Dysplastic Mitral Valve in Costello Syndrome.

Costello syndrome is an autosomal dominant condition caused by variants in the HRAS gene. Cardiac presentation includes valvular disease (usually valvar pulmonary stenosis), arrhythmias, and hypertrophic cardiomyopathy. To our knowledge, this is the first such report of dysplastic mitral valve associated with Costello syndrome.

Pilot study to evaluate the use of remote patient monitoring to guide the timing of valve intervention in patients with severe asymptomatic aortic stenosis (APRAISE-AS): study protocol for a randomised controlled trial delivered in two tertiary cardiac centres in the UK.

INTRODUCTION: Aortic stenosis (AS) is common affecting >13% of adults over the age of 75 years. In people who develop symptoms, without valve replacement, prognosis is dismal with mortality as high as 50% at 1 year. In asymptomatic patients, the timing of valve intervention is less well defined and a strategy of watchful waiting is recommended. Many, however, may develop symptoms and attribute this to age related decline, rather than worsening AS. Timely intervention in asymptomatic severe AS is critical, since delayed intervention often results in poor outcomes. Proactive surveillance of symptoms, quality of life and functional capacity should enable timely identification of people who will benefit from aortic valve replacement. There are no data however, to support the clinical and cost effectiveness of such an approach in a healthcare setting in the UK. The aim of this pilot trial is to test the feasibility of a full-scale randomised controlled trial (RCT) to determine the utility of proactive surveillance in people with asymptomatic severe AS to guide the timing of intervention. METHODS AND ANALYSIS: APRAISE-AS is a multi-centre, non-blinded, two-arm, parallel group randomised controlled trial of up to 66 participants aged >18 years with asymptomatic severe AS. Participants will be randomised to either standard care or standard care supplemented with the APRAISE-AS intervention. Primary outcomes will capture; adherence to and participant acceptability of the intervention, recruitment and retention rates, and completeness of data collection. The findings will be used to inform the sample size and most appropriate outcome measure(s) for a full-scale RCT and health economic evaluation. ETHICS AND DISSEMINATION: Ethical approval was granted by the Black Country REC, reference: 22/WM/0214. Results will be submitted for publication in peer-reviewed journals and disseminated at local, regional and national meetings where appropriate. TRIAL REGISTRATION NUMBER: ISRCTN19413194 registered on 14.07.2023.

Defining the cardiovascular phenotype of adults with Alström syndrome.

BACKGROUND: >40% of infants with Alström Syndrome (AS) present with a transient, severe cardiomyopathy in the first months of life, with apparent recovery in survivors. One in five individuals then develop a later-onset cardiomyopathy but wide clinical variability is observed, even within the same family. The rationale for this study is to provide a comprehensive evaluation of the cardiovascular phenotype in adults with AS. METHODS: Adults attending the National Centre for AS in England were studied. All patients underwent biochemical, 12- lead electrocardiography, echocardiography, and cardiovascular magnetic resonance imaging. RESULTS: 47 adults with AS (64% male; mean age 33 years; 66% white British) were studied. Seven (15%) survived infantile cardiomyopathy and 23 (49%) developed adult-onset cardiomyopathy. Conventional risk factors for cardiovascular disease were present in 39 (83%). Abnormalities were present on biomarkers in 16 (34%), ECG 30 (64%), echocardiography 19 (40%) and CMR 31 (66%). Coronary artery imaging was performed in six (13%), with abnormalities in two. Cardiac, renal, and liver markers were more often impaired in older patients, with impaired left ventricular ejection fraction, reduced global longitudinal strain and late enhancement. 6 (13%) had severe pulmonary hypertension (mean pulmonary artery pressure 46 mmHg) due to left heart disease on invasive testing. CONCLUSION: Cardiomyopathy is common in adults with AS, complicated in a significant proportion by atherosclerotic coronary artery disease and restrictive cardiomyopathy, confirmed on CMR and invasive testing. With advancing age, cardiovascular complications are compounded by contemporaneous renal and liver disease.

Prognostic Value of a 6-Minute Walk Test in Patients With Transthyretin Cardiac Amyloidosis.

