Lisa Nicholson

Cytoskeletal remodeling of desmin is a more accurate measure of cardiac dysfunction than fibrosis or myocyte hypertrophy

AIMS Fibrosis and myocyte hypertrophy are classical remodeling parameters in heart failure (HF); however, an intriguing possibility is that myocytes undergo intracellular remodeling which decrease compliance, contributing to diastolic dysfunction. The most obvious candidates are cytoskeletal proteins. The cytoskeletal protein desmin reinforces the sarcomeres, enabling force generation. As a contributor to sarcomere performance, desmin may represent a better appraisal of dysfunction than fibrosis or myocyte hypertrophy. MAIN METHODS HF was induced in sheep via coronary microembolization. Echocardiography was performed at baseline, 4-, and 12-months in HF. Desmin, fibrosis, and myocyte hypertrophy from infarcted LV posterior and noninfarcted LV anterior walls were measured using Western blot, immunohistochemistry, and digital image analysis. Multivariate regression analysis was performed, providing structure/function mechanisms. *p<0.05. KEY FINDINGS EF decreased from 55% to 24%*. LV end-diastolic area (LVEDA) increased 123%* at month-12. Fibrosis increased only in posterior LV whereas myocyte hypertrophy increased in both LV posterior and LV anterior regions but only at month-12. Desmin content progressively increased 121% at month-4 and 182%* at month-12 in both LV posterior and anterior walls. Multivariate linear regression (beta coefficient standardization) demonstrated that desmin was a much better predictor of EF (beta=-0.38*) and LVEDA (beta=0.58*) than fibrosis or myocyte hypertrophy. SIGNIFICANCE Desmin, fibrosis, and myocyte hypertrophy are temporally and spatially heterogeneous in HF. Desmin content more accurately correlated with remodeling than fibrosis or myocyte hypertrophy, suggesting that intra-myocyte responses, likely related to mechanical stretch, are better predictors of LV function and may represent novel targets for therapeutic intervention.

Erectile dysfunction in men with congenital heart disease.

There has been a tremendous focus on gynecologic health with the increasing number of women with congenital heart disease (CHD). Conversely, experience in providing sexual health screening to men with CHD is lacking. The purpose of this study was to identify sexual health issues in men with CHD. An anonymous survey was distributed to men in our adult CHD clinic. Age, type of CHD, medications, detailed sexual history including cardiovascular symptoms with intercourse, erectile dysfunction (ED), and willingness to discuss ED with a physician was obtained. A logistic regression analysis was performed to analyze the relation between medications, CHD complexity, and ED; 86 men completed the survey with a mean age of 34 +/- 10 years. The prevalence of ED was 38%. Men were treated with cardiac medications including beta blockers (BB; 24%), angiotensin-converting enzyme (ACE) inhibitors (8%), calcium-channel blockers (6%), and combination BB and ACE inhibitor therapy (16%). Men on BB were 3.13 times more likely to report ED (p = 0.045). Complexity of CHD did not increase the likelihood of ED symptoms (p >0.10). Although most men attributed symptoms to their underlying CHD, most were willing to discuss issues of ED with their cardiologist. In conclusion, ED is prevalent in young men with CHD. Although an emotional component may contribute, certain medications may exacerbate symptoms.

Predictors of Successful Early Extubation Following Congenital Cardiac Surgery in Neonates and Infants

BACKGROUND There is a paucity of literature discussing the predictive likelihood of successfully extubating neonates and infants in the operating room immediately following congenital cardiac surgery. Given the unknown consequences of anaesthetics on neurodevelopmental outcomes, minimising the exposure of this population to such agents may have long-term benefits. METHODS Retrospective chart review of 391 patients less than 1 year of age. RESULTS The probability of successfully extubating these patients was based on quantifiable, objective criteria. The relevant variables include age, weight, bypass time, lactate level and specific congenital anomaly. CONCLUSIONS The practice of immediate extubation of infants and neonates is achievable, safe and predicted based on specific patient variables. This practice will minimise the anaesthetic exposure of these especially young patients who may be at risk for long-term consequences related to anaesthetic exposure.

