) algorithm-based ultrasound cardiogram images in the diagnosis of pregnant hypertension patients. A total of 145 pregnant women (85 cases suffered from hypertension disease during pregnancy and 60 other normal women were healthy) were selected as the reference to the comparison and analysis of ultrasound cardiac function parameter, common carotid artery parameter, and the coupling relationship between hearts and cervical vessels of pregnant hypertension patients. The results demonstrated ultrasound cardiac function parameter of pregnant hypertension patients as follows. The maximum volume of the left atrium (LAVmax) was 35.65 mm, left ventricular end-systolic volume (LVESV) was 31.07 mm, and left ventricular end-diastolic volume (LVEDV) was 88.73 mm. All the above indexes were obviously higher than those of the normal control group (P < 0.05). Besides, intima-media thickness (IMT) of common carotid artery (465.84 µm), pulse wave velocity (PWV) (8.09 m/s), pressure of turning point 1 from isovolumic contraction phase to ejection phase (PT1) (126.5 mmHg), arterial enhancement pressure (AP) (6.14 mmHg), and arterial pressure enhancement index (8.58%) were all significantly higher than those of the normal control group (P < 0.05). In addition, the correlation between the coupling (E/A) of hearts and carotid artery of pregnant hypertension patients and PWV was not obvious (r = -0.08432, P > 0.05). The results of the research indicated that intima-media inside carotid artery of pregnant hypertension patients thickened obviously, and it became less elastic compared with that of normal healthy pregnant women. What is more, cardiac morphological changes were manifested mainly as the enlargement of the left atrial chamber and the thickening of the interventricular septum. Volume load and blood flow velocity both increased, and left ventricular diastolic function was damaged. XGBoost algorithm-based ultrasound cardiogram images could improve the diagnostic effects of hypertension during pregnancy effectively.

The placenta and preeclampsia: villain or victim?

Preeclampsia is a disease whose characterization has not changed in the 150 years since the cluster of signs associated with the disorder were first described. Although our understanding of the pathophysiology of preeclampsia has advanced considerably since then, there is still little consensus regarding the true etiology of preeclampsia. As a consequence, preeclampsia has earned the moniker "disease of theories," predominantly because the underlying biological mechanisms linking clinical epidemiologic findings to observed organ dysfunction in preeclampsia are far from clear. Despite the lack of cohesive evidence, expert consensus favors the hypothesis that preeclampsia is a primary placental disorder. However, there is now emerging evidence that suboptimal maternal cardiovascular performance resulting in uteroplacental hypoperfusion is more likely to be the cause of secondary placental dysfunction in preeclampsia. Preeclampsia and cardiovascular disease share the same risk factors, preexisting cardiovascular disease is the strongest risk factor (chronic hypertension, congenital heart disease) for developing preeclampsia, and there are now abundant data from maternal echocardiography and angiogenic marker studies that cardiovascular dysfunction precedes the development of preeclampsia by several weeks or months. Importantly, cardiovascular signs and symptoms (hypertension, cerebral edema, cardiac dysfunction) predominate in preeclampsia at clinical presentation and persist into the postnatal period with a 30% risk of chronic hypertension in the decade after birth. Placental malperfusion caused by suboptimal maternal cardiovascular performance may lead to preeclampsia, thereby explaining the preponderance of cardiovascular drugs (aspirin, calcium, statins, metformin, and antihypertensives) in preeclampsia prevention strategies. Despite the seriousness of the maternal and fetal consequences, we are still developing sensitive screening, reliable diagnostic, effective therapeutic, or improvement strategies for postpartum maternal cardiovascular legacy in preeclampsia. The latter will only become clear with an acceptance and understanding of the cardiovascular etiology of preeclampsia.

An integrated model of preeclampsia: a multifaceted syndrome of the maternal cardiovascular-placental-fetal array.

Maternal tolerance of the semiallogenic fetus necessitates conciliation of competing interests. Viviparity evolved with a placenta to mediate the needs of the fetus and maternal adaptation to the demands of pregnancy and to ensure optimal survival for both entities. The maternal-fetal interface is imagined as a 2-dimensional porous barrier between the mother and fetus, when in fact it is an intricate multidimensional array of tissues and resident and circulating factors at play, encompassing the developing fetus, the growing placenta, the changing decidua, and the dynamic maternal cardiovascular system. Pregnancy triggers dramatic changes to maternal hemodynamics to meet the growing demands of the developing fetus. Nearly a century of extensive research into the development and function of the placenta has revealed the role of placental dysfunction in the great obstetrical syndromes, among them preeclampsia. Recently, a debate has arisen questioning the primacy of the placenta in the etiology of preeclampsia, asserting that the maternal cardiovascular system is the instigator of the disorder. It was the clinical observation of the high rate of preeclampsia in hydatidiform mole that initiated the focus on the placenta in the etiology of the disease. Over many years of research, shallow trophoblast invasion with deficient remodeling of the maternal spiral arteries into vessels of higher capacitance and lower resistance has been recognized as hallmarks of the preeclamptic milieu. The lack of the normal decrease in uterine artery resistance is likewise predictive of preeclampsia. In abdominal pregnancies, however, an extrauterine pregnancy develops without remodeling of the spiral arteries, yet there is reduced resistance in the uterine arteries and distant vessels, such as the maternal ophthalmic arteries. Proponents of the maternal cardiovascular model of preeclampsia point to the observed maternal hemodynamic adaptations to pregnancy and maladaptation in gestational hypertension and preeclampsia and how the latter resembles the changes associated with cardiac disease states. Recognition of the importance of the angiogenic-antiangiogenic balance between placental-derived growth factor and its receptor soluble fms-like tyrosine kinase-1 and disturbance in this balance by an excess of a circulating isoform, soluble fms-like tyrosine kinase-1, which competes for and disrupts the proangiogenic receptor binding of the vascular endothelial growth factor and placental-derived growth factor, opened new avenues of research into the pathways to normal adaptation of the maternal cardiovascular and other systems to pregnancy and maladaptation in preeclampsia. The significance of the "placenta vs heart" debate goes beyond the academic: understanding the mutuality of placental and maternal cardiac etiologies of preeclampsia has far-reaching clinical implications for designing prevention strategies, such as aspirin therapy, prediction and surveillance through maternal hemodynamic studies or serum placental-derived growth factor and soluble fms-like tyrosine kinase-1 testing, and possible treatments to attenuate the effects of insipient preeclampsia on women and their fetuses, such as RNAi therapy to counteract excess soluble fms-like tyrosine kinase-1 produced by the placenta. In this review, we will present an integrated model of the maternal-placental-fetal array that delineates the commensality among the constituent parts, showing how a disruption in any component or nexus may lead to the multifaceted syndrome of preeclampsia.