Topic: Congenital

Abstract

Clinical characteristics, diagnosis, and risk stratification of pulmonary hypertension in severe tricuspid regurgitation and implications for transcatheter tricuspid valve repair.

Lurz P, Orban M, Besler C, Braun D, ... Hausleiter J, Rommel KP
Aims
Patients with pulmonary hypertension (PHT) are often excluded from surgical therapies for tricuspid regurgitation (TR). Transcatheter tricuspid valve repair (TTVR) with the MitraClip™ technique is a novel treatment option for these patients. We aimed to assess the role of PHT in severe TR and its implications for TTVR.
Methods and results
A total of 243 patients underwent TTVR at two centres. One hundred twenty-one patients were grouped as iPHT+ [invasive systolic pulmonary artery pressures (PAPs) ≥50 mmHg]. Patients were similarly stratified according to echocardiographic PAPs (ePHT). The occurrence of the combined clinical endpoint (death, heart failure hospitalization, and reintervention) was investigated during a follow-up of 330 (interquartile range 175-402) days. iPHT+ patients were at higher preoperative risk (P < 0.01), had more severe symptoms (P = 0.01), higher N-terminal pro-B-type natriuretic peptide levels (P < 0.01), more impaired right ventricular (RV) function (P < 0.01), and afterload corrected RV function (P < 0.01). Procedural TTVR success was similar in iPHT+ and iPHT- patients (84 vs. 84%, P = 0.99). The echocardiographic diagnostic accuracy to detect iPHT was only 55%. During follow-up, 35% of patients reached the combined clinical endpoint. The discordant diagnosis of iPHT+/ePHT- carried the highest risk for the combined clinical endpoint [HR 3.76 (CI 2.25-6.37), P < 0.01], while iPHT+/ePHT+ patients had a similar survival-free time from the combined endpoint compared to iPHT- patients (P = 0.48). In patients with isolated tricuspid procedure (n = 131) a discordant iPHT+/ePHT- diagnosis and an impaired afterload corrected RV function (P < 0.01 for both) were independent predictors for the occurrence of the combined endpoint.
Conclusion
The discordant echocardiographic and invasive diagnosis of PHT in severe TR predicts outcomes after TTVR.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Eur Heart J: 15 Mar 2020; epub ahead of print
Lurz P, Orban M, Besler C, Braun D, ... Hausleiter J, Rommel KP
Eur Heart J: 15 Mar 2020; epub ahead of print | PMID: 32176280
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Abstract

Functional tricuspid regurgitation of degenerative mitral valve disease: a crucial determinant of survival.

Essayagh B, Antoine C, Benfari G, Maalouf J, ... Avierinos JF, Enriquez-Sarano M
Aims 
To assess functional tricuspid regurgitation (FTR) determinants, consequences, and independent impact on outcome in degenerative mitral regurgitation (DMR).
Methods and results 
All patients diagnosed with isolated DMR 2003-2011, with structurally normal tricuspid leaflets, prospective FTR grading and systolic pulmonary artery pressure (sPAP) estimation by Doppler echocardiography at diagnosis were identified and long-term outcome analysed. The 5083 DMR eligible patients [63 ± 16 years, 47% female, ejection fraction (EF) 63 ± 7%, and sPAP 35 ± 13 mmHg] presented with FTR graded trivial in 45%, mild in 37%, moderate in 15%, and severe in 3%. While pulmonary hypertension (PHTN-sPAP ≥ 50 mmHg) was the most powerful FTR severity determinant, other strong FTR determinants were older age, female sex, lower left ventricle EF, DMR, and particularly atrial fibrillation (AFib) (all P ≤ 0.002). Functional tricuspid regurgitation moderate/severe was independently linked to more severe clinical presentation, more oedema, lower stroke volume, and impaired renal function (P ≤ 0.01). Survival (95% confidence interval) throughout follow-up [70% (69-72%) at 10 years] was strongly associated with FTR severity [82% (80-84%) for trivial, 69% (66-71%) for mild, 51% (47-57%) for moderate, and 26% (19-35%) for severe, P < 0.0001]. Excess mortality persisted after comprehensive adjustment [adjusted hazard ratio 1.40 (1.18-1.67) for moderate FTR and 2.10 (1.63-2.70) for severe FTR, P ≤ 0.01]. Excess mortality persisted adjusting for sPAP/right ventricular function (P < 0.0001), by matching [adjusted hazard ratios 2.08 (1.50-2.89), P < 0.0001] and vs. expected survival [risk ratio 1.79 (1.48-2.16), P < 0.0001]. Within 5-year of diagnosis valve surgery was performed in 73% (70-75%) and 15% (13-17%) of severe and moderate DMR and in only 26% (19-34%) and 6% (4-8%) of severe and moderate FTR. Valvular surgery improved outcome without alleviating completely higher mortality associated with FTR (P < 0.0001).
Conclusion 
In this large DMR cohort, FTR was frequent and causally, not only linked to PHTN but also to other factors, particularly AFib. Higher FTR severity is associated at diagnosis with more severe clinical presentation. Long term, FTR is independently of all confounders, associated with considerably worse mortality. Functional tricuspid regurgitation moderate and even severe is profoundly undertreated. Thus careful assessment, consideration for tricuspid surgery, and testing of new transcatheter therapy is warranted.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Eur Heart J: 15 Apr 2020; epub ahead of print
Essayagh B, Antoine C, Benfari G, Maalouf J, ... Avierinos JF, Enriquez-Sarano M
Eur Heart J: 15 Apr 2020; epub ahead of print | PMID: 32300779
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Abstract

Challenges and Special Aspects of Pulmonary Hypertension in Middle- to Low-Income Regions: JACC State-of-the-Art Review.

Hasan B, Hansmann G, Budts W, Heath A, ... Kumar RK,

Challenges and special aspects related to the management and prognosis of pulmonary hypertension (PH) in middle- to low-income regions (MLIRs) range from late presentation to comorbidities, lack of resources and expertise, cost, and rare options of lung transplantation. Expert consensus recommendations addressing the specific challenges for prevention and therapy of PH in MLIRs with limited resources have been lacking. To date, 6 MLIR-PH registries containing mostly adult patients with PH exist. Importantly, the global prevalence of PH is much higher in MLIRs compared with high-income regions: group 2 PH (left heart disease), pulmonary arterial hypertension associated with unrepaired congenital heart disease, human immunodeficiency virus, or schistosomiasis are highly prevalent. This consensus statement provides selective, tailored modifications to the current PH guidelines to address the specific challenges faced in MLIRs, resulting in the first pragmatic and cost-effective consensus recommendations for PH care providers, patients, and their families.

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 18 May 2020; 75:2463-2477
Hasan B, Hansmann G, Budts W, Heath A, ... Kumar RK,
J Am Coll Cardiol: 18 May 2020; 75:2463-2477 | PMID: 32408981
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Abstract

Effects of Chronic Nicotine Inhalation on Systemic and Pulmonary Blood Pressure and Right Ventricular Remodeling in Mice.

Oakes JM, Xu J, Morris TM, Fried ND, ... Gardner JD, Yue X

Cigarette smoking is the single most important risk factor for the development of cardiovascular and pulmonary diseases; however, the role of nicotine in the pathogenesis of these diseases is incompletely understood. The purpose of this study was to examine the effects of chronic nicotine inhalation on the development of cardiovascular and pulmonary disease with a focus on blood pressure and cardiac remodeling. Male C57BL6/J mice were exposed to air (control) or nicotine vapor (daily, 12 hour on/12 hour off) for 8 weeks. Systemic blood pressure was recorded weekly by radio-telemetry, and cardiac remodeling was monitored by echocardiography. At the end of the 8 weeks, mice were subjected to right heart catheterization to measure right ventricular systolic pressure. Nicotine-exposed mice exhibited elevated systemic blood pressure from weeks 1 to 3, which then returned to baseline from weeks 4 to 8, indicating development of tolerance to nicotine. At 8 weeks, significantly increased right ventricular systolic pressure was detected in nicotine-exposed mice compared with the air controls. Echocardiography showed that 8-week nicotine inhalation resulted in right ventricular (RV) hypertrophy with increased RV free wall thickness and a trend of increase in RV internal diameter. In contrast, there were no significant structural or functional changes in the left ventricle following nicotine exposure. Mechanistically, we observed increased expression of angiotensin-converting enzyme and enhanced activation of mitogen-activated protein kinase pathways in the RV but not in the left ventricle. We conclude that chronic nicotine inhalation alters both systemic and pulmonary blood pressure with the latter accompanied by RV remodeling, possibly leading to progressive and persistent pulmonary hypertension.



Hypertension: 15 Mar 2020:HYPERTENSIONAHA11914608; epub ahead of print
Oakes JM, Xu J, Morris TM, Fried ND, ... Gardner JD, Yue X
Hypertension: 15 Mar 2020:HYPERTENSIONAHA11914608; epub ahead of print | PMID: 32172623
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Abstract

Inherited Thoracic Aortic Disease: New Insights and Translational Targets.

Fletcher AJ, Syed MBJ, Aitman TJ, Newby DE, Walker NL

Inherited thoracic aortopathies denote a group of congenital conditions that predispose to disease of the thoracic aorta. Aortic wall weakness and abnormal aortic hemodynamic profiles predispose these patients to dilatation of the thoracic aorta, which is generally silent but can precipitate aortic dissection or rupture with devastating and often fatal consequences. Current strategies to assess the future risk of aortic dissection or rupture are based primarily on monitoring aortic diameter. However, diameter alone is a poor predictor of risk, with many patients experiencing dissection or rupture below current intervention thresholds. Developing tools that improve the risk assessment of those with aortopathy is internationally regarded as a research priority. A robust understanding of the molecular pathways that lead to aortic wall weakness is required to identify biomarkers and therapeutic targets that could improve patient management. Here, we summarize the current understanding of the genetically determined mechanisms underlying inherited aortopathies and critically appraise the available blood biomarkers, imaging techniques, and therapeutic targets that have shown promise for improving the management of patients with these important and potentially fatal conditions.



Circulation: 11 May 2020; 141:1570-1587
Fletcher AJ, Syed MBJ, Aitman TJ, Newby DE, Walker NL
Circulation: 11 May 2020; 141:1570-1587 | PMID: 32392100
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Abstract

Treatment With Treprostinil and Metformin Normalizes Hyperglycemia and Improves Cardiac Function in Pulmonary Hypertension Associated With Heart Failure With Preserved Ejection Fraction.

Wang L, Halliday G, Huot JR, Satoh T, ... Gladwin MT, Lai YC
Objective
Pulmonary hypertension (PH) due to left heart disease (group 2), especially in the setting of heart failure with preserved ejection fraction (HFpEF), is the most common cause of PH worldwide; however, at present, there is no proven effective therapy available for its treatment. PH-HFpEF is associated with insulin resistance and features of metabolic syndrome. The stable prostacyclin analog, treprostinil, is an effective and widely used Food and Drug Administration-approved drug for the treatment of pulmonary arterial hypertension. While the effect of treprostinil on metabolic syndrome is unknown, a recent study suggests that the prostacyclin analog beraprost can improve glucose intolerance and insulin sensitivity. We sought to evaluate the effectiveness of treprostinil in the treatment of metabolic syndrome-associated PH-HFpEF. Approach and Results: Treprostinil treatment was given to mice with mild metabolic syndrome-associated PH-HFpEF induced by high-fat diet and to SU5416/obese ZSF1 rats, a model created by the treatment of rats with a more profound metabolic syndrome due to double leptin receptor defect (obese ZSF1) with a vascular endothelial growth factor receptor blocker SU5416. In high-fat diet-exposed mice, chronic treatment with treprostinil reduced hyperglycemia and pulmonary hypertension. In SU5416/Obese ZSF1 rats, treprostinil improved hyperglycemia with similar efficacy to that of metformin (a first-line drug for type 2 diabetes mellitus); the glucose-lowering effect of treprostinil was further potentiated by the combined treatment with metformin. Early treatment with treprostinil in SU5416/Obese ZSF1 rats lowered pulmonary pressures, and a late treatment with treprostinil together with metformin improved pulmonary artery acceleration time to ejection time ratio and tricuspid annular plane systolic excursion with AMPK (AMP-activated protein kinase) activation in skeletal muscle and the right ventricle.
Conclusions
Our data suggest a potential use of treprostinil as an early treatment for mild metabolic syndrome-associated PH-HFpEF and that combined treatment with treprostinil and metformin may improve hyperglycemia and cardiac function in a more severe disease.



Arterioscler Thromb Vasc Biol: 08 Apr 2020:ATVBAHA119313883; epub ahead of print
Wang L, Halliday G, Huot JR, Satoh T, ... Gladwin MT, Lai YC
Arterioscler Thromb Vasc Biol: 08 Apr 2020:ATVBAHA119313883; epub ahead of print | PMID: 32268788
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Abstract

Subnational mapping of under-5 and neonatal mortality trends in India: the Global Burden of Disease Study 2000-17.


Background
India has made substantial progress in improving child survival over the past few decades, but a comprehensive understanding of child mortality trends at disaggregated geographical levels is not available. We present a detailed analysis of subnational trends of child mortality to inform efforts aimed at meeting the India National Health Policy (NHP) and Sustainable Development Goal (SDG) targets for child mortality.
Methods
We assessed the under-5 mortality rate (U5MR) and neonatal mortality rate (NMR) from 2000 to 2017 in 5 × 5 km grids across India, and for the districts and states of India, using all accessible data from various sources including surveys with subnational geographical information. The 31 states and groups of union territories were categorised into three groups using their Socio-demographic Index (SDI) level, calculated as part of the Global Burden of Diseases, Injuries, and Risk Factors Study on the basis of per-capita income, mean education, and total fertility rate in women younger than 25 years. Inequality between districts within the states was assessed using the coefficient of variation. We projected U5MR and NMR for the states and districts up to 2025 and 2030 on the basis of the trends from 2000 to 2017 and compared these projections with the NHP 2025 and SDG 2030 targets for U5MR (23 deaths and 25 deaths per 1000 livebirths, respectively) and NMR (16 deaths and 12 deaths per 1000 livebirths, respectively). We assessed the causes of child death and the contribution of risk factors to child deaths at the state level.
Findings
U5MR in India decreased from 83·1 (95% uncertainty interval [UI] 76·7-90·1) in 2000 to 42·4 (36·5-50·0) per 1000 livebirths in 2017, and NMR from 38·0 (34·2-41·6) to 23·5 (20·1-27·8) per 1000 livebirths. U5MR varied 5·7 times between the states of India and 10·5 times between the 723 districts of India in 2017, whereas NMR varied 4·5 times and 8·0 times, respectively. In the low SDI states, 275 (88%) districts had a U5MR of 40 or more per 1000 livebirths and 291 (93%) districts had an NMR of 20 or more per 1000 livebirths in 2017. The annual rate of change from 2010 to 2017 varied among the districts from a 9·02% (95% UI 6·30-11·63) reduction to no significant change for U5MR and from an 8·05% (95% UI 5·34-10·74) reduction to no significant change for NMR. Inequality between districts within the states increased from 2000 to 2017 in 23 of the 31 states for U5MR and in 24 states for NMR, with the largest increases in Odisha and Assam among the low SDI states. If the trends observed up to 2017 were to continue, India would meet the SDG 2030 U5MR target but not the SDG 2030 NMR target or either of the NHP 2025 targets. To reach the SDG 2030 targets individually, 246 (34%) districts for U5MR and 430 (59%) districts for NMR would need a higher rate of improvement than they had up to 2017. For all major causes of under-5 death in India, the death rate decreased between 2000 and 2017, with the highest decline for infectious diseases, intermediate decline for neonatal disorders, and the smallest decline for congenital birth defects, although the magnitude of decline varied widely between the states. Child and maternal malnutrition was the predominant risk factor, to which 68·2% (65·8-70·7) of under-5 deaths and 83·0% (80·6-85·0) of neonatal deaths in India could be attributed in 2017; 10·8% (9·1-12·4) of under-5 deaths could be attributed to unsafe water and sanitation and 8·8% (7·0-10·3) to air pollution.
Interpretation
India has made gains in child survival, but there are substantial variations between the states in the magnitude and rate of decline in mortality, and even higher variations between the districts of India. Inequality between districts within states has increased for the majority of the states. The district-level trends presented here can provide crucial guidance for targeted efforts needed in India to reduce child mortality to meet the Indian and global child survival targets. District-level mortality trends along with state-level trends in causes of under-5 and neonatal death and the risk factors in this Article provide a comprehensive reference for further planning of child mortality reduction in India.
Funding
Bill & Melinda Gates Foundation; and Indian Council of Medical Research, Department of Health Research, Ministry of Health and Family Welfare, Government of India.

© 2020 World Health Organization; licensee Elsevier. This is an Open Access article published under the CC BY 3.0 IGO license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products, or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article\'s original URL.

Lancet: 10 May 2020; epub ahead of print
Lancet: 10 May 2020; epub ahead of print | PMID: 32413293
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Abstract

Structure of nevanimibe-bound tetrameric human ACAT1.

Long T, Sun Y, Hassan A, Qi X, Li X

Cholesterol is an essential component of mammalian cell membranes, constituting up to 50% of plasma membrane lipids. By contrast, it accounts for only 5% of lipids in the endoplasmic reticulum (ER). The ER enzyme sterol O-acyltransferase 1 (also named acyl-coenzyme A:cholesterol acyltransferase, ACAT1) transfers a long-chain fatty acid to cholesterol to form cholesteryl esters that coalesce into cytosolic lipid droplets. Under conditions of cholesterol overload, ACAT1 maintains the low cholesterol concentration of the ER and thereby has an essential role in cholesterol homeostasis. ACAT1 has also been implicated in Alzheimer\'s disease, atherosclerosis and cancers. Here we report a cryo-electron microscopy structure of human ACAT1 in complex with nevanimibe, an inhibitor that is in clinical trials for the treatment of congenital adrenal hyperplasia. The ACAT1 holoenzyme is a tetramer that consists of two homodimers. Each monomer contains nine transmembrane helices (TMs), six of which (TM4-TM9) form a cavity that accommodates nevanimibe and an endogenous acyl-coenzyme A. This cavity also contains a histidine that has previously been identified as essential for catalytic activity. Our structural data and biochemical analyses provide a physical model to explain the process of cholesterol esterification, as well as details of the interaction between nevanimibe and ACAT1, which may help to accelerate the development of ACAT1 inhibitors to treat related diseases.



Nature: 29 Apr 2020; 581:339-343
Long T, Sun Y, Hassan A, Qi X, Li X
Nature: 29 Apr 2020; 581:339-343 | PMID: 32433613
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Abstract

Angiotensin Converting Enzyme 2: SARS-CoV-2 Receptor and Regulator of the Renin-Angiotensin System.

Gheblawi M, Wang K, Viveiros A, Nguyen Q, ... Grant MB, Oudit GY

Angiotensin-converting enzyme (ACE2) has a multiplicity of physiological roles that revolve around its trivalent function: a negative regulator of the renin-angiotensin system (RAS), facilitator of amino acid transport, and the SARS-CoV and SARS-CoV-2 receptor. ACE2 is widely expressed, including, in the lungs, cardiovascular system, gut, kidneys, central nervous system, and adipose tissue. ACE2 has recently been identified as the SARS-CoV-2 receptor, the infective agent responsible for COVID-19, providing a critical link between immunity, inflammation, ACE2, and cardiovascular disease. Although sharing a close evolutionary relationship with SARS-CoV, the receptor-binding domain of SARS-CoV-2 differs in several key amino acid residues, allowing for stronger binding affinity with the human ACE2 receptor, which may account for the greater pathogenicity of SARS-CoV-2. The loss of ACE2 function following binding by SARS-CoV-2 is driven by endocytosis and activation of proteolytic cleavage and processing. The ACE2 system is a critical protective pathway against heart failure with reduced and preserved ejection fraction including, myocardial infarction and hypertension, and against lung disease and diabetes. The control of gut dysbiosis and vascular permeability by ACE2 has emerged as an essential mechanism of pulmonary hypertension and diabetic cardiovascular complications. Recombinant ACE2, gene-delivery of Ace2, Ang 1-7 analogs, and Mas receptor agonists enhance ACE2 action and serve as potential therapies for disease conditions associated with an activated RAS. Recombinant human ACE2 has completed clinical trials and efficiently lowered or increased plasma angiotensin II and angiotensin 1-7 levels, respectively. Our review summarizes the progress over the past 20 years, highlighting the critical role of ACE2 as the novel SARS-CoV-2 receptor and as the negative regulator of the RAS, together with implications for the COVID-19 pandemic and associated cardiovascular diseases.



Circ Res: 07 Apr 2020; epub ahead of print
Gheblawi M, Wang K, Viveiros A, Nguyen Q, ... Grant MB, Oudit GY
Circ Res: 07 Apr 2020; epub ahead of print | PMID: 32264791
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Abstract

Implantable cardiac electronic device therapy for patients with a systemic right ventricle.

Barracano R, Brida M, Guarguagli S, Palmieri R, ... Gatzoulis MA, Wong T

The systemic right ventricle (SRV), defined as the morphological right ventricle supporting the systemic circulation, is relatively common in congenital heart disease (CHD). Our review aimed at examining the current evidence, knowledge gaps and technical considerations regarding implantable cardiac electronic device therapy in patients with SRV. The risk of sinus node dysfunction (SND) after atrial switch repair and/or complete heart block in congenitally corrected transposition of great arteries requiring permanent pacing increases with age. Similar to acquired heart disease, indication for pacing includes symptomatic bradycardia, SND and high degree atrioventricular nodal block. Right ventricular dysfunction and heart failure also represent important complications in SRV patients. Cardiac resynchronisation therapy (CRT) has been proposed to improve systolic function in SRV patients, although indications for CRT are not well defined and its potential benefit remains uncertain. Amongst adult CHD, patients with SRV are at the highest risk for sudden cardiac death (SCD). Nevertheless, risk stratification for SCD is scarce in this cohort and implantable cardioverter-defibrillator indication is currently limited to secondary prevention. Vascular access and the incidence of device-related complications, such as infections, inappropriate shocks and device system failure, represent additional challenges to implantable cardiac electronic device therapy in patients with SRV. A multidisciplinary approach with tertiary expertise and future collaborative research are all paramount to further the care for this challenging nonetheless ever increasing cohort of patients.

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 07 Apr 2020; epub ahead of print
Barracano R, Brida M, Guarguagli S, Palmieri R, ... Gatzoulis MA, Wong T
Heart: 07 Apr 2020; epub ahead of print | PMID: 32269130
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Abstract

Gut Pathology and Its Rescue by ACE2 (Angiotensin-Converting Enzyme 2) in Hypoxia-Induced Pulmonary Hypertension.

