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Background There are significant risks of parenteral prostacyclin use in patients with pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD), which may limit their use. Selexipag is an oral, selective prostacyclin analogue that has been shown to reduce disease progression and improve exercise capacity in patients with PAH-CHD. Administering Selexipag in patients with PAH-CHD could potentially overcome some of the risks of parenteral therapy while improving clinical outcomes. Case summary We report five cases highlighting the clinical uses of Selexipag in patients with PAH-CHD. In the first two cases, Selexipag was initiated as part of a Treat-to-close strategy. In the third case, initiation of Selexipag improved symptoms and objective exercise capacity in a patient with Eisenmenger syndrome. In the fourth and fifth cases, rapid cross-titration protocols were used to transition from parenteral prostacyclins to Selexipag. In the fourth case, Selexipag was initiated in the context of significant side effects limiting parenteral prostacyclin use. In the fifth case, Selexipag was used to down-titrate from parenteral prostacyclins following closure of a sinus venosus atrial septal defect and redirection of anomalous pulmonary veins. Discussion Selexipag is a promising oral therapy for patients with at various stages of the spectrum of PAH-CHD to improve symptoms, exercise capacity and, in some cases, haemodynamics. Our cases also highlight practical aspects of Selexipag use including targeting the individualized maximally tolerated dose for each patient, managing side effects and managing dose interruptions.

We present this case of a 22-year-old woman with congenital heart disease as the youngest reported patient, to the best of our knowledge, to successfully undergo treatment of medically refractory torrential tricuspid regurgitation with the MitraClip system as an adjunct to guideline directed therapy. (Level of Difficulty: Advanced.), Graphical abstract, We present this case of a 22-year-old woman with congenital heart disease as the youngest reported patient, to the best of our knowledge, to…

Myotonic dystrophy type 1 (DM1), the most common muscular dystrophy affecting adults and children, is a multi-systemic disorder affecting skeletal, cardiac, and smooth muscles as well as neurologic, endocrine and other systems. This review is on the cardiac pathology associated with DM1. The heart is one of the primary organs affected in DM1. Cardiac conduction defects are seen in up to 75% of adult DM1 cases and sudden death due to cardiac arrhythmias is one of the most common causes of death in DM1. Unfortunately, the pathogenesis of cardiac manifestations in DM1 is ill defined. In this review, we provide an overview of the history of cardiac studies in DM1, clinical manifestations, and pathology of the heart in DM1. This is followed by a discussion of emerging data about the utility of cardiac magnetic resonance imaging (CMR) as a biomarker for cardiac disease in DM1, and ends with a discussion on models of cardiac RNA toxicity in DM1 and recent clinical guidelines for cardiologic management of individuals with DM1.

Structured Abstract Background While percutaneous closure is preferred in adults with a patent ductus arteriosus (PDA), the extent of cardiac remodeling following percutaneous PDA closure in adults is not well understood. We performed a meta-analysis to characterize cardiac remodeling following percutaneous PDA closure in adults. Methods MEDLINE and EMBASE were systematically searched for original studies that reported echocardiographic variables at baseline, immediately post-procedure (24 h), and at follow-up (>1 month) in adults undergoing percutaneous PDA closure. Additionally, we included data from patients >18 years of age that underwent percutaneous PDA closure between January 2015–December 2019 at our centre. Weighted averages were calculated for parameters with sufficient data. Pooled differences were presented as weighted mean differences (WMD). Results After screening 278 abstracts, 5 studies were identified. When combined with our cohort, our meta-analysis encompassed 244 patients. Immediately post-procedure, LVEF was the only parameter to change significantly (64 vs 52%, WMD -8.64 95%, CI -14.04 to −3.25). All parameters significantly decreased from baseline to follow-up: LVEF: 64 vs 60% (WMD -3.95, CI -5.80 to −2.09), LVEDD: 62 vs 53 mm (WMD -8.79, CI -12.78 to −4.81) LVEDVI 172 vs 123 mL/m2 (WMD -26.60, CI -45.4 to −7.85), LVESD 42 vs 36 mm (WMD -4.64, CI -9.10 to −0.17) and LA dimension: 42 vs 37 mm (WMD -5.87, CI -9.85 to −1.90). Conclusions As compared to the baseline values, left ventricular and left atrial sizes decreased. The LVEF decreased immediately following PDA closure and, while it recovers, it remained lower on follow-up testing.

ObjectiveThis tertiary centre study aims to identify factors associated with adverse outcomes in adult survivors with total cavopulmonary connection (TCPC) Fontan palliation for single ventricle.MethodsThis retrospective review of medical records identified adult (≥18 years) survivors of TCPC Fontan palliation who were followed at a single tertiary centre between 1 January 2000 and 1 July 2019. Adverse outcomes were defined as arrhythmia, pacemaker/implantable cardioverter defibrillator placement, liver cirrhosis, protein losing enteropathy, hospitalisation for heart failure, thromboembolic complication and/or death.Results160 adult TCPC patients met the inclusion criteria: 117 (73.1%) extracardiac and 43 (26.9%) lateral tunnel. The median (IQR) duration of follow-up since TCPC palliation was 17.5 (11.8–21.3) years. An adverse outcome occurred in 87 (54.4%) patients. Adverse outcome-free survival rates at 10, 20 and 25 years post TCPC were 89% (95% CI 82% to 93%), 60% (95% CI 50% to 69%) and 24% (95% CI 15% to 35%), respectively. On multivariate analysis, extracardiac Fontan (HR 2.21, 95% CI 1.20 to 4.08, p=0.011) was observed to be an independent risk factor for adverse outcomes after adjusting for age, race, morphology of the systemic ventricle and history of fenestration.ConclusionsIn this single-centre retrospective study of adult survivors of TCPC palliation, extracardiac Fontan was associated with an increased hazard for adverse outcomes. This finding could guide clinicians in developing risk modification strategies and management decisions to improve long-term outcomes in these patients.

