Analysis of the hospitalization costs of surgical patients with congenital heart disease in the plateau region of western China, 2010-2019.

Background: Congenital heart disease (CHD) is one of the most common birth defects and consumes a substantial amount of health care resources. CHD leads to heavy economic burdens for families. However, there are limited data regarding the utilization of healthcare resources for CHD. The objectives of this study were to evaluate the composition, changing trends, and factors affecting hospitalization costs for patients with CHD in the western highlands area of China over a 10-year period. Methods: We conducted a study using the International Quality Improvement Collaborative for Congenital Heart Surgery (IQIC) database and information management system of The First Hospital of Lanzhou University between January 2010 and December 2019. Results: Among 3,087 patients hospitalized for CHD surgery, annual CHD hospitalization costs saw an increasing trend over the 10-year period, with an average growth rate of 4.6% per year. The major contributors to the hospitalization costs were surgery, surgical material, and drug costs. Length of stay (ß=0.203; 0.379; 0.474, P<0.01), age at hospitalization (ß=0.293, P<0.01), proportion of surgery (ß=0.090; -0.102; -0.122; -0.110, P<0.01) and drug costs (ß=-0.114; -0.147; -0.069, P<0.01), and use of traditional Chinese medicine (ß=0.141, P<0.01) were independent factors affecting average hospitalization costs. Conclusions: The financial burden of patients with CHD in the Chinese western highland region is high. Independent of inflation, CHD hospitalization costs are increasing. Measures taken by medical institutions to control the increase in drug costs, and to shorten the length of stay may be expected to have positive effects on reducing the financial burden of individuals with CHD and their families.

The Associations Between Preoperative Anthropometry and Postoperative Outcomes in Infants Undergoing Congenital Heart Surgery.

Aim: We explored the association between preoperative anthropometry and biochemistry, and postoperative outcomes in infants with CHD after cardiac surgery, as infants with congenital heart disease (CHD) often have feeding difficulties and malnutrition. Methodology: This was a retrospective review of infants (≤ 1-year-old) who underwent congenital heart surgery. Preoperative anthropometryin terms of preoperative weight-for-age z-score (WAZ), length-for-age z-score (LAZ), as well as preoperative serum albumin and hemoglobin concentrations, were evaluated against 6-month mortality, and morbidity outcomes including postoperative complications, vasoactive inotrope score, duration of mechanical ventilation, length of stay in the pediatric intensive care unit and in hospital, using the logistic regression or median regression models accounting for infant-level clustering. Results: One hundred and ninety-nine operations were performed in 167 infants. Mean gestational age at birth was 38.0 (SD 2.2) weeks (range 26 to 41 weeks). Thirty (18.0%) infants were born preterm (<37 weeks). The commonest acyanotic and cyanotic lesions were ventricular septal defect (26.3%, 44/167), and tetralogy of Fallot (13.8%, 23/167), respectively. Mean age at cardiac surgery was 94 (SD 95) days. Feeding difficulties, including increased work of breathing during feeding, diaphoresis, choking or coughing during feeding, and inability to complete feeds, was present in 54.3% (108/199) of infants prior to surgery, of which 21.6% (43/199) required tube feeding. The mean preoperative WAZ was-1.31 (SD 1.79). Logistic regression models showed that low preoperative WAZ was associated with increased risk of postoperative complications (odds ratio 1.82; p = 0.02), and 6-month mortality (odds ratio 2.38; p = 0.008) following CHD surgery. There was no meaningful association between the other preoperative variables and other outcomes. Conclusion: More than 50% of infants with CHD undergoing cardiac surgery within the first year of life have feeding difficulties, of which 22% require to be tube-fed. Low preoperative WAZ is associated with increased postoperative complications and 6-month mortality.

8-Oxoguanine DNA Glycosylase (OGG1) Deficiency Exacerbates Doxorubicin-Induced Cardiac Dysfunction.

