Forecasting the Economic Burden of Cardiovascular Disease and Stroke in the United States Through 2050: A Presidential Advisory From the American Heart Association.

BACKGROUND: Quantifying the economic burden of cardiovascular disease and stroke over the coming decades may inform policy, health system, and community-level interventions for prevention and treatment. METHODS: We used nationally representative health, economic, and demographic data to project health care costs attributable to key cardiovascular risk factors (hypertension, diabetes, hypercholesterolemia) and conditions (coronary heart disease, stroke, heart failure, atrial fibrillation) through 2050. The human capital approach was used to estimate productivity losses from morbidity and premature mortality due to cardiovascular conditions. RESULTS: One in 3 US adults received care for a cardiovascular risk factor or condition in 2020. Annual inflation-adjusted (2022 US dollars) health care costs of cardiovascular risk factors are projected to triple between 2020 and 2050, from $400 billion to $1344 billion. For cardiovascular conditions, annual health care costs are projected to almost quadruple, from $393 billion to $1490 billion, and productivity losses are projected to increase by 54%, from $234 billion to $361 billion. Stroke is projected to account for the largest absolute increase in costs. Large relative increases among the Asian American population (497%) and Hispanic American population (489%) reflect the projected increases in the size of these populations. CONCLUSIONS: The economic burden of cardiovascular risk factors and overt cardiovascular disease in the United States is projected to increase substantially in the coming decades. Development and deployment of cost-effective programs and policies to promote cardiovascular health are urgently needed to rein in costs and to equitably enhance population health.

Preoperative Feeding Fortification Among Infants with Congenital Heart Disease is Associated with Higher Growth Velocity in the First 30 Days Post-repair and Lower BMI Percentile for Age at 10 Years: A Retrospective Cohort Study.

It remains unclear how preoperative nutrition fortification impacts postoperative growth trajectories and nutritional status among infants with congenital heart disease. A single center retrospective cohort study was performed to evaluate measures of growth among patients who underwent cardiac repair at 0-18 months of age for atrial septal defect, ventricular septal defect, atrioventricular septal defect, or tetralogy of Fallot. Cohorts were analyzed at 0-30 and 31-60 days post-repair as well as at 2, 5, and 10 years of age. Records of 24 patients who received fortified nutrition and 60 patients who received unfortified nutrition preoperatively were reviewed. Those with fortified nutrition had higher growth velocities in the first 30 days post-repair compared to those with unfortified nutrition: 28.4 (23.8-83.3) grams per day versus 16.7 (7.1-21.4) grams per day, p = 0.004. Weight percentile for age was higher in the unfortified group at 2, 5, and 10 years of age (p = 0.02, p = 0.045, and p = 0.01). Body mass index (BMI) percentile for age was higher in the unfortified group at 5 and 10 years of age (p = 0.045 and p = 0.02) with a trend toward higher prevalence of either overweight or obesity compared to the fortified group (p = 0.13). reoperative nutrition fortification among infants with congenital heart disease is associated with higher growth velocity in the first 30 days post-repair and lower BMI percentile for age at 10 years. Further studies are needed to evaluate the association between preoperative nutrition fortification and postoperative outcomes, nutritional status, and prevalence of obesity in adolescence and adulthood.

Single operator experience, learning curve, outcomes, and insights gained with conduction system pacing.

BACKGROUND: Conduction system pacing (CSP) is increasingly utilized to prevent and correct dyssynchrony. Barriers to CSP adoption include limited training, methodologic variability, laboratory slot allocation, and few data on learning curves. We report learning curves/clinical outcomes from a single experienced electrophysiologist who was new to CSP, and share gained insights. METHODS: Retrospective analysis of all patients who underwent attempted CSP implantation (2016-2023). Patient characteristics, ECGs, echocardiograms, fluoroscopy/procedure times, lead data were recorded at implant and follow-up. RESULTS: CSP leads were implanted successfully in 167/191(87.4%) patients with a follow-up of 278 ± 378 days. His-bundle pacing (HBP = 59) and left-bundle-area pacing (LBAP = 108) had similar procedure/fluoroscopy times, QRS duration decreases, and ejection fraction improvements (all p > NS). Eight HBP lead revisions were required for high capture thresholds LBAP demonstrated lower pacing thresholds, higher lead impedances, and greater R-wave amplitudes at implant and follow-up. After 25 HBP cases, implant pacing thresholds, fluoroscopy, procedural times did not decrease. After 25 LBAP cases, there were significant decreases in all these parameters (p < 0.05). A separate analysis in LBAP patients with recorded Purkinje signals showed no differences in paced ECG characteristics between patients with pre- QRS Purkinje signals versus patients with Purkinje signals post-QRS onset. CONCLUSIONS: Experienced implanters who are new to CSP can achieve steady-state procedural/fluoroscopy times after a learning curve of 25 implants. LBAP showed lower capture thresholds and higher success rates. Adequate depth of lead deployment (as determined by published parameters) does not require Purkinje potential to be pre-QRS. Operators new to CSP.can forego HBP and directly implement LBAP.