Sharma RK, Oliveira AC, Yang T, Karas MM, ... Richards EM, Raizada MK

Therapeutic advances for pulmonary hypertension (PH) have been incremental because of the focus on the pulmonary vasculature in PH pathology. Here, we evaluate the concept that PH is, rather, a systemic disorder involving interplay among multiorgan systems, including brain, gut, and lungs. Therefore, the objective of this study was to evaluate the hypothesis that PH is associated with a dysfunctional brain-gut-lung axis and that global overexpression of ACE2 (angiotensin-converting enzyme 2) rebalances this axis and protects against PH. ACE2 knockin and wild-type (WT; C57BL/6) mice were subjected to chronic hypoxia (10% FIO2) or room air for 4 weeks. Cardiopulmonary hemodynamics, histology, immunohistochemistry, and fecal 16S rRNA microbial gene analyses were evaluated. Hypoxia significantly increased right ventricular systolic pressure, sympathetic activity as well as the number and activation of microglia in the paraventricular nucleus of the hypothalamus in WT mice. This was associated with a significant increase in muscularis layer thickening and decreases in both villi length and goblet cells and altered gut microbiota. Global overexpression of ACE2 prevented changes in hypoxia-induced pulmonary and gut pathophysiology and established distinct microbial communities from WT hypoxia mice. Furthermore, WT mice subjected to fecal matter transfer from ACE2 knockin mice were resistant to hypoxia-induced PH compared with their controls receiving WT fecal matter transfer. These observations demonstrate that ACE2 ameliorates these hypoxia-induced pathologies and attenuates PH. The data implicate dysfunctional brain-gut-lung communication in PH and provide novel avenues for therapeutic interventions.



Hypertension: 17 May 2020:HYPERTENSIONAHA12014931; epub ahead of print
Sharma RK, Oliveira AC, Yang T, Karas MM, ... Richards EM, Raizada MK
Hypertension: 17 May 2020:HYPERTENSIONAHA12014931; epub ahead of print | PMID: 32418496
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Abstract

Oral fluconazole use in the first trimester and risk of congenital malformations: population based cohort study.

Zhu Y, Bateman BT, Gray KJ, Hernandez-Diaz S, ... Straub L, Huybrechts KF
Objective
To examine the risk of congenital malformations associated with exposure to oral fluconazole at commonly used doses in the first trimester of pregnancy for the treatment of vulvovaginal candidiasis.
Design
Population based cohort study.
Setting
A cohort of pregnancies publicly insured in the United States, with data from the nationwide Medicaid Analytic eXtract 2000-14.
Participants
Pregnancies of women enrolled in Medicaid from three or more months before the last menstrual period to one month after delivery, and infants enrolled for three or more months after birth.
Interventions
Use of fluconazole and topical azoles was established by requiring one or more prescriptions during the first trimester of pregnancy.
Main outcome measures
Risk of musculoskeletal malformations, conotruncal malformations, and oral clefts (primary outcomes), associated with exposure to oral fluconazole, diagnosed during the first 90 days after delivery, were examined.
Results
The study cohort of 1 969 954 pregnancies included 37 650 (1.9%) pregnancies exposed to oral fluconazole and 82 090 (4.2%) pregnancies exposed to topical azoles during the first trimester. The risk of musculoskeletal malformations was 52.1 (95% confidence interval 44.8 to 59.3) per 10 000 pregnancies exposed to fluconazole versus 37.3 (33.1 to 41.4) per 10 000 pregnancies exposed to topical azoles. The risks of conotruncal malformations were 9.6 (6.4 to 12.7) versus 8.3 (6.3 to 10.3) per 10 000 pregnancies exposed to fluconazole and topical azoles, respectively; risks of oral clefts were 9.3 (6.2 to 12.4) versus 10.6 (8.4 to 12.8) per 10 000 pregnancies, respectively. The adjusted relative risk after fine stratification of the propensity score was 1.30 (1.09 to 1.56) for musculoskeletal malformations, 1.04 (0.70 to 1.55) for conotruncal malformations, and 0.91 (0.61 to 1.35) for oral clefts overall. Based on cumulative doses of fluconazole, the adjusted relative risks for musculoskeletal malformations, conotruncal malformations, and oral clefts overall were 1.29 (1.05 to 1.58), 1.12 (0.71 to 1.77), and 0.88 (0.55 to 1.40) for 150 mg of fluconazole; 1.24 (0.93 to 1.66), 0.61 (0.26 to 1.39), and 1.08 (0.58 to 2.04) for more than 150 mg up to 450 mg of fluconazole; and 1.98 (1.23 to 3.17), 2.30 (0.93 to 5.65), and 0.94 (0.23 to 3.82) for more than 450 mg of fluconazole, respectively.
Conclusions
Oral fluconazole use in the first trimester was not associated with oral clefts or conotruncal malformations, but an association with musculoskeletal malformations was found, corresponding to a small adjusted risk difference of about 12 incidents per 10 000 exposed pregnancies overall.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

BMJ: 19 May 2020; 369:m1494
Zhu Y, Bateman BT, Gray KJ, Hernandez-Diaz S, ... Straub L, Huybrechts KF
BMJ: 19 May 2020; 369:m1494 | PMID: 32434758
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Abstract

Prognostic value of von Willebrand factor in adult patients with congenital heart disease.

Ohuchi H, Hayama Y, Miike H, Suzuki D, ... Kurosaki KI, Nakai M
Objectives
von Willebrand factor (vWF) has prognostic value in patients with heart failure (HF) and in those with liver disease. Liver congestion, due to right-sided HF (RHF), is one of the major clinical pathophysiologic manifestations in adults with congenital heart disease (ACHD). The present study\'s purpose was to clarify the prognostic value of plasma levels of vWF antigen (vWF:Ag) in ACHD.
Methods
We measured vWF:Ag (%) in 382 consecutive patients (20 unrepaired cyanotic ACHD, 172 Fontan patients and 190 ACHD after biventricular repair) and compared the results with the clinical profiles and prognosis.
Results
The plasma vWF:Ag level was 130±53 (normal range: 55%-190%), and 48 patients (13%) showed high levels of vWF:Ag (≥190%). Older age, Fontan circulation, higher central venous pressure, lower arterial oxygen saturation and lower plasma levels of albumin were independently associated with high log (vWF:Ag) (p<0.05-0.0001). During the follow-up of 2.4±1.4 years, 15 patients died. High log (vWF:Ag) predicted the all-cause mortality (HR 1.63 per 0.1, 95% CI 1.40 to 1.96, p<0.0001). Specifically, patients with high vWF:Ag (≥165%) had a substantially higher risk of all-cause mortality (HR 56.4, 95% CI 11.4 to 1020, p<0.0001), and this prognostic value was independent of plasma levels of brain-type natriuretic peptide.
Conclusions
High vWF:Ag may reflect RHF severity and related liver dysfunction with a strong prognostic value of all-cause mortality in ACHD. Thus, vWF:Ag might be an excellent biomarker for monitoring ACHD with RHF.

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 17 Mar 2020; epub ahead of print
Ohuchi H, Hayama Y, Miike H, Suzuki D, ... Kurosaki KI, Nakai M
Heart: 17 Mar 2020; epub ahead of print | PMID: 32188625
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Abstract

Prevalence of Continuous Pulse Oximetry Monitoring in Hospitalized Children With Bronchiolitis Not Requiring Supplemental Oxygen.

Bonafide CP, Xiao R, Brady PW, Landrigan CP, ... Schondelmeyer A,
Importance
US national guidelines discourage the use of continuous pulse oximetry monitoring in hospitalized children with bronchiolitis who do not require supplemental oxygen.
Objective
Measure continuous pulse oximetry use in children with bronchiolitis.
Design, setting, and participants
A multicenter cross-sectional study was performed in pediatric wards in 56 US and Canadian hospitals in the Pediatric Research in Inpatient Settings Network from December 1, 2018, through March 31, 2019. Participants included a convenience sample of patients aged 8 weeks through 23 months with bronchiolitis who were not receiving active supplemental oxygen administration. Patients with extreme prematurity, cyanotic congenital heart disease, pulmonary hypertension, home respiratory support, neuromuscular disease, immunodeficiency, or cancer were excluded.
Exposures
Hospitalization with bronchiolitis without active supplemental oxygen administration.
Main outcomes and measures
The primary outcome, receipt of continuous pulse oximetry, was measured using direct observation. Continuous pulse oximetry use percentages were risk standardized using the following variables: nighttime (11 pm to 7 am), age combined with preterm birth, time after weaning from supplemental oxygen or flow, apnea or cyanosis during the present illness, neurologic impairment, and presence of an enteral feeding tube.
Results
The sample included 3612 patient observations in 33 freestanding children\'s hospitals, 14 children\'s hospitals within hospitals, and 9 community hospitals. In the sample, 59% were male, 56% were white, and 15% were black; 48% were aged 8 weeks through 5 months, 28% were aged 6 through 11 months, 16% were aged 12 through 17 months, and 9% were aged 18 through 23 months. The overall continuous pulse oximetry monitoring use percentage in these patients, none of whom were receiving any supplemental oxygen or nasal cannula flow, was 46% (95% CI, 40%-53%). Hospital-level unadjusted continuous pulse oximetry use ranged from 2% to 92%. After risk standardization, use ranged from 6% to 82%. Intraclass correlation coefficient suggested that 27% (95% CI, 19%-36%) of observed variation was attributable to unmeasured hospital-level factors.
Conclusions and relevance
In a convenience sample of children hospitalized with bronchiolitis who were not receiving active supplemental oxygen administration, monitoring with continuous pulse oximetry was frequent and varied widely among hospitals. Because of the apparent absence of a guideline- or evidence-based indication for continuous monitoring in this population, this practice may represent overuse.



JAMA: 20 Apr 2020; 323:1467-1477
Bonafide CP, Xiao R, Brady PW, Landrigan CP, ... Schondelmeyer A,
JAMA: 20 Apr 2020; 323:1467-1477 | PMID: 32315058
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Abstract

Cardiac catheter intervention complexity and safety outcomes in adult congenital heart disease.

Brida M, Diller GP, Nashat H, Barracano R, ... Rigby ML, Gatzoulis MA
Objective
To describe the intervention spectrum, complexity, and safety outcomes of catheter-based interventions in a contemporary adult congenital heart disease (ACHD) tertiary cohort.
Methods
All patients over 16 years who underwent a catheter-based intervention for ACHD in our centre between 2000 and 2016 were included. Baseline demographics, clinical characteristics, indications for and complexity of intervention, procedural complications and early and mid-term mortality were analysed.
Results
Overall, 1644 catheter-based interventions were performed. Intervention complexity ranged from simple (67.5%) to intermediate (26.4%) and to high (6.1%). Commonly performed procedures were atrial septal defect (33.4%) and patent foramen ovale closure (26.1%) followed by coarctation of the aorta (11.1%) and pulmonary artery interventions (7.0%). Age at index intervention was 40±16 years, 758 (46.1%) patients were male, 73.2% in New York Heart Association (NYHA) class I, 20.2% in NYHA class II, whereas 6.6% in NYHA class III/IV. In-hospital mortality was 0.7%. Median postinterventional length of stay was 1 day. Complications occurred in 129 (7.9%) with major adverse events in 21 (1.3%). One-year postintervention survival rates were 98.7% (95% CI 98.2 to 99.2). Over the study period, there was a notable shift in intervention complexity, with a predominance of simple procedures performed in early years and more complex procedures in later years. Furthermore, the case mix during the study broadened (p<0.001) with new catheter-based interventions and a more individualised approach to therapy.
Conclusion
This study shows an increasing complexity and expanding variability of ACHD catheter-based interventions, associated with low major complications, short hospital stays and low early and mid-term mortality. Ongoing investment in ACHD catheter interventions is warranted.

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 22 Mar 2020; epub ahead of print
Brida M, Diller GP, Nashat H, Barracano R, ... Rigby ML, Gatzoulis MA
Heart: 22 Mar 2020; epub ahead of print | PMID: 32205313
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Abstract

Severe Plasma Prekallikrein Deficiency: Clinical Characteristics, Novel KLKB1 Mutations, and Estimated Prevalence.

Barco S, Sollfrank S, Trinchero A, Adenaeuer A, ... Lämmle B, Rossmann H
Background
Severe plasma prekallikrein (PK) deficiency is an autosomal-recessive defect characterized by isolated aPTT prolongation. To date, no comprehensive methodologically-firm analysis investigated the diagnostic, clinical, and genetic characteristics of PK deficiency, and its prevalence remains unknown.
Patients/methods
We described new families with PK deficiency, retrieved clinical and laboratory information of cases systematically searched in the (grey) literature, and collected blood of these cases for complementary analyses. The Genome Aggregation Database (gnomAD) and the population-based Gutenberg Health Study served to study the prevalence of mutations and relevant genetic variants.
Results
We assembled a cohort of 111 cases from 89 families and performed new genetic analyses in eight families (three unpublished). We identified new KLKB1 mutations, excluded the pathogenicity of some of the previously described ones, and estimated a prevalence of severe PK deficiency of 1/155,668 overall and 1/4,725 among Africans. One individual reported with PK deficiency had, in fact, congenital kininogen deficiency associated with decreased PK activity. One-quarter of individuals had Factor XII clotting activity below the reference range. Four major bleeding events were described in 96 individuals, of which 3 were provoked, for a prevalence of 4% and an annualized rate of 0.1%. The prevalence of cardiovascular events was 15% (6% <40 years; 21% 40-65 years; 33% >65 years) for an annualized rate of 0.4%.
Conclusions
We characterized the genetic background of severe PK deficiency, critically appraised mutations, and provided prevalence estimates. Our data on laboratory characteristics and clinical course of severe PK deficiency may have clinical implications.

This article is protected by copyright. All rights reserved.

J Thromb Haemost: 22 Mar 2020; epub ahead of print
Barco S, Sollfrank S, Trinchero A, Adenaeuer A, ... Lämmle B, Rossmann H
J Thromb Haemost: 22 Mar 2020; epub ahead of print | PMID: 32202057
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Impact:
Abstract

Impact of Cardiac Resynchronization Therapy on Heart Transplant-Free Survival in Pediatric and Congenital Heart Disease Patients.

Chubb H, Rosenthal DN, Almond CS, Ceresnak SR, ... McElhinney DB, Dubin AM

- Cardiac resynchronization therapy (CRT) studies in pediatric and/or congenital heart disease (CHD) patients have shown an improvement in ejection fraction and heart failure symptoms. However, a survival benefit of CRT in this population has not been established. This study aimed to evaluate the impact of CRT upon heart transplant-free survival in pediatric and CHD patients, using a propensity score-matched analysis.- This single-center study compared CRT patients (implant date 2004-2017) and controls, matched by 1:1 propensity-score matching (PSM) using 21 comprehensive baseline indices for risk stratification. CRT patients were <21 years or had CHD; had systemic ventricular ejection fraction <;45%; symptomatic heart failure; and had significant electrical dyssynchrony, all prior to CRT implant. Controls were screened from non-selective imaging and ECG databases. Controls were retrospectively enrolled when they achieved the same inclusion criteria at an outpatient clinical encounter, within the same time period.- Of 133 patients who received CRT during the study period, 84 met all study inclusion criteria. 133 controls met all criteria at an outpatient encounter. Following PSM, 63 matched CRT-control pairs were identified with no significant difference between groups across all baseline indices. Heart transplant or death occurred in 12 (19%) PSM-CRT subjects and 37 (59%) PSM-controls with a median follow-up of 2.7 years (quartiles 0.8-6.1 years). CRT was associated with markedly reduced risk of heart transplant or death (hazard ratio 0.24 [95% CI 0.12-0.46], p<0.001). There was no CRT procedural mortality and one system infection at 54 months post-implant.- In pediatric and CHD patients with symptomatic systolic heart failure and electrical dyssynchrony, CRT was associated with improved heart transplant-free survival.



Circ Arrhythm Electrophysiol: 21 Mar 2020; epub ahead of print
Chubb H, Rosenthal DN, Almond CS, Ceresnak SR, ... McElhinney DB, Dubin AM
Circ Arrhythm Electrophysiol: 21 Mar 2020; epub ahead of print | PMID: 32202126
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Impact:
Abstract

Diffusing Capacity is an Independent Predictor of Outcomes in Pulmonary Hypertension Associated with Chronic Obstructive Pulmonary Disease.

Balasubramanian A, Kolb TM, Damico RL, Hassoun PM, McCormack MC, Mathai SC
Background
Patients with chronic obstructive pulmonary disease (COPD) who develop pulmonary hypertension (PH) have worse mortality than those with COPD alone. Predictors of poor outcomes in COPD-PH are not well described. Diffusing capacity of the lung (DLCO) assesses the integrity of the alveolar-capillary interface and thus may be a useful prognostic tool among those with COPD-PH.
Research question
Using a single center registry, we sought to evaluate DLCO as a predictor of mortality in a cohort of COPD-PH patients.
Study design and methods
This retrospective cohort study analyzed 71 COPD-PH patients from the Johns Hopkins Pulmonary Hypertension Registry with right heart catheterization (RHC)-proven PH and pulmonary function testing (PFT) data within 1 year of diagnostic RHC. Transplant-free survival was calculated from index RHC. Adjusted transplant-free survival was modelled using Cox proportional hazard methods, with age, pulmonary vascular resistance (PVR), FEV, oxygen use, and N-terminal pro-brain natriuretic peptide (NT-proBNP) included as covariates.
Results
Overall unadjusted transplant-free 1-, 3-, and 5-year survival was 87%, 60%, and 51% respectively. Survival was associated with reduced DLCO across the observed range of pulmonary artery pressures and PVR. Severe DLCO impairment was associated with poorer survival (log-rank ꭕ 13.07, p<0.001), and adjusting for covariates, for every percent predicted decrease in DLCO, mortality increased by 4% (HR 1.04; 95% CI:1.01-1.07).
Interpretation
Among patients with COPD-PH, severe gas transfer impairment is associated with higher mortality, even when adjusting for airflow obstruction and hemodynamics, suggesting that DLCO may be a useful prognostic marker in this population. Future studies are needed to further investigate the association between DLCO and morbidity, and to determine the utility of DLCO as a biomarker for disease risk and severity in COPD-PH.

Copyright © 2020. Published by Elsevier Inc.

Chest: 13 Mar 2020; epub ahead of print
Balasubramanian A, Kolb TM, Damico RL, Hassoun PM, McCormack MC, Mathai SC
Chest: 13 Mar 2020; epub ahead of print | PMID: 32184109
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Abstract

Obstructive sleep apnea and neurocognitive impairment in children with congenital heart disease.

Combs D, Edgin JO, Klewer S, Barber BJ, ... Abraham I, Parthasarathy S
Background
Children with congenital heart disease (CHD) have an increased risk of neurocognitive impairment. No prior studies have evaluated the role of obstructive sleep apnea (OSA), which is associated with neurocognitive impairment in children without CHD.
Research question
Is OSA is associated with neurocognitive impairment in children with CHD?
Study design and methods
Children age 6-17 years with corrected moderate-complex CHD without syndromes that may affect neurocognition were recruited from the pediatric cardiology clinic. Participants underwent home sleep testing and neurocognitive testing including a validated IQ test as well as validated tests of memory (Paired Associates Learning test), executive function (Intra-Extra Dimensional set shift test) and attention (Simple Reaction Test) from the CANTAB neurocognitive testing battery.
Results
Complete results were available for 30 children. Seventeen children (57%) were found to have OSA. Total IQ was markedly lower in children with CHD and comorbid OSA compared to children with CHD without comorbid OSA (mean 86 ± 12, vs 98 ± 11, p=0.01). Children with CHD and OSA did significantly worse on the Paired Associates Learning test, with a median of 8 total errors (interquartile range [IQR] 2.25-15) compared to children with CHD without OSA (median total errors 2, IQR 1-8), p=0.02.
Interpretation
Children with CHD and comorbid OSA have impaired neurocognition compared to children with CHD without comorbid OSA. OSA may be a reversible cause of neurocognitive impairment in children with CHD. Further research is needed to evaluate the effects of OSA treatment on neurocognitive impairment in children with CHD.

Copyright © 2020. Published by Elsevier Inc.

Chest: 24 Mar 2020; epub ahead of print
Combs D, Edgin JO, Klewer S, Barber BJ, ... Abraham I, Parthasarathy S
Chest: 24 Mar 2020; epub ahead of print | PMID: 32222588
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Abstract

Venoocclusive Disease With Both Hepatic and Pulmonary Involvement.

Tissot N, Montani D, Seronde MF, Degano B, Soumagne T

Pulmonary venoocclusive disease (PVOD) is a rare form of pulmonary vascular disease with pulmonary hypertension characterized by preferential involvement of the pulmonary venous system. Hepatic venoocclusive disease (HVOD), also known as sinusoidal obstruction syndrome, is a condition that occurs in 13% to 15% of patients after hematopoietic stem cell transplantation (HSCT). Although hepatic and pulmonary venoocclusive diseases may share some pathologic features as well as some etiologies such as HSCT, these two disorders have never been described together in a single adult patient. We report the case of a patient who received HSCT and developed HVOD and PVOD within 9 months. Despite their differences, PVOD and HVOD share common risk factors and associated conditions, suggesting that in the context of HSCT, the two diseases share common pathophysiological mechanisms. Optimal treatment for HSCT-related PVOD remains to be determined.

Copyright © 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Chest: 30 Mar 2020; 157:e107-e109
Tissot N, Montani D, Seronde MF, Degano B, Soumagne T
Chest: 30 Mar 2020; 157:e107-e109 | PMID: 32252933
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Impact:
Abstract

Contributions of maternal and fetal antiviral immunity in congenital disease.

Yockey LJ, Lucas C, Iwasaki A

Viral infections during pregnancy can have devastating consequences on pregnancy outcomes, fetal development, and maternal health. In this review, we examine fetal and maternal immune defense mechanisms that mediate resistance against viral infections and discuss the range of syndromes that ensue when such mechanisms fail, from fetal developmental defects to establishment of chronic infection. Further, we highlight the role of maternal immune activation, or uncontrolled inflammation triggered by viral infections during pregnancy, and its potential downstream pathological effects, including tissue damage and fetal demise. Insights into the respective contributions of direct viral toxicity versus fetal and maternal immune responses that underlie the pathogenesis of congenital disease will guide future treatment strategies.

Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Science: 07 May 2020; 368:608-612
Yockey LJ, Lucas C, Iwasaki A
Science: 07 May 2020; 368:608-612 | PMID: 32381717
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Impact:
Abstract

The Year in Review in Cardiac Electrophysiology.