BACKGROUND: The 6-minute walk test (6MWT) represents a comprehensive functional assessment that is commonly used in patients with heart failure; however, data are lacking in patients with transthyretin cardiac amyloidosis (ATTR-CA). OBJECTIVES: This study aimed to assess the prognostic importance of the 6MWT in patients with ATTR-CA. METHODS: A retrospective analysis of patients diagnosed with ATTR-CA at the National Amyloidosis Centre who underwent a baseline 6MWT between 2011 and 2023 identified 2,141 patients, of whom 1,118 had follow-up at 1 year. RESULTS: The median baseline 6MWT distance was 347 m (Q1-Q3: 250-428 m) and analysis by quartiles demonstrated an increased death rate with each distance reduction (deaths per 100 person-years: 6.3 vs 9.2 vs 13.6 vs 19.0; log-rank P < 0.001). A 6MWT distance of <350 m was associated with a 2.2-fold higher risk of mortality (HR: 2.15; 95% CI: 1.85-2.50; P < 0.001), with a similar increased risk across National Amyloidosis Centre disease stages (P for interaction = 0.761) and genotypes (P for interaction = 0.172). An absolute (reduction of >35 m) and relative worsening (reduction of >5%) of 6MWT at 1 year was associated with an increased risk of mortality (HR: 1.80; 95% CI: 1.51-2.15; P < 0.001 and HR: 1.89; 95% CI: 1.59-2.24; P < 0.001, respectively), which was similar across the aforementioned subgroups. When combined with established measures of disease progression (N-terminal pro-B-type natriuretic peptide progression and outpatient diuretic intensification), each incremental increase in progression markers was associated with an increased death rate (deaths per 100 person-years: 7.6 vs 13.9 vs 22.4 vs 32.9; log-rank P < 0.001). CONCLUSIONS: The baseline 6MWT distance can refine risk stratification beyond traditional prognosticators. A worsening 6MWT distance can stratify disease progression and, when combined with established markers, identifies patients at the highest risk of mortality.

Prevalence and Impact of Concomitant Atrial Fibrillation in Patients Undergoing Percutaneous Coronary Intervention for Acute Myocardial Infarction.

Background: Concomitant atrial fibrillation (AF) is associated with an adverse prognosis in patients with acute myocardial infarction (MI). However, it remains unclear whether this is due to a causal effect of AF or whether AF acts as a surrogate marker for comorbidities in this population. Furthermore, there are limited data on whether coronary artery disease distribution impacts the risk of developing AF. Methods: Consecutive patients admitted with acute MI and treated using percutaneous coronary intervention (PCI) at a single centre were retrospectively identified. Associations between AF and major adverse cardiac and cerebrovascular events (MACCEs) over a median of five years of follow-up were assessed using Cox regression, with adjustment for confounding factors performed using both multivariable modelling and a propensity-score-matched analysis. Results: AF was identified in N = 65/1000 (6.5%) of cases; these patients were significantly older (mean: 73 vs. 65 years, p < 0.001), with lower creatinine clearance (p < 0.001), and were more likely to have a history of cerebrovascular disease (p = 0.011) than those without AF. In addition, patients with AF had a greater propensity for left main stem (p = 0.001) or left circumflex artery (p = 0.004) involvement. Long-term MACCE rates were significantly higher in the AF group than in the non-AF group (50.8% vs. 34.2% at five years), yielding an unadjusted hazard ratio (HR) of 1.86 (95% CI: 1.32-2.64, p < 0.001). However, after adjustment for confounding factors, AF was no longer independently associated with MACCEs, either on multivariable (adjusted HR: 1.25, 95% CI: 0.81-1.92, p = 0.319) or propensity-score-matched (HR: 1.04, 95% CI: 0.59-1.82, p = 0.886) analyses. Conclusions: AF is observed in 6.5% of patients admitted with acute MI, and those with AF are more likely to have significant diseases involving left main or circumflex arteries. Although unadjusted MACCE rates were significantly higher in patients with AF, this effect was not found to remain significant after adjustment for comorbidities. As such, this study provided no evidence to suggest that AF is independently associated with MACCEs.

Arrhythmogenesis in Fabry Disease.