Conduction disturbances following TAVR are a common occurrence given the proximity of the various conduction system tissues, including the AV node, His-bundle, and bundle branches to the left ventricular outflow tract and aortic root. Impairment of these conduction system abnormalities may necessitate permanent pacemaker implantation, which increases morbidity and mortality, as well as length of stay, for the patient. The incidence, mechanisms, and predictors of conduction abnormalities and treatment options are discussed in this up-to-date review of the topic.

Lynch syndrome (LS) is defined by germline mutations in DNA mismatch repair (MMR) genes, and affected patients are at high risk for multiple cancers. Reflexive testing for MMR protein loss by immunohistochemistry (IHC) is currently only recommended for colorectal and endometrial cancers, although upper tract urothelial carcinoma (UTUC) is the third-most common malignancy in patients with LS. To study the suitability of universal MMR IHC screening for UTUC, we investigated MMR expression and microsatellite status in UTUC in comparison to bladder UC (BUC), and evaluated the clinicopathologic features of UTUC. We found that 9% of UTUC showed MMR IHC loss (8 MSH6 alone; 1 MSH2 and MSH6; 1 MLH1 and PMS2; n=117) compared with 1% of BUC (1 MSH6 alone; n=160) (P=0.001). Of these, 4/10 (40%) of UTUC (3% overall; 3 MSH6 alone; 1 MLH1 and PMS2) and none (0%) of BUC had high microsatellite instability on molecular testing (P=0.03). The only predictive clinicopathologic feature for MMR loss was a personal history of colorectal cancer (P=0.0003). However, UTUC presents at a similar age to colon carcinoma in LS and thus UTUC may be the sentinel event in some patients. Combining our results with those of other studies suggests that 1% to 3% of all UTUC cases may represent LS-associated carcinoma. LS accounts for 2% to 6% of both colorectal and endometrial cancers. As LS likely accounts for a similar percentage of UTUC, we suggest that reflexive MMR IHC screening followed by microsatellite instability testing be included in diagnostic guidelines for all UTUC.

A 50-year-old man presented in cardiogenic shock. Echocardiogram showed ejection fraction (EF) 22%, apical thrombus, and severe bicuspid aortic stenosis. Transcatheter aortic valve replacement (TAVR) was recommended, given his high surgical risk. Urgent TAVR was performed without complication, using transcatheter cerebral embolic protection and intracardiac echocardiography (ICE) for left-ventricular wire placement. The patient was discharged on warfarin, and follow-up echocardiogram showed no apical thrombus, EF 55%, and well-functioning bioprosthesis. This case shows a good TAVR outcome in bicuspid aortic stenosis despite apical thrombus and poor EF. Cerebral embolic protection and ICE can minimize risk of stroke.

Aortic stenosis (AS) is the most common acquired heart valve disease in the developed world. Traditional methods of grading AS have relied on the measurement of aortic valve area and transvalvular pressure gradient. Recent research has highlighted the existence of AS variants that do not meet classic criteria for severe AS such as low-flow, low-gradient AS. With the development of sophisticated multi-scale computational models, investigation into the left ventricular (LV) biomechanics of AS offers new insights into the pathophysiology that may guide treatment decisions surrounding AS. Building upon our prior study entailing LV-aortic coupling where AS conditions were applied to the idealized geometry of the Living Heart Human Model, we now describe the first patient-specific adaptation of the model to a case of low flow, low gradient AS. EKG-gated cardiac computed tomography images were segmented to provide surfaces to which the generic Living Heart model was adapted. The model was coupled to a lumped-parameter circulatory system; it was then calibrated to patient clinical data from echocardiography/cardiac catheterization with strong correlation (simulation versus clinical measurement): ascending aorta systolic pressure: 109mmHg vs 116mmHg, ascending aorta diastolic pressure 50mmHg vs 45mmHg, LV systolic pressure: 118mmHg vs 128mmHg, peak transvalvular gradient: 9mmHg vs 12mmHg, LV ejection fraction: 23% vs 25%. This work illustrates how the Living Heart Human Model geometry can be efficiently adapted to patient-specific parameters, enabling future biomechanics investigations into the LV dysfunction of AS.

The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has profoundly impacted all fields of medicine. Infection with SARS-CoV-2 and the resulting coronavirus of 2019 (COVID-19) syndrome has multiorgan effects. The pandemic has united researchers from bench to bedside in attempts to understand the pathophysiology of the disease and define optimal treatment strategies. Cardiovascular disease is highly prevalent and a leading cause of death across gender, race, and ethnic groups. As the pandemic spreads, there is increasing concern about the cardiovascular effects of the viral infection and the interaction of infection with existing cardiovascular disease. Additionally, there are concerns about the cardiac effects of the numerous treatment agents under study. It will be essential for cardiologists to understand the interplay between underlying cardiac comorbidities, acute cardiovascular effects of COVID-19 disease, and adverse effects of new treatments. Here we describe emerging evidence of the epidemiology of SARS-CoV-2 infection and underlying cardiovascular disease, the evidence for direct myocardial injury in SARS-CoV-2 infection, the specific presentations of cardiovascular involvement by SARS-CoV-2, and the cardiac effects of emerging treatments.

Introduction: Patent ductus arteriosus (PDA) is often recognized and treated with percutaneous closure in adults. However, the impact on cardiac reverse remodeling following PDA closure in adults is not clear. We performed a meta-analysis to characterize the extent of cardiac remodeling following percutaneous PDA closure in adults. Methods: MEDLINE and EMBASE were systematically searched for original studies that reported echocardiographic variables at baseline, immediately post-procedure (within 24 hours), and at follow-up (>1 month) in adults undergoing percutaneous PDA closure. Additionally, we included echocardiographic data from a cohort of patients >18 years of age that underwent percutaneous PDA closure between 01/2015 and 12/2019 at our centre. For parameters with sufficient data for pooling, weighted averages were calculated, and pooled differences were presented as weighted mean differences. Heterogeneity was assessed using the I 2 statistic. Results: After screening 278 abstracts, 5 studies were identified. When combined with our own cohort of 13 patients, our meta-analysis encompassed 244 patients. The weighted mean age of all patients was 33 years with all studies predominantly comprised of female patients and the median follow-up was 12 months (ranging from 1 month- 5 years across the studies). When compared to baseline, left ventricular ejection fraction (LVEF) decreased significantly immediately post-procedure and all parameters significantly decreased at follow-up (Table 1). Conclusions: As demonstrated by the decreases in the left ventricular and left atrial sizes, reverse remodeling was observed in adults who underwent percutaneous PDA closure. The significantly lower LVEF immediately post-procedure could reflect withdrawal of chronic volume overload or increased afterload. The clinical significance of the statistically significant lower LVEF on follow-up testing is unclear and requires further evaluation.

