Increased utilization of the hybrid procedure is not associated with improved early survival for newborns with hypoplastic left heart syndrome: a single-centre experience.

OBJECTIVES: The primary objectives were to examine utilization of the Hybrid versus the Norwood procedure for patients with hypoplastic left heart syndrome or variants and the impact on hospital mortality. The Hybrid procedure was 1st used at our institution in 2004. METHODS: Review of all subjects undergoing the Norwood or Hybrid procedure between 1 January 1984 and 31 December 2022. The study period was divided into 8 eras: era 1, 1984-1988; era 2, 1989-1993; era 3, 1994-1998; era 4, 1999-2003; era 5, 2004-2008; era 6, 2009-2014; era 7, 2015-2018 and era 8, 2019-2022. The primary outcome was in-hospital mortality. Mortality rates were computed using standard binomial proportions with 95% confidence intervals. Rates across eras were compared using an ordered logistic regression model with and adjusted using the Tukey-Kramer post-hoc procedure for multiple comparisons. In the risk-modelling phase, logistic regression models were specified and tested. RESULTS: The Norwood procedure was performed in 1899 subjects, and the Hybrid procedure in 82 subjects. Use of the Hybrid procedure increased in each subsequent era, reaching 30% of subjects in era 8. After adjustment for multiple risk factors, use of the Hybrid procedure was significantly and positively associated with hospital mortality. CONCLUSIONS: Despite the increasing use of the Hybrid procedure, overall mortality for the entire cohort has plateaued. After adjustment for risk factors, use of the Hybrid procedure was significantly and positively associated with mortality compared to the Norwood procedure.

Prospective Evaluation of High Titer Autoantibodies and Fetal Home Monitoring in the Detection of Atrioventricular Block Among Anti-SSA/Ro Pregnancies.

OBJECTIVE: This prospective study of pregnant patients, Surveillance To Prevent AV Block Likely to Occur Quickly (STOP BLOQ), addresses the impact of anti-SSA/Ro titers and utility of ambulatory monitoring in the detection of fetal second-degree atrioventricular block (AVB). METHODS: Women with anti-SSA/Ro autoantibodies by commercial testing were stratified into high and low anti-52-kD and/or 60-kD SSA/Ro titers applying at-risk thresholds defined by previous evaluation of AVB pregnancies. The high-titer group performed fetal heart rate and rhythm monitoring (FHRM) thrice daily and weekly/biweekly echocardiography from 17-26 weeks. Abnormal FHRM prompted urgent echocardiography to identify AVB. RESULTS: Anti-52-kD and/or 60-kD SSA/Ro met thresholds for monitoring in 261 of 413 participants (63%); for those, AVB frequency was 3.8%. No cases occurred with low titers. The incidence of AVB increased with higher levels, reaching 7.7% for those in the top quartile for anti-60-kD SSA/Ro, which increased to 27.3% in those with a previous child who had AVB. Based on levels from 15 participants with paired samples from both an AVB and a non-AVB pregnancy, healthy pregnancies were not explained by decreased titers. FHRM was considered abnormal in 45 of 30,920 recordings, 10 confirmed AVB by urgent echocardiogram, 7 being second-degree AVB, all <12 hours from normal FHRM and within another 0.75 to 4 hours to echocardiogram. The one participant with second/third-degree and two participants with third-degree AVB were diagnosed by urgent echocardiogram >17 to 72 hours from an FHRM. Surveillance echocardiograms detected no AVB when the preceding interval FHRM recordings were normal. CONCLUSION: High-titer antibodies are associated with an increased incidence of AVB. Anti-SSA/Ro titers remain stable over time and do not explain the discordant recurrence rates, suggesting that other factors are required. Fetal heart rate and rhythm (FHRM) with results confirmed by a pediatric cardiologist reliably detects conduction abnormalities, which may reduce the need for serial echocardiograms.