PURPOSE OF REVIEW: Fabry Disease (FD) is a rare lysosomal storage disorder characterised by multiorgan accumulation of glycosphingolipid due to deficiency in the enzyme α-galactosidase A. Cardiac sphingolipid accumulation triggers various types of arrhythmias, predominantly ventricular arrhythmia, bradyarrhythmia, and atrial fibrillation. Arrhythmia is likely the primary contributor to FD mortality with sudden cardiac death, the most frequent cardiac mode of death. Traditionally FD was seen as a storage cardiomyopathy triggering left ventricular hypertrophy, diastolic dysfunction, and ultimately, systolic dysfunction in advanced disease. The purpose of this review is to outline the current evidence exploring novel mechanisms underlying the arrhythmia substrate. RECENT FINDINGS: There is growing evidence that FD cardiomyopathy is a primary arrhythmic disease with each stage of cardiomyopathy (accumulation, hypertrophy, inflammation, and fibrosis) contributing to the arrhythmia substrate via various intracellular, extracellular, and environmental mechanisms. It is therefore important to understand how these mechanisms contribute to an individual's risk of arrhythmia in FD. In this review, we outline the epidemiology of arrhythmia, pathophysiology of arrhythmogenesis, risk stratification, and cardiac therapy in FD. We explore how advances in conventional cardiac investigations performed in FD patients including 12-lead electrocardiography, transthoracic echocardiography, and cardiac magnetic resonance imaging have enabled early detection of pro-arrhythmic substrate. This has allowed for appropriate risk stratification of FD patients. This paves the way for future work exploring the development of therapeutic initiatives and risk prediction models to reduce the burden of arrhythmia.

'The imitation game': a heart failure case report with a great diagnostic twist.

Background: Arrhythmogenic ventricular cardiomyopathy (AVC) is a hereditary cardiomyopathy that has been associated with mutations in genes encoding for components of the cardiac desmosome including desmoglein-2 (DSG-2). Case summary: A 49-year-old male presented with decompensated heart failure and ventricular arrythmias. A cardiac magnetic resonance scan demonstrated a dilated left ventricle (LV) with severely impaired systolic function and extensive subepicardial late gadolinium enhancement in the lateral wall. An 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) scan identified myocardial uptake consistent with inflammation. Following treatment with steroids for presumed cardiac sarcoidosis, a repeat FDG-PET confirmed resolution of inflammation. A dilated cardiomyopathy/AVC gene panel, however, subsequently identified a pathogenic variant in the DSG-2 gene. Discussion: We describe the case of a patient presenting with clinical and imaging features suggestive for cardiac sarcoidosis, however genetic testing established a diagnosis of DSG-2 associated AVC. DSG-2 mutations in AVC are associated with frequent LV involvement and heart failure. Active inflammation has been observed in other cardiomyopathies, specifically in desmoplakin cardiomyopathy which has a similar clinical course to DSG-2. To our knowledge, this is the first case of DSG-2 cardiomyopathy presenting in this manner. We encourage clinicians to have a high index of suspicion of inflammatory cardiomyopathies as a differential to myocarditis and cardiac sarcoidosis, when patients present with evidence of decompensated heart failure, arrhythmias, and active myocardial inflammation.

Extending the reach of expert amyloidosis care: A feasibility study exploring the staged implementation of a UK amyloidosis network.

There has been an exponential increase in the diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CA). In response, the Midlands Amyloidosis Service was launched with the aim of providing patients with a timely diagnosis, remote expertise from the National Amyloidosis Centre and access to emerging transthyretin (TTR)-directed therapies. This was a descriptive study of a pilot hub-and-spoke model of delivering specialist amyloidosis care. Patients with suspected amyloidosis were referred from the wider Midlands region, and seen in a consultant-led multidisciplinary clinic. The diagnosis of ATTR-CA was established according to either the validated non-biopsy criteria or histological confirmation of ATTR deposits with imaging evidence of amyloid. Study endpoints were the volume of service provision and the time to diagnosis from the receipt of referral. Patients (n=173, age 75±2 years; male 72 %) were referred between 2019 and 2021. Eighty patients (46 %) were found to have cardiac amyloidosis, of whom 68 (85 %) had ATTR-CA. The median time from referral to diagnosis was 43 days. By removing the need for patients to travel to London, an average of 187 patient-miles was saved. Fifteen (9 %) patients with wild-type ATTR-CA received tafamidis under the Early Access to Medicine scheme; 10 (6 %) were enrolled into phase 3 clinical trials of RNA interference or antisense oligonucleotide therapies. Our results suggest that implementing a UK amyloidosis network appears feasible and would enhance equity of access to specialised amyloidosis healthcare for the increasing numbers of older patients found to have ATTR-CA.