OBJECTIVES This study evaluates in-hospital, 30-day, and 1-year outcomes post-transcatheter aortic valve replacement (TAVR) in end stage liver disease (ESLD) and/or end stage renal disease (ESRD) compared with patients without these comorbidities. BACKGROUND TAVR is an alternative to surgical aortic valve replacement in patients with ESLD and ESRD, though current outcomes data are limited. METHODS We compared 309 patients (N = 29 ESLD and/or ESRD, N = 280 control) age > 18 who underwent transfemoral TAVR from 2014 to 2020 have been compared. RESULTS Patients with ESLD and ESRD were younger (69.9 ± 11.7 vs. 79.1 ± 9.8, p

This article highlights our current understanding of bicuspid aortic valve (BAV) syndrome and how genetics, pathology, imaging features, and clinical symptoms direct the clinical management, surveillance, and intervention of those with BAV. While randomized data and guidelines are lacking, transcatheter therapies are routinely used for BAV stenosis in medical centers throughout the world. Guidelines suggest that younger patients age less than 50 years undergo surgical aortic valve replacement (AVR) with a mechanical valve and the elderly > 70 years of age receive a bioprosthetic valve. For the age group 50–70 years, either option should be considered. Decision on type of intervention depends on specific features such as presence of stenosis or regurgitation, if there is any associated aortopathy, comorbid illnesses, contraindications, and patient preference. We have learned that the decision to intervene and mode of intervention is best achieved by a multidisciplinary valve team. Despite improvement in our understanding of BAV and the advancement of novel therapies particularly for BAV stenosis, much is still to be learned about the optimal treatment of BAV disease in the current era.

Aortic stenosis is the most common valvular heart disease in industrialized countries and the most common cause of left ventricular outflow tract (LVOT) obstruction. Transcatheter aortic valve replacement (TAVR) is an alternative to surgical aortic valve replacement for intermediate to high-risk surgical candidates with symptomatic severe aortic stenosis. Conduction system abnormalities, including atrioventricular (AV) and intraventricular (IV) block, are the most common complication of TAVR. In this review, we aim to explore the anatomical issues relevant to atrioventricular block, the relevant clinical and procedural aspects, and the management and long-term implications of AV and IV block.

Background The risk of surgical mitral valve replacement in patients with severe mitral annular calcification (MAC) is high. Several patients worldwide with severe MAC have been treated successfully with transcatheter mitral valve replacement (TMVR) using balloon-expandable aortic transcatheter valves. The TMVR in MAC Global Registry is a multicenter registry that collects data on outcomes of these procedures. Objectives The goal of this study was to evaluate 1-year outcomes in this registry. Methods This study was a multicenter retrospective review of clinical outcomes. Results A total of 116 extreme surgical risk patients with severe MAC underwent TMVR; 106 had a procedure date >1 year before data-lock and were included in the analysis. Their mean age was 73 ± 12 years, and 68% were female. The mean Society of Thoracic Surgeons score was 15.3 ± 11.6%, and 90% were in New York Heart Association functional class III or IV. Thirty-day and 1-year all-cause mortality was 25% and 53.7%, respectively. Most patients who survived 30 days were alive at 1 year (49 of 77 [63.6%]), and the majority (71.8%) were in New York Heart Association functional class I or II. Echocardiography data at 1 year were available in 34 patients. Mean left ventricular ejection fraction was 58.6 ± 11.2%, mean mitral valve area was 1.9 ± 0.5 cm2, mean mitral gradient was 5.8 ± 2.2 mm Hg, and 75% had zero or trace mitral regurgitation. Conclusions TMVR with balloon-expandable aortic valves in extreme surgical risk patients with severe MAC is feasible but associated with high 30-day and 1-year mortality. Most patients who survive the 30-day post-procedural period are alive at 1 year and have sustained improvement of symptoms and transcatheter valve performance. The role of TMVR in patients with MAC requires further evaluation in clinical trials.

Key Teaching Points • Transseptal puncture results in the formation of an iatrogenic atrial septal defect (ASD). In patients with right side–dominant cardiac pathologies (such as arrhythmogenic right ventricular cardiomyopathy), the transseptal pressure gradient from the right to left atrium promotes the formation of a right-to-left shunt across this ASD. • A right-to-left shunt across an iatrogenic ASD should be considered in these patients who present with dypsnea following their procedure, particularly if hypoxemic and cyanotic. • Potential strategies to minimize the risk of this complication in this population include avoiding “double sheathing” a single transeptal puncture, avoiding the use of larger sheaths, and assessing a right-to-left shunt at the conclusion of the case with echocardiography. • Patients who remain symptomatic of a right-to-left shunt should undergo ASD closure.

Background Mutations in the parkin gene (PRKN) are the most commonly identified genetic factors in early onset Parkinson disease (EOPD), with biallelic mutations, resulting in a clinical phenotype. However, normal variation is also common in PRKN, particularly in the form of copy number variation (CNV), challenging interpretation of genetic testing results. Here we report a case of a 29‐year‐old male with EOPD and two deletions in PRKN detected by chromosomal microarray (CMA). Methods The proband was clinically examined by a neurologist for postural instability with frequent falls, bradykinesia, gait freezing with festination, and hypophonia. Chromosomal microarray analysis (CMA) was performed on the proband and his parents using the Affymetrix CytoScan HD microarray. Subsequent fluorescence in situ hybridization (FISH) was performed on the proband and both parents. Results Chromosomal microarray detected the presence of two deletions of PRKN in the proband. Parental CMA analysis was performed to determine the clinical significance of this finding, as well as to demonstrate phase of these deletions. Parental CMA revealed that one deletion was paternally inherited and one deletion was de novo. A custom FISH approach was then successfully used to phase the deletions. Conclusion Chromosomal microarray and fluorescence in situ hybridization analysis of this trio identified two deletions in PRKN occurring in trans, providing a genetic etiology for the clinical diagnosis of EOPD. The determination of inheritance and phase of the deletions was critical to the proper interpretation of these results. These findings highlight the utility of CMA in the detection of clinically relevant CNVs in cases of EOPD, and also serve to emphasize the importance of follow‐up FISH and parental testing.

