Case report: Neuronal intranuclear inclusion disease presenting with acute encephalopathy.

Neuronal intranuclear inclusion disease (NIID), a neurodegenerative disease previously thought to be rare, is increasingly recognized despite heterogeneous clinical presentations. NIID is pathologically characterized by ubiquitin and p-62 positive intranuclear eosinophilic inclusions that affect multiple organ systems, including the brain, skin, and other tissues. Although the diagnosis of NIID is challenging due to phenotypic heterogeneity, a greater understanding of the clinical and imaging presentations can improve accurate and early diagnosis. Here, we present three cases of pathologically proven adult-onset NIID, all presenting with episodes of acute encephalopathy with protracted workups and lengthy time between symptom onset and diagnosis. Case 1 highlights challenges in the diagnosis of NIID when MRI does not reveal classic abnormalities and provides a striking example of hyperperfusion in the setting of acute encephalopathy, as well as unique pathology with neuronal central chromatolysis, which has not been previously described. Case 2 highlights the progression of MRI findings associated with multiple NIID-related encephalopathic episodes over an extended time period, as well as the utility of skin biopsy for antemortem diagnosis.

One Minute of EEG Data Provides Sufficient and Reliable Data for Identifying Lewy Body Dementia.

OBJECTIVE: To determine the minimum duration of electroencephalography (EEG) data necessary to differentiate EEG features of Lewy body dementia (LBD), that is, dementia with Lewy bodies and Parkinson disease dementia, from non-LBD patients, that is, Alzheimer disease and Parkinson disease. METHODS: We performed quantitative EEG analysis for 16 LBD and 14 non-LBD patients. After artifact removal, a fast Fourier transform was performed on 90, 60, and thirty 2-second epochs to derive dominant frequency; dominant frequency variability; and dominant frequency prevalence. RESULTS: In LBD patients, there were no significant differences in EEG features derived from 90, 60, and thirty 2-second epochs (all P >0.05). There were no significant differences in EEG features derived from 3 different groups of thirty 2-second epochs (all P >0.05). When analyzing EEG features derived from ninety 2-second epochs, we found that LBD had significantly reduced dominant frequency, reduced dominant frequency variability, and reduced dominant frequency prevalence alpha compared with the non-LBD group (all P <0.05). These same differences were observed between the LBD and non-LBD groups when analyzing thirty 2-second epochs. CONCLUSIONS: There were no differences in EEG features derived from 1 minute versus 3 minutes of EEG data, and both durations of EEG data equally differentiated LBD from non-LBD.

Relationship between indexed aortic area and aortic diameter in bicuspid aortic valve aortopathy: A retrospective cohort study.

BACKGROUND: Aortic dissection is a life-threatening complication of bicuspid aortic valve (BAV)-associated aortopathy. In these populations, whilst prophylactic replacement of proximal thoracic aortic aneurysms (TAAs) is generally recommended at threshold diameters ≥5.5 cm, dissection may occur in smaller aortas. An alternative size-based parameter, the cross-sectional aortic area/patient height ratio (indexed aortic area, IAA), correlates with increased dissection risk at abnormal values > 10 cm2/m. We sought to assess the utility of the IAA in identifying at-risk BAV-associated TAAs with abnormal IAA, albeit with sub-threshold aortic diameter. MATERIALS AND METHODS: We retrospectively identified 69 patients with BAV-associated TAAs who underwent surgical repair between 2010 and 2016. Aortic diameter was measured on pre-operative imaging, and IAA calculated, at the mid-sinus of Valsalva, sino-tubular junction and mid-ascending aorta for each patient. We determined proportions of aneurysms with IAA >10 cm2/m, median IAAs corresponding to aortic diameters <4.0 cm, 4.0-4.5 cm, 4.5-5.0 cm, 5.0-5.5 cm and >5.5 cm, and median aortic diameters corresponding to an abnormal IAA. RESULTS: 50.9%, 12.5% and 64.6% of aneurysms at the sinus of Valsalva, sino-tubular junction and mid-ascending aorta, respectively, had an abnormal IAA. 51.9% and 88.9% of patients with aortic diameter 4.5-5.0 cm and 5.0-5.5 cm, respectively, had an abnormal IAA. In aneurysms with abnormal IAA involving the sinus of Valsalva, sino-tubular junction, and mid-ascending aorta, median aortic diameters were 4.98 cm, 5.04 cm and 5.11 cm, respectively. Overall, 57/72 (79.2%) at-risk aneurysms with IAA >10 cm2/m had diameters smaller than the 5.5 cm guideline cut-off for surgical intervention. CONCLUSION: Significant proportions of BAV-associated TAAs are at increased risk of aortic dissection attending an IAA >10 cm2/m, whilst not fulfilling the size criteria indicating aortic surgery in contemporary guidelines. Further analysis of IAA in larger BAV cohorts is necessary to clarify its role in patient selection and optimal timing for prophylactic aortic replacement.

