Long term outcome in patients with silent versus symptomatic ischaemia during dobutamine stress echocardiography

OBJECTIVES: To compare the long term prognosis of patients having silent versus symptomatic ischaemia during dobutamine stress echocardiography (DSE). DESIGN: Observational study. SETTING: Tertiary referral centre. PATIENTS: 931 patients who experienced stress induced myocardial ischaemia during DSE. RESULTS: Silent ischaemia was present in 643 of 931 patients (69%). The number of dysfunctional segments at rest (mean (SD) 9.6 (5.1) v 8.8 (5.0), p = 0.1) and of ischaemic segments (3.5 (2.2) v 3.8 (2.1), p = 0.2) was comparable in both groups. During a mean (SD) follow up of 5.5 (3.3) years, there were 169 (18%) cardiac deaths and 86 (9%) non-fatal infarctions. Multivariable Cox regression analysis showed age (hazard ratio (HR) 1.1, 95% confidence interval (CI) 1.02 to 1.05), previous myocardial infarction (HR 1.4, 95% CI 1.1 to 2.0), and number of ischaemic segments during the test (HR 2.0, 95% CI 1.0 to 3.7) as independent predictors of cardiac death and myocardial infarction. For every additional ischaemic segment there was a twofold increment in risk of late cardiac events. The annual cardiac death or myocardial infarction rate was 3.0% in patients with symptomatic ischaemia and 4.6% in patients with silent ischaemia (p < 0.01). Silent induced ischaemia was an independent predictor of cardiac death and myocardial infarction (HR 1.7, 95% CI 1.1 to 2.0). During follow up symptomatic patients were treated more often with cardioprotective therapy (p < 0.01) and coronary revascularisation (145 of 288 (50%) v 174 of 643 (27%), p < 0.001). CONCLUSIONS: Patients with silent ischaemia had a similar extent of myocardial ischaemia during DSE compared to patients with symptomatic ischaemia but received less cardioprotective treatment and coronary revascularisation and experienced a higher cardiac event rate

Self-assembled amyloid fibrils with controllable conformational heterogeneity

Amyloid fibrils are a hallmark of neurodegenerative diseases and exhibit a conformational diversity that governs their pathological functions. Despite recent findings concerning the pathological role of their conformational diversity, the way in which the heterogeneous conformations of amyloid fibrils can be formed has remained elusive. Here, we show that microwave-assisted chemistry affects the self-assembly process of amyloid fibril formation, which results in their conformational heterogeneity. In particular, microwave-assisted chemistry allows for delicate control of the thermodynamics of the self-assembly process, which enabled us to tune the molecular structure of ??-lactoglobulin amyloid fibrils. The heterogeneous conformations of amyloid fibrils, which can be tuned with microwave-assisted chemistry, are attributed to the microwave-driven thermal energy affecting the electrostatic interaction during the self-assembly process. Our study demonstrates how microwave-assisted chemistry can be used to gain insight into the origin of conformational heterogeneity of amyloid fibrils as well as the design principles showing how the molecular structures of amyloid fibrils can be controlledopen0

Grey zones in the supportive treatments of cardiac amyloidosis

Recent advances in the diagnosis and treatment of cardiac amyloidosis (CA) have translated into a longer life expectancy of patients and more challenging clinical scenarios. Compared to the past, patients with CA and heart failure (HF) currently encountered in clinical practice are a more heterogeneous population and require tailored strategies. The perception of CA as a treatable disease has opened new possibilities for the management of these patients, but many grey areas remain to be explored. The aim of this review is to provide practical suggestions for daily clinical activity in the management of challenging scenarios in CA, including the effectiveness and tolerability of evidence-based HF medication; rate vs. rhythm control in atrial fibrillation, thromboembolic risk, and anticoagulation therapies; replacement of severe aortic valve stenosis; the impact of implantable cardioverter defibrillator on survival; and the usefulness of cardiac resynchronization therapy