Background:Deficiency of Adenosine Aminase deficiency 2 is monogenic disease presenting with multisystem involvement of vasculitis,Stroke1,hematological manifestations. We hereby present a young child who presented with PRES initially and later diagnosed as DADA2.Only one case of DADA2 presenting as PRES is reported so far2.This case highlights the atypical presentation of DADA2.Objectives:A case report to highlight the rare presentation of DADA2 vasculits.Methods:8 year old developmentally normal male child,born out of consanguineous marriage presented with with fever,abdominal pain, seizures 1 year back.Ultrasound of abdomen revelaed mesenteric lymphadenitis and MRI Brain was suggestive of Meningoencephalitis.He was managed with antivirals and antibiotics then.6 months later,he had fever,skin rash,pain abdomen,status epilepticus,hypertension followed by gangrene of fingers and toes.APLA,ANA,ANCA workup was negative. Complete Hemogram was normal. CRP was 130mg/dl. CT Abdomen was normal and no evidence of aneurysms. Renal Doppler Ultrasound was normal.CT upper limb showed left radial and ulnar artery significant narrowing with patchy occlusion. MRI Brain showed bilateral fronto parietal,occipital,putamen,left insula and subcortical and cortical T2W FLAIR hyperintensity without diffusion restriction suggestive of PRES. He was diagnosed as Childhood Polyarteritis Nodosa and treated with cyclophosphamide. Genetic Analysis of ADA2(CECR1) gene mutation by Sanger Sequencing of exons 2 to 10 showed a known variant (rs202134424) in ADA2 gene.Figure 1.Gangrene of left 1-5th digits and right 4th and 5th digit resorptionFigure 2.T2W FLAIR image showing bilateral fronto parietal,occipital,putamen,left insula and subcortical and cortical hyperintensity without diffusion restriction suggestive of PRES.Results:He was started on Infliximab and is on follow up. No further events noted so far.Rehabilitation of left upper hand was done.Conclusion:DADA2 can present with varied CNS manifestations like infarct,hemorrhage,aneurysms and PRES.High index of suspicion and early recognition can help in maintaining vascular integrity.References:[1]Ganhão S, Loureiro G, Oliveira D, dos-Reis-Maia R, Aguiar F, Quental R et al. Two cases of ADA2 deficiency presenting as childhood polyarteritis nodosa: novel ADA2 variant, atypical CNS manifestations, and literature review. Clinical Rheumatology. 2020;39(12):3853-3860.[2]Sharma A, Naidu G, Sharma V, Jha S, Dhooria A, Dhir V et al. Deficiency of Adenosine Deaminase 2 in Adults and Children: Experience From India. Arthritis & Rheumatology. 2020;73(2):276-285.Disclosure of Interests:None declared

Background:Progressive pseudorheumatoid dysplasia(PPRD) is considered as a degenerative genetic bone disorder. It is caused by loss of function mutation in WNT-1 inducible signaling pathway protein-3(WISP-3)1. WISP-3 gene function is required for the normal function of cartilage and skeletal development. The patients are normal at birth and start developing symptoms around 3-6 years of age2. The disease is characterised by stiffness, pain, deformity due to enlargement of the ends of short and long bones. Often, such patients are misdiagnosed as Juvenile idiopathic arthritis(JIA). In general, PPRD being considered as non-inflammatory disease, immunosuppressants or disease modifying anti rheumatic drugs(DMARDS) like methotrexate treatment are not used for treatment.Objectives:We report a patient with characteristic findings of PPRD but with coexisting clinical and imaging evidence of inflammation.Methods:16 year old male boy born of third degree consanguineous asymptomatic parents presented with progressive swelling, deformity of bilateral small and large joints of upper and lower limbs. He also had pain in both hip and knee for past two years. Pain is associated with difficulty in walking and squatting. On examination he had bony enlargement around bilateral elbow, wrist, proximal and distal interphalangeal joints(Figure 1A). He also had restriction of bilateral hip movements and swelling of bilateral knee with effusion. He had exaggerated lumbar lordosis and flexion deformity of bilateral hip, knee. His blood counts, ESR, CRP were normal. Analysis of Knee joint synovial fluid showed cell count of 200/mm3 with no crystals and sterile culture. USG knee showed evidence of synovial thickening with increased power Doppler signals. Skeletal survey showed typical findings of PPRD with enlargement of epiphysis and osteoarthritis changes(Figure 1B). MRI hip showed minimal effusion, synovial thickening, edema with STIR hyperintensity and enlargement of bilateral femoral epiphysis. MRI knee showed minimal effusion, marrow edema in patella(Figure 1C, arrow head), femoral condyle, diffuse synovial thickening with contrast enhancement(Figure 1D, arrow) and deformed patellar contour. Immunological tests showed negative RF, ACPA and positive ANA(Hep2) speckled 4+. Immunoblot for ENA was negative. His ophthalmological evaluation showed no evidence of uveitis.Figure 1.Clinical picture showing typical hand deformity and swelling at bone ends(A), hand radiograph showing epiphyseal enlargement(B), MRI knee T2 STIR showing bone marrow edema(arrow head) in patella(C) and synovial thickening(arrow) with contrast enhancement in fat saturated T1 MRI with contrast.Results:Patient tested positive for homozygous mutation in WISP-3 gene. He was treated with ibuprofen and supportive measures. Orthopedic consultation obtained and planned for hip, knee replacement during follow up. Follow up imaging and acute phase response was advised after three months.Conclusion:Although PPRD was classically described as a degenerative disease, the findings presented in our case show coexisting inflammation. Bone marrow edema in weight bearing areas, synovial effusion may be explained as part of cartilage degeneration like in osteoarthritis but synovial hypertrophy with contrast enhancement, power Doppler signals in ultrasound, ANA positivity may be signs of coexisting inflammatory or autoimmune phenomenon.References:[1]Hurvitz JR, Suwairi WM et al. Mutations in the CCN gene family member WISP3 cause progressive pseudorheumatoid dysplasia. Nat Genet. 1999 Sep;23(1):94-8. doi: 10.1038/12699. PMID: 10471507.[2]Garcia Segarra N, Mittaz L et al. The diagnostic challenge of progressive pseudorheumatoid dysplasia (PPRD): a review of clinical features, radiographic features, and WISP3 mutations in 63 affected individuals. Am J Med Genet C Semin Med Genet. 2012 Aug 15;160C(3):217-29. doi: 10.1002/ajmg.c.31333. Epub 2012 Jul 12. PMID: 22791401.Disclosure of Interests:None declared