Patterns of Aortic Dilation in Tetralogy of Fallot: An Analysis of 100 Fetal Echocardiograms Compared With Matched Controls.

Background Although aortic dilation is common in tetralogy of Fallot (TOF), its progression and risk of dissection are not well understood. The mechanism of dilation is primarily attributed to increased flow in utero; an alternative is unequal septation of the truncus arteriosus resulting in a larger aorta and inherently hypoplastic pulmonary artery (PA). If the latter is true, we hypothesize the aorta to PA ratio in TOF is stable throughout gestation, and sums of great artery dimensions are similar to controls. Methods and Results We performed a single-center retrospective study of fetuses with TOF (2014-2020) and matched controls. We compared sums of diameters, circumferences, and cross-sectional areas of the aorta and PA and evaluated the aorta to PA ratio across gestation in 2 TOF subtypes: pulmonary stenosis and atresia (TOF-PA). There were 100 echocardiograms with TOF (36% TOF-PA) with median gestational age of 31 weeks (interquartile range 26.5-34.4) and median maternal age of 34 years (interquartile range 30-37). There were no differences in sums of great artery dimensions between TOF-pulmonary stenosis and controls. In TOF-PA, sums were significantly lower than controls (P values <0.01). The aorta to PA ratio was stable throughout gestation (Pearson's r=0.08 [95% CI, -0.12 to 0.27], -0.06 [95% CI, -0.25 to 0.14]). Conclusions The aorta in fetal TOF is large but grows proportionally throughout gestation, with sums of great artery dimensions similar to controls. TOF-PA appears distinct from TOF-pulmonary stenosis (with smaller sums), warranting further investigation. In conclusion, our findings suggest an intrinsic developmental mechanism contributes to aortic dilation in TOF.

Impact of Ventricular Dysfunction and Atrioventricular Valve Regurgitation on Pre-Fontan Attrition.

BACKGROUND: There is a significant incidence of pre-Fontan attrition-defined as failure to undergo Fontan completion-after superior cavopulmonary connection. This study investigated the impact of at least moderate ventricular dysfunction (VD) and atrioventricular valve regurgitation (AVVR) on pre-Fontan attrition. METHODS: This single-center retrospective cohort study included all infants who underwent Norwood palliation from 2008 to 2020 and subsequently underwent superior cavopulmonary connection. Pre-Fontan attrition was defined as death, listing for heart transplantation before Fontan completion, or unsuitability for Fontan completion. The study's secondary outcome was transplant-free survival. RESULTS: Pre-Fontan attrition occurred in 34 of 267 patients (12.7%). Isolated VD was not associated with attrition. However, patients with isolated AVVR had 5 times the odds of attrition (odds ratio, 5.4; 95% CI 1.8-16.2), and patients with both VD and AVVR had 20 times the odds of attrition (odds ratio, 20.1; 95% CI 7.7-52.8) compared with patients without VD or AVVR. Only patients with both VD and AVVR had significantly worse transplant-free survival compared with patients without VD or AVVR (hazard ratio, 7.7; 95% CI 2.8-21.6). CONCLUSIONS: The additive effect of VD and AVVR is a powerful contributor to pre-Fontan attrition. Future research investigating therapies that can mitigate the degree of AVVR may help improve Fontan completion rates and long-term outcomes.

Combined ventricular dysfunction and atrioventricular valve regurgitation after the Norwood procedure are associated with attrition prior to superior cavopulmonary connection.