Feasibility study of Glucagon-like peptide-1 analogues for the optimization of Outcomes in obese patients undergoing AbLation for Atrial Fibrillation (GOAL-AF) protocol.

BACKGROUND: Catheter ablation for atrial fibrillation is recommended for symptomatic patients after failed medical therapy. Ablation has a higher failure rate in obese patients, and both the prevalence of atrial fibrillation and obesity are increasingly globally. The outcome of ablation can be improved if obese patients can achieve goal-oriented weight reduction prior to ablation. Conventional weight loss strategies, however, can be difficult to access and can delay ablation, thereby risking a lower chance of maintaining sinus rhythm. Effective weight-loss medications, such as the glucagon-like peptide inhibitor-1 drugs, offer the potential for incremental impact on weight loss over a shorter period of time as a bridging therapy. The aim of this study is to assess the feasibility of using liraglutide, a glucagon-like peptide inhibitor-1, in producing weight loss in obese patients before catheter ablation. METHODS: The study is an open-label, uncontrolled, prospective single-centre feasibility study of daily liraglutide injections in the treatment of obese patients for at least 13 weeks before and 52 weeks after AF ablation. Adult patients with symptomatic AF whose body mass index ≥ 30 will be recruited from those planning to undergo ablation. Feasibility will be determined based on the recruitment rate, adherence to the medication, and the amount of weight loss achieved over the study period. Exploratory outcomes include changes in atrial structure, function, and fibrosis with weight loss evaluated by cardiac magnetic resonance imaging, electroanatomic mapping, and patient-reported outcome measure. DISCUSSION: This study will allow us to determine whether the use of liraglutide in obese patients with atrial fibrillation undergoing ablation is feasible with adequate recruitment. The additional information on adherence and average weight loss over the study period will inform the design of a future definitive randomized controlled trial. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT05221229 ). Registered on 2 February 2022. TRIAL FUNDING: Metchley Park Medical Society and University of Birmingham Starter Fellowship, British Heart Foundation Accelerator Grant, Abbott Investigator-Initiated Study Grant.

Structural Progression in Patients with Definite and Non-Definite Arrhythmogenic Right Ventricular Cardiomyopathy and Risk of Major Adverse Cardiac Events.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare inherited disease characterised by early arrhythmias and structural changes. Still, there are limited echocardiography data on its structural progression. We studied structural progression and its impact on the occurrence of major adverse cardiovascular events (MACE). In this single-centre observational cohort study, structural progression was defined as the development of new major or minor imaging 2010 Task Force Criteria during follow-up. Of 101 patients, a definite diagnosis of ARVC was made in 51 patients, while non-definite 'early' disease was diagnosed in 50 patients. During 4 years of follow-up (IQR: 2-6), 23 (45%) patients with a definite diagnosis developed structural progression while only 1 patient in the non-definite (early) group gained minor imaging Task Force Criteria. Male gender was strongly associated with structural progression (62% of males progressed structurally, while 88% of females remained stable). Patients with structural progression were at higher risk of MACE (64% of patients with MACE had structural progression). Therefore, the rate of structural progression is an essential factor to be considered in ARVC studies.

Phenoage and longitudinal changes on transthoracic echocardiography in Alström syndrome: a disease of accelerated ageing?