Kapa S, Chung MK, Gopinathannair R, Noseworthy PA, ... Wan E, Wang PJ

In the past year there have been numerous advances in our understanding of arrhythmia mechanisms, diagnosis, and new therapies. We have seen advances in basic cardiac electrophysiology with data suggesting that secretoneurin may be a biomarker for patients at risk of ventricular arrhythmias and we have learned of the potential role of a natriuretic peptide receptor-C in atrial fibrosis and the role of an atrial specific two-pore potassium channel TASK-1 as a therapeutic target for atrial fibrillation. We have seen studies demonstrating role of sensory neurons in sleep apnea-related atrial fibrillation and the association between bariatric surgery and atrial fibrillation ablation outcomes. Artificial intelligence applied to electrocardiography has yielded estimates of age, gender, and overall health. We have seen new tools for collection of patient-centered outcomes following catheter ablation. There have been significant advances in the ability to identify ventricular tachycardia termination sites through high-density mapping of deceleration zones. We have learned that right ventricular dysfunction may be a predictor of survival benefit after ICD implantation in non-ischemic cardiomyopathy patients. We have seen further insights into the role of His bundle pacing on improving outcomes. As our understanding of cardiac laminopathies advance, we may have new tools to predict arrhythmic event rates in gene carriers. Finally, we have seen numerous advances in the treatment of arrhythmias in patients with congenital heart disease.



Circ Arrhythm Electrophysiol: 17 May 2020; epub ahead of print
Kapa S, Chung MK, Gopinathannair R, Noseworthy PA, ... Wan E, Wang PJ
Circ Arrhythm Electrophysiol: 17 May 2020; epub ahead of print | PMID: 32423252
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Abstract

Pectoral Nerve Blocks Decrease Postoperative Pain and Opioid Use After Pacemaker or Implantable Cardioverter-Defibrillator Placement in Children.

Yang JK, Char DS, Motonaga KS, Navaratnam M, ... Goodyer W, Ceresnak SR
Background
Pectoral nerve blocks (PECS) can reduce intra-procedural anesthetic requirements and postoperative pain. Little is known on the utility of PECS in reducing pain and narcotic use after pacemaker (PM) or implantable cardioverter defibrillator (ICD) placement in children.
Objective
To determine whether PECS can decrease postoperative pain and opioid use after PM or ICD placement in children.
Methods
A single center, retrospective review of pediatric patients undergoing transvenous PM or ICD placement between 2015-2020 was performed. Patients with recent cardiothoracic surgery or neurologic/developmental deficits were excluded. Demographics, procedural variables, postoperative pain, and postoperative opioid usage were compared between patients who underwent PECS and those who underwent conventional local anesthetic (CONTROL).
Results
A total of 74 patients underwent PM or ICD placement with 20 patients (27%) undergoing PECS. There were no differences between PECS and CONTROL with regard to age, weight, gender, type of device placed, presence of congenital heart disease, type of anesthesia, procedural time or complication rates. Patients who underwent PECS had lower pain scores at 1, 2, 6, 18, and 24-hours compared to CONTROL. PECS patients had a lower mean cumulative pain score [PECS 1.5 (95%-CI 0.8-2.2) vs CONTROL 3.1 (95%-CI 2.7-3.5); P<0.001] and lower total opioid use [PECS 6.0 MME/m (95%-CI 3.4-8.6) vs CONTROL 15.0 MME/m (95%-CI 11.8-18.2); P=0.001] over the 24-hours post-implant.
Conclusions
Pectoralis nerve blocks reduce postoperative pain scores and lower total opioid usage after ICD or PM placement. PECS should be considered at the time of transvenous device placement in children.

Copyright © 2020. Published by Elsevier Inc.

Heart Rhythm: 18 Mar 2020; epub ahead of print
Yang JK, Char DS, Motonaga KS, Navaratnam M, ... Goodyer W, Ceresnak SR
Heart Rhythm: 18 Mar 2020; epub ahead of print | PMID: 32201270
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Abstract

Atrial tachycardia eliminated at the ventricular side in patients with congenitally corrected transposition of the great arteries: Electrophysiological findings and anatomical concerns.

Jiang CX, Long DY, Du X, Sang CH, ... Dong JZ, Ma CS
Background
The unique malformation of congenitally corrected transposition of the great arteries (cc-TGA) makes the pulmonary outflow tract (POT) a possible origin of atrial tachycardia (AT).
Objective
The purpose of this study was to investigate the mapping characteristics of ATs successfully ablated at the POT in cc-TGA patients.
Methods
Cc-TGA patients with AT eliminated at the POT were analyzed. Activation mapping of the atria and the POT was performed under the guidance of a 3-D electroanatomic mapping system. The activation pattern of these chambers was investigated, with the local activation time (LAT, using coronary sinus ostium as reference) of the earliest activation site (EAS) compared.
Results
AT eliminated at the POT was documented in 5/6 cc-TGA patients. The EAS was at the right anteroseptal region with LAT of 33 (21-120)ms in the right atrium, and at the septal wall with comparable LAT (26ms, 47ms and 26ms, P=0.604) in the left atrium. The EAS of the POT was in the vicinity of the left-facing pulmonary sinus cusp in 3 cases and the non-facing pulmonary sinus cusp in 2 cases, with LAT of 106 (28-134)ms preceding both atria. Ablation at this site successfully eliminated the AT in all 5 cases.
Conclusions
AT arising adjacent to the POT is not an uncommon tachycardia in patients with the situs solitus type cc-TGA, and can be safely eliminated by ablation targeting the EAS in the POT.

Copyright © 2020. Published by Elsevier Inc.

Heart Rhythm: 18 Mar 2020; epub ahead of print
Jiang CX, Long DY, Du X, Sang CH, ... Dong JZ, Ma CS
Heart Rhythm: 18 Mar 2020; epub ahead of print | PMID: 32201269
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Impact:
Abstract

Performance and Interpretation of Invasive Hemodynamic Exercise Testing.

Jain CC, Borlaug BA

Exertional dyspnea is a common complaint for patients seen in pulmonary, cardiac and general medicine clinics, and elucidating the cause is often challenging, particularly when physical examination, echocardiography, radiography and pulmonary function test results are inconclusive. Invasive cardiopulmonary exercise testing (CPET) has emerged as the gold standard test to define causes of dyspnea and exertional limitation in this population. In this review, we describe the methods for performing and interpreting invasive CPET, with particular attention to the hemodynamic and blood sampling data as they apply to patients being evaluated for heart failure and pulmonary hypertension.

Copyright © 2020. Published by Elsevier Inc.

Chest: 27 May 2020; epub ahead of print
Jain CC, Borlaug BA
Chest: 27 May 2020; epub ahead of print | PMID: 32473950
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Impact:
Abstract

Phenotypes of Bronchopulmonary Dysplasia in Adults.

Cassady SJ, Lasso-Pirot A, Deepak J

Bronchopulmonary dysplasia (BPD), first described by Northway in 1967, is a process of neonatal lung injury that is most strongly associated with prematurity. The \"old\" form of the disease associated with the oxidative damage and volutrauma from perinatal mechanical ventilation has been increasingly supplanted by a \"new\" form resulting from interrupted growth of the lung at earlier stages of fetal development. Given the significant improvement in the survival of children with BPD since the 1980s, many more of these patients are living into adulthood and are being seen in adult pulmonary practices. In this review, we present three brief vignettes of patients from our practice to introduce three of the major patterns of disease seen in adult survivors of BPD, namely asthma-like disease, obstructive lung disease, and pulmonary hypertension. Additional factors shown to affect the lives of adult BPD survivors are also discussed. Finally, we discuss insights into the process of transitioning these complex patients from pediatric to adult pulmonary practices. As survivors of BPD enter adulthood and continue to require specialty pulmonary care, awareness of the disease\'s varied manifestations and responses to treatment will become increasingly important.

Copyright © 2020. Published by Elsevier Inc.

Chest: 27 May 2020; epub ahead of print
Cassady SJ, Lasso-Pirot A, Deepak J
Chest: 27 May 2020; epub ahead of print | PMID: 32473946
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Impact:
Abstract

Eligibility for subcutaneous implantable cardioverter-defibrillator in congenital heart disease.

Wang L, Javadekar N, Rajagopalan A, Rogovoy NM, ... Broberg CS, Tereshchenko LG
Background
Adult congenital heart disease (ACHD) patients can benefit from a subcutaneous implantable cardioverter-defibrillator (S-ICD).
Objective
The purpose of this study was to assess left- and right-sided S-ICD eligibility in ACHD patients, use machine learning to predict S-ICD eligibility in ACHD patients, and transform 12-lead electrocardiogram (ECG) to S-ICD 3-lead ECG, and vice versa.
Methods
ACHD outpatients (n = 101; age 42 ± 14 years; 52% female; 85% white; left ventricular ejection fraction [LVEF] 56% ± 9%) were enrolled in a prospective study. Supine and standing 12-lead ECG were recorded simultaneously with a right- and left-sided S-ICD 3-lead ECG. Peak-to-peak QRS and T amplitudes; RR, PR, QT, QTc, and QRS intervals; Tmax, and R/Tmax (31 predictor variables) were tested. Model selection, training, and testing were performed using supine ECG datasets. Validation was performed using standing ECG datasets and an out-of-sample non-ACHD population (n = 68; age 54 ± 16 years; 54% female; 94% white; LVEF 61% ± 8%).
Results
Forty percent of participants were ineligible for S-ICD. Tetralogy of Fallot patients passed right-sided screening (57%) more often than left-sided screening (21%; McNemar χP = .025). Female participants had greater odds of eligibility (adjusted odds ratio [OR] 5.9; 95% confidence interval [CI] 1.6-21.7; P = .008). Validation of the ridge models was satisfactory for standing left-sided (receiver operating characteristic area under the curve [ROC AUC] 0.687; 95% CI 0.582-0.791) and right-sided (ROC AUC 0.655; 95% CI 0.549-0.762) S-ICD eligibility prediction. Validation of transformation matrices showed satisfactory agreement (<0.1 mV difference).
Conclusion
Nearly half of the contemporary ACHD population is ineligible for S-ICD. The odds of S-ICD eligibility are greater for female than for male ACHD patients. Machine learning prediction of S-ICD eligibility can be used for screening of S-ICD candidates.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 29 Apr 2020; 17:860-869
Wang L, Javadekar N, Rajagopalan A, Rogovoy NM, ... Broberg CS, Tereshchenko LG
Heart Rhythm: 29 Apr 2020; 17:860-869 | PMID: 32354451
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Impact:
Abstract

Permanent conduction system pacing for congenitally corrected transposition of the great arteries: A Pediatric and Congenital Electrophysiology Society (PACES)/International Society for Adult Congenital Heart Disease (ISACHD) Collaborative Study.

Moore JP, Gallotti R, Shannon KM, Pilcher T, ... Nishimura T, Tung R
Background
Congenitally corrected transposition of the great arteries (CCTGA) is associated with spontaneous atrioventricular block and pacing-induced cardiomyopathy. Conduction system pacing is a potential alternative to conventional cardiac resynchronization therapy (CRT).
Objective
The purpose of this study was to determine the outcomes of conduction system pacing for CCTGA.
Methods
Retrospective data were collected from 10 international centers.
Results
His bundle (HBP) or left bundle branch pacing (LBBP) was attempted in 15 CCTGA patients (median age 23 years; 87% male). Previous surgery had been performed in 8 and chronic ventricular pacing in 7. Conduction system pacing (11 HBP, 2 LBBP 2; nonselective in 10, selective in 3) was acutely successful in 13 (86%) without complication. In 9 cases, electroanatomic mapping was available and identified the distal His bundle and proximal left bundle branches within the morphologic left ventricle below the pulmonary valve separate from the mitral annulus. Median implant HV interval was 42 ms (interquartile range [IQR] 35-48), R wave 6 mV (IQR 5-18), and threshold 0.5 V (IQR 0.5-1.2) at median 0.5 ms. QRSd was unchanged compared to junctional escape rhythm (124 vs 110 ms; P = .17) and decreased significantly compared to baseline ventricular pacing (112 vs 164 ms; P <.01). At a median of 8 months, all patients were alive without significant change in pacing threshold or lead dysfunction. New York Heart Association functional class improved in 5 patients.
Conclusion
Permanent conduction system pacing is feasible in CCTGA by either HBP or proximal LBBP. Narrow paced QRS and stable lead thresholds were observed at intermediate follow-up. Unique anatomic characteristics may favor this approach over conventional CRT.

Published by Elsevier Inc.

Heart Rhythm: 12 Mar 2020; epub ahead of print
Moore JP, Gallotti R, Shannon KM, Pilcher T, ... Nishimura T, Tung R
Heart Rhythm: 12 Mar 2020; epub ahead of print | PMID: 32243875
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Impact:
Abstract

Pregnancy Outcomes in Patients With Heart Disease in China.

Hu J, Ye Y, Lu A, Chen L, ... Huang G, Wang S

To analyze pregnancy outcomes of patients with heart disease in a single center and to explore the risk factors of adverse outcomes. One thousand thirty-three pregnant women with heart disease were retrospectively included from 2010 to 2017. We collected data of maternal, obstetric, and fetal outcomes. Among 1,086 pregnancies, 295 (27.1%) with congenital heart disease, 244 (22.5%) with rheumatic heart disease, 387 (35.6%) with arrhythmia, and 55 (5.1%) with cardiomyopathy. There were 8 (0.7%) maternal deaths. Risk factors of mortality were New York Heart Association (NYHA) classification IV (p <0.001), cardiac surgery during pregnancy (p <0.001), and general anesthesia (p <0.001). Maternal cardiac complications occurred in 6.7% of women, with most in the cardiomyopathy (26.0%) and rheumatic heart disease (32.9%) groups. Multivariate logistic regression modeling was used to analyze the potential risk factors. NYHA classification III and IV independently predicted worse maternal outcomes. Peripartum intensive care unit admission rate was 10.2%. Admission to intensive care unit was associated with NYHA classification II/III/IV, modified World Health Organization (mWHO) classification II-III/III/IV, and cardiac surgery during pregnancy. In conclusion, pregnancy with heart disease is at higher risk of complications for both women and neonates. In our findings, maternal morbidity is associated with NYHA classification and mWHO classification.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am J Cardiol: 15 Mar 2020; epub ahead of print
Hu J, Ye Y, Lu A, Chen L, ... Huang G, Wang S
Am J Cardiol: 15 Mar 2020; epub ahead of print | PMID: 32284176
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Impact:
Abstract

Pulmonary Function in Older Patients With Ventricular Septal Defect.

Eckerström F, Maagaard M, Boutrup N, Hjortdal VE

To better understand the evolvement of the pulmonary dysfunction in the aging ventricular septal defect (VSD) patient, we invited adult patients with a congenital VSD and healthy age- and gender-matched controls for static and dynamic spirometry, impulse oscillometry, multiple breath washout, and diffusion capacity for carbon monoxide testing. Primary outcome was forced expiratory volume in 1 second. In total, 30 patients with a surgically corrected VSD (mean age 51 ± 8 years), 30 patients with a small, unrepaired VSD (mean age 55 ± 1 years), and 2 groups of 30 age- and gender-matched, healthy controls (mean age 52 ± 9 years and 55 ± 10 years, respectively) were included. Median age of radical surgery was 6.3 (total range: 1.4 to 54) years and median follow-up after surgery was 40 years (total range: 3.4 to 54). Compared with healthy matched controls, surgically corrected VSD patients had lower forced expiratory volume in 1 second, 87 ± 19% versus 105 ± 14% of predicted, p <0.01, lower forced vital capacity, 92 ± 16% versus 107 ± 13% of predicted, p <0.01, and lower peak expiratory flow, 100 ± 21% versus 122 ± 16% of predicted, p <0.01. Furthermore, corrected VSD patients revealed increased airway resistance in the small airways, 30 ± 22% versus 15 ± 14% of total resistance, p <0.01, and reduced diffusion capacity, 84 ± 12% versus 101 ± 11%, p <0.01. Patients with a small, unrepaired VSD had comparable pulmonary function to their matched controls. In conclusion, VSD patients 40 years of age or older demonstrated significant impaired pulmonary function in terms of reduced dynamic pulmonary function, increased airway resistance in the small airways, and reduced diffusion capacity up to 54 years after defect closure compared with healthy age- and gender-matched controls.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am J Cardiol: 12 Mar 2020; epub ahead of print
Eckerström F, Maagaard M, Boutrup N, Hjortdal VE
Am J Cardiol: 12 Mar 2020; epub ahead of print | PMID: 32291090
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Abstract

Characteristics and outcomes of atrial fibrillation in patients without traditional risk factors: an RE-LY AF registry analysis.

Kloosterman M, Oldgren J, Conen D, Wong JA, ... Van Gelder IC, Healey JS
Aims 
Data on patient characteristics, prevalence, and outcomes of atrial fibrillation (AF) patients without traditional risk factors, often labelled \'lone AF\', are sparse.
Methods and results
The RE-LY AF registry included 15 400 individuals who presented to emergency departments with AF in 47 countries. This analysis focused on patients without traditional risk factors, including age ≥60 years, hypertension, coronary artery disease, heart failure, left ventricular hypertrophy, congenital heart disease, pulmonary disease, valve heart disease, hyperthyroidism, and prior cardiac surgery. Patients without traditional risk factors were compared with age- and region-matched controls with traditional risk factors (1:3 fashion). In 796 (5%) patients, no traditional risk factors were present. However, 98% (779/796) had less-established or borderline risk factors, including borderline hypertension (130-140/80-90 mmHg; 47%), chronic kidney disease (eGFR < 60 mL/min; 57%), obesity (body mass index > 30; 19%), diabetes (5%), excessive alcohol intake (>14 units/week; 4%), and smoking (25%). Compared with patients with traditional risk factors (n = 2388), patients without traditional risk factors were more often men (74% vs. 59%, P < 0.001) had paroxysmal AF (55% vs. 37%, P < 0.001) and less AF persistence after 1 year (21% vs. 49%, P < 0.001). Furthermore, 1-year stroke occurrence rate (0.6% vs. 2.0%, P = 0.013) and heart failure hospitalizations (0.9% vs. 12.5%, P < 0.001) were lower. However, risk of AF-related re-hospitalization was similar (18% vs. 21%, P = 0.09).
Conclusion
Almost all patients without traditionally defined AF risk factors have less-established or borderline risk factors. These patients have a favourable 1-year prognosis, but risk of AF-related re-hospitalization remains high. Greater emphasis should be placed on recognition and management of less-established or borderline risk factors.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: [email protected]

Europace: 25 Mar 2020; epub ahead of print
Kloosterman M, Oldgren J, Conen D, Wong JA, ... Van Gelder IC, Healey JS
Europace: 25 Mar 2020; epub ahead of print | PMID: 32215649
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Abstract

Associations between anthropometric indices and outcomes of congenital heart operations in infants and young children: An analysis of data from the Society of Thoracic Surgeons Database.

Ross FJ, Radman M, Jacobs ML, Sassano-Miguel C, ... Vener DF, Latham GJ
Background
Children with congenital heart disease are at risk for growth failure due to inadequate nutrient intake and increased metabolic demands. We examined the relationship between anthropometric indices of nutrition (height-for-age z-score [HAZ], weight-for-age z-score [WAZ], weight-for-height z-score [WHZ]) and outcomes in a large sample of children undergoing surgery for congenital heart disease.
Methods
Patients in the Society of Thoracic Surgeons Congenital Heart Surgery Database having index cardiac surgery at age 1 month to 10 years were included. Indices were calculated by comparing patients\' weight and height to population norms from the World Health Organization and Centers for Disease Control and Prevention. Outcomes included operative mortality, composite mortality or major complication, major postoperative infection, and postoperative length of stay. For each outcome and index, the adjusted odds ratio (aOR) (for mortality, composite outcome, and infection) and adjusted relative change in median (for postoperative length of stay) for a 1-unit decrease in index were estimated using mixed-effects logistic and log-linear regression models.
Results
Every unit decrease in HAZ was associated with 1.40 aOR of mortality (95% CI 1.32-1.48), and every unit decrease in WAZ was associated with 1.33 aOR for mortality (95% CI 1.25-1.41). The relationship between WHZ and outcome was nonlinear, with aOR of mortality of 0.84 (95% CI 0.76-0.93) for 1-unit decrease when WHZ ≥ 0 and a nonsignificant association for WHZ < 0. Trends for other outcomes were similar. Overall, the incidence of low nutritional indices was similar for 1-ventricle and 2-ventricle patients. Children between the age of 1 month and 1 year and those with lesions associated with pulmonary overcirculation had the highest incidence of low nutritional indices.
Conclusions
Lower HAZ and WAZ, suggestive of malnutrition, are associated with increased mortality and other adverse outcomes after cardiac surgery in infants and young children. Higher WHZ over zero, suggestive of obesity, is also associated with adverse outcomes.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 18 Mar 2020; 224:85-97
Ross FJ, Radman M, Jacobs ML, Sassano-Miguel C, ... Vener DF, Latham GJ
Am Heart J: 18 Mar 2020; 224:85-97 | PMID: 32353587
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Abstract

Permanent left bundle branch pacing: what is the mechanism of divergent responses during programmed stimulation?

Jastrzębski M

An 18-year-old girl with congenital complete AV block and epicardial VVI pacemaker implanted at the age of 4 months was admitted for endocardial DDD pacemaker implantation due to the development of pacing induced cardiomyopathy (exercise intolerance with left ventricular ejection fraction of 44%). Considering narrow QRS of the ventricular escape rhythm, permanent His bundle pacing was chosen as a potentially optimal pacing mode to prevent progression / reverse cardiomyopathy. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

J Cardiovasc Electrophysiol: 17 Mar 2020; epub ahead of print
Jastrzębski M
J Cardiovasc Electrophysiol: 17 Mar 2020; epub ahead of print | PMID: 32187413
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Abstract

Coil occlusion of a congenital left ventricular aneurysm in a newborn.

Hofbeck M, Sieverding L, Grözinger G, Kagan KO

We report interventional treatment of a congenital left ventricular aneurysm in a neonate. The aneurysm was detected prenatally at 20 weeks of gestation. Postnatally, the aneurysm increased in size during the first few days of life and therefore we opted for interventional closure to abolish the potential risk of rupture. The aneurysm was entered with a 2.7 French microcatheter, and complete occlusion was achieved by successive placement of three detachable large volume coils (Ruby Coil Penumbra , Alameda, California). To the best of our knowledge, this is the first report describing interventional occlusion of a congenital ventricular aneurysm in early infancy. Interventional occlusion with detachable large volume coils appears to be an attractive alternative to surgical resection in patients presenting with ventricular outpouchings and narrow base connection to the ventricle.