Doxorubicin is an anthracycline widely used for the treatment of various cancers; however, the drug has a common deleterious side effect, namely a dose-dependent cardiotoxicity. Doxorubicin treatment increases the generation of reactive oxygen species, which leads to oxidative stress in the cardiac cells and ultimately DNA damage and cell death. The most common DNA lesion produced by oxidative stress is 7,8-dihydro-8-oxoguanine (8-oxoguanine), and the enzyme responsible for its repair is the 8-oxoguanine DNA glycosylase (OGG1), a base excision repair enzyme. Here, we show that the OGG1 deficiency has no major effect on cardiac function at baseline or with pressure overload; however, we found an exacerbation of cardiac dysfunction as well as a higher mortality in Ogg1 knockout mice treated with doxorubicin. Our transcriptomic analysis also showed a more extensive dysregulation of genes in the hearts of Ogg1 knockout mice with an enrichment of genes involved in inflammation. These results demonstrate that OGG1 attenuates doxorubicin-induced cardiotoxicity and thus plays a role in modulating drug-induced cardiomyopathy.

Causative Variants for Inherited Cardiac Conditions in a Southeast Asian Population Cohort.

BACKGROUND: Variable penetrance and late-onset phenotypes are key challenges for classifying causal as well as incidental findings in inherited cardiac conditions. Allele frequencies of variants in ancestry-specific populations, along with clinical variant analysis and interpretation, are critical to determine their true significance. METHODS: Here, we carefully reviewed and classified variants in genes associated with inherited cardiac conditions based on a population whole-genome sequencing cohort of 4810 Singaporeans representing Southeast Asian ancestries. RESULTS: Eighty-nine (1.85%) individuals carried either pathogenic or likely pathogenic variants across 25 genes. Forty-six (51.7%) had variants in causal genes for familial hyperlipidemia, but there were also recurrent variants in SCN5A and MYBPC3, causal genes for inherited arrhythmia and cardiomyopathy, which, despite previous reports, we determined to lack criteria for pathogenicity. CONCLUSIONS: Our findings highlight the incidence of disease-related variants in inherited cardiac conditions and emphasize the value of large-scale sequencing in specific ancestries. Follow-up detailed phenotyping and analysis of pedigrees are crucial because assigning pathogenicity will significantly affect clinical management for individuals and their family members.

Effects of extended pharmacological disruption of zebrafish embryonic heart biomechanical environment on cardiac function, morphology, and gene expression.

BACKGROUND: Biomechanical stimuli are known to be important to cardiac development, but the mechanisms are not fully understood. Here, we pharmacologically disrupted the biomechanical environment of wild-type zebrafish embryonic hearts for an extended duration and investigated the consequent effects on cardiac function, morphological development, and gene expression. RESULTS: Myocardial contractility was significantly diminished or abolished in zebrafish embryonic hearts treated for 72 hours from 2 dpf with 2,3-butanedione monoxime (BDM). Image-based flow simulations showed that flow wall shear stresses were abolished or significantly reduced with high oscillatory shear indices. At 5 dpf, after removal of BDM, treated embryonic hearts were maldeveloped, having disrupted cardiac looping, smaller ventricles, and poor cardiac function (lower ejected flow, bulboventricular regurgitation, lower contractility, and slower heart rate). RNA sequencing of cardiomyocytes of treated hearts revealed 922 significantly up-regulated genes and 1,698 significantly down-regulated genes. RNA analysis and subsequent qPCR and histology validation suggested that biomechanical disruption led to an up-regulation of inflammatory and apoptotic genes and down-regulation of ECM remodeling and ECM-receptor interaction genes. Biomechanics disruption also prevented the formation of ventricular trabeculation along with notch1 and erbb4a down-regulation. CONCLUSIONS: Extended disruption of biomechanical stimuli caused maldevelopment, and potential genes responsible for this are identified.

The Role of Epigenetics in Congenital Heart Disease.

Congenital heart disease (CHD) is the most common birth defect among newborns worldwide and contributes to significant infant morbidity and mortality. Owing to major advances in medical and surgical management, as well as improved prenatal diagnosis, the outcomes for these children with CHD have improved tremendously so much so that there are now more adults living with CHD than children. Advances in genomic technologies have discovered the genetic causes of a significant fraction of CHD, while at the same time pointing to remarkable complexity in CHD genetics. For this reason, the complex process of cardiogenesis, which is governed by multiple interlinked and dose-dependent pathways, is a well investigated process. In addition to the sequence of the genome, the contribution of epigenetics to cardiogenesis is increasingly recognized. Significant progress has been made dissecting the epigenome of the heart and identified associations with cardiovascular diseases. The role of epigenetic regulation in cardiac development/cardiogenesis, using tissue and animal models, has been well reviewed. Here, we curate the current literature based on studies in humans, which have revealed associated and/or causative epigenetic factors implicated in CHD. We sought to summarize the current knowledge on the functional role of epigenetics in cardiogenesis as well as in distinct CHDs, with an aim to provide scientists and clinicians an overview of the abnormal cardiogenic pathways affected by epigenetic mechanisms, for a better understanding of their impact on the developing fetal heart, particularly for readers interested in CHD research.