To evaluate the effect of MRI blood pool contrast agent on 4D flow image quality and ventricular volume measurements. Adult patients referred for clinical cardiac MRI (n = 22) were imaged with 4D flow. Patients with renal failure (n = 10) received ferumoxytol, and the remainder (n = 12) received gadofosveset trisodium. Image quality was assessed with (1) signal-to-noise ratio (SNR); (2) contrast-to-noise ratio (CNR); and (3) 5-point Likert scale based on endocardial border definition (1 = none; 2 = partial but unable to visualize; 3 = able to roughly estimate; 4 = visible for most of the cardiac cycle; 5 = excellent definition). A subset (n = 15) had short axis steady-state free precession (SSFP) cine imaging allowing for comparison of standard volumetric measurement technique with 4D flow derived volumetric measurements. 4D flow studies using ferumoxytol demonstrated a higher median Likert score of 5 (IQR, 5–5) versus 3 (IQR, 2–3). Median cavity SNR and CNR were higher for ferumoxytol compared to gadofosveset trisodium [65 (IQR, 50–74) versus 22 (IQR, 14–28), p

Left ventricle—right atrial communication could be congenital (Gerbode defect) or acquired as a complication of surgery or infective endocarditis and leads to volume overloading of pulmonary circulation. Two types, direct and indirect types are known depending on the involvement of septal tricuspid leaflet. Transcatheter closure of this defect is feasible and appears an attractive alternative to surgical management. Various devices like Amplatzer duct occluder I, II, Muscular ventricular septal defect device etc. have been used to close this defect. We report two patients, a preteen boy with direct left ventricle-right atrial communication as post operative complication and an adult female with indirect communication who underwent transcatheter closure with Cera duct occluder (Lifetech Scientific (Shenzhen), China).

In the setting of synchronous pulmonary carcinomas, distinguishing between a monoclonal process with intrapulmonary metastasis and two independent tumors has significant therapeutic and prognostic implications. We describe two cases in which molecular profiling was used to characterize synchronous, primary pulmonary tumors and guide clinical management. In both cases, the patients underwent surgical resection without adjuvant chemotherapy or radiation and remain free of disease.

Background As patients with congenital heart disease ( CHD ) are living longer, understanding the comorbidities they develop as they age is increasingly important. However, there are no published population‐based estimates of the comorbidity burden among the US adult patients with CHD. Methods and Results Using the IBM MarketScan commercial claims database from 2010 to 2016, we identified adults aged ≥18 years with CHD and 2 full years of continuous enrollment. These were frequency matched with adults without CHD within categories jointly defined by age, sex, and dates of enrollment in the database. A total of 40 127 patients with CHD met the inclusion criteria (mean [ SD ] age, 36.8 [14.6] years; and 48.2% were women). Adults with CHD were nearly twice as likely to have any comorbidity than those without CHD ( P CHD ” (risk ratio, 9.41; 95% CI , 7.99–11.1), “other cardiovascular” (risk ratio, 1.73; 95% CI , 1.66–1.80), and “noncardiovascular” (risk ratio, 1.47; 95% CI , 1.41–1.52) comorbidities. After adjusting for covariates and considering interaction with age, patients with severe CHD had higher risks of previously recognized to be common in CHD and lower risks of other cardiovascular comorbidities than age‐stratified patients with nonsevere CHD . For noncardiovascular comorbidities, the risk was higher among patients with severe than nonsevere CHD before, but not after, the age of 40 years. Conclusions Our data underscore the unique clinical needs of adults with CHD compared with their peers. Clinicians caring for CHD may want to use a multidisciplinary approach, including building close collaborations with internists and specialists, to help provide appropriate care for the highly prevalent noncardiovascular comorbidities.

This study aimed to develop a cardiorespiratory-resolved 3D magnetic resonance imaging (5D MRI: x-y-z-cardiac-respiratory) approach based on 3D motion tracking for investigating the influence of respiration on cardiac ventricular function. A highly-accelerated 2.5-minute sparse MR protocol was developed for a continuous acquisition of cardiac images through multiple cardiac and respiratory cycles. The heart displacement along respiration was extracted using a 3D image deformation algorithm, and this information was used to cluster the acquired data into multiple respiratory phases. The proposed approach was tested in 15 healthy volunteers (7 females). Cardiac function parameters, including the end-systolic volume (ESV), end-diastolic volume (EDV), stroke volume (SV), and ejection fraction (EF), were measured for the left and right ventricle in both end-expiration and end-inspiration. Although with the proposed 5D cardiac MRI, there were no significant differences (p > 0.05, t-test) between end-expiration and end-inspiration measurements of the cardiac function in volunteers, incremental respiratory motion parameters that were derived from 3D motion tracking, such as the depth, expiration and inspiration distribution, correlated (p

Here we present a novel repair strategy of a rare aortic complication following transcatheter aortic valve repair (TAVR). A 73-year-old man with a history of mitral valve replacement secondary to endocarditis underwent a TAVR for severe aortic insufficiency at an outside hospital (Medtronic Evolut R