© 2020 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals, Inc.

Catheter Cardiovasc Interv: 18 Mar 2020; epub ahead of print
Hofbeck M, Sieverding L, Grözinger G, Kagan KO
Catheter Cardiovasc Interv: 18 Mar 2020; epub ahead of print | PMID: 32190972
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Impact:
Abstract

The Natural and Unnatural History of Ventricular Septal Defects Presenting in Infancy: An Echocardiography-Based Review.

Cox K, Algaze-Yojay C, Punn R, Silverman N
Background
Ventricular septal defect (VSD), the most common congenital heart defect, accounts for 40% of heart malformations. Despite this prevalence, there remains no consensus on the utility of echocardiography to guide modern-era treatment. In this study, we evaluated patients with isolated VSDs to test the hypothesis that echocardiographic evidence of left ventricular (LV) volume overload and type of VSD are associated with surgical intervention and to identify useful echocardiographic indicators for management of VSDs in infants and children.
Methods
We reviewed 350 patients with VSDs diagnosed during the first year of life. Echocardiographic measurements were made at the time of diagnosis and at the endpoint. The VSD area was calculated using inner edge to inner edge dimensions obtained from two planes and indexed to body surface area. Aortic annulus dimension, left atrium to aortic root ratio, LV end-diastolic diameter, left atrial volume, VSD velocity-time integral, ejection fraction, and pulmonary to systemic blood flow ratio (Qp:Qs) were measured using conventional methods.
Results
One hundred seventy-seven muscular (50.5%) and 162 perimembranous (46%) VSDs accounted for the vast majority of defects. Only seven (4%) muscular defects required surgical closure, while 76 (47%) perimembranous defects required surgery. Indexed VSD area, VSD to aortic valve ratio, indexed left atrium volume, LV end-diastolic diameter, VSD velocity-time integral, and Qp:Qs at diagnosis were significantly different between the surgical and nonsurgical groups. Ventricular septal defect area > 50 mm/m at initial diagnosis was independently associated with risk for surgery (P = .0055).
Conclusions
Indexed VSD area is an echocardiographic variable that can be easily measured at diagnosis and can provide insight into the likelihood of requiring surgical intervention regardless of the type and location of the defect.

Published by Elsevier Inc.

J Am Soc Echocardiogr: 01 Apr 2020; epub ahead of print
Cox K, Algaze-Yojay C, Punn R, Silverman N
J Am Soc Echocardiogr: 01 Apr 2020; epub ahead of print | PMID: 32249125
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Abstract

Icotinib attenuates monocrotaline-induced pulmonary hypertension by preventing pulmonary arterial smooth muscle cell dysfunction.

Peng LY, Yu M, Yang MX, Liu P, ... Kong H, Xie WP
Background
Aberrant activation of epidermal growth factor receptor (EGFR) signaling pathway is associated with the pathogenesis of pulmonary hypertension (PH). However, the effect of icotinib, a first-generation of EGFR tyrosine kinase inhibitor (EGFR-TKI), on PH remains to be elucidated.
Methods
PH rat model was established by a single intraperitoneal injection of monocrotaline (MCT, 60 mg/kg). Icotinib (15, 30, 60 mg/kg/day) was administered by oral gavage from the day of MCT injection. After 4 weeks, hemodynamic parameters and histological changes of the pulmonary arterial vessels were assessed, and the phenotypic switching of pulmonary vascular smooth muscle cells (PASMCs) was determined in vivo. Moreover, the effects of icotinib (10 μM) on EGF (50 ng/ml)-stimulated proliferation, migration, and phenotypic switching of human PASMCs were explored in vitro.
Results
Icotinib significantly reduced the right ventricular systolic pressure and right ventricle hypertrophy index in rats with MCT-induced PH. Moreover, icotinib improved MCT-induced pulmonary vascular remodeling. The expression of contractile marker (SM22α) and synthetic markers (osteopontin and vimentin) in pulmonary artery were restored by icotinib treatment. In vitro, icotinib suppressed EGF- induced PASMCs proliferation and migration. Meanwhile, icotinib inhibited EGF-induced down-regulation of α-SMA and SM22α and up-regulation of osteopontin and Collagen I in PASMCs, suggesting that icotinib could inhibit EGF-induced phenotypic switching of PASMCs. Mechanistically, these effects of icotinib were associated with the inhibition of EGFR-Akt/ERK signaling pathway.
Conclusions
Icotinib can attenuate MCT-induced pulmonary vascular remodeling and improve PH. This effect of icotinib might be attributed to preventing PASMC dysfunction by inhibiting EGFR-Akt/ERK signaling pathway.

© American Journal of Hypertension, Ltd 2020. All rights reserved. For Permissions, please email: [email protected]

Am J Hypertens: 16 Apr 2020; epub ahead of print
Peng LY, Yu M, Yang MX, Liu P, ... Kong H, Xie WP
Am J Hypertens: 16 Apr 2020; epub ahead of print | PMID: 32301965
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Impact:
Abstract

Adult Intraoperative Echocardiography: A Comprehensive Review of Current Practice.

Thaden JJ, Malouf JF, Rehfeldt KH, Ashikhmina E, ... Schaff HV, Michelena HI

Intraoperative transesophageal echocardiography is a mature imaging modality and critical component of contemporary heart surgery, in which it plays a key role in surgical planning, determination of cardiac chamber filling and function early after cardiopulmonary bypass, and timely assessment of surgical interventions. Intraoperative transesophageal echocardiography affords the unique opportunity to correct suboptimal surgical results before leaving the operating room. Herein, the authors provide a comprehensive review of their institution\'s experience with intraoperative transesophageal echocardiography, emphasizing a practical assessment of commonly encountered noncongenital surgical heart lesions in adults, anticipation of potential surgical complications, and imaging approaches to facilitate timely surgical correction of unsatisfactory results.

Copyright © 2020 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

J Am Soc Echocardiogr: 09 Apr 2020; epub ahead of print
Thaden JJ, Malouf JF, Rehfeldt KH, Ashikhmina E, ... Schaff HV, Michelena HI
J Am Soc Echocardiogr: 09 Apr 2020; epub ahead of print | PMID: 32284201
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Impact:
Abstract

Suspected myocardial injury in patients with COVID-19: Evidence from front-line clinical observation in Wuhan, China.

Deng Q, Hu B, Zhang Y, Wang H, ... Ping H, Zhou Q
Background
A novel coronavirus disease (COVID-19) in Wuhan has caused an outbreak and become a major public health issue in China and great concern from international community. Myocarditis and myocardial injury were suspected and may even be considered as one of the leading causes for death of COVID-19 patients. Therefore, we focused on the condition of the heart, and sought to provide firsthand evidence for whether myocarditis and myocardial injury were caused by COVID-19.
Methods
We enrolled patients with confirmed diagnosis of COVID-19 retrospectively and collected heart-related clinical data, mainly including cardiac imaging findings, laboratory results and clinical outcomes. Serial tests of cardiac markers were traced for the analysis of potential myocardial injury/myocarditis.
Results
112 COVID-19 patients were enrolled in our study. There was evidence of myocardial injury in COVID-19 patients and 14 (12.5%) patients had presented abnormalities similar to myocarditis. Most of patients had normal levels of troponin at admission, that in 42 (37.5%) patients increased during hospitalization, especially in those that died. Troponin levels were significantly increased in the week preceding the death. 15 (13.4%) patients have presented signs of pulmonary hypertension. Typical signs of myocarditis were absent on echocardiography and electrocardiogram.
Conclusions
The clinical evidence in our study suggested that myocardial injury is more likely related to systemic consequences rather than direct damage by the 2019 novel coronavirus. The elevation in cardiac markers was probably due to secondary and systemic consequences and can be considered as the warning sign for recent adverse clinical outcomes of the patients.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 06 Apr 2020; epub ahead of print
Deng Q, Hu B, Zhang Y, Wang H, ... Ping H, Zhou Q
Int J Cardiol: 06 Apr 2020; epub ahead of print | PMID: 32291207
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Impact:
Abstract

Pilot phase experience of the International Quality Improvement Collaborative catheterization registry.

Barry OM, Ali F, Ronderos M, Sudhaker A, ... Jenkins KJ, Hasan BS
Objectives
To describe the development of a quality collaborative for congenital cardiac catheterization centers in low and middle-income countries (LMICs) including pilot study data and a novel procedural efficacy measure.
Background
Absence of congenital cardiac catheterization registries in LMICs led to the development of the International Quality Improvement Collaborative Congenital Heart Disease Catheterization Registry (IQIC-CHDCR). As a foundation for this initiative, the IQIC is a collaboration of pediatric cardiac surgical programs from LMICs. Participation in IQIC has been associated with improved patient outcomes.
Methods
A web-based registry was designed through a collaborative process. A pilot study was conducted from October through December 2017 at seven existing IQIC sites. Demographic, hemodynamic, and adverse event data were obtained and a novel tool to assess procedural efficacy was applied to five specific procedures. Procedural efficacy was categorized using ideal, adequate, and inadequate.
Results
A total of 429 cases were entered. Twenty-five adverse events were reported. The five procedures for which procedural efficacy was measured represented 48% of cases (n = 208) and 71% had complete data for analysis (n = 146). Procedure efficacy was ideal most frequently in patent ductus arteriosus (95%) and atrial septal defect (90%) device closure, and inadequate most frequently in coarctation procedures (100%), and aortic and pulmonary valvuloplasties (50%).
Conclusions
The IQIC-CHDCR has designed a feasible collaborative to capture catheterization data in LMICs. The novel tool for procedural efficacy will provide valuable means to identify areas for quality improvement. This pilot study and lessons learned culminated in the full launch of the IQIC-CHDCR.

© 2020 Wiley Periodicals, Inc.

Catheter Cardiovasc Interv: 14 Apr 2020; epub ahead of print
Barry OM, Ali F, Ronderos M, Sudhaker A, ... Jenkins KJ, Hasan BS
Catheter Cardiovasc Interv: 14 Apr 2020; epub ahead of print | PMID: 32294315
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Impact:
Abstract

The cardiovascular burden of coronavirus disease 2019 (COVID-19) with a focus on congenital heart disease.

Tan W, Aboulhosn J

Coronavirus disease 2019 (COVID-19), caused by a novel betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first described in a cluster of patients presenting with pneumonia symptoms in Wuhan, China, in December of 2019. Over the past few months, COVID-19 has developed into a worldwide pandemic, with over 400,000 documented cases globally as of March 24, 2020. The SARS-CoV-2 virus is most likely of zoonotic origin, but has been shown to have effective human-to-human transmission. COVID-19 results in mild symptoms in the majority of infected patients, but can cause severe lung injury, cardiac injury, and death. Given the novel nature of COVID-19, no established treatment beyond supportive care exists currently, but extensive public-health measures to reduce person-to-person transmission of COVID-19 have been implemented globally to curb the spread of disease, reduce the burden on healthcare systems, and protect vulnerable populations, including the elderly and those with underlying medical comorbidities. Since this is an emerging infectious disease, there is, as of yet, limited data on the effects of this infection on patients with cardiovascular disease, particularly so for those with congenital heart disease. We summarize herewith the early experience with COVID-19 and consider the potential applicability to and implications for patients with cardiovascular disease in general and congenital heart disease in particular.

Copyright © 2020 Elsevier B.V. All rights reserved.

Int J Cardiol: 27 Mar 2020; epub ahead of print
Tan W, Aboulhosn J
Int J Cardiol: 27 Mar 2020; epub ahead of print | PMID: 32248966
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Impact:
Abstract

Epidemiology and Outcomes of Acute Decompensated Heart Failure in Children.

Lasa JJ, Gaies M, Bush L, Zhang W, ... Shekerdemian LS, Price JF
Background
Acute decompensated heart failure (ADHF) is a highly morbid condition among adults. Little is known about outcomes in children with ADHF. We analyzed the Pediatric Cardiac Critical Care Consortium registry to determine the epidemiology, contemporary treatments, and predictors of mortality in critically ill children with ADHF.
Methods
Cardiac intensive care unit (CICU) patients ≤18 years of age meeting Pediatric Cardiac Critical Care Consortium criteria for ADHF were included. ADHF was defined as systolic or diastolic dysfunction requiring continuous vasoactive or diuretic infusion, respiratory support, or mechanical circulatory support. Demographics, diagnosis, therapies, complications, and mortality are described for the cohort. Predictors of CICU mortality were identified using logistic regression.
Results
Among 26 294 consecutive admissions (23 centers), 1494 (6%) met criteria for analysis. Median age was 0.93 years (interquartile range, 0.1-9.3 years). Patients with congenital heart disease (CHD) comprised 57% of the cohort. Common therapies included the following: vasoactive infusions (88%), central venous catheters (86%), mechanical ventilation (59%), and high flow nasal cannula (46%). Common complications were arrhythmias (19%), cardiac arrest (10%), sepsis (7%), and acute renal failure requiring dialysis (3%). Median length of CICU stay was 7.9 days (interquartile range, 3-18 days) and the CICU readmission rate was 22%. Overall, CICU mortality was 15% although higher for patients with CHD versus non-CHD (19% versus 11%; <0.001). Independent risk factors associated with CICU mortality included age <30 days, CHD, vasoactive infusions, ventricular tachycardia, mechanical ventilation, sepsis, pulmonary hypertension, extracorporeal membrane oxygenation, and cardiac arrest.
Conclusions
ADHF in children is characterized by comorbidities, high mortality rates, and frequent readmission, especially among patients with CHD. Opportunities exist to determine best practices around appropriate use of mechanical support, cardiac arrest prevention, and optimal heart transplantation candidacy to improve outcomes for these patients.



Circ Heart Fail: 30 Mar 2020; 13:e006101
Lasa JJ, Gaies M, Bush L, Zhang W, ... Shekerdemian LS, Price JF
Circ Heart Fail: 30 Mar 2020; 13:e006101 | PMID: 32301336
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Impact:
Abstract

Transcatheter biventricular conversion in an adult patient with a 1.5 ventricle Glenn palliation and superior vena cava syndrome.

Tannous P, Popescu A, Forbess L, Nugent A

Covered stents have a continually expanding spectrum of applications for patients with congenital heart disease. Here we report use of covered stents to successfully perform a first-in-human percutaneous biventricular conversion of a 1.5 ventricle Glenn palliation in an adult born with pulmonary atresia. This case demonstrates that in patients considered borderline for biventricular repair, surgery can potentially be modified to promote growth of underdeveloped structures and setup for transcatheter biventricular conversion.

© 2020 Wiley Periodicals, Inc.

Catheter Cardiovasc Interv: 27 Apr 2020; epub ahead of print
Tannous P, Popescu A, Forbess L, Nugent A
Catheter Cardiovasc Interv: 27 Apr 2020; epub ahead of print | PMID: 32343465
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Impact:
Abstract

Outcome of arterial switch operation for transposition of the great arteries. A 35-year follow-up study.

Santens B, Van De Bruaene A, De Meester P, Gewillig M, ... Bogaert J, Budts W
Background
Arterial switch operation (ASO) is today the first-choice surgical treatment for patients with transposition of the great arteries. Long-term outcome data still remain scarce. Moreover, the course of these patients is not uneventful. Therefore, we wanted to evaluate long-term outcome and determine on which variables to focus during follow-up.
Methods
Clinical records of 318 patients who underwent ASO between October 1981 and July 2018 were reviewed. Perioperative, post-operative, and interventional data were collected to determine mortality and the need for re-intervention. Descriptive statistics and Kaplan-Meier survival analysis were performed.
Results
Mean follow-up time was 11.1 SD 8.5 years (range 0-35) with a mean age of 12.5 SD 9.0 years (range 0-37) at latest follow-up. In-hospital mortality was 7.5% and overall survival 90.9% for a maximum follow-up time of 35 years. Causes of early mortality were cardiogenic shock, severe pulmonary hypertension, septic shock and multiple organ failure. Causes of late mortality were cardiogenic shock, severe pulmonary hypertension, pacemaker lead fracture and fire death. Re-intervention free survival at 5-year was 91.6%, at 10-year 90.7%, at 20-year 79.2%. For all survivors, the most frequent sequelae after ASO were pulmonary artery stenosis (80.6%), of which 13.5% needed an intervention. The threshold for intervening on lesions at the level of the pulmonary artery bifurcation was higher and the percutaneous re-intervention rate was higher for non-bifurcation lesions.
Conclusions
Despite a relatively high peri-operative mortality, TGA patients have an excellent overall long-term survival. However, a large proportion of patients requires re-interventions, mainly for pulmonary artery stenosis.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 25 Apr 2020; epub ahead of print
Santens B, Van De Bruaene A, De Meester P, Gewillig M, ... Bogaert J, Budts W
Int J Cardiol: 25 Apr 2020; epub ahead of print | PMID: 32348813
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Impact:
Abstract

An ontology-based classification of Ebstein\'s anomaly and its implications in clinical adverse outcomes.

Tang X, Chen W, Zeng Z, Ding K, Zhou Z
Background
Ebstein\'s anomaly (EA) is a rare congenital heart disease with significantly phenotypic heterogeneity, accompanied with multiple associated phenotypes. The classification of cases with EA based on a standardized vocabulary of phenotypic abnormalities from Human Phenotype Ontology (HPO) and its association with adverse clinical outcomes has yet to be investigated.
Methods
We developed a deep phenotyping algorithm for Chinese electronic medical records (EMRs) from the Chinese National Cardiovascular Center at the Fuwai Hospital to ascertain EA cases. EA-associated phenotypes were standardized according to HPO annotation, and an unsupervised hierarchical cluster analysis was used to classify EA cases according to their phenotypic similarities. A survival analysis was conducted to study the association of the HPO-based cluster with survival or adverse clinical outcomes.
Results
The ascertained EA cases were annotated to have a single or multiple HPO terms. Three distinct clusters with different combinations of HPO term in these cases were identified. The HPO-based classification of EA cases was not significantly associated with survival or adverse clinical outcomes at a mid-term follow up.
Conclusions
Our study provided an important implication for studying the classification of congenital heart disease using HPO-based annotation. A long time follow up will enable to confirm its association with adverse clinical outcomes.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 25 Apr 2020; epub ahead of print
Tang X, Chen W, Zeng Z, Ding K, Zhou Z
Int J Cardiol: 25 Apr 2020; epub ahead of print | PMID: 32348812
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Impact:
Abstract

Progressive stiffening and relatively slow growth of the dilated ascending aorta in long-term Fontan survivors-Serial assessment for 15 years.

Hayama Y, Ohuchi H, Negishi J, Iwasa T, ... Tsuda E, Kurosaki K
Background
A stiffened, dilated ascending aorta may represent an important predictor of cardiovascular mortality, and has been reported in patients with congenital heart disease, including single ventricle. However, the serial conformational changes and determinants of reduced distensibility in ascending aorta have not been clarified.
Methods
This retrospective study investigated 115 postoperative Fontan survivors (median age at Fontan: 3.7 years). All patients underwent cardiac catheterization before and 1, 5, 10, and 15 years after the Fontan operation. We measured Z-scores for diameters and stiffness indexes (β) of the ascending aorta and descending aorta from angiograms. We also reviewed the clinical profiles, hemodynamic parameters, and exercise capacities of patients and compared them with results from 47 control subjects.
Results
Fontan survivors displayed significantly larger Z-score and β of the ascending aorta from before to 15 years after surgery than controls, whereas values for the descending aorta were comparable. Z-score for the ascending aorta was decreased, but β was elevated significantly according to the trend test. In multivariable analysis, β of the ascending aorta at 15 years after Fontan operation and its increasing trend were associated with older age at Fontan operation and elevated ventricular end-diastolic pressure. Reduced exercise capacity also correlated with stiffening of the ascending aorta.
Conclusions
Fontan survivors showed progressive stiffening and relatively slow growth of the dilated ascending aorta. Progressive stiffening of the ascending aorta may be coupled to diastolic dysfunction and reduced exercise capacity, suggesting the importance of lifelong management of subclinical Fontan pathophysiology.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 06 May 2020; epub ahead of print
Hayama Y, Ohuchi H, Negishi J, Iwasa T, ... Tsuda E, Kurosaki K
Int J Cardiol: 06 May 2020; epub ahead of print | PMID: 32389766
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Impact:
Abstract

Noggin regulates foregut progenitor cell programming and mis-expression leads to esophageal atresia.

Pinzon-Guzman C, Sangadala S, Riera KM, Popova EY, ... Boden SD, Goldenring JR

Esophageal atresia (EA/TEF) are common congenital abnormalities of the gastrointestinal tract. The etiology of EA/TEF is not well understood. We hypothesized that EA/TEF may be the direct consequence of abnormal expression of Noggin (NOG) signaling cascade. Here we showed that, in neonates with EA/TEF, NOG was missing from the atretic esophagus, resulting in immature esophagus that contains respiratory glands, and cilia. When using mouse esophageal organoid units (EOUs) or tracheal organoid units (TOU) as a model of foregut development in vitro, NOG determined the fate of foregut progenitors by allowing expression of esophageal epithelium proteins. When NOG was present in the culture of mTOU, it altered the cell morphology of the organoid unit epithelium, allowing expression of squamous cell proteins normally found in esophagus. On the other hand, when NOG was inhibited in mEOU, the organoid epithelium began to express respiratory markers mimicking the phenotype seen in pathology samples of human EA/TEF. Moreover, human EOU derived from EA/TEF patients were small, fibrotic and lack esophageal epithelium, but when NOG was added, the EOU grew larger, healthier and express esophageal proteins. These results indicate that Noggin is a critical regulator of cell fate decisions between esophageal and pulmonary morphogenesis.



J Clin Invest: 18 May 2020; epub ahead of print
Pinzon-Guzman C, Sangadala S, Riera KM, Popova EY, ... Boden SD, Goldenring JR
J Clin Invest: 18 May 2020; epub ahead of print | PMID: 32427591
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Impact:
Abstract

Left Atrial Diverticula: Innocent Bystanders or Wolves in Sheep\'s Clothing?