Mending a broken heart: In vitro, in vivo and in silico models of congenital heart disease.

Birth defects contribute to ∼0.3% of global infant mortality in the first month of life, and congenital heart disease (CHD) is the most common birth defect among newborns worldwide. Despite the significant impact on human health, most treatments available for this heterogenous group of disorders are palliative at best. For this reason, the complex process of cardiogenesis, governed by multiple interlinked and dose-dependent pathways, is well investigated. Tissue, animal and, more recently, computerized models of the developing heart have facilitated important discoveries that are helping us to understand the genetic, epigenetic and mechanobiological contributors to CHD aetiology. In this Review, we discuss the strengths and limitations of different models of normal and abnormal cardiogenesis, ranging from single-cell systems and 3D cardiac organoids, to small and large animals and organ-level computational models. These investigative tools have revealed a diversity of pathogenic mechanisms that contribute to CHD, including genetic pathways, epigenetic regulators and shear wall stresses, paving the way for new strategies for screening and non-surgical treatment of CHD. As we discuss in this Review, one of the most-valuable advances in recent years has been the creation of highly personalized platforms with which to study individual diseases in clinically relevant settings.

Cardiotoxicity After Anthracycline Chemotherapy for Childhood Cancer in a Multiethnic Asian Population.

Background: Anthracyclines are widely used to treat childhood cancers; however, they cause cardiotoxicity. To address the paucity of clinical data from Asian populations, this study investigated the epidemiology of pediatric anthracycline-induced cardiotoxicity, during and after chemotherapy, in a multiethnic Asian population. Procedure: This was a single-center, retrospective analysis of 458 anthracycline-treated pediatric oncology patients at KK Women's and Children's Hospital, a tertiary children's hospital in Singapore from 2005 through 2015. We investigated cardiotoxicity (defined as left ventricular fractional shortening <28% on echocardiography) and its risk factors using univariate logistic regression as well as survival estimates through the Kaplan-Meier method to compare survival distribution between patients with and without cardiotoxicity. Results: Over a follow-up period of almost 4 years, we found that 7% (32/458) of the cohort developed cardiotoxicity, with 37.5% (12/32) of these manifesting as clinical heart failure, whilst the rest were asymptomatic. The cardiotoxic cohort demonstrated a significantly higher mortality rate compared to the non-cardiotoxic group at 46.9 vs. 19.2% (p < 0.001), of whom 3 (9.4%) died from end-stage heart failure. We found that traditional predictors such as female sex, age at diagnosis, and cumulative doxorubicin equivalent dose were not predictors of cardiotoxicity. Conclusion: Our study reaffirms that freedom from symptoms does not ensure normal heart function and suggests that children with abnormal ventricular systolic function have higher mortality risk compared to those with normal systolic function. The findings contribute to improved understanding of the Asian burden to aid development of measures to prevent or reduce the risk of cardiotoxicity.

Multiscale modeling of a modified Blalock-Taussig surgery in a patient-specific tetralogy of Fallot.

Tetralogy of Fallot (TOF) is a congenital heart anomaly that causes a drastic reduction in the oxygen level. In this study, we coupled a lumped-parameter model with a patient-specific three-dimensional (3D) model which included a modified Blalock-Taussig (MBT) shunt. By forming a closed loop, we investigated the effects of certain parameters on the flow rates and the pressures at different locations of the developed network. A local sensitivity analysis on an initial zero-dimensional (0D) closed-loop model was conducted. The 0D lumped parameter (LP) model was then refined based on the results of the multiscale 0D-3D model and the local sensitivity analysis was repeated for the refined 0D model. It was shown that the maximum pressure of the pulmonary bed had the highest sensitivity of 94% to the diameter of MBT shunt. We observed that the existence of the flow in the shunt during the diastole caused an elevated wall shear stress (WSS) in the pulmonary artery. In this work, we calculated the flow velocity and pressure field in a 3D patient-specific aorta with an MBT shunt, and then we used the results to increase the accuracy of our LP model to simulate numerous 0D simulations in a significantly shorter time, which is potentially applicable for medical decision-making.

Echocardiographic assessment of fetal cardiac function in the uterine artery ligation rat model of IUGR.

