Pediatric Heart Network Trial of Losartan vs. Atenolol in Children and Young Adults with Marfan Syndrome: Impact on Prescription Practices.

The Pediatric Heart Network (PHN) trial showed similar efficacy of ß-blockers (BB) and angiotensin receptor blockers (ARB) for aortic root dilation in Marfan syndrome, but the impact on prescription practices is unknown. We hypothesized BB and ARB prescriptions would increase after the trial results were published (2014). Prescription data (2007-2016) were obtained from outpatient encounters (IBM Marketscan) for Marfan syndrome patients (6 months-25 years old). Excluding 2014 as a washout period, we analyzed two intervals: 2007-2013 and 2015-2016. Medication categories included BB, ARB, angiotensin converting enzyme inhibitors (ACEI), combination (BB/ARB and/or BB/ACEI), and no drug. Interrupted time-series analysis assessed immediate level change after publication and change in slope for the trend pre- and post-publication. Odds ratios (OR) and 95% confidence intervals from logistic regressions and generalized estimating equation methods accounted for correlation of prescriptions within patients. In 1499 patients (age 14.1 ± 6.1 years, 59% female) seen 2007-2013, BB trended lower [OR 0.91 (0.89, 0.93), p < 0.001] and ARB trended higher [OR 1.12 (1.07, 1.18), p < 0.001], while combination, ACEI, and no drug remained stable. This trend persisted, but was not significant, for BB [OR 0.54 (0.27, 1.08), p = 0.37] and ARB [OR 1.91 (0.55, 6.69), p = 0.31] in 2015-2016. Combination, ACEI, and no drug remained similar. In short term follow-up, changes in prescription practices following publication of the PHN trial were not statistically significant. This may be due to a change seen prior to publication with early adoption of ARBs that was maintained after confirmation of their effectiveness.

Association between pregnancy and long-term cardiac outcomes in individuals with congenital heart disease.

BACKGROUND: As early life interventions for congenital heart disease improve, more patients are living to adulthood and are considering pregnancy. Scoring and classification systems predict the maternal cardiovascular risk of pregnancy in the context of congenital heart disease, but these scoring systems do not assess the potential subsequent risks following pregnancy. Data on the long-term cardiac outcomes after pregnancy are unknown for most lesion types. This limits the ability of healthcare practitioners to thoroughly counsel patients who are considering pregnancy in the setting of congenital heart disease. OBJECTIVE: We aimed to evaluate the association between pregnancy and the subsequent long-term cardiovascular health of individuals with congenital heart disease. STUDY DESIGN: This was a retrospective longitudinal cohort study of individuals identifying as female who were receiving care in two adult congenital heart disease centers from 2014 to 2019. Patient data were abstracted longitudinally from a patient age of 15 years (or from the time of entry into the healthcare system) to the conclusion of the study, death, or exit from the healthcare system. The primary endpoint, a composite adverse cardiac outcome (death, stroke, heart failure, unanticipated cardiac surgery, or a requirement for a catheterized procedure), was compared between parous (at least one pregnancy >20 weeks' gestation) and nulliparous individuals. By accounting for differences in the follow-up, the effect of pregnancy was estimated based on the time to the composite adverse outcome in a proportional hazards regression model adjusted for the World Health Organization class, baseline cardiac medications, and number of previous sternotomies. Participants were also categorized according to their lesion type, including septal defects (ventricular septal defects, atrial septal defects, atrioventricular septal defects, or atrioventricular canal defects), right-sided valvular lesions, left-sided valvular lesions, complex cardiac anomalies, and aortopathies, to evaluate if there is a differential effect of pregnancy on the primary outcome when adjusting for lesion type in a sensitivity analysis. RESULTS: Overall, 711 individuals were eligible for inclusion; 209 were parous and 502 nulliparous. People were classified according to the World Health Organization classification system with 86 (12.3%) being classified as class I, 76 (10.9%) being classified as class II, 272 (38.9%) being classified as class II to III, 155 (22.1%) being classified as class III, and 26 (3.7%) being classified as class IV. Aortic stenosis, bicuspid aortic valve, dilated ascending aorta or aortic root, aortic regurgitation, and pulmonary insufficiency were more common in parous individuals, whereas dextro-transposition of the great arteries, Turner syndrome, hypoplastic right heart, left superior vena cava, and other cardiac diagnoses were more common in nulliparous individuals. In multivariable modeling, pregnancy was associated with the composite adverse cardiac outcome (36.4%% vs 26.1%%; hazard ratio, 1.83; 95% confidence interval, 1.25-2.66). Parous individuals were more likely to have unanticipated cardiac surgery (28.2% vs 18.1%; P=.003). No other individual components of the primary outcome were statistically different between parous and nulliparous individuals in cross-sectional comparisons. The association between pregnancy and the primary outcome was similar in a sensitivity analysis that adjusted for cardiac lesion type (hazard ratio, 1.61; 95% confidence interval, 1.10-2.36). CONCLUSION: Among individuals with congenital heart disease, pregnancy was associated with an increase in subsequent long-term adverse cardiac outcomes. These data may inform counseling of individuals with congenital heart disease who are considering pregnancy.