Veen D, Bruning TA, de Groot NMS
Introduction
The finding of left atria diverticula (LAD) on cardiac Computed Tomography (CT) images obtained from patients with atrial fibrillation (AF) referred for pulmonary vein isolation is not uncommon. Prior studies reporting on LAD do not always provide definitions of LAD resulting in confusion with other anatomical structures such as left atrial accessory appendages (LAAA) and atrial aneurysms. The aim of this review is to identify an accurate definition of LAD and to describe distinctive properties between LAD and other left atrial structures such as LAAA and aneurysms. Also, the relation between LAD and development of atrial tachyarrhythmias is discussed.
Methods
PubMed was searched for studies reporting on atrial aneurysms, left atrial diverticula, left atrial accessory appendages and atrial congenital aneurysms, resulting in 36 papers.
Results
LAD can be distinguished from LAAA by taking into account embryologic origins of the left atrium and their locations, resulting in the following definitions: 1) LAAA are contractile, trabeculated structures with circumscriptive ostia and narrow necks, originating from the primitive atria, 2) LAD are contractile, sac like structures with either smooth or trabeculated inner surfaces, circumscriptive ostia, narrow necks and variable morphologies, originating from the embryologic common pulmonary vein, that incorporates into the LA, 3) atrial aneurysms are non-contractile structures with wide necks and sac like bodies. There are no differences in prevalences of LAD between patients with sinus rhythm and AF.
Conclusion
The pathophysiology of LAD is not yet fully understood. It is unlikely, that LAD are related to the development of atrial tachycardia\'s and AF by either being a source of ectopic activity or being part of an arrhythmogenic substrate. No differences in LAD prevalences between patients with sinus rhythm and AF have been found. Thus, it is unlikely that LAD could potentially be wolves in sheep\'s clothing. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

J Cardiovasc Electrophysiol: 22 May 2020; epub ahead of print
Veen D, Bruning TA, de Groot NMS
J Cardiovasc Electrophysiol: 22 May 2020; epub ahead of print | PMID: 32445428
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Impact:
Abstract

The Effects of Inhaled Sodium Nitrite on Pulmonary Vascular Impedance in Patients with Pulmonary Hypertension Associated with HFpEF.

Bashline MJ, Bachman TN, Helbling NL, Nouraie M, Gladwin MT, Simon MA
Background
The severity of pulmonary hypertension (PH) is monitored by measuring pulmonary vascular resistance (PVR), which is a steady-state measurement and ignores the pulsatile load encountered by the right ventricle (RV). Pulmonary vascular impedance (PVZ) can depict both steady-state and pulsatile forces, thus may better predict clinical outcomes. We sought to calculate PVZ in patients with PH associated with HFpEF (PH-HFpEF), who were administered inhaled sodium nitrite to better understand the acute effects on afterload.
Methods and results
Fourteen patients with PH-HFpEF underwent right heart catherization and were administered inhaled sodium nitrite. A Fourier transform was used to calculate PVZ for both pre and post-nitrite for comparison. Inhaled sodium nitrite decreased characteristic impedance (Z, inversely related to proximal pulmonary artery compliance) and total work (W) performed by the RV. RV efficiency improved, defined by a reduction in the total work divided by cardiac output (W/CO). There was a mild reduction in pulmonary steady-state resistance (Z) after administration of inhaled sodium nitrite but this was not significant.
Conclusions
PVZ analysis showed administration of inhaled sodium nitrite was associated with an improvement in pulmonary vascular compliance, via a reduction in Z, more so than pulmonary steady-state resistance. This was associated with improved RV efficiency and total work.

Copyright © 2020 Elsevier Ltd. All rights reserved.

J Card Fail: 20 May 2020; epub ahead of print
Bashline MJ, Bachman TN, Helbling NL, Nouraie M, Gladwin MT, Simon MA
J Card Fail: 20 May 2020; epub ahead of print | PMID: 32446946
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Impact:
Abstract

New Comprehensive Reference Values for Arterial Vascular Parameters in Children.

Torigoe T, Dallaire F, Slorach C, Cardinal MP, ... Mertens L, Jaeggi E
Background
Noninvasive measurements of vascular parameters can be used for the detection and risk stratification of cardiovascular diseases. Most vascular parameters are influenced by age and body size, but pediatric reference values are scarce and limited to a few parameters. The aim of this study was to develop pediatric reference values and Z score equations for a comprehensive set of vascular parameters.
Methods
A total of 292 healthy subjects aged 0 to 18 years were prospectively recruited. Stiffness index β, pressure-strain elastic modulus, common carotid intima-media thickness, brachial flow-mediated dilation, radial augmentation index, central and right arm peripheral artery pulse-wave velocities, and pulse-wave velocity ratio were assessed. Normalization for age and anthropometric variables was performed using parametric multivariate regression modeling. Z scores were assessed for heteroscedasticity, residual association with age and body size, and distribution.
Results
Multivariate regression models with various combinations of height, weight, and age were used to obtain Z scores that were independent of age and body size. There was no residual association between Z scores and body size, age, or body mass index. There was no significant departure from the normal distribution.
Conclusions
The authors present reference values and Z score equations for a comprehensive set of vascular parameters during childhood. Further studies are necessary to assess their usefulness in detecting the vascular signs of subclinical atherosclerosis and chronic diseases, including congenital heart disease.

Copyright © 2020 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

J Am Soc Echocardiogr: 18 May 2020; epub ahead of print
Torigoe T, Dallaire F, Slorach C, Cardinal MP, ... Mertens L, Jaeggi E
J Am Soc Echocardiogr: 18 May 2020; epub ahead of print | PMID: 32444330
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Impact:
Abstract

Transbaffle/transconduit puncture using a simple CARTO-guided approach without echocardiography in patients with congenital heart disease.

Laredo M, Waldmann V, Soulat G, Amet D, ... Ladouceur M, Zhao A
Introduction
Catheter ablation (CA) of atrial tachyarrhythmias (ATs) in patients with complex congenital heart disease (CHD) often requires technically challenging transbaffle or transconduit puncture. The aim was to assess the feasibility and safety of transbaffle/transconduit puncture based on computed tomography (CT) 3D reconstruction merged with electro-anatomical mapping (EAM) without per-procedure echocardiographic guidance.
Methods and results
We included 18 consecutive CHD patients in two centers who had atrial-switch or Fontan surgery and underwent CA of AT by an antegrade approach requiring intracardiac puncture. Twelve patients with atrial-switch surgery and 6 patients with extracardiac Fontan surgery were referred for CA of atrial tachyarrhythmia. Cardiac CT with 3D reconstruction was performed before the procedure. The 3D volume of the systemic venous atrium or extracardiac conduit acquired by EAM was merged with the corresponding CT 3D reconstruction. The ablation catheter was positioned at the optimal puncture site. Under fluoroscopic guidance, the needle was positioned next to the ablation and the puncture was performed. Balloon expansion of the puncture site was performed in every case of transconduit puncture and in 2 (17%) cases of transbaffle puncture. Overall, 17 intra-atrial reentrant tachycarrythmias and 9 focal ATs were successfully ablated, with no acute complications. The median time to access the pulmonary atrium was 78.5 min (range 55-185) and total median fluoroscopy time was 23 min (range 7-53).
Conclusions
Transbaffle and transconduit punctures can be performed safely in CHD patients by using a simple technique relying on CT 3D reconstruction and EAM. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

J Cardiovasc Electrophysiol: 25 May 2020; epub ahead of print
Laredo M, Waldmann V, Soulat G, Amet D, ... Ladouceur M, Zhao A
J Cardiovasc Electrophysiol: 25 May 2020; epub ahead of print | PMID: 32458508
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Impact:
Abstract

Clinical and procedural implications of congenital vena cava anomalies in adults: A systematic review.

Shafi I, Hassan AAI, Akers KG, Bashir R, ... Weinberger JJ, Abidov A
Background
Although congenital vena cava (CVC) anomalies in adults have implications for surgical and radiological interventions, the literature is scare and disparate. The aim of this systematic review was to assess cardiovascular clinical and procedural implications of CVC anomalies in adults without congenital heart disease.
Methods and results
We searched PubMed and EMBASE from database conception through October 2018 for English-language studies describing the epidemiology of CVC anomalies or their clinical or procedural implications in humans. Two independent reviewers screened 7093 records and identified 16 relevant studies. We found two major implications of CVC anomalies: 1) congenital inferior vena cava (CIVC) anomalies are associated with a 50-100-fold higher risk of deep venous thrombosis, particularly among younger patients, and 2) persistent left superior vena cava (PLSVC) is associated with a 2-3-fold higher risk of supraventricular arrhythmias. PLSVC also poses technical challenges to cardiovascular electronic device implantation, requiring alterations in surgical approach and lengthening procedure and X-ray exposure times. Due to the large disparity in reported prevalence rates of CIVC anomalies, we performed a meta-analysis of CIVC anomaly prevalence including 8 studies, which showed a weighted prevalence of 6.8% (95% CI, 4.5-9.2%).
Conclusion
These findings challenge the notion that CVC anomalies are rare and asymptomatic in adults. Rather, the literature indicates that CVC anomalies are not uncommon and have important clinical and procedural implications. To further understand the prevalence and implications of CVC anomalies, a robust US population-based study and nationwide registry is warranted in the current era of venous interventions.

Copyright © 2020 Elsevier B.V. All rights reserved.

Int J Cardiol: 07 May 2020; epub ahead of print
Shafi I, Hassan AAI, Akers KG, Bashir R, ... Weinberger JJ, Abidov A
Int J Cardiol: 07 May 2020; epub ahead of print | PMID: 32434672
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Abstract

Patient care protocols and personal safety measures for health care professionals in cardiac catheterization rooms during the COVID-19 outbreak in the National Institute of Cardiology.

Eid-Lidt G, Farjat Pasos JI

The COVID-19 was first described in late 2019 that quickly became a pandemic affecting every health system as we know it. The high transmissibility among humans represents a well-known high burden of morbidity and mortality not only for cardiovascular patients but also for a higher risk between health care professionals that must deliver high-quality care to them in any scenario, and cardiac catheterization rooms are no exception. This creates a new dilemma, minimize exposure to patients and health care professionals to COVID-19 while maintaining high quality in cardiovascular therapeutics. In order to achieve this, several international recommendations on treatment algorithms modifications and in safety measures in the catheterization room have been published, always aiming to solve this dilemma in the best possible way. Hereby, we present a summary of the most recent treatment algorithms in the most important cardiovascular interventions (acute coronary syndromes, structural and congenital heart diseases) as well as specific safety measures with a step-by-step preparedness before and after any interventional procedure during COVID-19 outbreak. The objective of this document is to inform and to train health care professionals that works in cardiac catheterization rooms on the risks as well on the plan for containment, mitigation, and response to the global situation of COVID-19 infection in order to apply this in their own local work environments.

© 2020 Wiley Periodicals LLC.

Catheter Cardiovasc Interv: 31 May 2020; epub ahead of print
Eid-Lidt G, Farjat Pasos JI
Catheter Cardiovasc Interv: 31 May 2020; epub ahead of print | PMID: 32478472
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Abstract

Gadolinium contrast balloon pulmonary angioplasty for a patient with chronic thromboembolic pulmonary hypertension and severe iodine allergy.

Saito S, Ikeda N, Toi S, Nakamura M

Chronic thromboembolic pulmonary hypertension (CTEPH) is group 4 pulmonary hypertension caused by organized thrombi in the pulmonary arteries. Balloon pulmonary angioplasty (BPA) is an emerging treatment option for patients with inoperable CTEPH but needs contrast media. Therefore, management can be very difficult in patients who have severe iodine allergies. We present a case of a 61-year-old female with CTEPH. Right heart catheterization showed that the mean pulmonary arterial pressure (mPAP) was 47 mmHg. Her organized thrombi were not surgically accessible, so we performed BPA to improve her hemodynamic status. One session of BPA was performed, but the second session was halted because of iodine-induced anaphylactic shock. Despite the administration of pulmonary arterial hypertension-specific drugs for 3 months, the patient\'s mPAP was still 33 mmHg. CTEPH patients with mPAP ≥30 mmHg have a poor prognosis, so we decided to perform BPA using gadolinium contrast media. A total of six sessions of gadolinium contrast BPA (Gd-BPA) improved the patient\'s mPAP to the normal range. Gadolinium contrast media could also be used for visualizing pulmonary arteries during BPA. Our report is the first successful case of Gd-BPA, which improved the patient\'s hemodynamic status to the almost normal range. Gd-BPA may be an attractive treatment option for patients with inoperable CTEPH and severe iodine allergy.

© 2020 Wiley Periodicals LLC.

Catheter Cardiovasc Interv: 31 May 2020; epub ahead of print
Saito S, Ikeda N, Toi S, Nakamura M
Catheter Cardiovasc Interv: 31 May 2020; epub ahead of print | PMID: 32478464
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Impact:
Abstract

Thinking Inside the Box: Custom Pacemaker Improves Device Longevity in a Congenital Heart Patient.

Von Wald L, Brucker R, Salerno S, Ries A, Roukoz H

Patients with congenital heart disease have unique pacing challenges and often require epicardial systems. High pacing threshold is one of the major factors that decrease these systems\' durability. Sometimes surgical re-intervention or lead replacement is difficult or prohibitive in these patients due to repeated surgeries and extensive epicardial scar. We present a case report of a patient with Fontan physiology and chronically high epicardial lead pacing thresholds requiring frequent generator changes and a unique solution focusing on improving generator longevity. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

J Cardiovasc Electrophysiol: 03 Jun 2020; epub ahead of print
Von Wald L, Brucker R, Salerno S, Ries A, Roukoz H
J Cardiovasc Electrophysiol: 03 Jun 2020; epub ahead of print | PMID: 32495370
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Impact:
Abstract

Long-term changes of exercise hemodynamics and physical capacity in chronic thromboembolic pulmonary hypertension after pulmonary thromboendarterectomy.

Waziri F, Mellemkjær S, Clemmensen TS, Hjortdal VE, ... Nielsen SL, Poulsen SH
Background
A substantial number of chronic thromboembolic pulmonary hypertension (CTEPH) patients experience dyspnea on exertion and limited exercise capacity despite surgically successful pulmonary endarterectomy (PEA). We sought to prospectively evaluate resting and peak exercise hemodynamics before, 3 and 12 months after PEA in consecutive CTEPH-patients and correlate it to physical functional capacity.
Methods and results
Twenty consecutive CTEPH-patients were examined. Twelve months after PEA, 75% of patients with severely increased pre-PEA mean pulmonary arterial pressure (mPAP) at rest had normal or mildly increased mPAP. However, mPAP reduction was less pronounced during exercise where only 45% had normal or mildly increased mPAP at 12 months. Hemodynamic changes during exercise were tested using the pressure-flow relationship (i.e. mPAP/cardiac output (CO) slope). The average mPAP/CO slope was 7.5 ± 4.2 mm Hg/L/min preoperatively and 3.9 ± 3.0 mm Hg/L/min at 12 months (p < .005). CO reserve (CO increase from rest to peak exercise) was increased (5.7 ± 2.9 L/min) 12 months after PEA compared with pre-PEA (2.5 ± 1.8 L/min), p < .0001. However, 12 months after PEA, the CO reserve was only 49% of that of healthy controls, p < .0001. Changes in cardiac output (∆CO), calculated as the difference between CO before PEA and 12 months later, were significantly correlated with six-minute-walk-test and peak oxygen uptake (VO2), both at rest and peak exercise.
Conclusion
Invasive exercise hemodynamic examination in CTEPH-patients demonstrates that after otherwise successful PEA surgery, >50% of patients have a significant increase in exercise mPAP, and the CO reserve remains compromised 12 months after PEA. Improvement in physical capacity is correlated with ∆CO.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 31 May 2020; epub ahead of print
Waziri F, Mellemkjær S, Clemmensen TS, Hjortdal VE, ... Nielsen SL, Poulsen SH
Int J Cardiol: 31 May 2020; epub ahead of print | PMID: 32497568
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Impact:
Abstract

Increased myocardial oxygen consumption rates are associated with maladaptive right ventricular remodeling and decreased event-free survival in heart failure patients.

Ahmadi A, Renaud JM, Promislow S, Burwash IG, ... Beanlands RS, Mielniczuk LM
Background
Reduced left ventricular (LV) function is associated with increased myocardial oxygen consumption rate (MVO) and altered sympathetic activity, the role of which is not well described in right ventricular (RV) dysfunction.
Methods and results
33 patients with left heart failure were assessed for RV function/size using echocardiography. Positron emission tomography (PET) was used to measure C-acetate clearance rate (k), C-hydroxyephedrine (C-HED) standardized uptake value (SUV), and retention rate. RV MVO was estimated from k. C-HED SUV and retention indicated sympathetic neuronal function. A composite clinical endpoint was defined as unplanned cardiac hospitalization within 5 years. Patients with (n = 10) or without (n = 23) RV dysfunction were comparable in terms of sex (male: 70.0 vs 69.5%), LV ejection fraction (39.6 ± 9.0 vs 38.6 ± 9.4%), and systemic hypertension (70.0 vs 78.3%). RV dysfunction patients were older (70.9 ± 13.5 vs 59.4 ± 11.5 years; P = .03) and had a higher prevalence of pulmonary hypertension (60.0% vs 13.0%; P = .01). RV dysfunction was associated with increased RV MVO (.106 ± .042 vs .068 ± .031 mL/min/g; P = .02) and decreased C-HED SUV and retention (6.05 ± .53 vs 7.40 ± 1.39 g/mL (P < .001) and .08 ± .02 vs .11 ± .03 mL/min/g (P < .001), respectively). Patients with an RV MVO above the median had a shorter event-free survival (hazard ratio = 5.47; P = .01). Patients who died within the 5-year follow-up period showed a trend (not statistically significant) for higher RV MVO (.120 ± .026 vs .074 ± .038 mL/min/g; P = .05).
Conclusions
RV dysfunction is associated with increased oxygen consumption (also characterized by a higher risk for cardiac events) and impaired RV sympathetic function.



J Nucl Cardiol: 06 May 2020; epub ahead of print
Ahmadi A, Renaud JM, Promislow S, Burwash IG, ... Beanlands RS, Mielniczuk LM
J Nucl Cardiol: 06 May 2020; epub ahead of print | PMID: 32383088
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Abstract

Gynecological and obstetric outcome in the French cohort of women with factor XIII deficiency.

Rugeri L, Martinaud C, Beurrier P, Borg Y, ... Pan-Petesch B, Meunier S
Introduction
Congenital factor XIII deficiency is a very rare bleeding disorder affecting 33 patients in France. Besides its role in fibrin clot stabilization, factor XIII is involved in placental attachment. Fetal miscarriages represent a frequent and concerning issue for these patients. The aim of the present study was to describe clinical characteristics of women presenting severe congenital FXIII deficiency in France, to focus on gynecological and obstetrical events, and to report the management of these rare situations.
Methods
We conducted a retrospective study in the French Hemophilia Comprehensive Care and Clinical Hemostasis Centers. Women between 15 and 65 years with factor XIII activity <10 IU dL were included. Biological, clinical and therapeutic events that occurred to these patients during their gynecological and obstetrical period were recorded.
Results
Among 31 centers, eleven patients were included. The median age at diagnosis was 1.5 years (range: 0-35), and at inclusion it was 30 years (range: 15-63). Fetal miscarriage was the primary manifestations in 2 (18%) patients, the remaining were diagnosed during hemorrhage. Menorrhagias were reported by 2 women (27%), 13 pregnancies were reported by 9 women including one abortion. Every pregnancy was conducted under factor XIII substitution, no hemorrhagic episode was reported. Four patients (36%) experienced at least one fetal miscarriage with a total amount of 30 miscarriages with 6 occurring during substitution.
Conclusion
Altogether, our data confirmed the high incidence of miscarriage in women with factor XIII deficiency. Good outcome of pregnancies required prophylaxis in accordance with international guidelines.

Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.

Thromb Res: 20 Apr 2020; 191:22-25
Rugeri L, Martinaud C, Beurrier P, Borg Y, ... Pan-Petesch B, Meunier S
Thromb Res: 20 Apr 2020; 191:22-25 | PMID: 32360976
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Impact:
Abstract

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

Burkett DA, Patel SS, Mertens L, Friedberg MK, Ivy DD

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.



Circ Cardiovasc Imaging: 29 Apr 2020; 13:e009825
Burkett DA, Patel SS, Mertens L, Friedberg MK, Ivy DD
Circ Cardiovasc Imaging: 29 Apr 2020; 13:e009825 | PMID: 32408829
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Abstract

Neuropathology of Congenital Heart Disease in an Inpatient Autopsy Cohort 2000-2017.

Rettenmaier LA, Kirby PA, Reinking BE, Viaene AN, Hefti MM

Background As a result of medical and surgical advancements in the management of congenital heart disease (CHD), survival rates have improved substantially, which has allowed the focus of CHD management to shift toward neurodevelopmental outcomes. Previous studies of the neuropathology occurring in CHD focused on cases preceding 1995 and reported high rates of white matter injury and intracranial hemorrhage, but do not reflect improvements in management of CHD in the past 2 decades. The purpose of this study is therefore to characterize the neuropathological lesions identified in subjects dying from CHD in a more-recent cohort from 2 institutions. Methods and Results We searched the autopsy archives at 2 major children\'s hospitals for patients with cyanotic congenital cardiac malformations who underwent autopsy. We identified 50 cases ranging in age from 20 gestational weeks to 46 years. Acquired neuropathological lesions were identified in 60% (30 of 50) of subjects upon postmortem examination. The most common lesions were intracranial hemorrhage, most commonly subarachnoid (12 of 50; 24%) or germinal matrix (10 of 50; 20%), hippocampal injuries (10 of 50; 20%), and diffuse white matter gliosis (8 of 50; 16%). Periventricular leukomalacia was rare (3 of 50). Twenty-six subjects underwent repair or palliation of their lesions. Of the 50 subjects, 60% (30 of 50) had isolated CHD, whereas 24% (12 of 50) were diagnosed with chromosomal abnormalities (trisomy 13, 18, chromosomal deletions, and duplications) and 16% (8/50) had multiple congenital anomalies. Conclusions In the modern era of pediatric cardiology and cardiac surgery, intracranial hemorrhage and microscopic gray matter hypoxic-ischemic lesions are the dominant neuropathological lesions identified in patients coming to autopsy. Rates of more severe focal lesions, particularly periventricular leukomalacia, have decreased compared with historical controls.



J Am Heart Assoc: 06 Apr 2020; 9:e013575
Rettenmaier LA, Kirby PA, Reinking BE, Viaene AN, Hefti MM
J Am Heart Assoc: 06 Apr 2020; 9:e013575 | PMID: 32200729
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Impact:
Abstract

Invasive cardiovascular magnetic resonance (iCMR) for diagnostic right and left heart catheterization using an MR-conditional guidewire and passive visualization in congenital heart disease.