Alström syndrome (AS) is an ultra-rare disorder characterised by early-onset multi-organ dysfunction, such as insulin resistance, obesity, dyslipidaemia, and renal and cardiovascular disease. The objective is to explore whether AS is a disease of accelerated ageing and whether changes over time on echocardiography could reflect accelerated cardiac ageing. Cross-sectional measurement of Phenoage and retrospective analysis of serial echocardiography were performed between March 2012 and November 2022. The setting is a single national tertiary service jointly run by health service and patient charity. Forty-five adult patients aged over 16 years were included, 64% were male and 67% of White ethnicity. The median Phenoage was 48 years (interquartile range [IQR]: 35-72) in the 34 patients for whom this was calculable, which was significantly higher than the median chronological age of 29 years (IQR: 22-39, p<0.001). Phenoage was higher than chronological age in 85% (N=29) of patients, with a median difference of +18 years (IQR: +4, +34). On echocardiography, significant decreases were observed over time in left ventricular (LV) size at end-diastole (average of 0.046 cm per year, p<0.001) and end-systole (1.1% per year, p=0.025), with significant increase in posterior wall thickness at end-diastole (0.009 cm per year, p=0.008). LV systolic function measured by global longitudinal strain reduced (0.34 percentage points per year, p=0.020) and E/e'lat increased (2.5% per year, p=0.019). Most AS patients display a higher Phenoage compared to chronological age. Cardiac changes in AS patients were also reflective of accelerated ageing, with a reduction in LV size and increased wall thickening. AS may be a paradigm disease for premature ageing.

The atrial and ventricular myocardial proteome of end-stage lamin heart disease.

Lamins A/C (encoded by LMNA gene) can lead to dilated cardiomyopathy (DCM). This pilot study sought to explore the postgenomic phenotype of end-stage lamin heart disease. Consecutive patients with end-stage lamin heart disease (LMNA-group, n = 7) and ischaemic DCM (ICM-group, n = 7) undergoing heart transplantation were prospectively enrolled. Samples were obtained from left atrium (LA), left ventricle (LV), right atrium (RA), right ventricle (RV) and interventricular septum (IVS), avoiding the infarcted myocardial segments in the ICM-group. Samples were analysed using a discovery 'shotgun' proteomics approach. We found that 990 proteins were differentially abundant between LMNA and ICM samples with the LA being most perturbed (16-fold more than the LV). Abundance of lamin A/C protein was reduced, but lamin B increased in LMNA LA/RA tissue compared to ICM, but not in LV/RV. Carbonic anhydrase 3 (CA3) was over-abundant across all LMNA tissue samples (LA, LV, RA, RV, and IVS) when compared to ICM. Transthyretin was more abundant in the LV/RV of LMNA compared to ICM, while sarcomeric proteins such as titin and cardiac alpha-cardiac myosin heavy chain were generally less abundant in RA/LA of LMNA. Protein expression profiling and enrichment analysis pointed towards sarcopenia, extracellular matrix remodeling, deficient myocardial energetics, redox imbalances, and abnormal calcium handling in LMNA samples. Compared to ICM, end-stage lamin heart disease is a biventricular but especially a biatrial disease appearing to have an abundance of lamin B, CA3 and transthyretin, potentially hinting to compensatory responses.

Clinical utilisation of implantable loop recorders in adults with Fabry disease-a multi-centre snapshot study.

Fabry disease (FD) is an X-linked deficiency of alpha-galactosidase-A, leading to lysosomal storage of sphingolipids in multiple organs. Myocardial accumulation contributes to arrhythmia and sudden death, the most common cause of FD mortality. Therefore, there is a need for risk stratification and prediction to target device therapy. Implantable loop recorders (ILRs) allow for continual rhythm monitoring for up to 3 years. Here, we performed a retrospective study to evaluate current ILR utilisation in FD and quantify the burden of arrhythmia that was detected, which resulted in a modification of therapy. This was a snapshot assessment of 915 patients with FD across three specialist centres in England during the period between 1 January 2000 and 1 September 2022. In total, 22 (2.4%) patients underwent clinically indicated ILR implantation. The mean implantation age was 50 years and 13 (59%) patients were female. Following implantation, nine (41%) patients underwent arrhythmia detection, requiring intervention (six on ILR and three post-ILR battery depletion). Three patients experienced sustained atrial high-rate episodes and were started on anticoagulation. Three had non-sustained tachyarrhythmia and were started on beta blockers. Post-ILR battery depletion, one suffered complete heart block and two had sustained ventricular tachycardia, all requiring device therapy. Those with arrhythmia had a shorter PR interval on electrocardiography. This study demonstrates that ILR implantation in FD uncovers a high burden of arrhythmia. ILRs are likely to be underutilised in this pro-arrhythmic cohort, perhaps restricted to those with advanced FD cardiomyopathy. Following battery depletion in three patients as mentioned above, greater vigilance and arrhythmia surveillance are advised for those experiencing major arrhythmic events post-ILR monitoring. Further work is required to establish who would benefit most from implantation.