Assessing the methodology used to study the ascending aorta haemodynamics in bicuspid aortic valve.

Aims: Modern imaging techniques provide evermore-detailed anatomical and physiological information for use in computational fluid dynamics to predict the behaviour of physiological phenomena. Computer modelling can help plan suitable interventions. Our group used magnetic resonance imaging and computational fluid dynamics to study the haemodynamic variables in the ascending aorta in patients with bicuspid aortic valve before and after isolated tissue aortic valve replacement. Computer modelling requires turning a physiological model into a mathematical one, solvable by equations that undergo multiple iterations in four dimensions. Creating these models involves several steps with manual inputs, making the process prone to errors and limiting its inter- and intra-operator reproducibility. Despite these challenges, we created computational models for each patient to study ascending aorta blood flow before and after surgery. Methods and results: Magnetic resonance imaging provided the anatomical and velocity data required for the blood flow simulation. Patient-specific in- and outflow boundary conditions were used for the computational fluid dynamics analysis. Haemodynamic variables pertaining to blood flow pattern and derived from the magnetic resonance imaging data were calculated. However, we encountered problems in our multi-step methodology, most notably processing the flow data. This meant that other variables requiring computation with computational fluid dynamics could not be calculated. Conclusion: Creating a model for computational fluid dynamics analysis is as complex as the physiology under scrutiny. We discuss some of the difficulties associated with creating such models, along with suggestions for improvements in order to yield reliable and beneficial results.

The EXCEL Trial: The Surgeons' Perspective.

There have been several investigations comparing the efficacy of percutaneous coronary intervention and coronary artery bypass grafting surgery for treatment of left main stem disease. This includes the Evaluation of XIENCE versus Coronary Artery Bypass Graft Surgery for Effectiveness of Left Main Revascularizaton (EXCEL) trial, which has garnered significant controversy surrounding its experimental design and reporting of its results. The authors review the methodology, results, caveats and statements on the EXCEL trial. They also review the other trials in the management of left main stem disease comparing percutaneous coronary intervention with coronary artery bypass grafting, as well as the SYNTAX score and its role in future guidelines for revascularisation. These findings have significant implications for current practice, influencing the growing role for multidisciplinary team meeting and allowing clinicians and patients to make the right choice.

The role of fractional flow reserve in coronary artery bypass graft surgery: a meta-analysis.

OBJECTIVES: Fractional flow reserve (FFR) measures the drop in perfusion pressure across a stenosis, therefore representing its physiological effect on myocardial blood flow. Its use is widespread in percutaneous coronary interventions, though its role in coronary artery bypass graft (CABG) surgery remains uncertain. This systematic review and meta-analysis aims to evaluate current evidence on outcomes following FFR-guided CABG compared to angiography-guided CABG. METHODS: A literature search was conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to identify all relevant articles. Patient demographics and characteristics were extracted. The following outcomes were analysed: repeat revascularization, myocardial infarction (MI) and all-cause mortality. Pooled relative risks were analysed and their 95% confidence intervals (CIs) were estimated using random-effects models; P-value <0.05 was considered statistically significant. Heterogeneity was assessed with Cochran's Q score and quantified by I2 index. RESULTS: Nine studies with 1146 patients (FFR: 574, angiography: 572) were included. There was no difference in MI or repeat revascularization between the 2 groups (relative risk 0.76, 95% CI 0.41-1.43; P = 0.40, and relative risk 1.28, 95% CI 0.75-2.19; P = 0.36, respectively). There was a significant reduction in all-cause mortality in the FFR-guided CABG group compared to angiography-guided CABG, which was not specifically cardiac related (relative risk 0.58, 95% CI 0.38-0.90; P = 0.02). CONCLUSIONS: There was no reduction in repeat revascularization or postoperative MI with FFR. In this fairly small cohort, FFR-guided CABG provided a reduction in mortality, but this was not reported to be due to cardiac causes. There may be a role for FFR in CABG, but large-scale randomized trials are required to establish its value.