BACKGROUND: Intrauterine growth restriction (IUGR) leads to cardiac dysfunction and adverse remodeling of the fetal heart, as well as a higher risk of postnatal cardiovascular diseases. The rat model of IUGR, via uterine artery ligation, is a popular model but its cardiac sequelae is not well investigated. Here, we performed an echocardiographic evaluation of its cardiac function to determine how well it can represent the disease in humans. METHODS: Unilateral uterine artery ligation was performed at embryonic day 17 (E17) and echocardiography was performed at E19 and E20. RESULTS: Growth-restricted fetuses were significantly smaller and lighter, and had an higher placenta-to-fetus weight ratio. Growth-restricted fetal hearts had reduced wall thickness-to-diameter ratio, indicating left ventricular (LV) dilatation, and they had elevated trans-mitral and trans-tricuspid E/A ratios and reduced left and right ventricular fractional shortening (FS), suggesting systolic and diastolic dysfunction. These were similar to human IUGR fetuses. However, growth-restricted rat fetuses did not demonstrate head-sparing effect, displayed a lower LV myocardial performance index, and ventricular outflow velocities were not significantly reduced, which were dissimilar to human IUGR fetuses. CONCLUSIONS: Despite the differences, our results suggest that this IUGR model has significant cardiac dysfunction, and could be a suitable model for studying IUGR cardiovascular physiology. IMPACT: Animal models of IUGR are useful, but their fetal cardiac function is not well studied, and it is unclear if they can represent human IUGR fetuses. We performed an echocardiographic assessment of the heart function of a fetal rat model of IUGR, created via maternal uterine artery ligation. Similar to humans, the model displayed LV dilatation, elevated E/A ratios, and reduced FS. Different from humans, the model displayed reduced MPI, and no significant outflow velocity reduction. Despite differences with humans, this rat model still displayed cardiac dysfunction and is suitable for studying IUGR cardiovascular physiology.

Human fetal hearts with tetralogy of Fallot have altered fluid dynamics and forces.

Studies have suggested the effect of blood flow forces in pathogenesis and progression of some congenital heart malformations. It is therefore of interest to study the fluid mechanic environment of the malformed prenatal heart, such as the tetralogy of Fallot (TOF), especially when little is known about fetal TOF. In this study, we performed patient-specific ultrasound-based flow simulations of three TOF and seven normal human fetal hearts. TOF right ventricles (RVs) had smaller end-diastolic volumes (EDVs) but similar stroke volumes (SVs), whereas TOF left ventricles (LVs) had similar EDVs but slightly increased SVs compared with normal ventricles. Simulations showed that TOF ventricles had elevated systolic intraventricular pressure gradient (IVPG) and required additional energy for ejection but IVPG elevations were considered to be mild relative to arterial pressure. TOF RVs and LVs had similar pressures because of equalization via ventricular septal defect (VSD). Furthermore, relative to normal, TOF RVs had increased diastolic wall shear stresses (WSS) but TOF LVs were not. This was caused by high tricuspid inflow that exceeded RV SV, leading to right-to-left shunting and chaotic flow with enhanced vorticity interaction with the wall to elevate WSS. Two of the three TOF RVs but none of the LVs had increased thickness. As pressure elevations were mild, we hypothesized that pressure and WSS elevation could play a role in the RV thickening, among other causative factors. Finally, the endocardium surrounding the VSD consistently experienced high WSS because of RV-to-LV flow shunt and high flow rate through the over-riding aorta. NEW & NOTEWORTHY Blood flow forces are thought to cause congenital heart malformations and influence disease progression. We performed novel investigations of intracardiac fluid mechanics of tetralogy of Fallot (TOF) human fetal hearts and found essential differences from normal hearts. The TOF right ventricle (RV) and left ventricle had similar and elevated pressure but only the TOF RV had elevated wall shear stress because of elevated tricuspid inflow, and this may contribute to the observed RV thickening. TOF hearts also expended more energy for ejection.

Changes in Near-Infrared Spectroscopy After Congenital Cyanotic Heart Surgery.

