Showing papers by "St Bartholomew's Hospital published in 2018"

Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy

Abstract: Background Transthyretin amyloid cardiomyopathy is caused by the deposition of transthyretin amyloid fibrils in the myocardium. The deposition occurs when wild-type or variant transthyretin becomes unstable and misfolds. Tafamidis binds to transthyretin, preventing tetramer dissociation and amyloidogenesis. Methods In a multicenter, international, double-blind, placebo-controlled, phase 3 trial, we randomly assigned 441 patients with transthyretin amyloid cardiomyopathy in a 2:1:2 ratio to receive 80 mg of tafamidis, 20 mg of tafamidis, or placebo for 30 months. In the primary analysis, we hierarchically assessed all-cause mortality, followed by frequency of cardiovascular-related hospitalizations according to the Finkelstein–Schoenfeld method. Key secondary end points were the change from baseline to month 30 for the 6-minute walk test and the score on the Kansas City Cardiomyopathy Questionnaire–Overall Summary (KCCQ-OS), in which higher scores indicate better health status. Results In the prim...

Post-contrast acute kidney injury - Part 1: Definition, clinical features, incidence, role of contrast medium and risk factors : Recommendations for updated ESUR Contrast Medium Safety Committee guidelines.

Abstract: The Contrast Media Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR) has updated its 2011 guidelines on the prevention of post-contrast acute kidney injury (PC-AKI). The results of the literature review and the recommendations based on it, which were used to prepare the new guidelines, are presented in two papers. Topics reviewed include the terminology used, the best way to measure eGFR, the definition of PC-AKI, and the risk factors for PC-AKI, including whether the risk with intravenous and intra-arterial contrast medium differs. • PC-AKI is the preferred term for renal function deterioration after contrast medium. • PC-AKI has many possible causes. • The risk of AKI caused by intravascular contrast medium has been overstated. • Important patient risk factors for PC-AKI are CKD and dehydration.

Evolving Concepts in Dilated Cardiomyopathy

Abstract: Dilated cardiomyopathy (DCM) represents a particular aetiology of systolic heart failure that frequently has a genetic background and usually affects young patients with few co-morbidities. The prognosis of DCM has improved substantially during the last decades due to more accurate aetiological characterization, the red-flag integrated approach to the disease, early diagnosis through systematic familial screening, and the concept of DCM as a dynamic disease requiring constant optimization of medical and non-pharmacological evidence-based treatments. However, some important issues in clinical management remain unresolved, including the role of cardiac magnetic resonance for diagnosis and risk categorization and the interaction between genotype and clinical phenotype, and arrhythmic risk stratification. This review offers a comprehensive survey of these and other emerging issues in the clinical management of DCM, providing where possible practical recommendations.

IMmotion151: A Randomized Phase III Study of Atezolizumab Plus Bevacizumab vs Sunitinib in Untreated Metastatic Renal Cell Carcinoma (mRCC)

Abstract: 578Background: Atezolizumab (atezo; anti–PD-L1) + bevacizumab (bev; anti-VEGF) showed first-line (1L) anti-tumor activity with a manageable safety profile in PD-L1+ mRCC pts in a Phase II study (McDermott ASCO-GU 2017). Here we describe the first randomized Phase III trial of a PD-L1/PD-1 pathway inhibitor combined with an anti-VEGF agent in 1L mRCC. Methods: IMmotion151 (NCT02420821) enrolled treatment-naive pts regardless of prognostic risk group randomized 1:1 to receive atezo 1200 mg IV q3w + bev 15 mg/kg IV q3w or sunitinib (sun) 50 mg PO QD 4 wk on/2 wk off. Pts were stratified by PD-L1 status (< 1% vs ≥ 1% PD-L1 expression on tumor-infiltrating immune cells [IC]; SP142 IHC assay). Coprimary endpoints: progression-free survival (PFS; by investigator per RECIST v1.1) in PD-L1+ pts (≥ 1% IC) and overall survival (OS) in intent-to-treat (ITT) pts. Secondary endpoints included PFS in ITT pts, ORR and DOR. Results: Baseline characteristics were comparable between arms within PD-L1+ (40% of ITT) and ITT p...

Post-contrast acute kidney injury. Part 2: risk stratification, role of hydration and other prophylactic measures, patients taking metformin and chronic dialysis patients : Recommendations for updated ESUR Contrast Medium Safety Committee guidelines.