Haemodynamic assessment of bicuspid aortic valve aortopathy: a systematic review of the current literature.

Both genetic and haemodynamic theories explain the aetiology, progression and optimal management of bicuspid aortic valve aortopathy. In recent years, the haemodynamic theory has been explored with the help of magnetic resonance imaging and computational fluid dynamics. The objective of this review was to summarize the findings of these investigations with focus on the blood flow pattern and associated variables, including flow eccentricity, helicity, flow displacement, cusp opening angle, systolic flow angle, wall shear stress (WSS) and oscillatory shear index. A structured literature review was performed from January 1990 to January 2018 and revealed the following 3 main findings: (i) the bicuspid aortic valve is associated with flow eccentricity and helicity in the ascending aorta compared to healthy and diseased tricuspid aortic valve, (ii) flow displacement is easier to obtain than WSS and has been shown to correlate with valve morphology and type of aortopathy and (iii) the stenotic bicuspid aortic valve is associated with elevated WSS along the greater curvature of the ascending aorta, where aortic dilatation and aortic wall thinning are commonly found. We conclude that new haemodynamic variables should complement ascending aorta diameter as an indicator for disease progression and the type and timing of intervention. WSS describes the force that blood flow exerts on the vessel wall as a function of viscosity and geometry of the vessel, making it a potentially more reliable marker of disease progression.

Fate of the Aortic Arch Following Surgery on the Aortic Root and Ascending Aorta in Bicuspid Aortic Valve.

BACKGROUND: Recent guidelines support more aggressive surgery for aneurysms of the ascending aorta and root in patients with bicuspid aortic valve. However, the fate of the arch after surgery of the root and ascending aorta is unknown. We set out to assess outcomes following root and ascending aortic surgery and subsequent growth of the arch. METHODS: Between 2005 and 2016, 536 consecutive patients underwent surgery for aneurysm of the root and ascending aorta; 168 had bicuspid aortic valve. Patients with dissection were excluded. Arch diameter was measured before and after surgery, at 6 months and then annually. RESULTS: Of 168 patients, 127 (75.6%) had aortic root replacement and 41 (24.4%) had ascending replacement. Mean age was 57 ± 12.8 years, 82.7% were men, and 5 operations were performed during pregnancy. There was 1 (0.6%) hospital death. One (0.6%) patient had a stroke and 1 (0.6%) had resternotomy for bleeding. Median intensive care unit and hospital stays were 1 and 6 days, respectively. Follow-up was complete for 94% at a median of 5.9 years (range, 1 to 139 months). Aortic arch diameter was 2.9 cm preoperatively and 3.0 cm at follow-up. There was 97% freedom from reoperation and none of the patients required surgery on the arch. CONCLUSIONS: Prophylactic arch replacement during aortic root and ascending aortic surgery in patients with bicuspid aortic valve is not supported. Our data do not support long-term surveillance of the rest of the aorta in this population.

Analysis of aortic area/height ratio in patients with thoracic aortic aneurysm and Type A dissection.