BACKGROUND: Since oxygen saturation from pulse oximetry (SpO2) and partial pressure of arterial oxygen (PaO2) are observed to improve immediately after surgical correction of cyanotic congenital heart disease (CHD), we postulate that cerebral (CrO2) and somatic (SrO2) oximetry also improves immediately post-correction. We aim to prospectively examine CrO2 and SrO2, before, during, and after surgical correction as well as on hospital discharge in children with cyanotic CHD to determine if and when these variables increase. METHODS: This is a prospective observational trial. Eligibility criteria included children below 18 years of age with cyanotic CHD who required any cardiac surgical procedure. CrO2 and SrO2 measurements were summarized at six time-points for comparison: (1) pre-cardiopulmonary bypass (CPB); (2) during CPB; (3) post-CPB; (4) Day 1 in the pediatric intensive care unit (PICU); (5) Day 2 PICU; and (6) discharge. Categorical and continuous variables are presented as counts (percentages) and median (interquartile range), respectively. RESULTS: Twenty-one patients were analyzed. 15 (71.4%) and 6 (28.6%) patients underwent corrective and palliative surgeries, respectively. In the corrective surgery group, SpO2 increased immediately post-CPB compared to pre-CPB [99 (98, 100) vs. 86% (79, 90); p < 0.001] and remained in the normal range through to hospital discharge. Post-CPB CrO2 did not change from pre-CPB [72.8 (58.8, 79.0) vs. 72.1% (63.0, 78.3); p = 0.761] and even decreased on hospital discharge [60.5 (53.6, 62.9) vs. 72.1% (63.0, 78.3); p = 0.005]. Post-CPB SrO2 increased compared to pre-CPB [87.3 (77.2, 89.5) vs. 72.7% (65.6, 77.3); p = 0.001] but progressively decreased during PICU stay to a value lower than baseline at hospital discharge [66.9 (57.3, 76.9) vs. 72.7% (65.6, 77.3); p = 0.048]. CONCLUSION: CrO2 and SrO2 did not increase after corrective surgery of cyanotic CHD even up to hospital discharge. Future larger studies are required to validate these findings. (This study is registered with ClinicalTrials.gov ID: NCT02417259.).

Dynamic Myocardial Response to Exercise in Childhood Cancer Survivors Treated with Anthracyclines.

BACKGROUND: Anthracycline cardiotoxicity can cause significant long-term morbidity in childhood cancer survivors (CCS), but many CCS do not manifest clinical symptoms until adulthood. The aims of this study were to characterize the dynamic myocardial response to exercise of CCS at long-term follow-up by combining semisupine bicycle exercise stress echocardiography with myocardial imaging techniques and to establish whether semisupine bicycle exercise stress echocardiography could identify CCS with abnormal exercise response. METHODS: This was a single-center prospective cross-sectional study. One hundred CCS and 51 control subjects underwent semisupine bicycle exercise stress echocardiography. Color Doppler tissue imaging peak systolic (s') and diastolic (e') velocities, myocardial acceleration during isovolumic contraction, and longitudinal strain were measured at rest and at incremental heart rates in the left ventricular (LV) lateral wall, basal septum, and right ventricle. The relationship with increasing heart rate was evaluated for each parameter by plotting the values against heart rate at each stage of exercise. Kernel density estimate was used to establish the normality of the individual CCS exercise responses. RESULTS: At rest, no significant differences were found for LV lateral wall, right ventricular (RV), and basal septal systolic and diastolic velocities between CCS and control subjects. Only septal e' was lower in CCS. LV longitudinal strain was similar between groups, while RV longitudinal strain was lower in CCS. At peak exercise, LV lateral wall, RV, and septal s' were not different between groups, while e' were significantly lower in CCS. LV lateral wall and septal isovolumic acceleration were also reduced in CCS. LV longitudinal strain was different between groups, while RV longitudinal strain was similar. The dynamic response of Doppler tissue imaging velocities, isovolumic acceleration, and strain was similar between CCS and control subjects. Kernel density estimate analysis confirmed that most CCS responses were within the normal range. CONCLUSIONS: At 10-year follow-up, anthracycline-treated CCS with normal baseline ejection fractions have LV and RV systolic and diastolic myocardial exercise response comparable with that of control subjects. Minor differences were observed between CCS and control subjects at rest and at peak exercise, but the dynamic response is within the normal range.

Prelisting predictions of early postoperative survival in infant heart transplantation using classification and regression tree analysis.