A Synopsis of the Evidence for the Science and Clinical Management of Cardiovascular-Kidney-Metabolic (CKM) Syndrome: A Scientific Statement From the American Heart Association.

A growing appreciation of the pathophysiological interrelatedness of metabolic risk factors such as obesity and diabetes, chronic kidney disease, and cardiovascular disease has led to the conceptualization of cardiovascular-kidney-metabolic syndrome. The confluence of metabolic risk factors and chronic kidney disease within cardiovascular-kidney-metabolic syndrome is strongly linked to risk for adverse cardiovascular and kidney outcomes. In addition, there are unique management considerations for individuals with established cardiovascular disease and coexisting metabolic risk factors, chronic kidney disease, or both. An extensive body of literature supports our scientific understanding of, and approach to, prevention and management for individuals with cardiovascular-kidney-metabolic syndrome. However, there are critical gaps in knowledge related to cardiovascular-kidney-metabolic syndrome in terms of mechanisms of disease development, heterogeneity within clinical phenotypes, interplay between social determinants of health and biological risk factors, and accurate assessments of disease incidence in the context of competing risks. There are also key limitations in the data supporting the clinical care for cardiovascular-kidney-metabolic syndrome, particularly in terms of early-life prevention, screening for risk factors, interdisciplinary care models, optimal strategies for supporting lifestyle modification and weight loss, targeting of emerging cardioprotective and kidney-protective therapies, management of patients with both cardiovascular disease and chronic kidney disease, and the impact of systematically assessing and addressing social determinants of health. This scientific statement uses a crosswalk of major guidelines, in addition to a review of the scientific literature, to summarize the evidence and fundamental gaps related to the science, screening, prevention, and management of cardiovascular-kidney-metabolic syndrome.

Cardiovascular-Kidney-Metabolic Health: A Presidential Advisory From the American Heart Association.

Cardiovascular-kidney-metabolic health reflects the interplay among metabolic risk factors, chronic kidney disease, and the cardiovascular system and has profound impacts on morbidity and mortality. There are multisystem consequences of poor cardiovascular-kidney-metabolic health, with the most significant clinical impact being the high associated incidence of cardiovascular disease events and cardiovascular mortality. There is a high prevalence of poor cardiovascular-kidney-metabolic health in the population, with a disproportionate burden seen among those with adverse social determinants of health. However, there is also a growing number of therapeutic options that favorably affect metabolic risk factors, kidney function, or both that also have cardioprotective effects. To improve cardiovascular-kidney-metabolic health and related outcomes in the population, there is a critical need for (1) more clarity on the definition of cardiovascular-kidney-metabolic syndrome; (2) an approach to cardiovascular-kidney-metabolic staging that promotes prevention across the life course; (3) prediction algorithms that include the exposures and outcomes most relevant to cardiovascular-kidney-metabolic health; and (4) strategies for the prevention and management of cardiovascular disease in relation to cardiovascular-kidney-metabolic health that reflect harmonization across major subspecialty guidelines and emerging scientific evidence. It is also critical to incorporate considerations of social determinants of health into care models for cardiovascular-kidney-metabolic syndrome and to reduce care fragmentation by facilitating approaches for patient-centered interdisciplinary care. This presidential advisory provides guidance on the definition, staging, prediction paradigms, and holistic approaches to care for patients with cardiovascular-kidney-metabolic syndrome and details a multicomponent vision for effectively and equitably enhancing cardiovascular-kidney-metabolic health in the population.