Management of the pregnant woman with Marfan syndrome complicated by ascending aorta dilation.

INTRODUCTION: Marfan syndrome is a disorder of connective tissue associated with progressive dilation of the aorta and potential risk for aortic dissection. Women with Marfan syndrome who are, or wish to become, pregnant represent a unique and challenging patient population due to a risk for accelerated aortic growth and aortic dissection during pregnancy. Risk for aortic complications during pregnancy is related to the dimensions of the ascending aorta. Women with an aortic diameter ≥4.5 cm at the start of pregnancy are at higher risk for aortic dissection, and an aortic dimension >4.0 cm is considered a relative contraindication to pregnancy in the setting of Marfan syndrome. CONCLUSION: Multidisciplinary care involving specialists familiar with Marfan syndrome should be emphasized before, during, and after pregnancy with the involvement of Maternal Fetal Medicine, Genetics, Cardiology, Cardiothoracic Surgery, Anesthesia, and other specialties on a case-by-case basis. We review the important aspects of the evaluation and management of pregnant women with Marfan syndrome.

Predicting left ventricular recovery after replacement of a regurgitant aortic valve in pediatric and young adult patients: is it ever too late?

The management of pediatric and adolescent patients with pure aortic valve regurgitation remains challenging and controversial (Christos et al., Eur J Cardiothorac Surg 17:125-133, 2000; Gersony and Sommerville, ACC Curr J Rev 31:97-98, 2000; Hasaniya et al., J Thorac Cardiovasc Surg 127:970-974, 2004; Sabet et al., Mayo Clin 74:14-26, 1999; Tweddell et al., J Thorac Cardiovasc Surg 129:551-558, 2005). We evaluated pediatric and young adult patients who underwent aortic valve replacement (AVR) primarily for aortic regurgitation in an effort to identify preoperative echocardiographic variables that are predictive of left ventricular (LV) recovery following AVR. Twenty-one patients with severe aortic valve regurgitation who underwent AVR were identified. Retrospective chart review for each patient was performed and transthoracic echocardiograms prior to and 6-months after AVR were analyzed. Improvement in LV size based on preoperative LV end-systolic dimension index when compared to 6-months post-AVR was observed in 68% of the patients. Patients with persistent dilation of their left ventricles had a greater preoperative LV end-systolic dimension index (p ≤ 0.05), a greater preoperative LV end-systolic dimension z-score (p ≤ 0.002), and a lower preoperative ejection fraction (EF) (p ≤ 0.001). A similar trend was present between the two cohorts in regards to LV end-diastolic parameters (LV end-diastolic dimension index and z-score), with patients with abnormal LV size at 6-month follow-up having larger preoperative dimensions. Increasing LV systolic dimensions and declining EF appear to be predictors of poor LV recovery following AVR in pediatric and young adult patients. LV end-systolic indices appear to be more predictive than LV end-diastolic indices. AVR should be performed prior to severe LV enlargement defined as an LV end-systolic dimension z-score >4.5.

Pediatric Infective Endocarditis: A Clinical Update.

This article presents updates and an overview of pediatric infective endocarditis. It includes a discussion of presentation of illness, diagnosis of this disorder, differential diagnosis, treatment recommendation, and associated morbidity and mortality.

Outcomes of a hepatitis C screening protocol in at-risk adults with prior cardiac surgery.

BACKGROUND: Symptoms associated with hepatitis C infection often do not develop until an advanced stage of liver disease. Prior to 1992, reliable testing for hepatitis C was unavailable, resulting in potential patient exposure during cardiopulmonary bypass. As the hepatitis C prevalence in our center was unknown, a screening protocol for patients who underwent surgery prior to 1992 was developed. METHODS: Patients evaluated in the Wisconsin Adult Congenital Heart Disease program who underwent surgery prior to 1992 were screened for hepatitis C as part of their initial clinical evaluation. The hepatitis C-positive patients were assessed for risk factors, level of hepatic involvement, whether they received treatment, and whether viral clearance was obtained. RESULTS: A total of 147 patients (53% male) underwent testing. Seven (4.8%) patients had evidence of chronic hepatitis C infection, which is higher than the Wisconsin reported prevalence of 0.3%. Six of the seven patients had elevated liver enzymes at time of diagnosis. No relationship was found between hepatitis C infection and number of surgeries, year of surgery, or age at surgery. Four patients had hepatitis C genotype 1, but none achieved viral clearance despite three having received treatment. Three had genotype 2, were treated, and had viral clearance. No hepatitis C-positive patient developed cirrhosis or required liver transplant. CONCLUSION: Hepatitis C infection in patients with congenital heart disease who underwent surgical palliation prior to 1992 is common, with prevalence higher than the general population. Our data emphasize the continued importance of screening the high-risk adult congenital heart disease patients.