T1 mapping in cardiac MRI

Quantitative myocardial and blood T1 have recently achieved clinical utility in numerous pathologies, as they provide non-invasive tissue characterization with the potential to replace invasive biopsy. Native T1 time (no contrast agent), changes with myocardial extracellular water (edema, focal or diffuse fibrosis), fat, iron, and amyloid protein content. After contrast, the extracellular volume fraction (ECV) estimates the size of the extracellular space and identifies interstitial disease. Spatially resolved quantification of these biomarkers (so-called T1 mapping and ECV mapping) are steadily becoming diagnostic and prognostically useful tests for several heart muscle diseases, influencing clinical decision-making with a pending second consensus statement due mid-2017. This review outlines the physics involved in estimating T1 times and summarizes the disease-specific clinical and research impacts of T1 and ECV to date. We conclude by highlighting some of the remaining challenges such as their community-wide delivery, quality control, and standardization for clinical practice

Redefining the histopathologic profile of acute aortic syndromes: Clinical and prognostic implications

Objectives: The study objectives were to describe the aortic histopathologic substrates in patients with type A surgically treated acute aortic syndromes, to provide clinico-pathological correlations, and to identify the possible prognostic role of histology. Methods: We assessed the aortic wall degenerative or inflammatory alterations of 158 patients according to the histopathologic consensus documents. Moreover, we correlated these histologic patterns with the patients' clinical data and long-term follow-up for mortality, major aorta-related events, and nonaorta-related events (including cardiovascular ones). Results: We identified 2 histopathologic patterns: 122 patients (77%) with degenerative alterations and 36 patients (23%) with mixed degenerative-atherosclerotic lesions. Patients with mixed alterations were older (mean 69.6 \ub1 8.7 years vs 62.2 \ub1 12.4 years, P = .001) and more hypercholesterolemic (33.3% vs 13.9%, P = .017). The degenerative subgroup showed more intralamellar-mucoid extracellular matrix accumulation (86% vs 66.7%, P = .017) and a lower prevalence of translamellar collagen increase (9.8% vs 50%, P &lt; .001). Patients with mixed degenerative-atherosclerotic abnormalities more frequently had long-term nonaorta-related events compared with those with degenerative abnormalities alone (P = .046); no differences were found between the groups with respect to mortality, major aorta-related events, and cardiovascular nonaorta-related events. Conclusions: Although degenerative lesions of the medial layer were present in all specimens, substantial atherosclerosis coexisted in approximately one quarter of cases. Patients with mixed degenerative-atherosclerotic abnormalities had a coherent clinical risk profile, a clinical presentation frequently mimicking acute coronary syndrome, and a higher incidence of nonaorta-related events during follow-up. Histopathologic characterization may improve the long-term prognostic stratification of patients after surgical treatment. \ua9 2018 The American Association for Thoracic Surger

Influenza vaccination for immunocompromised patients: systematic review and meta-analysis from a public health policy perspective.

Immunocompromised patients are vulnerable to severe or complicated influenza infection. Vaccination is widely recommended for this group. This systematic review and meta-analysis assesses influenza vaccination for immunocompromised patients in terms of preventing influenza-like illness and laboratory confirmed influenza, serological response and adverse events

99mTc-DPD scintigraphy in immunoglobulin light chain (AL) cardiac amyloidosis

AIMS: Technetium-99m-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD scintigraphy) is recognized as highly accurate for the non-invasive diagnosis of transthyretin (ATTR) cardiac amyloidosis (CA). A proportion of patients with immunoglobulin light chain (AL) CA have also been reported to show cardiac 99mTc-DPD uptake. Herein, we assessed the frequency and degree of cardiac 99mTc-DPD uptake and its clinical significance among patients with AL CA. METHODS AND RESULTS: Between 2010 and 2017, 292 consecutive patients with AL CA underwent 99mTc-DPD scintigraphy and were included in this study: 114 (39%) had cardiac 99mTc-DPD uptake: grade 1 in 75%, grade 2 in 17%, and grade 3 in 8% of cases. Patients with cardiac 99mTc-DPD uptake had poorer cardiac systolic function and higher N-terminal pro-brain natriuretic peptide. No differences were noted in cardiac magnetic resonance parameters between patients with and without cardiac 99mTc-DPD uptake (N = 19 and 42, respectively). Patients with cardiac 99mTc-DPD uptake showed a trend to worse survival than those with no uptake (log-rank P = 0.056). Among 22 patients who underwent serial 99mTc-DPD scintigraphy, 5 (23%) showed reduction in the grade of cardiac uptake. CONCLUSIONS: In this large cohort of patients with AL CA, 99mTc-DPD scintigraphy ∼40% of cases showed cardiac uptake, including grade 2-3 in 10% of all patients (25% of those with cardiac 99mTc-DPD uptake). Cardiac 99mTc-DPD uptake was associated with poorer cardiac function and outcomes. These data highlight the critical importance of ruling out AL amyloidosis in all patients with cardiac 99mTc-DPD uptake to ensure such patients are not assumed to have ATTR CA