Abstract: The Contrast Media Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR) has updated its 2011 guidelines on the prevention of post-contrast acute kidney injury (PC-AKI) The results of the literature review and the recommendations based on it, which were used to prepare the new guidelines, are presented in two papers Topics reviewed include stratification of PC-AKI risk, the need to withdraw nephrotoxic medication, PC-AKI prophylaxis with hydration or drugs, the use of metformin in diabetic patients receiving contrast medium and the need to alter dialysis schedules in patients receiving contrast medium • In CKD, hydration reduces the PC-AKI risk • Intravenous normal saline and intravenous sodium bicarbonate provide equally effective prophylaxis • No drugs have been consistently shown to reduce the risk of PC-AKI • Stop metformin from the time of contrast medium administration if eGFR < 30 ml/min/173 m 2 • Dialysis schedules need not change when intravascular contrast medium is given

Rewiring urea cycle metabolism in cancer to support anabolism

Abstract: Cancer cells reprogramme metabolism to maximize the use of nitrogen and carbon for the anabolic synthesis of macromolecules that are required during tumour proliferation and growth. To achieve this aim, one strategy is to reduce catabolism and nitrogen disposal. The urea cycle (UC) in the liver is the main metabolic pathway to convert excess nitrogen into disposable urea. Outside the liver, UC enzymes are differentially expressed, enabling the use of nitrogen for the synthesis of UC intermediates that are required to accommodate cellular needs. Interestingly, the expression of UC enzymes is altered in cancer, revealing a revolutionary mechanism to maximize nitrogen incorporation into biomass. In this Review, we discuss the metabolic benefits underlying UC deregulation in cancer and the relevance of these alterations for cancer diagnosis and therapy.

Reappraising myocardial fibrosis in severe aortic stenosis: an invasive and non-invasive study in 133 patients.

Abstract: Aims To investigate myocardial fibrosis (MF) in a large series of severe aortic stenosis (AS) patients using invasive biopsy and non-invasive imaging. Methods and results One hundred thirty-three patients with severe, symptomatic AS accepted for surgical aortic valve replacement underwent cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) and extracellular volume fraction (ECV) quantification. Intra-operative left ventricular (LV) biopsies were performed by needle or scalpel, yielding tissue with (n = 53) and without endocardium (n = 80), and compared with 10 controls. Myocardial fibrosis occurred in three patterns: (i) thickened endocardium with a fibrotic layer; (ii) microscopic scars, with a subendomyocardial predominance; and (iii) diffuse interstitial fibrosis. Collagen volume fraction (CVF) was elevated (P < 0.001) compared with controls, and higher (P < 0.001) in endocardium-containing samples with a decreasing CVF gradient from the subendocardium (P = 0.001). Late gadolinium enhancement correlated with CVF (P < 0.001) but not ECV. Both LGE and ECV correlated independently (P < 0.001) with N-terminal pro-brain natriuretic peptide and high-sensitivity-troponin T. High ECV was also associated with worse LV remodelling, left ventricular ejection fraction and functional capacity. Combining high ECV and LGE better identified patients with more adverse LV remodelling, blood biomarkers and histological parameters, and worse functional capacity than each parameter alone. Conclusion Myocardial fibrosis in severe AS is complex, but three main patterns exist: endocardial fibrosis, microscars (mainly in the subendomyocardium), and diffuse interstitial fibrosis. Neither histological CVF nor the CMR parameters ECV and LGE capture fibrosis in its totality. A combined, multi-parametric approach with ECV and LGE allows best stratification of AS patients according to the response of the myocardial collagen matrix.

Echocardiographic assessment of pulmonary hypertension: a guideline protocol from the British Society of Echocardiography.