British Society of Echocardiography guideline for the transthoracic echocardiographic assessment of cardiac amyloidosis.

These guidelines form an update of the BSE guideline protocol for the assessment of restrictive cardiomyopathy (Knight et al. in Echo Res Prac, 2013). Since the original recommendations were conceived in 2013, there has been an exponential rise in the diagnosis of cardiac amyloidosis fuelled by increased clinician awareness, improvements in cardiovascular imaging as well as the availability of new and effective disease modifying therapies. The initial diagnosis of cardiac amyloidosis can be challenging and is often not clear-cut on the basis of echocardiography, which for most patients presenting with heart failure symptoms remains the first-line imaging test. The role of a specialist echocardiographer will be to raise the suspicion of cardiac amyloidosis when appropriate, but the formal diagnosis of amyloid sub-type invariably requires further downstream testing. This document seeks to provide a focused review of the literature on echocardiography in cardiac amyloidosis highlighting its important role in the diagnosis, prognosis and screening of at risk individuals, before concluding with a suggested minimum data set, for use as an aide memoire when reporting.

Patent foramen ovale in carcinoid heart disease: The potential role for and risks of percutaneous closure prior to cardiothoracic surgery.

Neuroendocrine tumours (NETs) are rare but once metastasised, can lead to the release of vasoactive substances into the systemic circulation, and the classical features of carcinoid syndrome (CS) such as flushing and diarrhoea. A consequence of CS is carcinoid heart disease (CHD) which primarily affects the right-sided heart valves and can eventually lead to right heart failure. In this cohort, tricuspid and/or pulmonary valve replacement provides symptomatic relief. A patent foramen ovale (PFO) in patients with CHD can lead to the shunting of oxygen deficient blood to the systemic circulation causing hypoxaemia and reduced exercise tolerance. Additionally, the haemodynamic changes caused by regurgitant right-sided heart valves can increase the patency of a PFO allowing the passage of vasoactive substances to the systemic circulation thereby affecting the left-sided heart valves. We present data on the incidence of PFO in patients referred for surgery at our centre, in which the standard approach is to close the defect at time of cardiothoracic surgery. In addition, we present a series of four cases that highlight how the option of percutaneous PFO closure prior to open valve surgery may reduce haemodynamic instability and open a window of opportunity to enhance preoperative status. Percutaneous PFO closure then acts as a bridge to definitive cardiothoracic surgery, although there are risks in such an approach.

A Sticky Situation: An Uncommon Cardiac Complication of Cyanoacrylate Glue Injection.

This case report describes an uncommon cardiac complication related to the endoscopic injection of cyanoacrylate glue to treat gastric variceal bleeding. The presentation and management options are reviewed and compared with our step-by-step approach in a patient requiring a liver transplant. (Level of Difficulty: Advanced.).

Increased cardiac involvement in Fabry disease using blood-corrected native T1 mapping.

Fabry disease (FD) is a rare lysosomal storage disorder resulting in myocardial sphingolipid accumulation which is detectable by cardiovascular magnetic resonance as low native T1. However, myocardial T1 contains signal from intramyocardial blood which affects variability and consequently measurement precision and accuracy. Correction of myocardial T1 by blood T1 increases precision. We therefore deployed a multicenter study of FD patients (n = 218) and healthy controls (n = 117) to investigate if blood-correction of myocardial native T1 increases the number of FD patients with low T1, and thus reclassifies FD patients as having cardiac involvement. Cardiac involvement was defined as a native T1 value 2 standard deviations below site-specific means in healthy controls for both corrected and uncorrected measures. Overall low T1 was 135/218 (62%) uncorrected vs. 145/218 (67%) corrected (p = 0.02). With blood-correction, 13/83 previously normal patients were reclassified to low T1. This reclassification appears clinically relevant as 6/13 (46%) of reclassified had focal late gadolinium enhancement or left ventricular hypertrophy as signs of cardiac involvement. Blood-correction of myocardial native T1 increases the proportion of FD subjects with low myocardial T1, with blood-corrected results tracking other markers of cardiac involvement. Blood-correction may potentially offer earlier detection and therapy initiation, but merits further prospective studies.