OBJECTIVES: Significant proportions of aortic dissections occur at aortic diameters <5.5 cm. By indexing aortic area to height and correlating with absolute aortic diameter, we sought to identify those aneurysm patients with aortic diameters <5.5 cm who do not meet current size thresholds for surgery, yet with corresponding abnormal indexed aortic areas (IAAs) >10 cm2/m, are at increased risk of aortic complications. METHODS: IAAs were calculated at 3 aortic locations in 187 aneurysm and 66 dissection patients operated on between 2010 and 2016 at our tertiary aortic centre. Proportions of patients with IAA >10 cm2/m, mean IAAs corresponding to aortic diameters <4.0 cm, 4.0-4.5 cm, 4.5-5.0 cm, 5.0-5.5 cm and >5.5 cm, and mean aortic diameters corresponding to IAAs 10-12 cm2/m, 12-14 cm2/m and >14 cm2/m were determined. RESULTS: Proportions of patients with abnormal IAAs were similar in both groups. In all, 49.1% of aneurysm patients with aortic diameters 4.5-5.0 cm, and 98.5% with aortic diameters 5.0-5.5 cm had abnormal IAAs. Out of 200 separate aneurysms with IAAs >10 cm2/m between the mid-sinus and mid-ascending aorta, 139 (69.5%) would not warrant surgery according to existing guidelines. CONCLUSIONS: Using the IAA, we identified a significant proportion of patients with thoracic aortic aneurysms who are at increased risk of aortic complications, despite current aortic guidelines not endorsing surgical intervention in this group. Our data suggests the IAA may be useful in preoperative risk evaluation and as a criterion for surgery.

Simulator Teaching of Cardiopulmonary Bypass Complications: A Prospective, Randomized Study.

OBJECTIVE: Complications of cardiopulmonary bypass (CPB) are rare, but life-threatening events that need prompt and rehearsed actions involving a team. This is not adequately taught to cardiothoracic surgical trainees. The objective of this study was to assess the knowledge of cardiothoracic trainees required to manage these events after simulation-based vs. lecture-based teaching. PARTICIPANTS AND DESIGN: Totally, 17 cardiac surgical trainees with no formal teaching in intraoperative complications of CPB management were randomly assigned by computer to either a study group receiving simulation-based complications of CPB teaching via the Orpheus simulator (n = 9) or a control group receiving complications of CPB teaching via a lecture (n = 8). Each subject undertook a written test comprising 20 multiple choice questions on complications of CPB before and after teaching. Trainees were then asked to rate their satisfaction with each session from 1 to 5, with 5 being most satisfied. SETTING: St George Simulation and Clinical Skills Laboratory, St George's Hospital, London. RESULTS: There was no significant difference in the pretest scores between the 2 groups (p = 0.29). After teaching, both groups showed a statistically significant improvement in their knowledge (p < 0.05). The trainees in the simulation group performed better than the lecture-based group; however, this was not statistically significant (p = 0.21). Satisfaction levels in both the lecture session and the simulation session were very high with means of 4.4/5 and 4.8/5, respectively. CONCLUSION: Despite the familiarity with CPB during surgery, the simulation group performed at least as well as the lecture group. Cardiothoracic trainees would benefit from formal teaching of complications of CPB management via either learning modality being incorporated into their training.

A Survey of Cardiothoracic Surgical Training in the United Kingdom: Realities of a 6-Year Integrated Training Program.

BACKGROUND: In recent years, cardiothoracic (CT) surgical training has faced several challenges, including a reduction in working hours and trainees favoring shorter training programs. We carried out a national survey in the United Kingdom (UK) to assess the CT 6-year training program. METHODS: All CT trainees in the UK (n = 121) were sent an online survey. This was combined with a debate at the Society for CT Surgery of Great Britain and Ireland. RESULTS: Ninety-one (75.2%) of all trainees responded. Despite 56 (68.1%) being rostered for more than a 48-hour week, 31 (34.1%) of all trainees work an extra 10 hours. The majority (56, 61.5%) thought that on-calls and night duty are useful. Just over half of the trainees (47, 51.6%) spend at least 2 full days in the operating room, but 79 (86.8%) thought that this is too little and would spend voluntary time operating. Simulation of operations is thought to be useful; however, few thought that this should take more precedence in their training program. The majority of trainees thought that the current assessment of surgical training is suboptimal and does not examine surgical skill. Similarly, the majority thought that a defined number of operations is required before qualification. CONCLUSIONS: Trainees remain committed to their profession and are willing to dedicate more time perfecting their art. They believe that despite wanting extra operating experience, they will be ready for independent practice at the completion of their training. It rests with training bodies to find alternative assessments for surgical ability and to define experience at the exit point of training.

Optimal thromboprophylaxis following bioprosthetic aortic valve replacement: still a matter of debate?