Effect of Phacoemulsification on Intraocular Pressure in Eyes with Functioning Tube Shunts.

Purpose: To evaluate the effect of phacoemulsification on intraocular pressure (IOP) in eyes with functioning tube shunts. Methods: This was a retrospective chart review of primary open-angle glaucoma (POAG) patients with a functioning tube who underwent phacoemulsification and had ≥24 months of follow-up. The primary end point was defined as surgical failure (IOP > 21 mmHg) at month 24, progression to no light perception (NLP) vision, glaucoma reoperation, or implant removal. Surgical failure defined as IOP >18 and >15 mmHg, changes in visual acuity (VA), IOP, and number of medications were assessed. Results: Twenty-seven eyes of 27 patients with moderate or severe POAG were included. The mean age of the patients was 64.2 ± 10.8 years. The interval between the tube shunt and phacoemulsification was 28.8 ± 25.0 months. At the end of the study, four (14.8%) eyes met the failure criteria; the average time to failure was 9.3 ± 3.8 months. The causes of failure were high IOP in two (50.0%) and glaucoma reoperation in two (50.0%) eyes; however, no eyes progressed to NLP vision. Surgical failure defined as IOP >18 and >15 mmHg showed an increasing failure rate (18.5% and 48.5%, respectively).Themean IOP and medications number remained stable at month 24 compared to baseline (P = 0.131 and P = 0.302, respectively). Initially, VA showed improvement, with the greatest improvement at 6 months (P = 0.001), but at 24 months the improvement was no longer significant (P = 0.430). Conclusion: Phacoemulsification in patients with functioning tubes did not change the mean IOP in most of the patients (86.2%); the number of medications also did not increase.

Hemorrhagic Complications Following Trabecular Bypass Microstent Surgery in the Setting of Antithrombotic Therapy.

PRCIS: In this retrospective study, the use of chronic antithrombotic therapy (ATT) did not increase the risk of hemorrhagic complications after trabecular bypass microstent surgery and phacoemulsification. Stent type and female sex were associated with hyphema. PURPOSE: To report the incidence of hemorrhagic complications after trabecular bypass microstent surgery and phacoemulsification with and without (ATT). METHODS: Retrospective case series on glaucoma patients on chronic ATT who underwent trabecular bypass microstent surgery (iStent, iStent inject, and Hydrus) combined with phacoemulsification between 2013 and 2019 with ≥3-month follow-up. The primary outcome measure was the incidence of hemorrhagic complications within a 3-month postoperative period. Generalized estimating equations were created to account for inter-eye correlation and logistic regression analysis was performed to identify factors predictive of hemorrhagic complications. RESULTS: Of 333 patients (435 eyes), 161 patients (211 eyes) were on ATT and 172 patients (224 eyes) were not on ATT; both groups were similar in age and baseline ocular characteristics. The only hemorrhagic complication was hyphema, which occurred in 84 (19.3%) eyes (41 ATT, 43 non-ATT eyes; P = 1.00). Onset was at postoperative day 1 in 98.8% of eyes, with a duration of 1 week in 73.8% of eyes, without difference between ATT and non-ATT groups. Hyphema was most common with Hydrus microstent (36.4%) versus iStent (19.9%) and iStent inject (8.5%) ( P = 0.003). In the multivariate model, the female sex was a predictor of hyphema [hazard ratio (HR) = 2.062; P = 0.009], iStent inject was protective against hyphema (HR = 0.379; P = 0.033), whereas Hydrus did not reach statistical significance (HR = 2.007; P = 0.081). Age, systemic comorbidities, ATT use, and baseline ocular characteristics were not significant predictors. CONCLUSIONS: Hemorrhagic complications after trabecular bypass microstent surgery were limited to transient hyphema and were not associated with chronic ATT use. Stent type and female sex were associated with hyphema.

Management of routine postoperative pain for children undergoing cardiac surgery: a Paediatric Acute Care Cardiology Collaborative Clinical Practice Guideline.