Infants listed for heart transplantation experience high waitlist and early post-transplant mortality, and thus, optimal allocation of scarce donor organs is required. Unfortunately, the creation and validation of multivariable regression models to identify risk factors and generate individual-level predictions are challenging. We sought to explore the use of data mining methods to generate a prediction model. CART analysis was used to create a model which, at the time of listing, would predict which infants listed for heart transplantation would survive at least 3 months post-transplantation. A total of 48 infants were included; 13 died while waiting, and six died within 3 months of heart transplant. CART analysis identified RRT, blood urea nitrogen, and hematocrit as terminal nodes with alanine transaminase as an intermediate node predicting death. No patients listed on RRT (n = 10) survived and only three of 12 (25%) patients listed on ECLS survived >3 months post-transplant. CART analysis overall accuracy was 83%, with sensitivity of 95% and specificity 76%. This study shows that CART analysis can be used to generate accurate prediction models in small patient populations. Model validation will be necessary before incorporation into decision-making algorithms used to determine transplant candidacy.

The Utility of Cardiopulmonary Exercise Testing for the Prediction of Outcomes in Ambulatory Children With Dilated Cardiomyopathy.

BACKGROUND: Unlike adult patients, the utility of cardiopulmonary exercise testing (CPET) in children as a prognostic tool is unclear. We sought to examine the associations of CPET with outcomes in children with dilated cardiomyopathy (DCM). METHODS: This was a single-center, retrospective review of children with DCM who underwent CPET. The primary endpoint for this study was a time-dependent composite outcome of hospitalization for management of decompensated heart failure, initiation of mechanical circulatory support, heart transplant, or death. RESULTS: We examined 52 children with DCM who underwent CPET at median age 12.6 years (interquartile range [IQR], 9.9-14.6 years). At first CPET, the median peak heart rate was 80% (IQR, 70-88%) of predicted, median peak oxygen consumption 62% (IQR, 45-77%) of predicted, and median minute ventilation/carbon dioxide production slope 34.9 (IQR, 27.9-39.4). Eighteen (35%) patients reached the composite outcome during follow-up. Univariable factors associated with the composite outcome included: lower peak heart rate predicted, lower blood pressure response, lower peak oxygen consumption predicted, and higher minute ventilation/carbon dioxide production slope. The association between exercise performance and composite outcome was linear; thus, no reliable cutoff point could be identified. Serial CPET had been performed in 30 patients; clinically, those with deterioration of exercise capacity had poorer outcomes. CONCLUSIONS: Cardiopulmonary exercise testing is feasible in children with DCM and is useful to predict outcomes. The finding of lower exercise capacity and lower blood pressure response should prompt closer follow-up. In those with serial testing, a decline in exercise capacity may be a marker of clinical deterioration.

Intramyocardial Hematoma After Ebstein Anomaly Repair.

Intramyocardial hematoma is a rare condition and is an incomplete form of myocardial rupture, which may occur after myocardial infarction, cardiac surgery, trauma, percutaneous coronary intervention, or spontaneously. We describe a case of a 16-year-old girl with intramyocardial hematoma mimicking an intracavitary thrombus following repair of Ebstein anomaly. The intramyocardial hematoma was incorrectly diagnosed on echocardiography as a right ventricular thrombus, and the true nature of the lesion was only realized during repeat surgical intervention for severe tricuspid regurgitation. The hematoma was managed conservatively and spontaneously resolved.

Left Ventricular Myocardial and Hemodynamic Response to Exercise in Young Patients after Endovascular Stenting for Aortic Coarctation.

BACKGROUND: Endovascular stenting has emerged as a treatment option for children with coarctation of the aortic (CoA), but the impact on left ventricular (LV) function has been poorly documented. The aim of this study was to characterize the LV myocardial and hemodynamic response to exercise in young patients who underwent endovascular stenting for CoA during childhood using semisupine bicycle exercise stress echocardiography. METHODS: This was a single-center prospective cross-sectional study including 30 patients with CoA and 30 age- and gender-matched control subjects who underwent semisupine bicycle exercise stress echocardiography. Color Doppler tissue imaging peak systolic (s') and early diastolic (e') velocities in the LV lateral wall and basal septum, LV myocardial acceleration during isovolumic acceleration were measured at rest and with incremental heart rate (HR). The relationship with increasing HR was evaluated for each parameter by plotting the values at each stage of exercise versus HR. RESULTS: At rest, HR was similar between the two groups. LV ejection fraction and fractional shortening were within the normal range in the CoA group. LV lateral wall and basal septal s' and e' velocities did not differ between the two groups, but isovolumic acceleration values were significantly lower in the CoA group. At peak exercise, HR was similar between the groups, but all Doppler tissue imaging parameters were lower in patients than in control subjects. When assessing the increase of each parameter versus HR, the increase in slope was significantly lower in patients than in control subjects for LV lateral wall Doppler tissue imaging s' and e' velocities, and septal e' velocity, but not for septal s'. The relationship of isovolumic acceleration with HR was significantly reduced in the CoA group. CONCLUSION: The results of this study demonstrate reduced systolic and diastolic myocardial reserve in patients with CoA compared with control subjects. An abnormal myocardial contractile response to exercise was also found, as shown by an abnormal LV force-frequency relationship in patients with stented CoA. The prognostic clinical implications require further study.