Optimal thromboprophylaxis following bioprosthetic aortic valve replacement (AVR) remains controversial. The main objective, which is the effective prevention of central nervous or peripheral embolic events, especially in the early postoperative period, will have to be weighed against the haemorrhagic risk that is associated with the utilization of different antithrombotic regimes. Most governing bodies in cardiovascular medicine have issued recommendations on thromboprophylaxis after the surgical implantation of aortic bioprostheses. However, the level of evidence to support these recommendations remains low, largely due to the inherent limitations of conducting appropriately randomized and adequately powered clinical research in this area. It is apparent from the recent surveys and large registries that there is a great variability in antithrombotic practice at an institutional or individual-clinician level reflecting this controversy and the lack of robust evidence. While organizational, financial or conceptual limitations could hinder the conduct and availability of conclusive research on optimal thromboprophylaxis after aortic bioprosthesis, it is imperative that all evidence is presented in a systematic way in order to assist the decision-making for the modern clinician. In this review, we provide an outline of the current recommendations for thromboprophylaxis, followed by a comprehensive and analytical presentation of all comparative studies examining anticoagulation vs. antiplatelet therapy after bioprosthetic AVR.

Aspergillus endocarditis: a case of near complete left ventricular outflow obstruction.

A 60-year old woman presented with dyspnoea and fatigue. She was frail and cachectic (BMI 17.5) with a pancytopenia. Previously she had received chemotherapy for chronic lymphatic leukaemia. She relapsed one year ago necessitating a reduced intensity conditioning allogeneic haematopoietic cell transplantation. Subsequently, graft versus host disease required high-dose immunosuppressants. Computerized tomography on admission showed bilateral lung nodules and a suspicious cardiac mass. Bronchial biopsies demonstrated abundant hypae consistent with Aspergillus fumigatus infection. Echocardiography demonstrated a large fungus ball attached to the right coronary cusp of the aortic valve with near complete obliteration of the left ventricular outflow tract. Due to the high risk of embolization this was resected under cardiopulmonary bypass. The mass was attached subvalvularly to the ventricular septal free wall and eroding through it. It peeled off leaving intact aortic leaflets. Unresectable fungal deposits were discovered on the interventricular septum, the left ventricle free wall and posterior aortic wall. High-dose systemic antifungal therapy (Voriconazole and Amphoteracin B) was given for 4 months. After discharge she remained well till a 4-month follow-up, after which she eventually succumbed to her disease. We discuss the clinical difficulties in managing patients with fungal infective endocarditis and present a brief review of cardiac aspergillosis management.

Transapical transcatheter aortic valve implantation in a complex aortic surgical patient: A case involving the youngest valve-in-valve implantation with a 29 mm transcather valve.

The present article reports a case involving a 29-year-old man who developed severe cardiac failure (New York Heart Association class IV). He had a complex surgical history, beginning with the repair of an anterior sinus of Valsalva aneurysm and closure of a ventricular septal defect at eight months of age. His residual Valsalva aneurysm and mixed aortic valve disease necessitated mechanical aortic valve replacement at 14 years of age. One year later, he developed coagulase-negative staphylococcal prosthetic valve infective endocarditis, necessitating an additional replacement of his valve with a pulmonary homograft. Subsequent follow-up revealed a dilated ascending aorta (6 cm) and increased regurgitation through his homograft, with significant dilation of the left ventricle. At 20 years of age, he underwent excision of the aneurysmal ascending aorta and arch of the aorta, and the aortic valve was replaced with a 29 mm bioprosthetic valve. This proved satisfactory for nine years until he presented at Guy's and St Thomas' National Health Services Foundation Trust (London, United Kingdom) with severe aortic regurgitation. His logistic EuroScore was 5.9 and Parsonnet score was 17 but, due to extensive previous surgery, he was considered and accepted for transcatheter aortic valve implantation. A 29 mm Edwards Sapien valve (Edwards Lifesciences, USA) was successfully implanted using a valve-in-valve procedure. The patient remained well and symptom free at early follow-up. Technical aspects of this complex adult congenital case that, to the authors' knowledge is the youngest case of transcatheter aortic valve implantation and the first 29 mm valve-in-valve procedure, are discussed.

Strategies in the surgical management of atrial fibrillation.