Helicobacter infection is considered the major predisposing factor for gastric mucosa-associated lymphoid tissue (MALT) lymphoma with initial infection likely occurring in childhood. Primary gastric MALT lymphoma most commonly occurs in patients older than 50 years which is attributed to the lengthy chronic infection time required before the development of MALT lymphoma. Our study analyzes the histologic features and presence of immunoglobulin heavy chain (IGH) clonality in Helicobacter-associated chronic gastritis (62 cases) and Helicobacter-negative chronic gastritis (17 cases) biopsies within the pediatric population, diagnosed between 1996 and 2018. Helicobacter-associated gastritis was more likely to show active inflammation (P=0.01), with no significant difference in number of germinal centers or the strength, linear property, or depth of the inflammatory infiltrate. In total, 47% (29/62) of the Helicobacter-associated cases had at least 1 lymphoepithelial lesion, equivocal or definitive (a modified Wotherspoon score of 3 to 5), compared with 24% (4/17) of the Helicobacter-negative cases (P=0.5). All cases with lymphoepithelial lesions were assessed for IGH clonality, showing the presence of monoclonality in 27% (8/30) of evaluable cases. None of our patients were diagnosed with gastric lymphoma within available follow-up data. Although 4% of our cases could be considered MALT lymphoma in an adult patient based on prominent lymphoepithelial lesions and IGH monoclonality, caution is advised when diagnosing lymphoma in the pediatric population given the good prognosis of Helicobacter-associated gastritis in this age group. It is unclear if these monoclonal lymphoid proliferations require close follow-up.

Aims There is growing interest in families of enterally fed children regarding the use of blended diet via gastrostomy as an alternative to commercial formulas. Reported benefits include reduced reflux, constipation and general systemic improvement. There are also numerous concerns including possible tube blockage and bacterial contamination. Liquidised feed is discouraged by BDA, ESPHGAN and EPSG. This had led to barriers to implementation in many areas of the UK and loss of the therapeutic alliance between healthcare professionals and carers. This study aimed to assess patients already commenced on a blended diet in a district general hospital. Methods Six patients were identified as being on a blended diet via gastrostomy. One patient was excluded due to poor engagement and care mainly residing in tertiary services. The BDA Practice Toolkit for liquidised diet by gastrostomy was adapted; medical and dietetic notes reviewed and questionnaires sent to families. Results All of the children had a complex neurodisability with ages ranging from 4%–16. 60% had a 14Fr and 40% had a 12Fr gastrostomy. Families started a blended diet due to poor tolerance of feeds including vomiting and retching non-responsive to medications; increased seizures; constipation; and weight loss. None of the patients had a risk assessment prior to commencement. Diets were augmented to varying extents with commercial formulas/supplements. Families encountered barriers including lack of policies and lost respite days. Information was obtained, not from healthcare professionals, but instead personal research including Facebook. Benefits included reduced reflux, constipation, chest infections and hospital admissions. An improved quality of life for their child was perceived. Sparse records of nutritional indices were found, only weight was recorded which either improved or was static. Nutritional status bloods weren’t taken although incidental blood tests were normal. There was no change in the frequency of button changes and no tube blockages nor diarrhoeal illness were reported. The study was limited as it was a small study group, without wider nutritional details or costings included. Conclusion This group experienced positive changes in using a blended diet for their children but further research is warranted.

© 2016 Informa UK Limited, trading as Taylor & Francis Group. Introduction: Patent foramen ovale (PFO) is a common congenital cardiac abnormality and that has been associated with several disease processes including transient ischemic attacks (TIA), stroke, migraine headaches with aura, decompression sickness, platypnea-orthodeoxia syndrome, and shunt induced cyanosis. Controversy exists regarding closure of PFO as a therapeutic treatment modality for these disease processes. This review addresses the contemporary clinical indications for PFO closure. Areas covered: We conducted a comprehensive literature search of contemporary research studies focusing on randomized trials and meta-analyses comparing medical therapy and device closure of PFOs for the treatment of PFO associated clinical syndromes. We synthesized this literature into a review addressing indications for PFO closure in stroke, TIA, migraine headaches with aura, decompression sickness, platypnea-orthodeoxia syndrome, and shunt induced cyanosis. Expert commentary: Because in many PFO associated conditions it can be difficult to determine the degree to which the PFO is a causative factor in the disease process, we recommend a comprehensive diagnostic evaluation to exclude other obvious etiologies of PFO associated conditions before implicating the PFO and proceeding with closure. However in the properly selected patient population there is growing clinical experience and experimental evidence suggesting that closure of PFO is a safe and effective treatment modality.

Background The most common reason for reintervention after a Bjork modification of the Fontan procedure, in which the right ventricle (RV) is incorporated into the pulmonary circulation by connecting the right atrial (RA) appendage to the RV directly or with an extra-anatomic graft, is obstruction or regurgitation of the RA–RV connection. Transcatheter implantation of a valved stent is an appealing option for the treatment of RA–RV conduit dysfunction in these patients. In the present study, we assessed early and intermediate results after transcatheter valve implantation within an obstructed or regurgitant RA–RV modified Fontan pathway. Methods Through a retrospective multicenter registry, we collected data from 16 patients with a modified Fontan circulation who were treated with percutaneous Melody or Sapien valve implantation for dysfunction of an extra-anatomic RA–RV conduit or valve. Results All patients had successful and uncomplicated implantation of a Melody (n = 15) or Sapien 3 (n = 1) valve with hemodynamic and, in most cases, clinical improvement. During a median follow-up of 3.3 years, 3 patients died of cardiovascular causes unrelated to the procedure or the valve, and no major valve dysfunction was observed. Conclusion Percutaneous transcatheter valve deployment to treat a dysfunctional RA–RV connection after a Bjork modification of the Fontan procedure is a viable alternative to surgery, with low procedural risk, and appears to offer good early and intermediate results.© 2016 Wiley Periodicals, Inc.