Abstract: Pulmonary hypertension is defined as a mean arterial pressure of ≥25 mmHg as confirmed on right heart catheterisation. Traditionally, the pulmonary arterial systolic pressure has been estimated on echo by utilising the simplified Bernoulli equation from the peak tricuspid regurgitant velocity and adding this to an estimate of right atrial pressure. Previous studies have demonstrated a correlation between this estimate of pulmonary arterial systolic pressure and that obtained from invasive measurement across a cohort of patients. However, for an individual patient significant overestimation and underestimation can occur and the levels of agreement between the two is poor. Recent guidance has suggested that echocardiographic assessment of pulmonary hypertension should be limited to determining the probability of pulmonary hypertension being present rather than estimating the pulmonary artery pressure. In those patients in whom the presence of pulmonary hypertension requires confirmation, this should be done with right heart catheterisation when indicated. This guideline protocol from the British Society of Echocardiography aims to outline a practical approach to assessing the probability of pulmonary hypertension using echocardiography and should be used in conjunction with the previously published minimum dataset for a standard transthoracic echocardiogram.

Outcomes of Patients With Asymptomatic Aortic Stenosis Followed Up in Heart Valve Clinics.

Abstract: Importance The natural history and the management of patients with asymptomatic aortic stenosis (AS) have not been fully examined in the current era. Objective To determine the clinical outcomes of patients with asymptomatic AS using data from the Heart Valve Clinic International Database. Design, Setting, and Participants This registry was assembled by merging data from prospectively gathered institutional databases from 10 heart valve clinics in Europe, Canada, and the United States. Asymptomatic patients with an aortic valve area of 1.5 cm2or less and preserved left ventricular ejection fraction (LVEF) greater than 50% at entry were considered for the present analysis. Data were collected from January 2001 to December 2014, and data were analyzed from January 2017 to July 2018. Main Outcomes and Measures Natural history, need for aortic valve replacement (AVR), and survival of asymptomatic patients with moderate or severe AS at entry followed up in a heart valve clinic. Indications for AVR were based on current guideline recommendations. Results Of the 1375 patients included in this analysis, 834 (60.7%) were male, and the mean (SD) age was 71 (13) years. A total of 861 patients (62.6%) had severe AS (aortic valve area less than 1.0 cm2). The mean (SD) overall survival during medical management (mean [SD] follow up, 27 [24] months) was 93% (1%), 86% (2%), and 75% (4%) at 2, 4, and 8 years, respectively. A total of 104 patients (7.6%) died under observation, including 57 patients (54.8%) from cardiovascular causes. The crude rate of sudden death was 0.65% over the duration of the study. A total of 542 patients (39.4%) underwent AVR, including 388 patients (71.6%) with severe AS at study entry and 154 (28.4%) with moderate AS at entry who progressed to severe AS. Those with severe AS at entry who underwent AVR did so at a mean (SD) of 14.4 (16.6) months and a median of 8.7 months. The mean (SD) 2-year and 4-year AVR-free survival rates for asymptomatic patients with severe AS at baseline were 54% (2%) and 32% (3%), respectively. In those undergoing AVR, the 30-day postprocedural mortality was 0.9%. In patients with severe AS at entry, peak aortic jet velocity (greater than 5 m/s) and LVEF (less than 60%) were associated with all-cause and cardiovascular mortality without AVR; these factors were also associated with postprocedural mortality in those patients with severe AS at baseline who underwent AVR (surgical AVR in 310 patients; transcatheter AVR in 78 patients). Conclusions and Relevance In patients with asymptomatic AS followed up in heart valve centers, the risk of sudden death is low, and rates of overall survival are similar to those reported from previous series. Patients with severe AS at baseline and peak aortic jet velocity of 5.0 m/s or greater or LVEF less than 60% have increased risks of all-cause and cardiovascular mortality even after AVR. The potential benefit of early intervention should be considered in these high-risk patients.

British Thoracic Society Guideline for the investigation and management of malignant pleural mesothelioma

Abstract: Section 3: Clinical features which predict the presence of mesothelioma Recommendations Section 4: Staging systems Recommendation Section 5: Imaging modalities for diagnosing and staging Recommendations Section 6: Pathological diagnosis Recommendations

Is the use of unrelated donor transplantation leveling off in Europe? The 2016 European Society for Blood and Marrow Transplant activity survey report.