Amyloid deposits and fibrosis on left ventricular endomyocardial biopsy correlate with extracellular volume in cardiac amyloidosis

BACKGROUND: The relative contribution of amyloid and fibrosis to extracellular volume expansion in cardiac amyloidosis (CA) has never been defined. METHODS AND RESULTS: We included all patients diagnosed with amyloid light-chain (AL) or transthyretin cardiac amyloidosis at a tertiary referral center between 2014 to 2020 and undergoing a left ventricular endomyocardial biopsy. Patients (n=37) were more often men (92%), with a median age of 72 years (interquartile range, 68–81). Lambda-positive AL was found in 14 of 19 AL cases (38%) and kappa-positive AL in 5 of 19 (14%), while transthyretin was detected in the other 18 cases (48%). Amyloid deposits accounted for 15% of tissue sample area (10%–30%), without significant differences between AL and transthyretin amyloidosis. All patients displayed myocardial fibrosis, with a median extent of 15% of tissue samples (10%–23%; range, 5%–60%), in the absence of spatial overlap with amyloid deposits. Interstitial fibrosis was often associated with mild and focal subendocardial fibrosis. The extent of fibrosis or the combination of amyloidosis and fibrosis did not differ significantly between transthyretin amyloidosis and AL subgroups. In 20 patients with myocardial T1 mapping at cardiac magnetic resonance, the combined amyloid and fibrosis extent displayed a modest correlation with extracellular volume (r=0.661, P=0.001). The combined amyloid and fibrosis extent correlated with high-sensitivity troponin T (P=0.035) and N-terminal pro-B-type natriuretic peptide (P=0.002) serum levels. CONCLUSIONS: Extracellular spaces in cardiac amyloidosis are enlarged to a similar extent by amyloid deposits and fibrotic tissue. Their combination can better explain the increased extracellular volume at cardiac magnetic resonance and circulating biomarkers than amyloid extent alone

Narrowing the gap between eye care needs and service provision: the service-training nexus

<p>Abstract</p> <p>Background</p> <p>The provision of eye care in the developing world has been constrained by the limited number of trained personnel and by professional cultures. The use of personnel with specific but limited training as members of multidisciplinary teams has become increasingly important as health systems seek to extract better value from their investments in personnel. Greater positive action is required to secure more efficient allocation of roles and resources. The supply of professional health workers is a factor of the training system, so it stands to reason that more cost-effective, flexible and available education methods are needed. This paper presents a highly flexible competencies-based multiple entry and exit training system that matches and adapts training to the prevailing population and service needs and demands, while lifting overall standards over time and highlighting the areas of potential benefit.</p> <p>Methods</p> <p>Literature surveys and interviews in five continents were carried out. Based on this and the author's own experience, a encies-based multiple entry and exit scheme for eye care in a developing country was derived, modeled and critically reviewed by interested parties in one country.</p> <p>Results</p> <p>The scheme was shown to be highly cost-effective and readily adaptable to the anticipated eye care needs of the population. Eye care players in one selected country have commented favourably on the scheme.</p> <p>Conclusion</p> <p>The underlying principles used to derive this model can be applied to many eye care systems in many developing countries. The model can be used in other disciplines with similar constructs to eye care.</p