Background: Infants with hypoplastic left heart syndrome (HLHS) or a variant are at risk of ventricular dysfunction (VD) and atrioventricular valve regurgitation (AVVR) prior to superior cavopulmonary connection (SCPC). Although the impact of these complications in isolation has been described, their effect in combination on attrition is poorly defined. Methods: A retrospective observational study of patients with HLHS or variants undergoing a Norwood procedure between 2008 and 2020 at a single center was performed. VD and AVVR were defined as moderate or severe when seen on 2 sequential echocardiograms outside the perioperative period. Attrition was defined as death, listing for heart transplant, or unsuitability for SCPC or transplant. Descriptive statistics and regression models were used for analysis. Results: A total of 397 patients were included, of whom 75% had HLHS and 57% had received a Blalock-Thomas-Taussig shunt. Isolated VD occurred in 9% of patients, AVVR occurred in 13%, and both occurred in 6%. Attrition prior to SCPC occurred in 19% of the overall cohort, in 52% of patients with combined VD and AVVR (odds ratio [OR], 5.2; 95% confidence interval [CI], 2.3-12.0; P < .01), 26% of those with VD (OR, 1.5; 95% CI, 0.7-3.3; P = .32), 25% of those with AVVR (OR, 1.5; 95% CI, 0.7-2.9; P = .27), and 15% in those with neither (OR, 0.3; 95% CI, 0.2-0.6; P < .01). Other factors associated with attrition included prematurity, total bypass time at Norwood, and extracorporeal membrane oxygenation after Norwood, whereas later year of Norwood was protective (P < .01 for all). Conclusions: The presence of combined VD and AVVR markedly increases the likelihood of attrition prior to SCPC, identifying a high-risk group.

Novel approaches to the surveillance and management of fetuses at risk for anti-Ro/SSA mediated atrioventricular block.

Approximately one percent of pregnant women will produce anti-Sjogren's syndrome-related antigen A (anti-Ro/SSA) antibodies. Of these pregnancies, one to three percent will have a fetus that develops atrioventricular (AV) block. Earlier stages of AV block (1° or 2°) may respond to anti-inflammatory treatment, but complete (3°) AV block, which can occur within 24 hours of a normal fetal rhythm, is likely irreversible and carries substantial risk for significant morbidity and for mortality. Emerging data has shown that ambulatory fetal heart rhythm monitoring can detect the transition period from normal rhythm to 2° AV block, the time during which treatment with IVIG and dexamethasone can potentially restore normal sinus rhythm. Weekly or biweekly fetal echocardiograms occur too infrequently to detect this transition period but may still be useful in diagnosing extranodal anti-Ro antibody mediated cardiac disease. In this review, we evaluate the most innovative methods for surveillance and treatment of this disease.

Left Ventricular Measurements and Strain in Pediatric Patients Evaluated for Systemic Hypertension and the Effect of Adequate Anti-hypertensive Treatment.

Pediatric hypertension (HTN) is an epidemic that is associated with HTN in adulthood and adverse cardiovascular outcomes. We hypothesized that children with HTN would have left ventricular (LV) hypertrophy and abnormal LV global longitudinal strain (GLS) on echocardiogram and that these values would differ by weight, race, and HTN treatment. Data were collected from first visits to the HTN Program from 12/2011 to 9/2018, excluding patients with cardiac disease or heart transplantation. LV measurements including LV mass index (LVMI), LV GLS, and diastolic indices were compared between groups. Multivariable logistic regression was used to identify risk factors for an abnormal LVMI. There were 212 patients with an interquartile age range of 13-18 years. On univariate analysis, LVMI was higher in hypertensive, obese, and African American patients. LV strain was less negative in obese and African American patients. Adequately treated patients with HTN had a higher LVMI and a higher E/e' ratio compared to patients with no HTN. On multivariate analysis, only obesity was associated with an LVMI ≥ 95th percentile (OR 2.9, 95% CI 1.4, 5.8). LVMI is higher in hypertensive, obese, and African American patients; however, in the multivariate analysis, obesity was the only independent risk factor for an abnormal LVMI. LVMI was still higher in those adequately treated for HTN compared to patients without HTN, possibly due to concomitant obesity. Future studies should focus on subclinical changes in LV performance seen in obese and hypertensive patients and the impact on long-term health.

Maternal Hyperoxygenation Testing in Fetuses with Hypoplastic Left-Heart Syndrome: Association with Postnatal Atrial Septal Restriction.