Abstract: Hematopoietic cell transplantation (HCT) is an established procedure for acquired and congenital disorders of the hematopoietic system. In 2016, there was a tendency for continued activity in this field with 43,636 HCT in 39,313 patients [16,507 allogeneic (42%), 22,806 autologous (58%)] reported by 679 centers in 49 countries in 2016. The main indications were myeloid malignancies 9547 (24%; 96% allogeneic), lymphoid malignancies 25,618 (65%; 20% allogeneic), solid tumors 1516 (4%; 2% allogeneic), and non-malignant disorders 2459 (6%; 85% allogeneic). There was a remarkable leveling off in the use of unrelated donor HCT being replaced by haploidentical HCT. Continued growth in allogeneic HCT for marrow failure, AML, and MPN was seen, whereas MDS appears stable. Allogeneic HCT for lymphoid malignancies vary in trend with increases for NHL and decreases for Hodgkin lymphoma and myeloma. Trends in CLL are not clear, with recent increases after a decrease in activity. In autologous HCT, the use in myeloma continues to expand but is stable in Hodgkin lymphoma. There is a notable increase in autologous HCT for autoimmune disease. These data reflect the most recent advances in the field, in which some trends and changes are likely to be related to development of non-transplant technologies.

Sudden Cardiac Death and Arrhythmias.

Abstract: Sudden cardiac death (SCD) and arrhythmia represent a major worldwide public health problem, accounting for 15-20 % of all deaths. Early resuscitation and defibrillation remains the key to survival, yet its implementation and the access to public defibrillators remains poor, resulting in overall poor survival to patients discharged from hospital. Novel approaches employing smart technology may provide the solution to this dilemma. Though the majority of cases are attributable to coronary artery disease, a thorough search for an underlying cause in cases where the diagnosis is unclear is necessary. This enables better management of arrhythmia recurrence and screening of family members. The majority of cases of SCD occur in patients who do not have traditional risk factors for arrhythmia. New and improved large scale screening tools are required to better predict risk in the wider population who represent the majority of cases of SCD.

Diagnostic accuracy and prognostic value of simultaneous hybrid 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging in cardiac sarcoidosis.

Abstract: Aims Cardiac death is the leading cause of mortality in patients with sarcoidosis, yet cardiac involvement often remains undetected. Cardiovascular magnetic resonance imaging (CMR) and 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) have been used to diagnose cardiac sarcoidosis (CS) yet never simultaneously in a cohort. This study sought to assess the diagnostic and prognostic utility of simultaneous hybrid cardiac PET/MR. Methods and results Fifty-one consecutive patients with suspected CS (age 50 ± 13 years, 31 males) underwent simultaneous PET/MR following a high-fat/low-carbohydrate diet and 12-h fast. Blinded image analysis of FDG uptake and late gadolinium enhancement (LGE) was performed using the American Heart Association (AHA) 16-segment model. The sensitivity and specificity of PET/MR for diagnosing CS was estimated using the Japanese Ministry of Health and Welfare guidelines. The primary endpoint was a composite of death, aborted sudden cardiac death, sustained ventricular arrhythmia, complete heart block, and hospital admission with decompensated heart failure. The secondary endpoints were a fall in left ventricular ejection fraction (LVEF) >10%, non-sustained ventricular tachycardia and other cardiac-related hospital admission. The prevalence of CS was 65% (n = 33). The sensitivity of PET and CMR alone for detecting CS was 0.85 and 0.82, respectively. Hybrid PET/MR was superior for detecting CS with sensitivity, specificity, positive, and negative predictive values of 0.94, 0.44, 0.76, and 0.80, respectively. There was poor inter-modality agreement for the location of cardiac abnormalities (k = 0.02). Over the median follow-up of 2.2 years, there were 18 (35%) adverse events. Cardiac RV PET abnormalities and presence of LGE were independent predictors of adverse events. Abnormalities found on both PET and magnetic resonance imaging was the strongest predictor of major adverse cardiac events. Conclusion Simultaneous PET/MR is an accurate method for diagnosing CS. FDG-PET and CMR combined offers complementary information on disease pathophysiology. The presence of LGE and FDG uptake on PET/MR identifies patients at higher risk of adverse events. PET and CMR should therefore be considered in the assessment of disease presence, stage, and prognosis in CS.

Atezolizumab (MPDL3280A) Monotherapy for Patients With Metastatic Urothelial Cancer: Long-term Outcomes From a Phase 1 Study.