Survey of How Pediatric Cardiologists Noninvasively Evaluate Patients with Hypoplastic Left Heart Syndrome

BACKGROUND The evaluation of right ventricular (RV) function is important in patients with hypoplastic left heart syndrome (HLHS). Echocardiographic qualitative grading has been the prevalent method used in the past, but newer technologies allowing for quantitative assessment of RV function may have changed this fact. The goal of this study was to determine the current routine noninvasive evaluation of patients with HLHS and what, if any, methods are used to assess systolic and diastolic function in this population. METHODS Web-based survey was conducted using various listservs. Timing of echocardiograms between surgical stages was assessed. Methods of assessing systolic and diastolic function were evaluated. RESULTS Two hundred seventy-seven physicians who averaged 12.8 ± 9.6 years removed from training responded. Largest percentage of respondents was echocardiographers (44.2%) in a university-based practice (73.3%) from North America (91.7%). There were 54.3% of respondents who performed echocardiograms monthly between stages I and II, 48.8% who performed echocardiograms every 6 months between stages II and III, and 67.0% who performed echocardiograms annually after stage III procedure. The main method for systolic grading was qualitative grading (95.5%) and for diastolic grading were tricuspid blood inflow velocities (56.8%). Qualitative grading was considered the method of choice for systolic grading for 38.8% of respondents and tissue Doppler velocities was the method of choice for diastolic grading for 35.3% of respondents. There were 4.0% of respondents who routinely perform a cardiac magnetic resonance imaging (cMRI) between stages I and II, 8.0% between stages II and III, and 24.2% after stage III procedure. CONCLUSION Variability in the noninvasive assessment of the RV in patients with HLHS continues to exist. Qualitative RV systolic assessment was still the predominant method used to assess function despite newer imaging techniques to allow for quantification. Future studies are needed to determine which values are most useful in reviewing function in this complex patient population.

Intestinal location of necrotizing enterocolitis among infants with congenital heart disease

Objective:To determine whether differences exist in the location of necrotizing enterocolitis (NEC) in infants with congenital heart disease (CHD) versus those without CHD.Study design:Retrospective cohort study utilizing 11 years of patient data. Inclusion criterion was surgical exploration for NEC. Presence or absence of CHD was determined. Surgical and/or pathology reports were reviewed to identify the location of NEC. Data were analyzed by t-tests and χ2 analyses.Result:One hundred and sixty-seven patients met the inclusion criteria. CHD infants had a higher percentage of mortality. There was no difference in the location of NEC between non-CHD and CHD patients, with the predominant location being the small intestine in both. In addition, there was no difference in the location of NEC between preterm non-CHD patients and full-term CHD patients with the small intestine again being the primary site.Conclusion:Despite differences in gestational age between non-CHD and CHD patients, the location of NEC in these infants did not differ.

Anxiety Scores in Caregivers of Children with Hypoplastic Left Heart Syndrome.

OBJECTIVES Caring for children with congenital heart disease places significant stress on caregivers. Minimal data exist evaluating stress levels in caregivers of children with hypoplastic left heart syndrome (HLHS). The goal of this study was to obtain baseline stress scores for caregivers of children with HLHS and determine if associations exist between scores and specific caregiver factors. STUDY DESIGN A cross-sectional study using a web-based survey targeted towards caregivers of children with HLHS was performed. Baseline demographics of the caregiver and child with HLHS were obtained. Caregivers completed three validated questionnaires including the Pediatric Quality of Life Inventory (PedsQL), Parenting Stress Index- Short Form (PSI-SF) and the Pediatric Inventory for Parents (PIP). RESULTS Four hundred fifty-nine caregivers completed at least one questionnaire. PSI-SF total score was 80.5 ± 23.1 (> 86 = significant stress), PIP frequency total score was 119.0 ± 37.2, and PIP difficulty total score was 118.1 ± 35.7. Lower quality of life was significantly correlated with higher scores on the PSI-SF (r = -0.6), the presence of a developmental issue in the child (r = 0.3) as well as higher scores on the PIP frequency (r = -0.5) and difficulty scales (r = 0.4). Other demographic values for the caregiver and child did not significantly correlate with PSI or PIP total scores. CONCLUSIONS Anxiety/stress scores of caregivers with children with HLHS are correlated with how well the child is perceived to be doing physically and developmentally by the caregivers. Caregivers with physical and/or developmental concerns may need added psychosocial support.

Caregiver anxiety due to interstage feeding concerns.

INTRODUCTION Improved weight gain during the interstage (IS) period has been shown to improve overall outcomes in patients with single ventricle physiology (SVP). This emphasis on nutrition may have untoward effects, such as increasing anxiety/stress levels in caregivers, who are already known to be at risk for increased anxiety/stress levels. The goal of this study was to evaluate anxiety/stress levels of caregivers as it pertains to feeding during the IS period and to determine if certain characteristics were associated with higher anxiety/stress scores. METHODS Caregivers of children with SVP who completed the IS period, defined as the time between the first and second cardiac surgeries, were recruited. Baseline demographics were obtained. Anxiety/stress levels were measured via eight questions using a 0- to 10-point scale. Correlations were performed between demographic variables and anxiety/stress level scores. RESULTS Fifty-six surveys were completed (39 males, 27 females) on 43 children. Fourteen children required tube feeds during the IS period. There were significant correlations between anxiety/stress scores and caregivers gender, caregivers age, caregivers level of education, percent of time a caregiver spent feeding the child, if caregivers were taking medications for anxiety, and if the child was seen in the emergency room during the IS period. There were no correlation of anxiety/stress scores with caregivers race, childs underlying cardiac diagnosis, age of child, route of feeding during the IS period, birth order of the child or number of children in the family, relationship status, or distance from the hospital. CONCLUSION In general, caregivers of children with SVP experience anxiety/stress during the IS period specifically due to feeding concerns. Certain intrinsic and extrinsic characteristics were associated with higher anxiety/stress levels. Future studies are needed to determine how to minimize anxiety/stress levels during this stressful time period.