INTRODUCTION: In fetuses with hypoplastic left-heart syndrome (HLHS), maternal hyperoxygenation (MHO) may aid risk stratification. We hypothesized that pulmonary vein (Pvein) velocity time integral (VTI) change with MHO would more reliably identify neonates who undergo emergent atrial septoplasty (EAS) than changes in pulmonary arterial pulsatility index (PA PI). METHODS: Fetuses with HLHS who underwent MHO testing at our institution between 2014 and 2019 were identified. Data were reviewed in a blinded, retrospective manner. Pvein VTI ratio (prograde:retrograde) was calculated. The primary outcome was neonatal EAS. RESULTS: Twenty-seven HLHS fetuses underwent MHO, and 5 (19%) underwent EAS. Without MHO, a Pvein VTI ratio <3 conferred 60% sensitivity and 100% specificity for EAS. With MHO, a Pvein VTI ratio <6.5 conferred 100% sensitivity and specificity. For an intermediate group of fetuses with a baseline Pvein VTI ratio 3-7, the ratio decrease with MHO conferred 100% sensitivity and specificity. Compared to the Pvein VTI ratio, PA PI was less accurate in identifying EAS neonates. DISCUSSION/CONCLUSION: Addition of MHO appears to improve the diagnostic ability of the Pvein VTI ratio to identify HLHS fetuses who undergo EAS. The Pvein VTI ratio change may more accurately identify fetuses who undergo EAS than change in PA PI and has less interobserver variability.

Attrition between the superior cavopulmonary connection and the Fontan procedure in hypoplastic left heart syndrome.

OBJECTIVE: We investigated the incidence and predictors of failure to undergo the Fontan in children with hypoplastic left heart syndrome who survived superior cavopulmonary connection. METHODS: The cohort consists of all patients with hypoplastic left heart syndrome who survived to hospital discharge after superior cavopulmonary connection between 1988 and 2017. The primary outcome was attrition, which was defined as death, nonsuitability for the Fontan, or cardiac transplantation before the Fontan. Subjects were excluded if they were awaiting the Fontan, were lost to follow-up, or underwent biventricular repair. The study period was divided into 4 eras based on changes in operative or medical management. Attrition was estimated with 95% confidence intervals, and predictors were identified using adjusted, logistic regression models. RESULTS: Of the 856 hospital survivors after superior cavopulmonary connection, 52 died, 7 were deemed unsuitable for Fontan, and 12 underwent or were awaiting heart transplant. Overall attrition was 8.3% (71/856). Attrition rate did not change significantly across eras. A best-fitting multiple logistic regression model was used, adjusting for superior cavopulmonary connection year and other influential covariates: right ventricle to pulmonary artery shunt at Norwood (P < .01), total support time at superior cavopulmonary connection (P < .01), atrioventricular valve reconstruction at superior cavopulmonary connection (P = .02), performance of other procedures at superior cavopulmonary connection (P = .01), and length of stay after superior cavopulmonary connection (P < .01). CONCLUSIONS: In this study spanning more than 3 decades, 8.3% of children with hypoplastic left heart syndrome failed to undergo the Fontan after superior cavopulmonary connection. This attrition rate has not decreased over 30 years. Use of a right ventricle to pulmonary artery shunt at the Norwood procedure was associated with increased attrition.

Decreasing Interstage Mortality After the Norwood Procedure: A 30-Year Experience.