Abstract: Importance Atezolizumab (anti–programmed death ligand 1) has demonstrated safety and activity in advanced and metastatic urothelial carcinoma, but its long-term clinical profile remains unknown. Objective To report long-term clinical outcomes with atezolizumab therapy for patients with metastatic urothelial carcinoma. Design, Setting, and Participants Patients were enrolled in an expansion cohort of an ongoing, open-label, phase 1 study. Median follow-up was 37.8 months (range, >0.7 to 44.4 months). Enrollment occurred between March 2013 and August 2015 at US and European academic medical centers. Eligible patients had measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1, Eastern Cooperative Oncology Group performance status 0 to 1, and a representative tumor sample. Programmed death ligand 1 expression on immune cells was assessed (VENTANA SP142 assay). Interventions Atezolizumab was given intravenously every 3 weeks until unacceptable toxic effects, protocol nonadherence, or loss of clinical benefit. Main Outcomes and Measures Primary outcome was safety. Secondary outcomes included objective response rate, duration of response, and progression-free survival. Response and overall survival were assessed in key baseline subgroups. Results Ninety-five patients were evaluable (72 [76%] male; median age, 66 years [range, 36-89 years]). Forty-five (47%) received atezolizumab as third-line therapy or greater. Nine patients (9%) had a grade 3 to 4 treatment-related adverse event, mostly within the first treatment year; no serious related adverse events were observed thereafter. One patient (1%) discontinued treatment due to a related event. No treatment-related deaths occurred. Responses occurred in 26% (95% CI, 18%-36%) of patients. Median duration of response was 22.1 months (range, 2.8 to >41.0 months), and median progression-free survival was 2.7 months (95% CI, 1.4-4.3 months). Median overall survival was 10.1 months (95% CI, 7.3-17.0 months); 3-year OS rate was 27% (95% CI, 17%-36%). Response occurred in 40% (95% CI, 26%-55%; n = 40) and 11% (95% CI, 4%-25%; n = 44) of patients with programmed death ligand 1 expression of at least 5% tumor-infiltrating immune cells (IC2/3) or less than 5% (IC0/1), respectively. Median overall survival in patients with IC2/3 and IC0/1 was 14.6 months (95% CI, 9.0 months to not estimable) and 7.6 months (95% CI, 4.7 to 13.9 months), respectively. Conclusions and Relevance Atezolizumab remained well tolerated and provided durable clinical benefit to a heavily pretreated metastatic urothelial carcinoma population in this long-term study. Trial Registration clinicaltrials.gov Identifier:NCT01375842

Left ventricular systolic function evaluated by strain echocardiography and relationship with mortality in patients with severe sepsis or septic shock: a systematic review and meta-analysis.

Abstract: Sepsis-induced myocardial dysfunction is associated with poor outcomes, but traditional measurements of systolic function such as left ventricular ejection fraction (LVEF) do not directly correlate with prognosis. Global longitudinal strain (GLS) utilizing speckle-tracking echocardiography (STE) could be a better marker of intrinsic left ventricular (LV) function, reflecting myocardial deformation rather than displacement and volume changes. We sought to investigate the prognostic value of GLS in patients with sepsis and/or septic shock. We conducted a systematic review (PubMed and Embase up to 26 October 2017) and meta-analysis to investigate the association between GLS and mortality at longest follow up in patients with severe sepsis and/or septic shock. In the primary analysis, we included studies reporting transthoracic echocardiography data on GLS according to mortality. A secondary analysis evaluated the association between LVEF and mortality including data from studies reporting GLS. We included eight studies in the primary analysis with a total of 794 patients (survival 68%, n = 540). We found a significant association between worse LV function and GLS values and mortality: standard mean difference (SMD) − 0.26; 95% confidence interval (CI) − 0.47, − 0.04; p = 0.02 (low heterogeneity, I2 = 43%). No significant association was found between LVEF and mortality in the same population of patients (eight studies; SMD, 0.02; 95% CI − 0.14, 0.17; p = 0.83; no heterogeneity, I2 = 3%). Worse GLS (less negative) values are associated with higher mortality in patients with severe sepsis or septic shock, while such association is not valid for LVEF. More critical care research is warranted to confirm the better ability of STE in demonstrating underlying intrinsic myocardial disease compared to LVEF.