BACKGROUND: Pain following surgery for cardiac disease is ubiquitous, and optimal management is important. Despite this, there is large practice variation. To address this, the Paediatric Acute Care Cardiology Collaborative undertook the effort to create this clinical practice guideline. METHODS: A panel of experts consisting of paediatric cardiologists, advanced practice practitioners, pharmacists, a paediatric cardiothoracic surgeon, and a paediatric cardiac anaesthesiologist was convened. The literature was searched for relevant articles and Collaborative sites submitted centre-specific protocols for postoperative pain management. Using the modified Delphi technique, recommendations were generated and put through iterative Delphi rounds to achieve consensus. RESULTS: 60 recommendations achieved consensus and are included in this guideline. They address guideline use, pain assessment, general considerations, preoperative considerations, intraoperative considerations, regional anaesthesia, opioids, opioid-sparing, non-opioid medications, non-pharmaceutical pain management, and discharge considerations. CONCLUSIONS: Postoperative pain among children following cardiac surgery is currently an area of significant practice variability despite a large body of literature and the presence of centre-specific protocols. Central to the recommendations included in this guideline is the concept that ideal pain management begins with preoperative counselling and continues through to patient discharge. Overall, the quality of evidence supporting recommendations is low. There is ongoing need for research in this area, particularly in paediatric populations.

Mini-Mental State Examination and Montreal Cognitive Assessment as Tools for Following Cognitive Changes in Alzheimer's Disease Neuroimaging Initiative Participants.

BACKGROUND: Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) are two commonly used cognitive screening and diagnostic tools. OBJECTIVE: Our goal was to assess their efficacy for monitoring cognitive changes, as well as the correlation between the two tests. METHODS: At baseline, participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) were divided into four groups based on their cognitive diagnoses: healthy control (HC), early mild cognitive impairment (EMCI), late mild cognitive impairment (LMCI), and Alzheimer's disease (AD). MMSE or MoCA scores were compared among the four groups using an analysis of variance (ANOVA) model with repeated measures with post-hoc Bonferroni correction. For those participants who had both MMSE and MoCA assessments done, a Pearson correlation analysis was performed between the two assessments for each visit. RESULTS: The MMSE scores were significantly different among the four groups at baseline, which was true for each of the three annual follow-up visits. By contrast, the MoCA scores were not significantly different between HC and EMCI groups at either baseline or any of the follow-up visits. For participants with a diagnosis of LMCI, the cognitive performance deteriorated in a linear manner 12 months after the baseline, which was independent of MMSE or MoCA. At last, the MMSE scores were moderately related to MoCA scores, which got stronger along with the time of follow-up. CONCLUSION: MMSE and MoCA are comparable as cognitive assessment tools to monitor cognitive changes. In addition, the measurements of MMSE and MoCA are moderately correlated for the follow-up visits.

Hepatic abnormalities in youth with Turner syndrome.

BACKGROUND & AIMS: Liver disease in children with Turner Syndrome (TS) is poorly understood relative to associated growth, cardiac and reproductive complications. This study sought to better characterize hepatic abnormalities in a large national cohort of youth with TS. METHODS: Using electronic health record data from PEDSnet institutions, 2145 females with TS were matched to 8580 females without TS on eight demographic variables. Outcomes included liver enzymes (AST and ALT) stratified as normal, 1-2 times above the upper limit of normal (ULN), 2-3 times ULN and >3 times ULN, as well as specific liver disease diagnoses. RESULTS: Fifty-eight percent of youth with TS had elevated liver enzymes. Patients with TS had higher odds of enzymes 1-2 times ULN (OR: 1.7, 95% CI: 1.4-1.9), 2-3 times ULN (OR: 2.7, 95% CI: 1.7-3.3) and >3 times ULN (OR: 1.7, 95% CI: 1.3-2.2). They also had higher odds of any liver diagnosis (OR: 2.4, 95% CI: 1.7-3.3), fatty liver disease (OR: 1.9, 95% CI: 1.1-3.2), hepatitis (OR: 3.7, 95% CI: 1.9-7.1), cirrhosis/fibrosis (OR: 5.8, 95% CI: 1.3-25.0) and liver tumour/malignancy (OR: 4.8, 95% CI: 1.4-17.0). In a multinomial model, age, BMI and presence of cardiovascular disease or diabetes significantly increased the odds of elevated liver enzymes in girls with TS. CONCLUSIONS: Youth with TS have higher odds for elevated liver enzymes and clinically significant liver disease compared with matched controls. These results emphasize the need for clinical screening and additional research into the aetiology and treatment of liver disease in TS. LAY SUMMARY: Turner Syndrome, a chromosomal condition in which females are missing the second sex chromosome, is often associated with short stature, infertility and cardiac complications. Liver abnormalities are less well described in the literature. In this study, nearly 60% of youth with TS have elevated liver enzymes. Furthermore, patients with TS had a diagnosis of liver disease more often than patients without TS. Our results support the importance of early and consistent liver function screening and of additional research to define mechanisms that disrupt liver function in paediatric TS females.