Background The superior cavo-pulmonary connection was introduced at our institution in 1988 for infants undergoing surgery for hypoplastic left heart syndrome. Patients with hypoplastic left heart syndrome remain at high risk for mortality in the time period between the Norwood procedure and the superior cavo-pulmonary connection. The primary objectives of this study were to compare interstage mortality across 4 eras and analyze factors that may impact interstage mortality. Methods and Results Patients with hypoplastic left heart syndrome who underwent the Norwood procedure, were discharged from the hospital, and were eligible for superior cavo-pulmonary connection between January 1, 1988, and December 31, 2017, were included. The study period was divided into 4 eras based on changes in operative or medical management. Mortality rates were estimated with 95% CIs. Adjusted and unadjusted logistic regression models were used to identify risk factors for mortality. There were 1111 patients who met the inclusion criteria. Overall, interstage mortality was 120/1111 (10.8%). Interstage mortality was significantly lower in era 4 relative to era 1 (4.6% versus 13.4%; P=0.02) during the time that age at the superior cavo-pulmonary connection was the lowest (135 days; P<0.01) and the interstage monitoring program was introduced. In addition, use of the right ventricle to pulmonary artery shunt was associated with decreased interstage mortality (P=0.02) and was more routinely practiced in era 4. Conclusions During this 30-year experience, the risk of interstage mortality decreased significantly in the most recent era. Factors that coincide with this finding include younger age at superior cavo-pulmonary connection, introduction of an interstage monitoring program, and increased use of the right ventricle to pulmonary artery shunt.

Outcomes for the superior cavopulmonary connection in children with hypoplastic left heart syndrome: a 30-year experience.

OBJECTIVES: The objective of this study was to estimate hospital mortality and length of stay (LOS) for children with hypoplastic left heart syndrome undergoing superior cavopulmonary connection (SCPC). METHODS: All hypoplastic left heart syndrome interstage survivors who underwent SCPC between 1 January 1988 and 31 December 2017 were included. The study period was divided into 4 eras based on changes in operative or medical management. Mortality rates were estimated using standard binomial proportions. Adjusted and unadjusted logistic regression models were used to identify risk factors for mortality and LOS. RESULTS: The most common procedures for the cohort (n = 958) were Hemi-Fontan (57.3%) or Bidrectional Glenn shunt (35.7%). The mortality was 4.1% overall and decreased in all 3 later eras compared to era 1. Factors associated with mortality in a multiple covariate model included longer total support time, earlier gestational age, longer LOS at the Norwood Procedure and need for additional procedures. Overall, the median LOS was 7.0 days with a decrease from eras 1 to 2 and plateaued in eras 3 and 4. Predictors of longer LOS included genetic anomaly, longer Norwood LOS, additional procedures, lower weight at surgery and longer total support time. The type of SCPC was not associated with mortality or LOS. CONCLUSIONS: In this large cohort of patients with hypoplastic left heart syndrome undergoing SCPC, hospital mortality has decreased significantly. LOS initially declined but plateaued in recent eras. The risk factors for mortality and longer LOS are related to patient and procedural complexity, especially the need for additional procedures at the time of SCPC.

The Impact of Early Recognition and Treatment of Systemic Hypertension on Reducing Blood Pressure: The Hypertension and Vascular Evaluation Program.

This study aimed to evaluate the effect of an outpatient systemic hypertension program and associated factors with attending recommended follow-up visit. All visits were tracked in the program, 2011 to 2018. We examined patient characteristics by follow-up status and changes in systolic blood pressure (SBP) and the risk of hypertension in follow-up patients using a mixed-effects regression model. Among 310 patients with first visits, 113 patients returned for a follow-up visit. Patients who did not attend a follow-up were older and less likely to have a severe chronic condition or a family history of hypertension than followed-up patients. The risk of hypertension was significantly reduced by the number of follow-up visits (odds ratio = 0.53, 95% confidence interval = 0.31-0.92). Adolescent SBP and body mass index percentiles decreased with more follow-up visits. As the risk of hypertension is significantly reduced with follow-up visits, additional effort should be made to improve the likelihood of follow-up attendance.

Clinical Innovation: A Multidisciplinary Program for the Diagnosis and Treatment of Systemic Hypertension in Children and Adolescents.