Veeram Reddy SR, Arar Y, Zahr RA, Gooty V, ... Nugent AW, Hussain T
Background
Today\'s standard of care, in the congenital heart disease (CHD) population, involves performing cardiac catheterization under x-ray fluoroscopy and cardiac magnetic resonance (CMR) imaging separately. The unique ability of CMR to provide real-time functional imaging in multiple views without ionizing radiation exposure has the potential to be a powerful tool for diagnostic and interventional procedures. Limiting fluoroscopic radiation exposure remains a challenge for pediatric interventional cardiologists. This pilot study\'s objective is to establish feasibility of right (RHC) and left heart catheterization (LHC) during invasive CMR (iCMR) procedures at our institution in the CHD population. Furthermore, we aim to improve simultaneous visualization of the catheter balloon tip, MR-conditional guidewire, and cardiac/vessel anatomy during iCMR procedures.
Methods
Subjects with CHD were enrolled in a pilot study for iCMR procedures at 1.5 T with an MR-conditional guidewire. The CMR area is located adjacent to a standard catheterization laboratory. Using the interactive scanning mode for real-time control of the imaging location, a dilute gadolinium-filled balloon-tip catheter was used in combination with an MR-conditional guidewire to obtain cardiac saturations and hemodynamics. A recently developed catheter tracking technique using a real-time single-shot balanced steady-state free precession (bSSFP), flip angle (FA) 35-45°, echo time (TE) 1.3 ms, repetition time (TR) 2.7 ms, 40° partial saturation (pSAT) pre-pulse was used to visualize the gadolinium-filled balloon, MR-conditional guidewire, and cardiac structures simultaneously. MR-conditional guidewire visualization was enabled due to susceptibility artifact created by distal markers. Pre-clinical phantom testing was performed to determine the optimum imaging FA-pSAT combination.
Results
The iCMR procedure was successfully performed to completion in 31/34 (91%) subjects between August 1st, 2017 to December 13th, 2018. Median age and weight were 7.7 years and 25.2 kg (range: 3 months - 33 years and 8 - 80 kg). Twenty-one subjects had single ventricle (SV) anatomy: one subject was referred for pre-Glenn evaluation, 11 were pre-Fontan evaluations and 9 post-Fontan evaluations for protein losing enteropathy (PLE) and/or cyanosis. Thirteen subjects had bi-ventricular (BiV) anatomy, 4 were referred for coarctation of the aorta (CoA) evaluations, 3 underwent vaso-reactivity testing with inhaled nitric oxide, 3 investigated RV volume dimensions, two underwent branch PA stenosis evaluation, and the remaining subject was status post heart transplant. No catheter related complications were encountered. Average time taken for first pass RHC, LHC/aortic pull back, and to cross the Fontan fenestration was 5.2, 3.0, and 6.5 min, respectively. Total success rate to obtain required data points to complete Fick principle calculations for all patients was 331/337 (98%). Subjects were transferred to the x-ray fluoroscopy lab if further intervention was required including Fontan fenestration device closure, balloon angioplasty of pulmonary arteries/conduits, CoA stenting, and/or coiling of aortopulmonary (AP) collaterals. Starting with subject #10, an MR-conditional guidewire was used in all subsequent subjects (15 SV and 10 BiV) with a success rate of 96% (24/25). Real-time CMR-guided RHC (25/25 subjects, 100%), retrograde and prograde LHC/aortic pull back (24/25 subjects, 96%), CoA crossing (3/4 subjects, 75%) and Fontan fenestration test occlusion (2/3 subjects, 67%) were successfully performed in the majority of subjects when an MR-conditional guidewire was utilized.
Conclusion
Feasibility for detailed diagnostic RHC, LHC, and Fontan fenestration test occlusion iCMR procedures in SV and BiV pediatric subjects with complex CHD is demonstrated with the aid of an MR-conditional guidewire. A novel real-time pSAT GRE sequence with optimized FA-pSAT angle has facilitated simultaneous visualization of the catheter balloon tip, MR-conditional guidewire, and cardiac/vessel anatomy during iCMR procedures.



J Cardiovasc Magn Reson: 25 Mar 2020; 22:20
Veeram Reddy SR, Arar Y, Zahr RA, Gooty V, ... Nugent AW, Hussain T
J Cardiovasc Magn Reson: 25 Mar 2020; 22:20 | PMID: 32213193
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Impact:
Abstract

Recommendations for exercise in adolescents and adults with congenital heart disease.

Tran D, Maiorana A, Ayer J, Lubans DR, ... d\'Udekem Y, Cordina R

The population of adults living with congenital heart disease (CHD) has grown rapidly in recent decades due to major advances in surgical and medical care. Although the benefits of physical activity (PA) and exercise are well recognised in the management of chronic diseases, the therapeutic role of exercise for the CHD population has been under-studied and under-recognised. In fact, people living with complex CHD have traditionally been advised against participation in moderate or vigorous PA due to safety concerns. However, a small but growing body of literature has demonstrated that PA and exercise are safe and beneficial for the vast majority of people with CHD following appropriate screening. Exercise training (ET) is a potent therapy to improve well-being and cardiorespiratory fitness, which likely has important implications for prognosis. This has led to ET becoming an increasingly important adjunct to medical therapy in the management of this group who frequently have significant exercise limitation and complex medical issues. However, there is currently limited evidence-based guidance that has been published regarding appropriate exercise prescription in adults with CHD. This article aims to provide an overview of different congenital heart conditions, their impact on the exercise response and to provide considerations and recommendations for ET in adolescents and adults living with CHD based on the available literature.

Copyright © 2020. Published by Elsevier Inc.

Prog Cardiovasc Dis: 18 Mar 2020; epub ahead of print
Tran D, Maiorana A, Ayer J, Lubans DR, ... d'Udekem Y, Cordina R
Prog Cardiovasc Dis: 18 Mar 2020; epub ahead of print | PMID: 32201288
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Impact:
Abstract

Association of Rare PTGIS Variants With Susceptibility and Pulmonary Vascular Response in Patients With Idiopathic Pulmonary Arterial Hypertension.

Wang XJ, Xu XQ, Sun K, Liu KQ, ... Zhang X, Jing ZC
Importance
Idiopathic pulmonary arterial hypertension (IPAH) is a fatal disease with high heritability; however, the bone morphogenetic protein receptor 2 (BMPR2) gene only accounts for 17% of IPAH. The genetic basis of IPAH needs further investigation.
Objective
To identify novel IPAH susceptibility genes other than BMPR2.
Design, setting, and participants
This 2-stage, case-control genetic association study enrolled 230 patients with IPAH from 2 referral pulmonary hypertension centers in China. Eligible patients had no BMPR2 variants and were compared with 968 healthy control participants. Data were collected from January 1, 2000, to July 31, 2015, and analyzed from August 1, 2015, to May 30, 2018.
Exposures
PTGIS rare variants.
Main outcomes and measures
Whole-genome sequencing was performed to identify putative IPAH genes in a discovery cohort, with validation in an independent referral cohort. Correlation of genotype and hemodynamic characteristics was then evaluated at baseline and after pulmonary vasodilator testing. Functional assessments were conducted to analyze the effects of identified genetic variants on transcript splicing, enzymatic activity, and endothelial cell phenotypes.
Results
Among 230 patients with IPAH (164 female [71.3%]; mean [SD] age, 34 [18] years), an enrichment of rare variants in a gene encoding prostacyclin synthase (PTGIS) was identified in the discovery cohort. The association of PTGIS rare variants with IPAH was confirmed in the replication cohort. In the combined data set, PTGIS rare variants were found in 14 of 230 cases (6.1%) and 8 of 968 controls (0.8%) (odds ratio, 7.8; 95% CI, 3.2-18.8; P = 5 × 10-6, logistic regression). Compared with patients without PTGIS variants, inhaled iloprost induced a more significant decrease of pulmonary vascular resistance (difference in the least square mean, -21.7%; 95% CI, -31.4% to -12.0%; P < .001, linear regression model) and an increase of cardiac index (difference in the least square mean, 18.3%; 95% CI, 8.8%-27.8%; P < .001, linear regression model) in patients with PTGIS variants. The minigene assay indicated that the c.521 + 1G>A variant resulted in aberrant messenger RNA transcripts. The functional studies showed that the 2 missense rare variants (R252Q and A447T) resulted in a decrease in prostacyclin production and increased cell death of pulmonary microvascular endothelial cells.
Conclusions and relevance
This study identified 3 rare loss-of-function variants in the PTGIS gene from 2 independent cohorts with IPAH. The genetic variants of PTGIS predispose pulmonary vascular responses to the iloprost stimulation. These findings suggest that PTGIS variants may be involved in the pathogenesis of IPAH.



JAMA Cardiol: 31 Mar 2020; epub ahead of print
Wang XJ, Xu XQ, Sun K, Liu KQ, ... Zhang X, Jing ZC
JAMA Cardiol: 31 Mar 2020; epub ahead of print | PMID: 32236489
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Abstract

Determinants of Sudden Cardiac Death in Adult Patients With Eisenmenger Syndrome.

Chiriac A, Riley DC, Russell M, Moore JP, ... Asirvatham SJ, McLeod CJ

Background Patients with Eisenmenger syndrome are known to have a high incidence of sudden cardiac death (SCD), yet the underlying causes are not well understood. We sought to define the predictors of SCD in this population. Methods and Results A retrospective analysis of all patients with Eisenmenger syndrome from 2 large tertiary referral centers was performed. ECGs, prolonged ambulatory recordings, echocardiograms, and clinical histories were reviewed; and the cause of death was identified. A total of 246 patients (85 [34.6%] men) with a mean age of 37.3 (±14.2) years were followed up for a median of 7 years. Over the study period, 136 patients died, with 40 experiencing SCD and 74 experiencing cardiac death (sudden and nonsudden). Age, atrial fibrillation, prolonged QRS duration, complete heart block, right atrial enlargement, right bundle branch block, increased right atrial pressure, impaired biventricular function, and the presence of a pacemaker were associated with increased risk of SCD, whereas advanced pulmonary hypertension therapies were protective. Atrial fibrillation (11.45-fold increased risk; <0.001) and QRS duration ≥120 ms (2.06-fold increased risk; =0.034) remained significant predictors of SCD in the multivariate analysis, whereas advanced pulmonary hypertension therapies were strongly protective against SCD (<0.001). Conclusions Atrial arrhythmias, impaired ventricular function, and conduction system disease were associated with increased risk of SCD in this cohort of patients with Eisenmenger syndrome, providing an opportunity for early risk stratification and potential intervention. Clinical heart failure symptoms (New York Heart Association class ≥II) were predictive of increased mortality but not of SCD, suggesting a potential arrhythmic cause behind SCD.



J Am Heart Assoc: 16 Mar 2020; 9:e014554
Chiriac A, Riley DC, Russell M, Moore JP, ... Asirvatham SJ, McLeod CJ
J Am Heart Assoc: 16 Mar 2020; 9:e014554 | PMID: 32174228
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Abstract

Piezo1 and outflow tract and aortic valve development.

Faucherre A, Maati HMO, Nasr N, Pinard A, ... Zaffran S, Jopling C
Aims
During embryogenesis, the onset of circulatory blood flow generates a variety of hemodynamic forces which reciprocally induce changes in cardiovascular development and performance. It has been known for some time that these forces can be detected by as yet unknown mechanosensory systems which in turn promote cardiogenic events such as outflow tract and aortic valve development. PIEZO1 is a mechanosensitive ion channel present in endothelial cells where it serves to detect hemodynamic forces making it an ideal candidate to play a role during cardiac development. We sought to determine whether PIEZO1 is required for outflow tract and aortic valve development.
Methods and results
By analysing heart development in zebrafish we have determined that piezo1 is expressed in the developing outflow tract where it serves to detect hemodynamic forces. Consequently, disrupting Piezo1 signalling leads to defective outflow tract and aortic valve development and indicates this gene may be involved in the etiology of congenital heart diseases. Based on these findings, we analysed genomic data generated from patients who suffer from left ventricular outflow tract obstructions (LVOTO) and identified 3 probands who each harboured potentially pathogenic variants in PIEZO1. Subsequent in vitro and in vivo assays indicates that these variants behave as dominant negatives leading to an inhibition of normal PIEZO1 mechanosensory activity. Expressing these dominant negative PIEZO1 variants in zebrafish endothelium leads to defective aortic valve development.
Conclusion
These data indicate that the mechanosensitive ion channel piezo1 is required for OFT and aortic valve development.

Copyright © 2019. Published by Elsevier Ltd.

J Mol Cell Cardiol: 02 Apr 2020; epub ahead of print
Faucherre A, Maati HMO, Nasr N, Pinard A, ... Zaffran S, Jopling C
J Mol Cell Cardiol: 02 Apr 2020; epub ahead of print | PMID: 32251670
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Abstract

Sizing heart transplant donors in adults with congenital heart disease.

Clark DE, Byrne RD, Mazurek JA, Opotowsky AR, ... Zalawadiya S, Menachem JN
Objective
Optimal donor sizing for heart transplantation (HT) in adults with congenital heart disease (CHD) remains unclear, given the propensity for pulmonary hypertension related to shunting, staged repairs, and periods of pulmonary overcirculation. We studied HT outcomes related to donor size matching in the adult CHD population.
Methods
We conducted a retrospective cohort analysis of patients with CHD undergoing HT in the United States from January 1, 2000, to December 31, 2015. Patients were selected from the United Network for Organ Sharing database; 827 patients met inclusion criteria and were analyzed.
Results
At a median follow-up of 1462 days, 548 (66.3%) subjects were alive and 279 (33.7%) were deceased. All-cause mortality did not differ based on donor sizing (by predicted heart mass ratio: hazard ratio, 1.03; confidence interval, 0.86-1.23; P = .74). Pulmonary hypertension was not significantly associated with survival (by predicted heart mass ratio, χ = 2.01, P = .73).
Conclusions
Our data demonstrate that donor oversizing, to the extent used in current practice, does not affect survival after HT in adults with CHD. Our findings from the United Network for Organ Sharing database demonstrate that donor oversizing in these patients is not associated with improved mortality.

Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

J Thorac Cardiovasc Surg: 27 Mar 2020; epub ahead of print
Clark DE, Byrne RD, Mazurek JA, Opotowsky AR, ... Zalawadiya S, Menachem JN
J Thorac Cardiovasc Surg: 27 Mar 2020; epub ahead of print | PMID: 32222406
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Abstract

Environmental and Socioeconomic Factors Influence the Live-Born Incidence of Congenital Heart Disease: A Population-Based Study in California.

Peyvandi S, Baer RJ, Chambers CD, Norton ME, ... Jelliffe-Pawlowski LL, Steurer MA

Background The development of congenital heart disease (CHD) is multifactorial with genetic and environmental influences. We sought to determine the relationship between socioeconomic and environmental factors with the incidence of CHD among live-born infants in California and to determine whether maternal comorbidities are in the causal pathway. Methods and results This was a population-based cohort study in California (2007-2012). The primary outcome was having significant CHD. Predictors included socioeconomic status and environmental exposure to pollutants determined by U.S. Census data. A social deprivation index and environmental exposure index was assigned based on neighborhood socioeconomic variables, categorized into 4 quartiles. Quartile 1 was the best with the least exposure to pollutants and social deprivation, and quartile 4 was the worst. Multivariate logistic regression and mediation analyses were performed. Among 2 419 651 live-born infants, the incidence of CHD was 3.2 per 1000 live births. The incidence of CHD was significantly higher among those in quartile 4 compared with quartile 1 (social deprivation index: 0.35% versus 0.29%; odds ratio [OR], 1.31; 95% CI, 1.21-1.41; environmental exposure index: 0.35% versus 0.29%; OR, 1.23; 95% CI, 1.15-1.31) after adjusting for maternal race/ethnicity and age and accounting for the relationship between the 2 primary predictors. Maternal comorbidities explained 13% (95% CI, 10%-20%) of the relationship between social deprivation index and environmental exposure index with the incidence of CHD. CONCLUSIONS Increased social deprivation and exposure to environmental pollutants are associated with the incidence of live-born CHD in California. Maternal comorbidities explain some, but not all, of this relationship. These findings identify targets for social policy initiatives to minimize health disparities.



J Am Heart Assoc: 18 Apr 2020:e015255; epub ahead of print
Peyvandi S, Baer RJ, Chambers CD, Norton ME, ... Jelliffe-Pawlowski LL, Steurer MA
J Am Heart Assoc: 18 Apr 2020:e015255; epub ahead of print | PMID: 32306820
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Abstract

Chronic Disease Burden After Congenital Heart Surgery: A 47-Year Population-Based Study With 99% Follow-Up.

Raissadati A, Haukka J, Pätilä T, Nieminen H, Jokinen E

Background Postoperative morbidity is an increasingly important outcome measure of patients who have undergone congenital heart surgery (CHS). We examined late postoperative morbidity after CHS on the basis of patients\' government-issued medical special reimbursement rights. Methods and Results Between 1953 and 2009, 10 635 patients underwent CHS at <15 years of age in Finland. We excluded early deaths and mental disabilities. Noncyanotic and cyanotic defects were divided into simple and severe groups, respectively. We obtained 4 age-, sex-, birth time-, and hospital district-matched control subjects per patient. The Social Insurance Institution of Finland provided data on all medical special reimbursement rights granted between 1966 and 2012. Follow-up started at the first operation and ended at death, date of emigration, or December 31, 2012. A total of 8623 patients met inclusion criteria. Follow-up was 99.9%. A total of 3750 patients (43%) required special reimbursements rights for a chronic disease. Cardiovascular disease was the most common late morbidity among patients (28%), followed by obstructive pulmonary disease (9%), neurologic disease (3%), and psychiatric disease (2%). Heart failure (simple hazard ratio [HR], 56.3 [95% CI, 35.4-89.7]; severe HR, 918.0 [95% CI, 228.9-3681.7]) and arrhythmia (simple HR, 11.0 [95% CI, 7.1-17.0]; severe HR, 248.0 [95% CI, 61.3-1002.7]) were the most common cardiovascular morbidities. Hypertension was common among patients with coarctation of the aorta (13%; incidence risk ratio [RR], 8.9; 95% CI, 7.5-10.7). Psychiatric disease was more common among simple defects, particularly ventricular septal defects. Conclusions Chronic cardiac and noncardiac sequelae are common after CHS regardless of the severity of the defect, underscoring the importance of long-term follow-up of all patients after CHS.



J Am Heart Assoc: 21 Apr 2020:e015354; epub ahead of print
Raissadati A, Haukka J, Pätilä T, Nieminen H, Jokinen E
J Am Heart Assoc: 21 Apr 2020:e015354; epub ahead of print | PMID: 32316818
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Abstract

Prevalence and Prognostic Association of a Clinical Diagnosis of Depression in Adult Congenital Heart Disease: Results of the Boston Adult Congenital Heart Disease Biobank.

Carazo MR, Kolodziej MS, DeWitt ES, Kasparian NA, ... Singh MN, Opotowsky AR

Background In adults with acquired heart disease, depression is common and associated with adverse outcomes. Depression may also be important in adults with congenital heart disease (CHD). Methods and Results We conducted a cohort study of outpatients with CHD, aged ≥18 years, enrolled in a prospective biobank between 2012 and 2017. Clinical data were extracted from medical records. Survival analysis assessed the relationship between depression, defined by a history of clinical diagnosis of major depression, with all-cause mortality and a composite outcome of death or nonelective cardiovascular hospitalization. A total of 1146 patients were enrolled (age, 38.5±13.8 years; 49.6% women). Depression had been diagnosed in 219 (prevalence=19.1%), and these patients were more likely to have severely complex CHD (41.3% versus 33.7%; =0.028), cyanosis (12.1% versus 5.7%; =0.003), and worse functional class (≥II; 33.3% versus 20.4%; <0.0001), and to be taking antidepressant medication at time of enrollment (68.5% versus 5.7%; <0.0001). Depression was associated with biomarkers indicative of inflammation (hsCRP [high-sensitivity C-reactive protein], 1.71 [25th-75th percentile, 0.82-4.47] versus 1.10 [0.45-2.40]; <0.0001) and heart failure (NT-proBNP [N-terminal pro-B-type natriuretic peptide], 190 [92-501] versus 111 [45-264]; <0.0001). During follow-up of 605±547 days, 137 participants (12.0%) experienced the composite outcome, including 33 deaths (2.9%). Depression was associated with increased risk for both all-cause mortality (multivariable hazard ratio, 3.0; 95% CI, 1.4-6.4; =0.005) and the composite outcome (multivariable hazard ratio, 1.6; 95% CI, 1.1-2.5; =0.025), adjusting for age, sex, history of atrial arrhythmia, systolic ventricular function, CHD complexity, and corrected QT interval. Conclusions In adults with CHD, major depression is associated with impaired functional status, heart failure, systemic inflammation, and increased risk for adverse outcomes.



J Am Heart Assoc: 27 Apr 2020:e014820; epub ahead of print
Carazo MR, Kolodziej MS, DeWitt ES, Kasparian NA, ... Singh MN, Opotowsky AR
J Am Heart Assoc: 27 Apr 2020:e014820; epub ahead of print | PMID: 32342722
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Abstract

Balloon pulmonary angioplasty improves right atrial reservoir and conduit functions in chronic thromboembolic pulmonary hypertension.

Yamasaki Y, Abe K, Kamitani T, Hosokawa K, ... Tsutsui H, Yabuuchi H
Aims
Right atrial (RA) function largely contributes to the maintenance of right ventricular (RV) function. This study investigated the effect of balloon pulmonary angioplasty (BPA) on RA functions in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) using cardiac magnetic resonance imaging (CMRI).
Methods and results
CMRI and RV catheterization were performed before BPA sessions and at the follow-up periods in 29 CTEPH patients. Reservoir [RA longitudinal strain (RA-LS)], passive conduit [RA early LS rate (LSR)], and active (RA late LSR) phases were assessed by using cine CMRI and a feature-tracking algorithm. The relationships between the changes in RA functions and in brain natriuretic peptide (BNP) were evaluated in both the dilated and non-dilated RA groups. RA-LS (32.4% vs. 42.7%), RA LSR (6.3% vs. 8.3%), and RA early LSR (-2.3% vs. -4.3%) were improved after BPA, whereas no significant change was seen in RA late LSR. The changes in RA peak LS and in RA early LSR were significantly correlated with the changes in BNP (ΔRA-LS: r = -0.63, ΔRA-early LSR: r = 0.65) and pulmonary vascular resistance (PVR) (ΔRA-LS: r = -0.69, ΔRA-early LSR: r = 0.66) in the nondilated RA group.
Conclusion
The RA reservoir and passive conduit functions were impaired in inoperable CTEPH, whereas RA active function was preserved. BPA markedly reversed these impaired functions. The improvements in RA reservoir and conduit functions were significantly correlated with the changes in BNP levels and PVR in CTEPH patients with normal RA sizes.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Imaging: 30 Apr 2020; epub ahead of print
Yamasaki Y, Abe K, Kamitani T, Hosokawa K, ... Tsutsui H, Yabuuchi H
Eur Heart J Cardiovasc Imaging: 30 Apr 2020; epub ahead of print | PMID: 32359071
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Abstract

4D flow cardiovascular magnetic resonance for monitoring of aortic valve repair in bicuspid aortic valve disease.