Infective endocarditis following heart transplantation: A systematic review.

PURPOSE: Infective endocarditis (IE) is a rare but potentially fatal complication following heart transplantation (HTx). There is a lack of literature regarding the patterns and clinical course of IE development following HTx. We sought to pool the existing data in regards to defining characteristics, management options, and outcomes of IE following HTx. METHODS: An electronic search of Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, Ovid Medline, and the Scopus databases were performed to identify all articles in the English literature that report IE following HTx in adult patients. Patient-level data were extracted and analyzed. RESULTS: Systematic search yielded 57 patients from 32 articles. Median patient age was 52 [IQR 43, 59] and 75% of patients (43/57) were male. Median time to IE presentation post-HTx was 8.4 [IQR 3.0, 35.8] months. IE of the mitral valve was observed in 36.8% (21/57) of patients, followed by mural IE in 24.6% (14/57), and tricuspid valve IE in 21.1% (12/57). The most common organisms were Staphylococcus aureus in 26.3% (15/57), Aspergillus fumigatus in 19.3% (11/57), Enterococcus faecalis in 12.3% (7/57), and an undetermined or unspecified organism in 14.0% (8/57) patients. Overall case fatality was 44.6% (25/56). Fungal IE was associated with a significantly higher case fatality 75.0% (9/12) than that of bacterial IE 36.1% (13/36) (p = 0.02). Surgical management of post-HTx IE was observed in 35.1% (20/57) of patients. This included valve surgery for 70.0% (14/20), including the mitral valve in 50.0% (7/14), aortic valve in 35.7% (5/14), and the tricuspid valve in 14.3% (2/14) of patients. CONCLUSION: In addition to bacterial organisms, fungi also represent a frequent cause of IE in post-HTx patients. Overall HTx patient survival in the setting of IE is poor and may be worse if caused by A. fumigatus.

High Acuity Therapy Variation Across Pediatric Acute Care Cardiology Units: Results from the Pediatric Acute Care Cardiology Collaborative Hospital Surveys.

We utilized the multicenter Pediatric Acute Care Cardiology Collaborative (PAC3) 2017 and 2019 surveys to describe practice variation in therapy availability and changes over a 2-year period. A high acuity therapies (ATs) score was derived (1 point per positive response) from 44 survey questions and scores were compared to center surgical volume. Of 31 centers that completed the 2017 survey, 26 also completed the 2019 survey. Scores ranged from 11 to 34 in 2017 and 11 to 35 in 2019. AT scores in 2019 were not statistically different from 2017 scores (29/44, IQR 27-32.5 vs. 29.5/44, IQR 27-31, p = 0.9). In 2019, more centers reported initiation of continuous positive airway pressure (CPAP) and Bi-level positive airway pressure (BiPAP) in Acute Care Cardiology Unit (ACCU) (19/26 vs. 4/26, p < 0.001) and permitting continuous CPAP/BiPAP (22/26 vs. 14/26, p = 0.034) compared to 2017. Scores in both survey years were significantly higher in the highest surgical volume group compared to the lowest, 33 ± 1.5 versus 25 ± 8.5, p = 0.046 and 32 ± 1.7 versus 23 ± 5.5, p = 0.009, respectively. Variation in therapy within the ACCUs participating in PAC3 presents an opportunity for shared learning across the collaborative. Experience with PAC3 was associated with increasing available respiratory therapies from 2017 to 2019. Whether AT scores impact the quality and outcomes of pediatric acute cardiac care will be the subject of further investigation using a comprehensive registry launched in early 2019.

Dyslipidemia in childhood and adolescence: from screening to management.