The Role of Transthoracic Echocardiography for Assessment of Mortality in Patients with Carcinoid Heart Disease Undergoing Valve Replacement.

Patients with carcinoid heart disease (CHD) are referred for valve replacement if they have severe symptomatic disease or evidence of right ventricular (RV) failure and an anticipated survival of at least 12 months. Data are lacking, however, on the role of transthoracic echocardiography in predicting outcomes. We carried out a retrospective, single-centre cohort study of patients with a biopsy-confirmed neuroendocrine tumour (NET) and CHD undergoing valve replacement for severe valve disease and symptoms of right heart failure. The aim was to identify factors associated with postoperative mortality, both within one year of surgery and during long-term follow-up. Of 88 patients with NET, 49 were treated surgically (mean age: 64.4 ± 7.6 years; 55% male), of whom 48 had a bioprosthetic tricuspid valve replacement for severe tricuspid regurgitation; 39 patients had a pulmonary valve replacement. Over a median potential follow-up of 96 months (interquartile range: 56-125), there were 37 deaths, with 30-day and one-year mortality of 14% (n = 7) and 39% (n = 19), respectively. A significant relationship between RV size and one-year mortality was observed, with 57% of those with severe RV dilatation dying within a year of surgery, compared to 33% in those with normal RV size (p = 0.039). This difference remained significant in the time-to-event analysis of long-term survival (p = 0.008). RV size was found to reduce significantly with surgery (p < 0.001). Those with persisting RV dilatation (p = 0.007) or worse RV function (p = 0.001) on postoperative echocardiography had significantly shorter long-term survival. In this single-centre retrospective study of patients undergoing surgery for CHD, increasingly severe RV dilatation on preoperative echocardiography predicted adverse outcomes, yielding a doubling of the one-year mortality rate relative to normal RV size. These data support the possibility that early surgery might deliver greater long-term benefits in this patient cohort.

Adipose tissue function and insulin sensitivity in syndromic obesity of Bardet-Biedl syndrome.

BACKGROUND: Bardet-Biedl syndrome (BBS) is a rare autosomal recessive syndromic obesity of childhood onset among many other features. To date, the excess risk of metabolic complications of severe early-onset obesity in BBS remains controversial. In-depth investigation of adipose tissue structure and function with detailed metabolic phenotype has not been investigated yet. OBJECTIVE: To investigate adipose tissue function in BBS. DESIGN: A prospective cross-sectional study. MAIN OUTCOME MEASURE: To determine if there are differences in insulin resistance, metabolic profile, adipose tissue function and gene expression in patients with BBS compared to BMI-matched polygenic obese controls. METHOD: 9 adults with BBS and 10 controls were recruited from the national centre for BBS, Birmingham, UK. An in-depth study of adipose tissue structure and function along with insulin sensitivity was performed using hyperinsulinemic-euglycemic clamp studies, adipose tissue microdialysis, histology and RNA sequencing, and measurement of circulating adipokines and inflammatory biomarkers. RESULTS: Adipose tissue structure, gene expression and in vivo functional analysis between BBS and polygenic obesity cohorts were similar. Using hyperinsulinemic-euglycemic clamp and surrogate markers of insulin resistance, we found no significant differences in insulin sensitivity between BBS and obese controls. Furthermore, no significant changes were noted in an array of adipokines, cytokines, pro-inflammatory markers and adipose tissue RNA transcriptomic. CONCLUSION: Although childhood-onset extreme obesity is a feature of BBS, detailed studies of insulin sensitivity and adipose tissue structure and function are similar to common polygenic obesity. This study adds to the literature by suggesting that it is the quality and quantity of adiposity not the duration that drives the metabolic phenotype.