Objectives This study sought to evaluate the outcomes of the early experience of transcatheter mitral valve replacement (TMVR) with balloon-expandable valves in patients with severe mitral annular calcification (MAC) and reports the first large series from a multicenter global registry. Background The risk of surgical mitral valve replacement in patients with severe MAC is high. There are isolated reports of successful TMVR with balloon-expandable valves in this patient population. Methods We performed a multicenter retrospective review of clinical outcomes of patients with severe MAC undergoing TMVR. Results From September 2012 to July of 2015, 64 patients in 32 centers underwent TMVR with compassionate use of balloon-expandable valves. Mean age was 73 ± 13 years, 66% were female, and mean Society of Thoracic Surgeons score was 14.4 ± 9.5%. The mean mitral gradient was 11.45 ± 4.4 mm Hg and the mean mitral area was 1.18 ± 0.5 cm 2 . SAPIEN valves (Edwards Lifesciences, Irvine, California) were used in 7.8%, SAPIEN XT in 59.4%, SAPIEN 3 in 28.1%, and Inovare (Braile Biomedica, Brazil) in 4.7%. Access was transatrial in 15.6%, transapical in 43.8%, and transseptal in 40.6%. Technical success according to Mitral Valve Academic Research Consortium criteria was achieved in 46 (72%) patients, primarily limited by the need for a second valve in 11 (17.2%). Six (9.3%) had left ventricular tract obstruction with hemodynamic compromise. Mean mitral gradient post-procedure was 4 ± 2.2 mm Hg, paravalvular regurgitation was mild or absent in all. Thirty-day all-cause mortality was 29.7% (cardiovascular = 12.5% and noncardiac = 17.2%); 84% of the survivors with follow-up data available were in New York Heart Association functional class I or II at 30 days (n = 25). Conclusions TMVR with balloon-expandable valves in patients with severe MAC is feasible but may be associated with significant adverse events. This strategy might be an alternative for selected high-risk patients with limited treatment options.

SummaryBackgroundEndovascular stenting is a recognised treatment strategy for aortic coarctation (CoA) in adults. We assessed systemic hypertension control and the need for antihypertensive therapy after CoA stenting in adults.MethodsData were collected prospectively on 54 patients (36 men; mean age: 34±16 years) who underwent endovascular stenting for CoA over a 7-year period. Five patients were excluded as they did not attend follow-up appointments. Patients underwent clinical examination, including right arm systolic blood pressure (SBP) and 24-hour ambulatory blood pressure monitoring at baseline, 6–12 weeks and 9–12 months.ResultsThere was a significant fall in mean peak-to-peak systolic gradient (PG) across the CoA after stenting (26±11mmHg vs. 5±4mmHg; P25mmHg before stenting); baseline SBP was significantly higher in severe versus non-severe patients (160mmHg vs. 148mmHg; P=0.02). The absolute reduction in PG after stenting was significantly higher in the severe group (31±7mmHg vs. 14±5mmHg; P

Background Advances in clinical management have improved life expectancy in the ACHD population; as a result, implantable cardiac devices remain in situ for longer periods than ever before. These patients pose unique challenges, including; young age at implant, multiple device procedures during their lifetime, complex venous and cardiac anatomy, and co-morbidities which may predispose to infection. In the non-ACHD population, there is useful long-term research which helps to guide clinical decision-making; however, small numbers and incomplete outcome data has lead to limited comparability against ACHD patients. Aims This study aimed to examine 20 years of pacing experience in a large ACHD centre, using novel data-mining techniques to generate comprehensive lead survival data. Methodology A retrospective analysis was performed of pacing and defibrillator leads implanted between June 1996 and December 2016 in a 173 patient ACHD cohort. Automated text searching algorithms with manual review of over 1 00 000 pieces of clinical correspondence was used to maximise identification of outcomes. Lead-specific complications, non-elective removal and overall lead survival were compared for surgical and transvenous leads in patients with complex and non-complex ACHD anatomy. Results 340 leads with complete implant and follow-up data were identified of which 53% were in patients with complex ACHD anatomy and 15% were in patients with tricuspid valve abnormalities. Median lead survival time was 13.6 years in transvenous leads and 15.9 years in surgical leads (p=n .s.) Transvenous leads were associated with a higher risk of major infection than were surgically-implanted leads (11.5% vs 0% p Conclusion In this large cohort of patients with ACHD, lead survival appears to be reasonable regardless of whether a transvenous or surgical approach is used. A higher incidence of infection in transvenous leads is offset by a higher electrical failure rate in surgical leads. Further work examining large cohorts is required to determine optimal pacing strategies tailored to patient-specific anatomical challenges.

Right ventricular outflow tract (RVOT) dysfunction is a common hemodynamic challenge for adults with congenital heart disease (ACHD), including patients with repaired tetralogy of Fallot (TOF), truncus arteriosus (TA), and those who have undergone the Ross procedure for congenital aortic stenosis and the Rastelli repair for transposition of great vessels. Pulmonary valve replacement (PVR) has become one of the most common procedures performed for ACHD patients. Areas covered: Given the advances in transcatheter technology, we conducted a detailed review of the available studies addressing the indications for PVR, historical background, evolving technology, procedural aspects, and the future direction, with an emphasis on ACHD patients. Expert commentary: Transcatheter pulmonary valve implantation (TPVI) is widely accepted as an alternative to surgery to address RVOT dysfunction. However, current technology may not be able to adequately address a subset of patients with complex RVOT morphology. As the technology continues to evolve, new percutaneous valves will allow practitioners to apply the transcatheter approach in such patients. We expect that with the advancement in transcatheter technology, novel devices will be added to the TPVI armamentarium, making the transcatheter approach a feasible alternative for the majority of patients with RVOT dysfunction in the near future.

We describe a hybrid surgical interventional technique for minimally invasive implantation of a transcatheter aortic valve in the mitral position. This technique does not require circular mitral annular calcification and minimizes the risk of left ventricular outflow tract obstruction. We believe this technique represents a useful approach for surgeons and interventional cardiologists until specialized transcatheter mitral valve devices become available.