PURPOSE OF REVIEW: To summarize types of dyslipidemia frequently encountered during childhood and adolescence, with a focus on screening, diagnosis, and management. RECENT FINDINGS: It is important that screening for atherosclerotic cardiovascular disease (ASCVD) begin in childhood. Genetic testing allows for increased awareness of dyslipidemia and more targeted intervention. Pharmacologic treatment of pediatric dyslipidemias has a good safety profile and can reduce adult ASCVD risk. SUMMARY: Much of what is known about pediatric dyslipidemia has been extrapolated from adult data, but recently, there have been increasing investigations within the pediatric population to better guide diagnosis and management of these disorders.

The added value of the advanced practice provider in paediatric acute care cardiology.

OBJECTIVES: Advanced practice providers (APPs) are being employed at increasing rates in order to meet new in-hospital care demands. Utilising the Paediatric Acute Care Cardiology Collaborative (PAC3) hospital survey, we evaluated variations in staffing models regarding first-line providers and assessed associations with programme volume, acuity of care, and post-operative length of stay (LOS). STUDY DESIGN: The PAC3 hospital survey defined staffing models and resource availability across member institutions. A resource acuity score was derived for each participating acute care cardiology unit. Surgical volume was obtained from The Society of Thoracic Surgeons database. Pearson's correlation coefficients were used to evaluate the relationship between staffing models and centre volume as well as unit acuity. A previously developed case-mix adjustment model for total post-operative LOS was utilised in a multinomial regression model to evaluate the association of APP patient coverage with observed-to-expected post-operative LOS. RESULTS: Surveys were completed by 31 (91%) PAC3 centres in 2017. Nearly all centres (94%) employ APPs, with a mean of 1.7 (range 0-5) APPs present on weekday rounds. The number of APPs present has a positive correlation with surgical volume (r = 0.49, p < 0.01) and increased acuity (r = 0.39, p = 0.03). In the multivariate model, as coverage by APPs increased from low to moderate or high, there was greater likelihood of having a shorter-than-expected post-operative LOS (p < 0.001). CONCLUSIONS: The incorporation of paediatric acute care cardiology APPs is associated with reduced post-operative LOS. Future studies are necessary to understand how APPs impact these patient-specific outcomes.

Consensus recommendations for the use of retinoids in ichthyosis and other disorders of cornification in children and adolescents.

Topical and systemic retinoids have long been used in the treatment of ichthyoses and other disorders of cornification. Due to the need for long-term use of retinoids for these disorders, often beginning in childhood, numerous clinical concerns must be considered. Systemic retinoids have known side effects involving bone and eye. Additionally, potential psychiatric and cardiovascular effects need to be considered. Contraceptive concerns, as well as the additive cardiovascular and bone effects of systemic retinoid use with hormonal contraception must also be deliberated for patients of childbearing potential. The Pediatric Dermatology Research Alliance (PeDRA) Use of Retinoids in Ichthyosis Work Group was formed to address these issues and to establish best practices regarding the use of retinoids in ichthyoses based on available evidence and expert opinion.

Beginning With the End in Mind: The Case for Primordial and Primary Cardiovascular Prevention in Youth.

Cardiovascular disease remains the leading cause of death worldwide. Although there is little direct evidence that ties the presence of risk factors in childhood with adult cardiovascular disease, there are multiple indirect lines of evidence that, when synthesized, make a strong case for maintaining cardiovascular health through childhood and adolescence as well as screening for and treating risk factors when they develop to diminish lifetime risk. This review summarizes these lines of evidence and asserts that it is imperative that primordial and primary cardiovascular risk reduction begins early.

Relationship Between Left Ventricular Geometry and Invasive Hemodynamics in Pediatric Pulmonary Hypertension.

Background Ventricular septal flattening, frequently present in pulmonary hypertension (PH), can be quantified using eccentricity index (EI). EI has not been evaluated by concurrent echocardiography and cardiac catheterization and traditionally does not account for postsystolic septal flattening, often seen in PH. We evaluated left ventricular shape, including a novel measure of maximal EI to account for postsystolic septal flattening, to establish the relationship with concurrent invasive hemodynamics. Methods Echocardiography was performed at 2 institutions in 78 pediatric PH patients during cardiac catheterization and in 78 matched controls. From midpapillary parasternal short-axis views, EI and right-to-left ventricular diameter ratio were assessed. Results EI and right-to-left ventricular measures were significantly increased in PH compared with controls. Shape measures correlated with invasive hemodynamics and PH outcome measures (PH-related hospitalization, functional class, medical therapy escalation, and BNP [brain natriuretic peptide]). End-systolic EI of 1.16 best identified the presence of PH, whereas a maximal EI of 1.42 and 1.94 best identified half-systemic and systemic PH, respectively. A maximal EI of 1.27 was associated with an odds ratio of 16.16 (95% CI, 6.62-39.46) for PH-related hospitalization or escalation of therapy. Conclusions Using simultaneous echocardiography and catheterization in the largest study population to date, we demonstrate that EI and right-to-left ventricular ratio correlate with invasive hemodynamics and outcomes measures, and EI can accurately define those with clinically important PH. These measures strengthen the ability of echocardiography to identify and follow pediatric PH patients, especially in the absence of methods to quantify right ventricular systolic pressures.