Lenz A, Petersen J, Riedel C, Weinrich JM, ... Girdauskas E, Bannas P
Background
Aortic valve repair has become a treatment option for adults with symptomatic bicuspid (BAV) or unicuspid (UAV) aortic valve insufficiency. Our aim was to demonstrate the feasibility of 4D flow cardiovascular magnetic resonance (CMR) to assess the impact of aortic valve repair on changes in blood flow dynamics in patients with symptomatic BAV or UAV.
Methods
Twenty patients with adult congenital heart disease (median 35 years, range 18-64; 16 male) and symptomatic aortic valve regurgitation (15 BAV, 5 UAV) were prospectively studied. All patients underwent 4D flow CMR before and after aortic valve repair. Aortic valve regurgitant fraction and systolic peak velocity were estimated. The degree of helical and vortical flow was evaluated according to a 3-point scale. Relative flow displacement and wall shear stress (WSS) were quantified at predefined levels in the thoracic aorta.
Results
All patients underwent successful aortic valve repair with a significant reduction of aortic valve regurgitation (16.7 ± 9.8% to 6.4 ± 4.4%, p < 0.001) and systolic peak velocity (2.3 ± 0.9 to 1.9 ± 0.4 m/s, p = 0.014). Both helical flow (1.6 ± 0.6 vs. 0.9 ± 0.5, p < 0.001) and vortical flow (1.2 ± 0.8 vs. 0.5 ± 0.6, p = 0.002) as well as both flow displacement (0.3 ± 0.1 vs. 0.25 ± 0.1, p = 0.031) and WSS (0.8 ± 0.2 N/m vs. 0.5 ± 0.2 N/m, p < 0.001) in the ascending aorta were significantly reduced after aortic valve repair.
Conclusions
4D flow CMR allows assessment of the impact of aortic valve repair on changes in blood flow dynamics in patients with bicuspid aortic valve disease.



J Cardiovasc Magn Reson: 29 Apr 2020; 22:29
Lenz A, Petersen J, Riedel C, Weinrich JM, ... Girdauskas E, Bannas P
J Cardiovasc Magn Reson: 29 Apr 2020; 22:29 | PMID: 32354361
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Abstract

Screening Rheumatic Heart Disease in 1530 New Caledonian Adolescents.

Chatard JC, Dubois T, Espinosa F, Kamblock J, ... Tarpinian E, Da Costa A

Background In New Caledonia, a South Pacific archipelago whose inhabitants comprise Melanesians, Europeans/whites, Wallisians, Futunans, Polynesians, and Asians, the prevalence of rheumatic heart disease (RHD) is 0.9% to 1% at ages 9 and 10. It could be higher at the age of 16, but this remains to be verified. Methods and results A total of 1530 Melanesian, Métis, white, Wallisian, Futunan, Polynesian, and Asian adolescents benefited from a transthoracic echocardiogram. Definite or borderline RHD, nonrheumatic valve lesions, congenital heart defects, family and personal history of acute rheumatic fever, and socioeconomic factors were collected. The prevalence of cardiac abnormalities was 8.1%, made up of 4.1% RHD including 2.4% definite and 1.7% borderline RHD, 1.7% nonrheumatic valve lesions, and 2.3% congenital anomalies. In whites and Asians, there were no cases of RHD. RHD was higher in the Wallisian, Futunan, and Polynesian group (7.6%) when compared with Melanesians (5.3%) and Métis (2.9%). The number of nonrheumatic valve lesions was not statistically different in the different ethnicities. The prevalence of RHD was higher in adolescents with a personal history of acute rheumatic fever, in those living in overcrowded conditions, and in those whose parents were unemployed or had low-income occupations, such as the farmers or manual workers. CONCLUSIONS RHD was 4 times higher in adolescents at age 16 than at ages 9 and 10 (4.1% versus 0.9%-1%). No cases of RHD were observed in whites and Asians. The determining factors were history of acute rheumatic fever and socioeconomic factors.



J Am Heart Assoc: 25 Apr 2020:e015017; epub ahead of print
Chatard JC, Dubois T, Espinosa F, Kamblock J, ... Tarpinian E, Da Costa A
J Am Heart Assoc: 25 Apr 2020:e015017; epub ahead of print | PMID: 32336214
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Abstract

Value of Echocardiographic Right Ventricular and Pulmonary Pressure Assessment in Predicting Transcatheter Tricuspid Repair Outcome.

Karam N, Mehr M, Taramasso M, Besler C, ... Maisano F, Hausleiter J
Objectives
The aim of this study was to assess the value of echocardiographic right ventricular (RV) and systolic pulmonary artery pressure (sPAP) assessment in predicting transcatheter tricuspid edge-to-edge valve repair (TTVR) outcome.
Background
RV dysfunction and pulmonary hypertension are associated with poor prognosis and are systematically sought during tricuspid regurgitation evaluation. The value of echocardiographic assessment in predicting TTVR outcome is unknown.
Methods
Data were taken from the TriValve (Transcatheter Tricuspid Valve Therapies) registry, which includes patients undergoing TTVR at 14 European and North American centers. The primary outcome was 1-year survival free from hospitalization for heart failure, and secondary outcomes were 1-year survival and absence of hospital admission for heart failure at 1 year.
Results
Overall, 249 patients underwent TTVR between June 2015 and 2018 (mean tricuspid annular plane systolic excursion [TAPSE] 15.8 ± 15.3 mm, mean sPAP 43.6 ± 16.0 mm Hg). Tricuspid regurgitation grade ≥3+ was found in 96.8% of patients at baseline and 29.4% at final follow-up; 95.6% were in New York Heart Association functional class III or IV initially, compared with 34.3% at follow-up (p < 0.05). Final New York Heart Association functional class did not differ among TAPSE and sPAP quartiles, even when both low TAPSE and high sPAP were present. Rates of 1-year survival and survival free from hospitalization for heart failure were 83.9% and 78.7%, respectively, without significant differences according to baseline echocardiographic RV characteristics (TAPSE, fractional area change, and end-diastolic area) and sPAP (p > 0.05 for all).
Conclusions
TTVR provides clinical improvement, with 1-year survival free from hospital readmission >75% in patients with severe tricuspid regurgitation. Conventional echocardiographic parameters used to assess RV function and sPAP did not predict clinical outcome after TTVR.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Cardiovasc Interv: 26 Apr 2020; epub ahead of print
Karam N, Mehr M, Taramasso M, Besler C, ... Maisano F, Hausleiter J
JACC Cardiovasc Interv: 26 Apr 2020; epub ahead of print | PMID: 32360260
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Abstract

Factors Associated With Potentially Inappropriate Phosphodiesterase-5 Inhibitor Use for Pulmonary Hypertension in the United States, 2006 to 2015.

Gillmeyer KR, Rinne ST, Glickman ME, Lee KM, ... Miller DR, Wiener RS

Background Use of phosphodiesterase-5 inhibitors (PDE5i) for groups 2 and 3 pulmonary hypertension (PH) is rising nationally, despite guidelines recommending against this low-value practice. Although receiving care across healthcare systems is encouraged to increase veterans\' access to specialists critical for PH management, receiving care in 2 systems may increase risk of guideline-discordant prescribing. We sought to identify factors associated with prescribing of PDE5i for group 2/3 PH, particularly, to test the hypothesis that veterans prescribed PDE5i for PH in the community (through Medicare) will have increased risk of subsequently receiving potentially inappropriate treatment in Veterans Health Administration (VA). Methods and Results We constructed a retrospective cohort of 34 775 Medicare-eligible veterans with group 2/3 PH by linking national patient-level data from VA and Medicare from 2006 to 2015. We calculated adjusted odds ratios (ORs) of receiving daily PDE5i treatment for PH in VA using multivariable models with facility-specific random effects. In this cohort, 1556 veterans received VA prescriptions for PDE5i treatment for group 2/3 PH. Supporting our primary hypothesis, the variable most strongly associated with PDE5i treatment in VA for group 2/3 PH was prior treatment through Medicare (OR, 6.5 [95% CI, 4.9-8.7]). Other variables strongly associated with increased likelihood of VA treatment included more severe disease as indicated by recent right heart failure (OR, 3.3 [95% CI, 2.8-3.9]) or respiratory failure (OR, 3.7 [95% CI, 3.1-4.4]) and prior right heart catheterization (OR, 3.8 [95% CI, 3.4-4.3]). Conclusions Our data suggest a missed opportunity to reassess treatment appropriateness when pulmonary hypertension patients seek prescriptions from VA-a relevant finding given policies promoting shared care across VA and community settings. Interventions are needed to reinforce awareness that pulmonary vasodilators are unlikely to benefit group 2/3 pulmonary hypertension patients and may cause harm.



Circ Cardiovasc Qual Outcomes: 11 May 2020:CIRCOUTCOMES119005993; epub ahead of print
Gillmeyer KR, Rinne ST, Glickman ME, Lee KM, ... Miller DR, Wiener RS
Circ Cardiovasc Qual Outcomes: 11 May 2020:CIRCOUTCOMES119005993; epub ahead of print | PMID: 32393128
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Abstract

Direct measurement of atrioventricular valve regurgitant jets using 4D flow cardiovascular magnetic resonance is accurate and reliable for children with congenital heart disease: a retrospective cohort study.

Jacobs K, Rigdon J, Chan F, Cheng JY, ... Vasanawala S, Maskatia SA
Background
3D-time resolved flow (4DF) cardiovascular magnetic resonance (CMR) with retrospective analysis of atrioventricular valve regurgitation (AVVR) allows for internal validation by multiple direct and indirect methods. Limited data exist on direct measurement of AVVR by 4DF CMR in pediatric congenital heart disease (CHD). We aimed to validate direct measurement of the AVVR jet as accurate and reliable compared to the volumetric method (clinical standard by 2D CMR) and as a superior method of internal validation than the annular inflow method.
Methods
We identified 44 consecutive patients with diverse CHD referred for evaluation of AVVR by CMR. 1.5 T or 3 T scanners, intravenous contrast, and a combination of parallel imaging and compressed sensing were used. Four methods of measuring AVVR volume (RVol) were used: volumetric method (VOL; the clinical standard) = stroke volume by 2D balanced steady-state free precession - semilunar valve forward flow (SLFF); annular inflow method (AIM) = atrioventricular valve forward flow [AVFF] - semilunar valve net flow (SLNF); and direct measurement (JET). AVFF was measured using static and retrospective valve tracking planes. SLFF, SLNF, AVFF, and JET were measured by 4DF phase contrast. Regurgitant fraction was calculated as [RVol/(RVol+SLNF)]× 100. Statistical methods included Spearman, Wilcoxon rank sum test/Student paired t-test, Bland Altman analysis, and intra-class coefficient (ICC), where appropriate.
Results
Regurgitant fraction by JET strongly correlated with the indirect methods (VOL and AIM) (ρ = 0.73-0.80, p < 0.001) and was similar to VOL with a median difference (interquartile range) of - 1.5% (- 8.3-7.2%; p = 0.624). VOL had weaker correlations with AIM and JET (ρ = 0.69-0.73, p < 0.001). AIM underestimated RF by 3.6-6.9% compared to VOL and JET, p < 0.03. Intra- and inter- observer reliability were excellent for all methods (ICC 0.94-0.99). The mean (±standard deviation) inter-observer difference for VOL was 2.4% (±5.1%), p < 0.05.
Conclusions
In a diverse cohort of pediatric CHD, measurement of AVVR using JET is accurate and reliable to VOL and is a superior method of internal validation compared to AIM. This study supports use of 4DF CMR for measurement of AVVR, obviating need for expert prospective prescription during image acquisition by 2D CMR.



J Cardiovasc Magn Reson: 13 May 2020; 22:33
Jacobs K, Rigdon J, Chan F, Cheng JY, ... Vasanawala S, Maskatia SA
J Cardiovasc Magn Reson: 13 May 2020; 22:33 | PMID: 32404159
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Abstract

Congenital Heart Disease and Risk of Suicide and Self-Harm: A Danish Nationwide Cohort Study.

Udholm S, Nyboe C, Lundbye-Christensen S, Nordentoft M, Hjortdal VE

Background In this nationwide study, we used the unique Danish registries to estimate the risk of suicide and deliberate self-harm in patients with congenital heart disease (CHD). Methods and Results We identified all Danish citizens receiving a diagnosis of CHD between 1977 and 2007. As a reference cohort, we randomly selected 10 citizens for each patient, matched by sex and birth year. Using the Fine and Gray competing risk regression, we estimated the cumulative incidences of suicide and self-harm, and Cox proportional regression analysis was used to compare the risk of suicide and deliberate self-harm in patients with CHD with the reference cohort. We identified 14 433 patients with CHD. Mean follow-up was 21.3 years, with a maximum follow-up of 42 years. Since the time of diagnosis, 2659 patients had died, with a median age of death of 23 years. A total of 15 patients had died by suicide, compared with 232 suicides in the reference cohort. Patients with CHD had a low and similar risk of dying by suicide when compared with the reference cohort (cause-specific hazard ratio, 0.81; 95% CI, 0.48-1.37; and subhazard ratio, 0.68; 95% CI, 0.41-1.16). We identified 336 events of self-harm among patients with CHD, and 3484 events in the reference group. The overall risk of deliberate self-harm was not increased in patients with CHD when compared with the reference group (subhazard ratio, 0.95; 95% CI, 0.85-1.06). Conclusions This is the first study to estimate the risk of suicide and deliberate self-harm in patients with CHD. We found that patients with CHD do not have an increased risk of suicide or deliberate self-harm when compared with a large reference cohort.



J Am Heart Assoc: 07 May 2020:e015735; epub ahead of print
Udholm S, Nyboe C, Lundbye-Christensen S, Nordentoft M, Hjortdal VE
J Am Heart Assoc: 07 May 2020:e015735; epub ahead of print | PMID: 32384010
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Abstract

Coronavirus Disease 2019 (COVID-19) Pandemic Implications in Pediatric and Adult Congenital Heart Disease.

Alsaied T, Aboulhosn JA, Cotts TB, Daniels CJ, ... Oster ME, Saidi A

The corona virus disease -2019 (COVID-19) is a recently described infectious disease caused by the severe acute respiratory syndrome corona virus 2 with significant cardiovascular implications. Given the increased risk for severe COVID-19 observed in adults with underlying cardiac involvement, there is concern that patients with pediatric and congenital heart disease (CHD) may likewise be at increased risk for severe infection. The cardiac manifestations of COVID-19 include myocarditis, arrhythmia and myocardial infarction. Importantly, the pandemic has stretched health care systems and many care team members are at risk for contracting and possibly transmitting the disease which may further impact the care of patients with cardiovascular disease. In this review, we describe the effects of COVID-19 in the pediatric and young adult population and review the cardiovascular involvement in COVID-19 focusing on implications for patients with congenital heart disease in particular.



J Am Heart Assoc: 21 May 2020:e017224; epub ahead of print
Alsaied T, Aboulhosn JA, Cotts TB, Daniels CJ, ... Oster ME, Saidi A
J Am Heart Assoc: 21 May 2020:e017224; epub ahead of print | PMID: 32441586
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Abstract

Atrioventricular Valve Regurgitation in Single Ventricle Heart Disease: A Common Problem Associated With Progressive Deterioration and Mortality.

Tseng SY, Siddiqui S, Di Maria MV, Hill GD, ... Quintessenza JA, Alsaied T

The Fontan procedure has provided patients with single ventricle physiology extended survival into adulthood and in many cases has improved their quality of life. Atrioventricular valve regurgitation (AVVR) is common in single ventricle patients and is associated with increased risk of mortality. AVVR is more common in patients with a systemic tricuspid or common atrioventricular valve but is generally progressive irrespective of underlying valve morphology. AVVR can be attributable to diverse structural and functional abnormalities at multiple levels of the valvar apparatus, as well as ventricular dysfunction and dilation. Multiple imaging modalities including recent advances in 3-dimensional echocardiography and cross-sectional imaging have been used to further understand AVVR. Surgery to address AVVR must be tailored to the underlying mechanism and the timing of surgical repair should be chosen carefully. In this review, we discuss the etiologies, treatment options, surgical timing, and outcomes of valve repair or replacement for AVVR in patients with single ventricle congenital heart disease, with a focus on those with a Fontan circulation as AVVR is associated with increased risk for Fontan failure and mortality. In-depth understanding of the current literature will help guide clinicians in their approach and management of AVVR in this population.



J Am Heart Assoc: 15 May 2020:e015737; epub ahead of print
Tseng SY, Siddiqui S, Di Maria MV, Hill GD, ... Quintessenza JA, Alsaied T
J Am Heart Assoc: 15 May 2020:e015737; epub ahead of print | PMID: 32419552
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Abstract

Neuropsychological Status and Structural Brain Imaging in Adults With Simple Congenital Heart Defects Closed in Childhood.

Asschenfeldt B, Evald L, Heiberg J, Salvig C, ... Eskildsen SF, Hjortdal VE

Background Neurodevelopmental impairments are common in survivors of complex congenital heart defects (CHD). We report neuropsychological and brain imaging assessments in adults operated for isolated septal defects. Methods and Results Patients (mean age 25.6 yrs) who underwent childhood surgery for isolated atrial septal defect (n=34) or ventricular septal defect (n=32), and healthy matched peers (n=40), underwent a standard battery of neuropsychological tests and a 3.0T brain magnetic resonance imaging scan. Patient intelligence was affected with lower scores on Full-Scale intelligence quotient (<0.001), Verbal Comprehension (<0.001), Perceptual Reasoning (=0.007), and Working Memory (<0.001) compared with controls. Also, the CHD group had poorer visuospatial abilities (Immediate Recall, =0.033; Delayed Recall, =0.018), verbal memory (Trial 1, =0.015; Total Learning, <0.001; Delayed Recall, =0.007), executive function (Executive Composite Score, <0.001), and social recognition (Reading the Mind in the Eyes Test, =0.002) compared with controls. Self-reported levels of executive dysfunction, attention deficits and hyperactivity behavior, and social cognition dysfunction were higher in the CHD group compared with population means and controls. We found similar global and regional morphometric brain volumes and a similar frequency of brain magnetic resonance imaging abnormalities in the 2 groups. The CHD group had a high occurrence of psychiatric disease and a larger need for special teaching during school age. Conclusions Children operated for simple CHD demonstrate poorer neurodevelopmental outcomes in adulthood when compared with healthy controls and expected population means. REGISTRATION URL: https://www.clini​caltr​ials.gov. Unique identifier: NCT03871881.



J Am Heart Assoc: 18 May 2020:e015843; epub ahead of print
Asschenfeldt B, Evald L, Heiberg J, Salvig C, ... Eskildsen SF, Hjortdal VE
J Am Heart Assoc: 18 May 2020:e015843; epub ahead of print | PMID: 32427039
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Abstract

Selexipag for the treatment of children with pulmonary arterial hypertension: First multicenter experience in drug safety and efficacy.

Hansmann G, Meinel K, Bukova M, Chouvarine P, ... Koestenberger M,
Background
The European Pediatric Pulmonary Vascular Disease Network (EPPVDN) investigated the safety and efficacy of add-on selexipag, an oral prostacyclin receptor agonist approved for pulmonary arterial hypertension (PAH) in adults, in the largest, exploratory pediatric cohort to date.
Methods
This is a prospective observational study of 15 consecutive children with PAH, treated with oral add-on selexipag at 3 centers. Most patients underwent cardiac catheterizations at baseline and median of 8 months follow-up. All patients had clinical, echocardiographic, and N-terminal pro b-type natriuretic peptide studies, including the EPPVDN pediatric pulmonary hypertension (PH) risk score.
Results
There was no death during the use of selexipag. Two of 15 patients ultimately underwent lung transplantation. One patient with heritable PAH died on intravenous treprostinil (off selexipag). The mean right atrial pressure, the ratio of pulmonary arterial pressure (PAP) to systemic arterial pressure (SAP) (mean PAP/mean SAP, diastolic PAP/diastolic SAP: -17%), and transpulmonary pressure gradients (TPG) (mean TPG: -17%; p < 0.01; diastolic TPG: -6 mm Hg; p < 0.05) were improved after the therapy (n = 10). Selexipag therapy was associated with a better right ventricular systolic function (tricuspid annular plane systolic excursion: +14.5%; p < 0.01) and functional class. Improvement was seen in non-invasive and combined invasive/non-invasive PH risk scores (lower risk: +18%-22%, higher risk: 35%-37%; p < 0.05). Overall, the efficacy of selexipag was variable, often with a better response in less sick patients.
Conclusions
Oral selexipag use in children with PAH is well tolerated and safe when closely monitored. Add-on selexipag therapy improved several outcome-relevant variables in about 50% of patients and prevented disease progression in additional 27% of patients. The novel EPPVDN pediatric PH risk score indicated these drug effects properly, can be useful in clinical follow-up, and should be validated in larger prospective studies.

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 06 Apr 2020; epub ahead of print
Hansmann G, Meinel K, Bukova M, Chouvarine P, ... Koestenberger M,
J Heart Lung Transplant: 06 Apr 2020; epub ahead of print | PMID: 32362477
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Abstract

Quantifying the Influence of Wedge Pressure, Age, and Heart Rate on the Systolic Thresholds for Detection of Pulmonary Hypertension.

Amsallem M, Tedford RJ, Denault A, Sweatt AJ, ... Zamanian R, Haddad F

Background The strong linear relation between mean (MPAP) and systolic (SPAP) pulmonary arterial pressure (eg, SPAP=1.62×MPAP) has been mainly reported in precapillary pulmonary hypertension. This study sought to quantify the influence of pulmonary arterial wedge pressure (PAWP), heart rate, and age on the MPAP-SPAP relation. Methods and Results An allometric equation relating invasive MPAP and SPAP was developed in 1135 patients with pulmonary arterial hypertension, advanced lung disease, chronic thromboembolic pulmonary hypertension, or left heart failure. The equation was validated in 60 885 patients from the United Network for Organ Sharing (UNOS) database referred for heart and/or lung transplant. The MPAP/SPAP longitudinal stability was assessed in pulmonary arterial hypertension with repeated right heart catheterization. The equation obtained was SPAP=1.39×MPAP×PAWP×(60/heart rate)×age (<0.001). It was validated in the UNOS cohort (=0.93, <0.001), regardless of the type of organ(s) patients were listed for (mean bias [-1.96 SD; 1.96 SD] was 0.94 [-8.00; 9.88] for heart, 1.34 [-7.81; 10.49] for lung and 0.25 [-16.74; 17.24] mm Hg for heart-lung recipients). Thresholds of SPAP for MPAP=25 and 20 mm Hg were lower in patients with higher PAWP (37.2 and 29.8 mm Hg) than in those with pulmonary arterial hypertension (40.1 and 32.0 mm Hg). In 186 patients with pulmonary arterial hypertension, the predicted MPAP/SPAP was stable over time (0.63±0.03 at baseline and follow-up catheterization, =0.43). Conclusions This study quantifies the impact of PAWP, and to a lesser extent heart rate and age, on the MPAP-SPAP relation, supporting lower SPAP thresholds for pulmonary hypertension diagnosis in patients with higher PAWP for echocardiography-based epidemiological studies.