Catheterization diastolic pressures correlate with diastolic dyssynchrony in patients with single right ventricles.

Diastolic dyssynchrony has correlated with pulmonary capillary wedge pressures in patients with normal cardiac anatomy. No data exist in single right ventricle (sRV) patients. Goal of this study was to determine if diastolic dyssynchrony in sRV patients correlates with ventricular end‐diastolic pressures (VEDP).

Ultrasound assessment of mesenteric blood flow in neonates with hypoplastic left heart before and after hybrid palliation.

BACKGROUND Altered mesenteric perfusion may be a contributor to the development of necrotising enterocolitis in patients with hypoplastic left heart syndrome. The goal of this study was to document mesenteric flow patterns in patients with hypoplastic left heart syndrome pre- and post-hybrid procedure. METHODS A prospective study on all patients with hypoplatic left heart syndrome undergoing the hybrid procedure was conducted. Doppler ultrasound analysis of the coeliac and superior mesenteric artery was performed. RESULTS A total of 13 patients were evaluated. There was a significant difference in the coeliac artery effective velocity-time intergral pre- and post-hybrid procedure (8.69±3.84 versus 12.51±4.95 cm, respectively). There were significant differences in the superior mesenteric artery antegrade velocity-time integral pre- and post-hybrid procedure (6.86±2.45 versus 10.52±2.64 cm, respectively) and superior mesenteric artery effective velocity-time integral pre- and post-hybrid procedure (6.22±2.68 versus 9.73±2.73 cm, respectively). There were no significant differences between the coeliac and superior mesenteric artery Doppler indices in the pre-hybrid procedure; there were, however, significant differences in the post-hybrid procedure between coeliac and superior mesenteric artery antegrade velocity-time integral (13.8 2±5.60 versus 10.52±2.64 cm, respectively) and effective velocity-time integral (13.04±4.71 versus 9.73±2.73 cm, respectively). CONCLUSION Doppler mesenteric indices of perfusion improve in patients with hypoplastic left heart syndrome after the hybrid procedure; however, there appears to be preferential flow to the coeliac artery versus the superior mesenteric artery in these patients post-procedure.

Differences in mortality characteristics in neonates with Down’s syndrome

Objective:Neonates with Down’s syndrome (nDS) may have multiple medical issues that place them at increased risk for mortality during the newborn period. Goal of this study was to determine if there are differences in baseline characteristics, medical complications or procedures performed during hospitalization between nDS who survived versus those who died during initial hospitalization.Study Design:Data from 2000 to 2014 were reviewed using the Pediatric Health Information Systems (PHIS) database on all DS patients admitted to the hospital <30 days postnatal life. Baseline demographics, medical complications, procedures performed and mortality were recorded. Patients were divided into nDS patients who were discharged alive (nDS-a) versus nDS patients who died (nDS-d). Multivariate logistic analysis with odds ratios was performed to determine significant predictors of death. A P<0.05 was considered significant.Results:A total of 5737 nDS were evaluated. Overall mortality was 7.5% (431/5737). nDS-d were more likely than nDS-a to have a lower birth weight (1.0 (0.9 to 1.0)), presence of a diaphragmatic hernia (6.9 (1.9 to 25.1), or a cardiac diagnosis of a pulmonary venous abnormality (6.8 (1.9 to 24.4)), Ebstein’s anomaly (3.2 (1.2 to 8.5)) or left-sided obstructive lesion (2.0 (1.3 to 3.0). nDS-d were more likely to develop hydrops (5.7 (3.5 to 9.5)) and necrotizing enterocolitis (1.7 (1.2 to 2.6)). In addition, nDS-d had significantly higher odds of requiring mechanical ventilation (20.7 (9.9 to 43.1)) or extracorporeal membrane oxygenation (8.7 (4.7 to 16.1)).Conclusions:A number of characteristics, specifically certain cardiac diagnosis, place nDS at increased risk for mortality. Furthermore, development of specific medical complications or need for particular procedures increases the odds for mortality in nDS. Caregivers should be cognizant that they are taking care of a high-risk population nDS with an increased risk for mortality if these variables are present.