Alteration of cardiolipin biosynthesis and remodeling in single right ventricle congenital heart disease.

Despite advances in both medical and surgical therapies, individuals with single ventricle heart disease (SV) remain at high risk for the development of heart failure (HF). However, the molecular mechanisms underlying remodeling and eventual HF in patients with SV are poorly characterized. Cardiolipin (CL), an inner mitochondrial membrane phospholipid, is critical for proper mitochondrial function, and abnormalities in CL content and composition are known in various cardiovascular disease etiologies. The purpose of this study was to investigate myocardial CL content and composition in failing and nonfailing single right ventricle (RV) samples compared with normal control RV samples, to assess mRNA expression of CL biosynthetic and remodeling enzymes, and to quantitate relative mitochondrial copy number. A cross-sectional analysis of RV myocardial tissue from 22 failing SV (SVHF), 9 nonfailing SV (SVNF), and 10 biventricular control samples (BVNF) was performed. Expression of enzymes involved in CL biosynthesis and remodeling were analyzed using RT-qPCR and relative mitochondrial DNA copy number determined by qPCR. Normal phase high-pressure liquid chromatography coupled to electrospray ionization mass spectrometry was used to quantitate total and specific CL species. While mitochondrial copy number was not significantly different between groups, total CL content was significantly lower in SVHF myocardium compared with BVNF controls. Despite having lower total CL content however, the relative percentage of the major tetralinoleoyl CL species is preserved in SVHF samples relative to BVNF controls. Correspondingly, expression of enzymes involved in CL biosynthesis and remodeling were upregulated in SVHF samples when compared with both SVNF samples and BVNF controls.NEW & NOTEWORTHY The mechanisms underlying heart failure in the single ventricle (SV) congenital heart disease population are largely unknown. In this study we identify alterations in cardiac cardiolipin metabolism, composition, and content in children with SV heart disease. These findings suggest that cardiolipin could be a novel therapeutic target in this unique population of patients.

Exercise Performance at Increased Altitude After Fontan Operation: Comparison to Normal Controls and Correlation with Cavopulmonary Hemodynamics.

Exercise performance declines as patients who have undergone Fontan operation enter adolescence. However, the effect of altitude on functional capacity after Fontan remains inadequately studied. Our aim was to describe exercise performance in a cohort of patients with Fontan physiology living at increased altitude and compare to a normal control group and relate these data to invasively derived hemodynamics. We hypothesized that peak oxygen consumption ([Formula: see text]) would be decreased, in association with elevated mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVRi). Patients were evaluated in a multidisciplinary clinic for patients with Fontan physiology. Evaluation included cardiopulmonary exercise test and cardiac catheterization at predetermined intervals. Descriptive statistics were calculated. Associations of catheterization and exercise testing measures with [Formula: see text] were estimated with Spearman correlation coefficients. One hundred patients with age- and gender-matched controls were included in the analysis. The mean age was 13.3 ± 3.9 years, with mean weight of 47.1 ± 18.4 kg. The mean [Formula: see text] was 29.0 ± 7.8 ml/kg/min, significantly lower than the control group, 40.2 ± 8.4 ml/kg/min (p < 0.0001). There was no statistically significant linear correlation between [Formula: see text] and mPAP or PVRi. We characterized exercise performance in a large cohort with Fontan physiology living at increased altitude and showed a decrease in [Formula: see text] compared to controls. Our data do not support the hypothesis that moderately increased altitude has a detrimental effect on exercise performance, nor is there a substantial link between poor cavopulmonary hemodynamics and exercise in this setting.