Patterns of Mechanical Inefficiency in Pediatric Dilated Cardiomyopathy and Their Relation to Left Ventricular Function and Clinical Outcomes.

BACKGROUND: Pediatric dilated cardiomyopathy (DCM) is associated with death or transplantation and is typically considered a homogeneous process affecting global left ventricular (LV) function. However, assessment of regional abnormalities that contribute to pumping inefficiencies is lacking. The aim of this study was to define regional strain patterns of mechanical inefficiency in the broader context of LV discoordination (dysfunction and timing abnormalities) and to evaluate their associations with LV function and clinical outcomes. METHODS: Multiplanar apical LV echocardiographic images from patients with pediatric DCM (n = 56) and control subjects (n = 20) were analyzed by two-dimensional longitudinal speckle-tracking strain analysis to identify segmental strain patterns and global contraction groups. Clinical outcome (death or transplantation vs transplantation-free survival) and echocardiographic data were evaluated. Outcome groups were compared using the Fisher exact test, the χ(2) test, or analysis of variance (with P values ≤ .05 considered to indicate statistical significance). RESULTS: Of 56 patients with DCM, 29 (52%) progressed to death or transplantation. Five segmental strain patterns were observed that were used to define seven contraction groups by regional contractility and/or timing discoordination. The group(s) with the most discoordination had the most LV dysfunction (P = .0004) and a trend toward the highest frequency of death or transplantation (P = .069). Interreader reproducibility of segmental strain patterns agreed in 165 or 180 (92%) segments tested (κ = 0.90). Control subjects had normal strain patterns. CONCLUSIONS: A heterogeneous mixture of abnormalities in the regional wall mechanics that lead to inefficient pump mechanics through functional and timing abnormalities were seen in this cohort and were categorized into natural subgroups. More severe LV discoordination was associated with increased LV dysfunction and a trend toward death or transplantation.

Diffuse Myocardial Fibrosis in Children After Heart Transplantations: A Magnetic Resonance T1 Mapping Study.

BACKGROUND: It is unclear whether the myocardium undergoes accelerated fibrotic remodeling in children after heart transplantation (HTx). METHODS: In this prospective study, cardiac magnetic resonance (CMR) studies in 17 patients 1.3 years (median, range 0.03-12.6 years) after HTx (mean age, 9.8 ± 6.2 years; 8 girls) were compared to CMR studies in 9 healthy controls (mean age, 12.4 ± 2.4 years; 4 girls). T1 measurements were performed at a midventricular short axis slice before (ie, native T1 times) and after the application of 0.2 mmol/kg gadopentetate dimeglumine in the interventricular septum, left ventricular (LV) free wall and encompassing the entire LV myocardium. The tissue-blood partition coefficient (TBPC), reflecting the degree of diffuse myocardial fibrosis, was calculated as a function of the ratio of T1 change of myocardium compared to blood. Native T1 times and TBPC were correlated with echocardiographic parameters of diastolic function. RESULTS: Native T1 times were significantly higher in HTx patients compared to controls in all regions assessed (LV free wall 973 ± 42 vs 923 ± 12 ms; P < 0.005; interventricular septum 1003 ± 31 vs 974 ± 21 ms, P < 0.05; entire LV myocardium 987 ± 33 vs 951 ± 16 ms; P < 0.005) and correlated with LV E/e' as an echocardiographic marker of diastolic dysfunction (r = 0.54, P < 0.05). The TBPC was elevated in the LV free wall (0.45 ± 0.06 vs 0.40 ± 0.03, P < 0.005) and the entire LV myocardium (0.47 ± 0.06 vs 0.43 ± 0.03, P < 0.05). CONCLUSIONS: Evidence of diffuse myocardial fibrosis and is already present in children after HTx. It appears to be associated with diastolic dysfunction.