J Am Heart Assoc: 15 May 2020:e016265; epub ahead of print
Amsallem M, Tedford RJ, Denault A, Sweatt AJ, ... Zamanian R, Haddad F
J Am Heart Assoc: 15 May 2020:e016265; epub ahead of print | PMID: 32419583
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Abstract

Artificial intelligence for early prediction of pulmonary hypertension using electrocardiography.

Kwon JM, Kim KH, Medina-Inojosa J, Jeon KH, Park J, Oh BH
Background
Screening and early diagnosis of pulmonary hypertension (PH) are critical for managing progression and preventing associated mortality; however, there are no tools for this purpose. We developed and validated an artificial intelligence (AI) algorithm for predicting PH using electrocardiography (ECG).
Methods
This historical cohort study included data from consecutive patients from 2 hospitals. The patients in one hospital were divided into derivation (56,670 ECGs from 24,202 patients) and internal validation (3,174 ECGs from 3,174 patients) datasets, whereas the patients in the other hospital were included in only an external validation (10,865 ECGs from 10,865 patients) dataset. An AI algorithm based on an ensemble neural network was developed using 12-lead ECG signal and demographic information from the derivation dataset. The end-point was the diagnosis of PH. In addition, the interpretable AI algorithm identified which region had the most significant effect on decision making using a sensitivity map.
Results
During the internal and external validation, the area under the receiver operating characteristic curve of the AI algorithm for detecting PH was 0.859 and 0.902, respectively. In the 2,939 individuals without PH at initial echocardiography, those patients that the AI defined as having a higher risk had a significantly higher chance of developing PH than those in the low-risk group (31.5% vs 5.9%, p < 0.001) during the follow-up period. The sensitivity map showed that the AI algorithm focused on the S-wave, P-wave, and T-wave for each patient by QRS complex characteristics.
Conclusions
The AI algorithm demonstrated high accuracy for PH prediction using 12-lead and single-lead ECGs.

Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 22 Apr 2020; epub ahead of print
Kwon JM, Kim KH, Medina-Inojosa J, Jeon KH, Park J, Oh BH
J Heart Lung Transplant: 22 Apr 2020; epub ahead of print | PMID: 32381339
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Abstract

Development of a Novel Adult Congenital Heart Disease-Specific Patient-Reported Outcome Metric.

Cedars AM, Ko JM, John AS, Vittengl J, ... Kutty S, Spertus JA

Background Patient-reported outcome metrics (PROs) quantify important outcomes in clinical trials and can be sensitive measures of patient experience in clinical practice. Currently, there is no validated disease-specific PRO for adults with congenital heart disease (ACHD). Methods and Results We conducted a preliminary psychometric validation of a novel ACHD PRO. ACHD patients were recruited prospectively from 2 institutions and completed a series of questionnaires, a physician health assessment, and a 6-minute walk test. Participants returned to complete the same questionnaires and assessment 3 months±2 weeks later. We tested the internal consistency and test-retest reliability by comparing responses among clinically stable patients at the 2 study visits. We assessed convergent and divergent validity by comparison of ACHD PRO responses to existing validated questionnaires. We assessed responsiveness by comparison with patient-reported clinical change. One hundred three patients completed 1 study visit and 81 completed both. The ACHD PRO demonstrated good internal consistency in each of its 5 domains (Cronbach\'s α: 0.87; 0.74; 0.74; 0.90; and 0.89, respectively) and in the overall summary score (0.92). Test-retest reliability was good with an intraclass correlation ≥0.73 for all domains and 0.78 for the Summary Score. The ACHD PRO accurately assessed domain concepts based on comparison with validated standards. Preliminary estimates of responsiveness suggest sensitivity to clinical status. Conclusions These studies provide initial support for the validity and reliability of the ACHD PRO. Further studies are needed to assess its sensitivity to changes in clinical status.



J Am Heart Assoc: 15 May 2020:e015730; epub ahead of print
Cedars AM, Ko JM, John AS, Vittengl J, ... Kutty S, Spertus JA
J Am Heart Assoc: 15 May 2020:e015730; epub ahead of print | PMID: 32419592
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Abstract

Pressure Overload Greatly Promotes Neonatal Right Ventricular Cardiomyocyte Proliferation: A New Model for the Study of Heart Regeneration.

Ye L, Wang S, Xiao Y, Jiang C, ... Xu Z, Hong H

Background Current mammalian models for heart regeneration research are limited to neonatal apex amputation and myocardial infarction, both of which are controversial. RNAseq has demonstrated a very limited set of differentially expressed genes between sham and operated hearts in myocardial infarction models. Here, we investigated in rats whether pressure overload in the right ventricle, a common phenomenon in children with congenital heart disease, could be used as a better animal model for heart regeneration studies when considering cardiomyocyte proliferation as the most important index. Methods and Results In the rat model, pressure overload was induced by pulmonary artery banding on postnatal day 1 and confirmed by echocardiography and hemodynamic measurements at postnatal day 7. RNA sequencing analyses of purified right ventricular cardiomyocytes at postnatal day 7 from pulmonary artery banding and sham-operated rats revealed that there were 5469 differentially expressed genes between these 2 groups. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis showed that these genes mainly mediated mitosis and cell division. Cell proliferation assays indicated a continuous overproliferation of cardiomyocytes in the right ventricle after pulmonary artery banding, in particular for the first 3 postnatal days. We also validated the model using samples from overloaded right ventricles of human patients. There was an approximately 2-fold increase of Ki67/pHH3/aurora B-positive cardiomyocytes in human-overloaded right ventricles compared with nonoverloaded right ventricles. Other features of this animal model included cardiomyocyte hypotrophy with no fibrosis. Conclusions Pressure overload profoundly promotes cardiomyocyte proliferation in the neonatal stage in both rats and human beings. This activates a regeneration-specific gene program and may offer an alternative animal model for heart regeneration research.



J Am Heart Assoc: 29 May 2020:e015574; epub ahead of print
Ye L, Wang S, Xiao Y, Jiang C, ... Xu Z, Hong H
J Am Heart Assoc: 29 May 2020:e015574; epub ahead of print | PMID: 32475201
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Abstract

Intracorporeal VAD Outcomes in the ACTION Quality Improvement Network.

Sutcliffe DL, Barnes AP, Davies RR, Machado DS, ... Murray JM, Villa CR
Purpose
The initial project of ACTION (Advanced Cardiac Therapies Improving Outcomes Network) is focused on improving stroke rates in patients implanted with a ventricular assist devices (VAD) in participating centers. The initial interventions targeted improving communication, anticoagulation, and blood pressure management. We sought to describe the characteristics and outcomes of patients implanted with intracorporeal, continuous flow VADs (cfVAD).
Methods
The ACTION registry was used to determine the stroke frequency in cfVAD implanted patients between April 2018 and September 2019, the time from development of the quality improvement bundle to the present.
Results
Sixty two patients (33 Heartmate3 [HM3] and 29 Heartware [HVAD]) were identified (Table). The majority had dilated cardiomyopathy (76%). Of the 12 (20%) patients with congenital heart disease (CHD), 9 (75%) had single ventricle (SV) physiology. The HM3 patients were older (16.5 yr vs 12.8 yr) and larger (64.2 kg vs 51.9 kg) than the HVAD patients. No significant difference was observed in diagnosis, duration of support, device strategy, or clinical outcome. One patient (2%) experienced a stroke during 6,920 days of support. Forty of the 45 (89%) patients to reach a clinical endpoint experienced a positive outcome (transplant or explant for recovery) while 17 (27%) patients remain on device.
Conclusion
The stroke rate is low and survival good among patients implanted with an intracorporeal cfVAD at ACTION centers using the clinical protocols developed within the network. The HVAD is currently being used more frequently in younger and smaller patients. There has been an appreciable increase in the number and frequency of implants in patients with CHD, especially SV disease, as compared to previous reports. Future efforts within ACTION will focus on improving clinical outcomes as devices are increasingly used at individual centers and as the number of VAD-supported patients with congenital heart disease continues to grow.

Copyright © 2020. Published by Elsevier Inc.

J Heart Lung Transplant: 30 Mar 2020; 39:S84
Sutcliffe DL, Barnes AP, Davies RR, Machado DS, ... Murray JM, Villa CR
J Heart Lung Transplant: 30 Mar 2020; 39:S84 | PMID: 32466046
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Abstract

Clinical presentation and outcomes of adults with bicuspid aortic valves: 2020 update.

Yang LT, Tribouilloy C, Masri A, Bax JJ, ... Enriquez-Sarano M, Michelena HI

The congenital bicuspid aortic valve (BAV) is a heterogeneous condition that is better understood considering 3 types of valvulo-aortopathy presentations: A typical-presentation valvulo-aortopathy, a complex-presentation valvulo-aortopathy and an uncomplicated/undiagnosed-presentation. The burden of BAV-related complications has been elucidated in patients with the typical-presentation valvulo-aortopathy and is discussed in this review. These patients enjoy an overall normal expected long-term survival as long as complications are identified and treated in a timely manner. This notion and the fact that the most dreaded complications (infective endocarditis and aortic dissection) are infrequent, represent important reassuring points for the BAV patient. Common complications such as valve dysfunction and aorta dilatation must be the subject of focused research in prevention and treatment. Conversely, BAV patients with complex-presentation valvulo-artopathy, as well as typical valvulo-aortopathy BAV patients who are older, with advanced valvular dysfunction, and possible late-referral to specialized care, may incur a survival penalty as compared to the general population. An evidence-based discussion of these concepts is provided in this review.

Copyright © 2020. Published by Elsevier Inc.

Prog Cardiovasc Dis: 29 May 2020; epub ahead of print
Yang LT, Tribouilloy C, Masri A, Bax JJ, ... Enriquez-Sarano M, Michelena HI
Prog Cardiovasc Dis: 29 May 2020; epub ahead of print | PMID: 32485187
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Abstract

Impact of Iron Deficiency Anemia in Patients with Pulmonary Arterial Hypertension.

Siddiqui OM, Kaur B, Garcia A, Gaznabi S, ... Schilz R, El Amm C
Purpose
The impact of iron deficiency anemia on hospital length of stay and in hospitalization mortality has not been investigated in patients whose main reason for admission is pulmonary arterial hypertension. We sought to compare the outcomes in hospitalization in patients with pulmonary arterial hypertension (PAH) with a diagnosis of iron deficiency anemia (IDA) versus those without from a large sample database.
Methods
The National Inpatient Sample (NIS) was used to identify all patients hospitalized 18 years of age and older in 2016 with a primary or secondary diagnosis of PAH by ICD-10 code I270. Within each hospitalization, the diagnosis of IDA was further identified using ICD-10 code D50.xx. We then examined the relative risk profile, and outcomes of interests including length of stay (LOS), total charges, number of diagnoses, Elixhauser[EC1] mortality, readmission score and in hospital mortality of each group. Categorical variables were analyzed with logistic regression models while continuous variables were assessed using two sample t-tests. All analyses were conducted using SAS v 9.4 and accounted for the NIS sampling design and updated hospital trend weights.
Results
A total of 10,300 patients with a primary or secondary diagnosis of PAH were identified, and of those, 8.45% had a diagnosis of IDA[EC2] . The cohort with IDA had a majority of women (80% vs 68%, p=<0.0001[EC3]), and were more likely to be black (24.5% vs 18.4%, p<0.0001). The number of hospital diagnoses in the IDA group was higher as well (17.0 vs 19.24, p=<0.0001). The IDA cohort were more likely to obese (28.74% vs 23.12%, p = 0.0061), have heart failure (52.30% vs 46.24%, p=0.0350), and have high risk features such as a pericardial effusion (6.32% vs 2.97%, p=0.0015). The IDA cohort were also more likely to be readmitted (mean readmission scores 35.19, p<0.0001), but there was no significant difference in length of stay, in hospital mortality, or hospital charges.
Conclusion
Patients with primary pulmonary hypertension and IDA are more likely to be female and non-Caucasian, obese, have heart failure, or pericardial effusion, higher number of co-morbidities, and are more likely to be readmitted that those without IDA.

Copyright © 2020. Published by Elsevier Inc.

J Heart Lung Transplant: 30 Mar 2020; 39:S511
Siddiqui OM, Kaur B, Garcia A, Gaznabi S, ... Schilz R, El Amm C
J Heart Lung Transplant: 30 Mar 2020; 39:S511 | PMID: 32465962
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Abstract

Role of a Prediction Score of Heart Failure with Left Ventricular Preserved Ejection Fraction in the Differential Diagnosis of Pulmonary Hypertension.

Djellal Y, Vachiery J, Dewachter C, Roussoulières A
Purpose
The distinction between pulmonary hypertension (PH) due to heart failure with left ventricular preserved ejection fraction (HFpEF) and idiopathic pulmonary arterial hypertension (IPAH) has important clinical implications. These distinction between pre and post-capillary PH is based on a cutoff value of pulmonary arterial wedge pressure value (PAPW) >15 mmHg in the latter. However, a value between 12 and 15 mmHg is associated with a higher probability of post-capillary pulmonary hypertension. In addition, the probability of HFpEF may be assessed by the non invasive H2FPEF score. We sought to evaluate the performance of the latter in the differential diagnosis of pulmonary hypertension and its discriminating power when the PAPW is between 12 and 15 mmHg.
Methods
In this single center retrospective study, we included patients with left ventricular ejection fraction >45% and PH confirmed by right cardiac catheterization between 01/01/2010 and 31/12/2018. The H2FPEF score was calculated for the entire population and then as a function of the PAPW value (<12 mmHg, between 12 and 15 mmHg and >15 mmHg). Each component of the score was analyzed to determine if there is a dominant factor.
Results
In 303 patients, an H2FPEF score = 4.5 predicts the presence of PAPW >15 mmHg with a sensitivity of 65% and a specificity of 74%. To predict a PAPW between 12 and 15 mmHg the ROC curve of the H2FPEF score has an area under the curve of 0.52 (AUC = 0.52 [95% CI 0.45-0.59]). Variables that are independently associated with a PAPW > 15mmHg are: treatment with 2 or more antihypertensive drugs (OR = 2.9, IC [95%: 1.5-5.8], p = 0.002), and the presence of atrial fibrillation (OR = 4.8, IC [95%: 1.7 -13.8], p = 0.003).
Conclusion
The H2FPEF score may be used to guide the diagnosis of post-capillary PH, mainly in the presence of atrial fibrillation and prescription of two antihypertensive drugs. The score is not efficient when the PAPW is measured between 12 and 15 mmHg.

Copyright © 2020. Published by Elsevier Inc.

J Heart Lung Transplant: 30 Mar 2020; 39:S511-S512
Djellal Y, Vachiery J, Dewachter C, Roussoulières A
J Heart Lung Transplant: 30 Mar 2020; 39:S511-S512 | PMID: 32465960
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Abstract

Safety and Feasibility of Home INR Monitoring for Outpatient Ventricular Assist Device Support in Children.

Hawkins BM, Ventresco C, Hellinger A, VanderPluym C, Knoll C
Purpose
The use of intracorporeal continuous flow (CF) ventricular assist devices- namely the Heartware™ HVAD™- has expanded dramatically in the children, with many being discharged home. We sought to evaluate the feasibility and outcomes of children discharged home with point of care (POC) INR monitors for their warfarin anticoagulation management.
Methods
This is a retrospective single center review of all pediatric patients, aged ≤19 years at time of implantation, who were discharged home for longer than 1 week. Efficacy of warfarin anticoagulation and outcomes were evaluated in those with home POC monitors as compared to children who went to laboratory.
Results
Between November 11, 2012 and January 1, 2018, a total of 12 patients, 33% female, aged median 14.5 years (range 10-18 years), weighing median 65.8kg (range 18.0-89.5 kg) were discharged home or to rehab with HeartWare as a bridge to transplantation. Underlying diagnosis included dilated cardiomyopathy in 67% (n=8), arrhythmogenic right ventricular dysplasia (ARVD) in 8% (n=1), and biventricular congenital heart disease (CHD) in 25% (n=3).Two patients were discharged to rehab before returning home. All patients were discharged with Coagucheck XS™ POC INR machines, with goal INR of 2-3 in first 3 patients (23%) and goal INR of 2.5-3.5 in later 10 patients. There were a median number of INR tests of 27 (range 1-99) at home, over the course of a median 185 days (25-625) outpatient VAD support days. Overall median time in the therapeutic range(TTR) was 62.1%(range 20.0-70.7%). There was 100% adherence to clinician recommended INR testing at home. There was 4 bridging events with low molecular weight heparin for sub-therapeutic INR. There were no pump thrombosis or other thrombotic events. There were no major bleeding or clinically relevant non major bleeding events. Epistaxis was the most common minor bleeding event that was mitigated by dose reductions and preventative strategies. All patients were bridged to transplantation with no mortality.
Conclusion
Use if home POC INR machines in children with intracorporeal VADs, in the outpatient setting was associated with 100% adherence to recommended testing regime. Despite low TTR, there was no major bleeding or thrombotic events.

Copyright © 2020. Published by Elsevier Inc.

J Heart Lung Transplant: 30 Mar 2020; 39:S495
Hawkins BM, Ventresco C, Hellinger A, VanderPluym C, Knoll C
J Heart Lung Transplant: 30 Mar 2020; 39:S495 | PMID: 32465911
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Abstract

Lung and Heart-Lung Transplantation for Children with PAH: Dramatic Benefits from the Implementation of High Priority Allocation Program in France.

Le Pavec J, Feuillet S, Mercier O, Pradère P, ... Humbert M, Fadel E
Purpose
Pulmonary arterial hypertension (PAH) is rare but remains a fatal disease in infants and children despite the recent introduction of targeted therapies. Lung transplantation (LT), first performed in pediatric patients in the 1980s, is the only potentially life-extending option in patients with end-stage PAH but is possible only in tightly selected patients. Size-matching challenges severely restrict the donor organ pool which, in addition to peculiarities of PAH in infants, results in high mortality while on the waiting list.
Aim of the study
To investigate the impact on survival of a high-priority allocation program (HPAL) in children with PAH listed for double lung (DLT) or heart-lung (HLT) transplantation Methods: We conducted a single-center, retrospective, before-after study of consecutive children with severe Group 1 PAH listed for DLT or HLT between 1988 and 2019. The HPAL was implemented in France in 2006 and 2007 for HLT and DLT, respectively.
Results
Fifty-four children with PAH were listed for transplantation. Mean age of transplantation was 15.8 ± 2.8 years. Main etiologies of PAH were idiopathic (65%) and congenital heart disease (25%). 72% had a heart-lung transplantation. HPAL implementation resulted in the following significant benefits: decrease in the cumulative incidence of waiting-list death within 1 and 2 years (P<0.0001); increase in the cumulative incidence of transplantation within 6 months, from 44% to 67% (P<0.01); and improved survival after listing (61%, 50%, and 44% vs. 92%, 84%, and 72% 1, 3, and 5 years before and after HAPL implementation, respectively; P=0.02).
Conclusion
HAPL implementation significantly improved access to transplantation and survival after listing in children with end-stage PAH.

Copyright © 2020. Published by Elsevier Inc.

J Heart Lung Transplant: 30 Mar 2020; 39:S68
Le Pavec J, Feuillet S, Mercier O, Pradère P, ... Humbert M, Fadel E
J Heart Lung Transplant: 30 Mar 2020; 39:S68 | PMID: 32466007
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Abstract

Efficacy of Oral Iron Replacement Therapy in Pediatric Patients with Heart Failure.

Puri K, Spinner JA, Powers JM, Tunuguntla HP, ... Shah MD, Price JF
Purpose
Iron deficiency (ID) is associated with worse outcomes in children with systolic heart failure (HF). Oral iron replacement therapy (IRT) is first line therapy for ID in children but the efficacy of oral IRT in children with HF is unknown. We hypothesized that less than half of children with HF and ID would have replenishment of their iron stores with oral IRT.
Methods
We performed a single center retrospective cohort study of patients aged ≤ 21 years with systolic HF and ID who received oral IRT (2-5mg/kg/day) between 01/2017 and 12/2018. ID was defined as ≥2 of the following: serum iron <50 mcg/dL, serum ferritin <20 ng/mL, transferrin >300 ng/mL, transferrin saturation <15%. Iron studies and hematologic indices pre and post IRT were compared in patients who received ≥6 weeks of therapy (to allow adequate duration of IRT to assess response) using paired-samples Wilcoxon test.
Results
Forty-two independent courses of oral IRT (in 40 patients) met inclusion criteria. The cohort was 52% male with median age 13 yrs (IQR 5 - 16 yrs). HF etiologies included cardiomyopathy (57%), congenital heart disease (31%), and history of heart transplantation with graft dysfunction (12%). Patients received ferrous sulfate (40/42) or ferrous gluconate (2/42). Median duration of IRT was 68d (IQR 32 - 145d). Twenty-nine patients received ≥6 weeks of IRT and were included for the analysis for response to oral IRT. Post IRT iron testing was available in 18 patients and post IRT hemogram was available in 26 patients. Serum iron and hematologic indices of the overall cohort as well as comparison of indices pre and post oral IRT are shown (Table). While there was an improvement in serum iron studies, 50% (9/18) of the patients remained iron deficient.
Conclusion
This is the first report about oral IRT in children with HF. Though median values of some iron parameters increased after 6weeks of oral IRT, half of the children with HF remained iron deficient and hence non-responsive to oral IRT. Further studies are needed to find the most suitable IRT for children with HF.

Copyright © 2020. Published by Elsevier Inc.

J Heart Lung Transplant: 30 Mar 2020; 39:S451
Puri K, Spinner JA, Powers JM, Tunuguntla HP, ... Shah MD, Price JF
J Heart Lung Transplant: 30 Mar 2020; 39:S451 | PMID: 32465778
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This program is still in alpha version.