Repeat doses of antibody to serum amyloid P component clear amyloid deposits in patients with systemic amyloidosis

Abstract: Systemic amyloidosis is a fatal disorder caused by pathological extracellular deposits of amyloid fibrils that are always coated with the normal plasma protein, serum amyloid P component (SAP). The small-molecule drug, miridesap, [(R)-1-[6-[(R)-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid (CPHPC)] depletes circulating SAP but leaves some SAP in amyloid deposits. This residual SAP is a specific target for dezamizumab, a fully humanized monoclonal IgG1 anti-SAP antibody that triggers immunotherapeutic clearance of amyloid. We report the safety, pharmacokinetics, and dose-response effects of up to three cycles of miridesap followed by dezamizumab in 23 adult subjects with systemic amyloidosis (ClinicalTrials.gov identifier: NCT01777243). Amyloid load was measured scintigraphically by amyloid-specific radioligand binding of 123I-labeled SAP or of 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid. Organ extracellular volume was measured by equilibrium magnetic resonance imaging and liver stiffness by transient elastography. The treatment was well tolerated with the main adverse event being self-limiting early onset rashes after higher antibody doses related to whole body amyloid load. Progressive dose-related clearance of hepatic amyloid was associated with improved liver function tests. 123I-SAP scintigraphy confirmed amyloid removal from the spleen and kidneys. No adverse cardiac events attributable to the intervention occurred in the six subjects with cardiac amyloidosis. Amyloid load reduction by miridesap treatment followed by dezamizumab has the potential to improve management and outcome in systemic amyloidosis.

The Cardiomyopathy Registry of the EURObservational Research Programme of the European Society of Cardiology: baseline data and contemporary management of adult patients with cardiomyopathies.

Abstract: Aims The Cardiomyopathy Registry of the EURObservational Research Programme is a prospective, observational, and multinational registry of consecutive patients with four cardiomyopathy subtypes: hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), and restrictive cardiomyopathy (RCM). We report the baseline characteristics and management of adults enrolled in the registry. Methods and results A total of 3208 patients were enrolled by 69 centres in 18 countries [HCM (n = 1739); DCM (n = 1260); ARVC (n = 143); and RCM (n = 66)]. Differences between cardiomyopathy subtypes (P < 0.001) were observed for age at diagnosis, history of familial disease, history of sustained ventricular arrhythmia, use of magnetic resonance imaging or genetic testing, and implantation of defibrillators. When compared with probands, relatives had a lower age at diagnosis (P < 0.001), but a similar rate of symptoms and defibrillators. When compared with the Long-Term phase, patients of the Pilot phase (enrolled in more expert centres) had a more frequent rate of familial disease (P < 0.001), were more frequently diagnosed with a rare underlying disease (P < 0.001), and more frequently implanted with a defibrillator (P = 0.023). Comparing four geographical areas, patients from Southern Europe had a familial disease more frequently (P < 0.001), were more frequently diagnosed in the context of a family screening (P < 0.001), and more frequently diagnosed with a rare underlying disease (P < 0.001). Conclusion By providing contemporary observational data on characteristics and management of patients with cardiomyopathies, the registry provides a platform for the evaluation of guideline implementation. Potential gaps with existing recommendations are discussed as well as some suggestions for improvement of health care provision in Europe.

Myocardial Extracellular Volume Quantification by Cardiovascular Magnetic Resonance and Computed Tomography.

Abstract: This review article discusses the evolution of extracellular volume (ECV) quantification using both cardiovascular magnetic resonance (CMR) and computed tomography (CT). Visualizing diffuse myocardial fibrosis is challenging and until recently, was restricted to the domain of the pathologist. CMR and CT both use extravascular, extracellular contrast agents, permitting ECV measurement. The evidence base around ECV quantification by CMR is growing rapidly and just starting in CT. In conditions with high ECV (amyloid, oedema and fibrosis), this technique is already being used clinically and as a surrogate endpoint. Non-invasive diffuse fibrosis quantification is also generating new biological insights into key cardiac diseases. CMR and CT can estimate ECV and in turn diffuse myocardial fibrosis, obviating the need for invasive endomyocardial biopsy. CT is an attractive alternative to CMR particularly in those individuals with contraindications to the latter. Further studies are needed, particularly in CT.

Myocardial native T1 and extracellular volume with healthy ageing and gender.