Atrial fibrillation (AF) is associated with substantial morbidity, mortality, and economic burden and confers a lifetime risk of up to 25%. Current medical management involves thromboembolism prevention, rate, and rhythm control. An increased understanding of AF pathophysiology has led to enhanced pharmacological and medical therapies; however this is often limited by toxicity, variable symptom control, and inability to modulate the atrial substrate. Surgical AF ablation has been available since the original description of the Cox Maze procedure, either as a standalone or concomitant intervention. Advances in novel energy delivery systems have allowed the development of less technically demanding procedures potentially eliminating the need for median sternotomy and cardiopulmonary bypass. Variations in the definition, duration, and reporting of AF have produced methodological limitations impacting on the validity of interstudy comparisons. Standardization of these parameters may, in future, allow us to further evaluate clinical endpoints and establish the efficacy of these techniques.

Primary cardiac pheochromocytoma with multiple endocrine neoplasia.

PURPOSE: Cardiac pheochromocytoma with multiple endocrine neoplasia syndrome (MENS) is rare. We present a rare case of concurrent cardiac pheochromocytoma and pituitary adenoma, a rare variant of the MEN syndromes and a review of the literature with special emphasis on diagnosis and treatment. METHODS: Different from the single MENS type I or type II, Variant MENS' symptoms and signs are so nontypical that it is easy to make a misdiagnosis or missed diagnosis. One patient with variant MENS was treated surgically and relevant case data were collected. RESULTS: The perioperative course was uneventful. At 24-month follow-up, catecholamine levels returned to normal and no symptoms of pheochromocytoma was found. CONCLUSIONS: Cardiac pheochromocytoma with Multiple Endocrine Neoplasia can be treated by operation with good prognosis. Surgical removal to provide relief or effective control of symptoms is the treatment of choice.

Protective effect of epicardial adiponectin on atrial fibrillation following cardiac surgery.

OBJECTIVE: Inflammation has been implicated in the pathogenesis of postoperative atrial fibrillation (AF). Adipose tissue secretes both pro-inflammatory cytokines such as interleukin-6 (IL-6) and anti-inflammatory mediators such as adiponectin. We set out to examine the association of adiponectin and IL-6, both circulating and locally produced by the epicardial adipose tissue, with AF development after cardiac surgery. METHODS: A total of 90 consecutive patients undergoing cardiac surgery were evaluated. Blood samples were collected before induction of anaesthesia. Epicardial fat was obtained upon commencement of cardiopulmonary bypass. IL-6 and adiponectin levels were determined in serum and supernatant of epicardial adipose tissue organ cultures with two-site enzyme-linked immunosorbent assay (ELISA). Heart rhythm was assessed with continuous tele-monitoring for 72 h postoperatively, and with 6-hourly clinical examinations and daily electrocardiograms (ECGs) thereafter. RESULTS: A total of 36 patients developed postoperative AF (40%). Baseline-serum IL-6 and adiponectin were not associated with AF (p = 0.86 and 0.95, respectively). Epicardial adipose tissue IL-6 levels did not correlate with the development of the arrhythmia either (p = 0.37). However, epicardial adiponectin release was lower in patients who developed AF than in those who remained in sinus rhythm (76 (interquartile range (IQR) 35-98) vs 53 ((IQR) 35-69) ng h(-1)g(-1) of tissue cultured, p = 0.066). Following linear regression, the association of epicardial adiponectin with AF almost reached statistical significance (p = 0.066). Multivariate logistic regression analysis of identified risk factors for AF, with the inclusion of epicardial adiponectin as an independent variable, revealed increased age (odds ratio (OR) 1.09, 95% confidence interval (CI) 1.02-1.17, p = 0.013) and epicardial adiponectin levels (OR 0.98, 95% CI 0.97-1.00, p = 0.054) as independent predictors of postoperative AF. CONCLUSIONS: Increased epicardial adiponectin is associated with maintenance of sinus rhythm following cardiac surgery. This reinforces the inflammatory hypothesis in the pathogenesis of postoperative AF and may represent a novel therapeutic target for its effective prevention.

Surgical aortic-valve replacement with a transcatheter implant.

We describe a bailout procedure when surgical aortic-valve replacement was not possible due to severe calcification of the ascending aorta and the root and a very small annulus. A 21-mm CoreValve Revalving prosthesis was inserted via the aortotomy in the presence of a mitral prosthesis.