Pediatric systemic hypertension (HTN) is underdiagnosed and undertreated. The Divisions of Cardiology and Nephrology at our institution developed a comprehensive outpatient HTN program to (1) screen children at risk for HTN, (2) assess cardiovascular health, and (3) optimize medical management. We report our findings during all initial visits (n = 304) from December 2011 to September 2018. Of the cohort, 38% were obese and 36% reported little to no exercise. More than half of patients ≥11 years old did not have recommended lipid screening. When evaluating ambulatory blood pressure monitoring results, clinic blood pressure did not accurately diagnose patients with or without HTN and many patients on antihypertensive medications were inadequately treated. Visit recommendations included addition of or changes to antihypertensive medication in 35% of patients. A multidisciplinary program dedicated to pediatric HTN helps screen patients who are at risk. Ambulatory blood pressure monitoring identifies HTN in patients with normal clinic blood pressure and those on antihypertensive medication.

Thirty years and 1663 consecutive Norwood procedures: Has survival plateaued?

OBJECTIVE: Hypoplastic left heart syndrome is one of the most common and challenging lesions requiring surgical intervention in the neonatal period. The Norwood procedure for hypoplastic left heart syndrome was first reported in 1983. The objective of this study was to describe early outcomes after the Norwood procedure at a single institution over 30 years. METHODS: This retrospective cohort study included all patients with hypoplastic left heart syndrome (and variants) who underwent the Norwood procedure between January 1984 and May 2014 at a single institution. The study period was divided into 6 eras: era 1, 1984 to 1988; era 2, 1989 to 1993; era 3, 1994 to 1998; era 4, 1999 to 2003; era 5, 2004 to 2008; and era 6, 2009 to 2014. The primary outcome was in-hospital mortality after the Norwood procedure. Binomial point estimates complete with 95% confidence intervals (CL0.95) were computed for the entire cohort and by era. RESULTS: During the study period, 1663 infants underwent the Norwood procedure. Overall in-hospital mortality was 25.9% (CL0.95, 23.8-28.0). Mortality by chronologic era was 40.4% (CL0.95, 34.9-45.9), 33.6% (CL0.95, 29.2-37.9), 28.7% (CL0.95, 22.8-34.6), 14.9% (CL0.95, 10.4-19.3), 11.2% (CL0.95, 7.4-15.0), and 15.7% (CL0.95, 10.3-21.1). Survival was improved in eras 4 to 6 compared with eras 1 to 3 (P all < .03). Anomalous pulmonary drainage, moderate to severe atrioventricular valve regurgitation, lower birth weight, earlier era, younger gestational age, genetic anomaly, preterm birth, race other than white or African-American, and lower weight at the Norwood procedure were associated with increased mortality. Mortality was greatest in patients with 3 or more risk factors. In the best-fitting multiple covariate model, anomalous pulmonary venous drainage, gestational age in weeks, genetic anomaly, and race other than white and African American were statistically significant contributors, after adjusting for era. CONCLUSIONS: Survival after the Norwood procedure has plateaued despite improvements in diagnosis, perioperative care, and surgical techniques. Nonmodifiable patient characteristics are important determinants of the risk of mortality.

The association of elevated maternal genetic risk scores for hypertension, type 2 diabetes and obesity and having a child with a congenital heart defect.