Myotonic dystrophy type 1 (DM1), the most prevalent muscular dystrophy in adults, is characterized by progressive muscle wasting and multi-systemic complications. DM1 is the prototype for disorders caused by RNA toxicity. Currently, no therapies exist. Here, we identify that fibroblast growth factor-inducible 14 (Fn14), a member of the tumor necrosis factor receptor super-family, is induced in skeletal muscles and hearts of mouse models of RNA toxicity and in tissues from DM1 patients, and that its expression correlates with severity of muscle pathology. This is associated with downstream signaling through the NF-κB pathways. In mice with RNA toxicity, genetic deletion of Fn14 results in reduced muscle pathology and better function. Importantly, blocking TWEAK/Fn14 signaling with an anti-TWEAK antibody likewise improves muscle histopathology and functional outcomes in affected mice. These results reveal new avenues for therapeutic development and provide proof of concept for a novel therapeutic target for which clinically available therapy exists to potentially treat muscular dystrophy in DM1.

Introduction Patients undergoing structural heart interventions often require large-sized sheath insertion into femoral arteries and veins. Clinical outcome data on the use of suture-mediated devices for large femoral arterial access in structural heart interventions is limited. We assessed the efficacy of the Perclose™ (Abbott Vascular Devices, Santa Clara, CA, USA) suture-mediated device using the pre-closure technique in achieving hemostasis in femoral arterial access sites following large sheath insertion (≥8 Fr). Methods One hundred consecutive patients underwent 101 femoral artery access sites closures with the Perclose device using the pre-closure technique. Sixty-two percent of the patients were male and their mean (SD) age was 52 (±26) years. All patients received heparin. Results Mean arterial access site sheath diameter was 13 ± 2 Fr. Immediate hemostasis was achieved in 96/101 (96%) procedures (≤2 min). Two patients (2%) had access site-related complications requiring further interventions. On clinical follow up [mean (SD) follow-up of 24 (±12) months and median follow-up of 8.5 months], no complications were seen in the arterial access sites. Conclusion Pre-closure of large-size femoral arterial access sheath sites using the suture-mediated Perclose device is efficacious in achieving rapid hemostasis in patients undergoing structural interventions. On 1-year follow-up, there were no arterial access site complications requiring further investigations or interventions. Electronic supplementary material The online version of this article (doi:10.1007/s40119-014-0034-7) contains supplementary material, which is available to authorized users.

Summary Background Liver disease (LD) is a long-term complication in patients with a single ventricle who have had the Fontan operation. A decline in cardiopulmonary exercise testing (CPET) variables is associated with increased risk of hospitalization, but its association with LD is unknown. Aim To determine the association between CPET variables and LD in adults who have had the Fontan operation. Methods We retrospectively reviewed the medical records from two tertiary institutions. Results We identified 114 adults (≥ 18 years; mean 30.9 ± 7.4 years) who had undergone the Fontan operation: 56% were women; 63% had total cavopulmonary connection; 66% had New York Heart Association (NYHA) class I status; 42% had arrhythmias; 22% had systemic right ventricle; and 35% had ventricular dysfunction. Of 81 patients with liver-imaging data, 41% had LD (i.e. imaging evidence of cirrhosis, with or without portal hypertension, splenomegaly or varices). There were no differences in clinical or echocardiographic variables between those with and without LD. Among the 58 patients with CPET data, mean peak oxygen consumption (VO2) was 18.6 ± 5.7 mL/kg/min, per-cent-predicted peak VO2 was 53.9 ± 15.5%, peak oxygen pulse was 9.3 ± 2.9 mL/beat and per-cent-predicted peak oxygen pulse was 82.6 ± 21.5%. Of the 44 patients with liver and CPET data, each standard deviation decrease in per-cent-predicted peak VO2 (16%) and per-cent-predicted peak oxygen pulse (22%) was associated with a 2.3-fold increase in the odds of LD, after adjusting for NYHA, institution and Fontan type (P = 0.04). Similarly, each standard deviation decrease in per-cent-predicted peak VO2 and oxygen pulse was associated with an estimated 5.9-year and 4.9-year earlier onset of LD, respectively (P > 0.05). Conclusions Decline in per-cent-predicted peak VO2 and oxygen pulse was associated with increased odds of LD in adults who had undergone the Fontan operation. Our study supports more rapid hepatic evaluation among patients with abnormal or worsening CPET variables.

Background Computed tomography angiography (CTA) is the test of choice for pre-procedure imaging of transcatheter aortic valve replacement (TAVR) candidates. The iodinated contrast required, however, increases the risk of renal dysfunction in patients with pre-existing renal failure. Ferumoxytol is a magnetic resonance imaging (MRI) contrast agent that can be used with renal failure. Its long vascular resonance time allows gated MRA sequences that approach CTA in image quality. We present respiratory and cardiac gated MRA enabled by ferumoxytol that can be post-processed in an analogous fashion to CTA. Methods Seven patients with renal failure presenting for TAVR were imaged with respiratory and cardiac gated MRA at 3T using ferumoxtyol for contrast. Aortic annulus, root and peripheral access dimensions were calculated in a fashion identical to that used for CTA. Of these, 6 patients underwent a TAVR procedure and 5 had intraoperative valve assessment with transesophageal echocardiograph (TEE) using standard clinical protocols that employed both two- and three-dimensional techniques. Results Good correlation between MRA aortic annulus measurements and those from TEE were shown in 5 patients with mean annulus area of 392.4mm 2 (290–470 range) versus 374.1mm 2 (285–440 range), with a pairwise correlation coefficient of 0.92, p=0.029. All patients received Sapien valve implants (one 20mm, three 23mm, and two 26mm valves). Access decisions were guided by MRA with no complications. Annulus sizing resulted in no greater than trace/mild aortic regurgitation in all patients. Conclusions Ferumoxytol MRA is a safe alternative to CTA in patients with renal failure for pre-TAVR analysis of the aortic root and peripheral access.

Transcatheter heart valve implantation is a well-established alternative to surgical valve replacement for specific types of valvular heart disease [(1–4)][1]. We report the first case of implantation of an Edwards SAPIEN XT transcatheter heart valve (Edwards Lifesciences, Irvine, California) in

A 77-year-old man with long-standing persistent atrial fibrillation, coronary artery disease, and systolic heart failure underwent left atrial appendage (LAA) ligation with a Lariat suture delivery device (SentreHEART, Redwood City, California), and subsequent pulmonary vein isolation. One month