BACKGROUND: Maternal hypertension, type 2 diabetes (T2D) and obesity are associated with an increased risk of having offspring with conotruncal heart defects (CTDs). Prior studies have identified sets of single nucleotide polymorphisms (SNPs) that are associated with risk for each of these three adult phenotypes. We hypothesized that these same SNPs are associated with maternal risk of CTDs in offspring. METHODS AND RESULTS: We evaluated the parents of children with a CTD ascertained from the Children's Hospital of Philadelphia (n = 466) and by the Pediatric Cardiac Genomic Consortium (n = 255). We used a family-based design to assess the association between CTDs and the maternal genotype for individual hypertension, T2D, and obesity-related SNPs and found no association between CTDs and the maternal genotype for any individual SNP. In addition, we calculated genetic risk scores (GRS) for hypertension, T2D, and obesity using previously published GRS formulas. When comparing the GRS of mothers to fathers, there were no statistically significant differences in the mean for the combined GRS or the GRS for each individual condition. However, when we categorized the mothers and fathers of cases with CTDs as having high (>95th percentile) or low (≤95th percentile) scores, compared to fathers, mothers had almost two times the odds of having a high GRS for hypertension (OR 1.7, 95% CI 1.0, 2.8) and T2D (OR 1.8, 95% CI 1.1, 3.1). CONCLUSIONS: Our results support a link between maternal genetic risk for hypertension/T2D and CTDs in their offspring. These associations might be independent of maternal phenotype at conception.

Characterising adequacy or inadequacy of the borderline left ventricle: what tools can we use?

Borderline left ventricle refers to a spectrum of left ventricular underdevelopment, typically associated with other cardiac anomalies. The left ventricle may be mildly hypoplastic, as is sometimes seen accompanying aortic coarctation, or it can be severely hypoplastic, as is seen in hypoplastic left heart syndrome. For patients with a borderline left ventricle that is at either extreme, the treatment decision is relatively straightforward. Those with the most severe form of left ventricle hypoplasia will require single ventricle palliation or cardiac transplantation, whereas those with the mildest form may not need any intervention. It is the management strategy of children that fall within the grey zone of the spectrum, which continues to be controversial and remains variable within and among different institutions. Cardiac diseases with associated left ventricle hypoplasia include critical aortic stenosis, mitral stenosis, coarctation of the aorta, arch hypoplasia, cor triatriatum, unbalanced common atrioventricular canal, Shone's complex, total anomalous pulmonary venous return, and complex conotruncal abnormalities. In this review, we will discuss the assessment and management of infants with borderline left ventricle with critical aortic stenosis or arch obstruction and associated mitral anomalies.

Sustained Domestic Vector Exposure Is Associated With Increased Chagas Cardiomyopathy Risk but Decreased Parasitemia and Congenital Transmission Risk Among Young Women in Bolivia.

BACKGROUND: We studied women and their infants to evaluate risk factors for congenital transmission and cardiomyopathy in Trypanosoma cruzi-infected women. METHODS: Women provided data and blood for serology and quantitative polymerase chain reaction (PCR). Infants of infected women had blood tested at 0 and 1 month by microscopy, PCR and immunoblot, and serology at 6 and 9 months. Women underwent electrocardiography (ECG). RESULTS: Of 1696 women, 456 (26.9%) were infected; 31 (6.8%) transmitted T. cruzi to their infants. Women who transmitted had higher parasite loads than those who did not (median, 62.0 [interquartile range {IQR}, 25.8-204.8] vs 0.05 [IQR, 0-29.6]; P < .0001). Transmission was higher in twin than in singleton births (27.3% vs 6.4%; P = .04). Women who had not lived in infested houses transmitted more frequently (9.7% vs 4.6%; P = .04), were more likely to have positive results by PCR (65.5% vs 33.9%; P < .001), and had higher parasite loads than those who had lived in infested houses (median, 25.8 [IQR, 0-64.1] vs 0 [IQR, 0-12.3]; P < .001). Of 302 infected women, 28 (9.3%) had ECG abnormalities consistent with Chagas cardiomyopathy; risk was higher for older women (odds ratio [OR], 1.06 [95% confidence interval {CI}, 1.01-1.12] per year) and those with vector exposure (OR, 3.7 [95% CI, 1.4-10.2]). We observed a strong dose-response relationship between ECG abnormalities and reported years of living in an infested house. CONCLUSIONS: We hypothesize that repeated vector-borne infection sustains antigen exposure and the consequent inflammatory response at a higher chronic level, increasing cardiac morbidity, but possibly enabling exposed women to control parasitemia in the face of pregnancy-induced Th2 polarization.