Abstract: Aims To determine how native myocardial T1 and extracellular volume (ECV) change with age, both to understand aging and to inform on normal reference ranges. Methods and results Ninety-four healthy volunteers with no a history or symptoms of cardiovascular disease or diabetes underwent cardiovascular magnetic resonance at 1.5 T. Mid-ventricular short axis native and post-contrast T1 maps by Shortened MOdified Look-Locker Inversion-recovery (ShMOLLI), MOdified Look-Locker Inversion Recovery (MOLLI) [pre-contrast: 5s(3s)3s, post-contrast: 4s(1s)3s(1s)2s] and saturation recovery single-shot acquisition (SASHA) were acquired and ECV by these three techniques were derived for the mid anteroseptum. Mean age was 50 ± 14 years (range 20-76), male 52%, with no age difference between genders (males 51 ± 14 years; females 49 ± 15 years, P = 0.55). Quoting respectively ShMOLLI, MOLLI, SASHA throughout, mean myocardial T1 was 957 ± 30 ms, 1025 ± 38 ms, 1144 ± 45 ms (P < 0.0001) and ECV 28.4 ± 3.0% [95% confidence interval (CI) 27.8-29.0], 27.3 ± 2.7 (95% CI 26.8-27.9), 24.1 ± 2.9% (95% CI 23.5-24.7) (P < 0.0001), with all values higher in females for all techniques (T1 +18 ms, +35 ms, +51 ms; ECV +2.7%, +2.6%, +3.4%). Native myocardial T1 reduced slightly with age (R2 = 0.042, P = 0.048; R2 = 0.131, P < 0.0001-on average by 8-11 ms/decade-but not for SASHA (R2 = 0.033 and P = 0.083). ECV did not change with age (R2 = 0.003, P = 0.582; R2 = 0.002, P = 0.689; R2 = 0.003, P = 0.615). Heart rate decreased slightly with age (R2 = 0.075, coefficient = -0.273, P = 0.008), but there was no relationship between age and other blood T1 influences (haematocrit, iron, high density lipoprotein-cholesterol). Conclusion Gender influences native T1 and ECV with women having a higher native T1 and ECV. Native T1 measured by MOLLI and ShMOLLI was slightly lower with increasing age but not with SASHA and ECV was independent of age for all techniques.

Persistent sex disparities in clinical outcomes with percutaneous coronary intervention: Insights from 6.6 million PCI procedures in the United States.

Abstract: Background Prior studies have reported inconsistencies in the baseline risk profile, comorbidity burden and their association with clinical outcomes in women compared to men. More importantly, there is limited data around the sex differences and how these have changed over time in contemporary percutaneous coronary intervention (PCI) practice. Methods and results We used the Nationwide Inpatient Sample to identify all PCI procedures based on ICD-9 procedure codes in the United States between 2004–2014 in adult patients. Descriptive statistics were used to describe sex-based differences in baseline characteristics and comorbidity burden of patients. Multivariable logistic regressions were used to investigate the association between these differences and in-hospital mortality, complications, length of stay and total hospital charges. Among 6,601,526 patients, 66% were men and 33% were women. Women were more likely to be admitted with diagnosis of NSTEMI (non-ST elevation acute myocardial infarction), were on average 5 years older (median age 68 compared to 63) and had higher burden of comorbidity defined by Charlson score ≥3. Women also had higher in-hospital crude mortality (2.0% vs 1.4%) and any complications compared to men (11.1% vs 7.0%). These trends persisted in our adjusted analyses where women had a significant increase in the odds of in-hospital mortality men (OR 1.20 (95% CI 1.16,1.23) and major bleeding (OR 1.81 (95% CI 1.77,1.86). Conclusion In this national unselected contemporary PCI cohort, there are significant sex-based differences in presentation, baseline characteristics and comorbidity burden. These differences do not fully account for the higher in-hospital mortality and procedural complications observed in women.

Agalsidase alfa versus agalsidase beta for the treatment of Fabry disease: an international cohort study

Abstract: Background Two recombinant enzymes (agalsidase alfa 0.2 mg/kg/every other week and agalsidase beta 1.0 mg/kg/every other week) have been registered for the treatment of Fabry disease (FD), at equal high costs. An independent international initiative compared clinical and biochemical outcomes of the two enzymes. Methods In this multicentre retrospective cohort study, clinical event rate, left ventricular mass index (LVMI), estimated glomerular filtration rate (eGFR), antibody formation and globotriaosylsphingosine (lysoGb3) levels were compared between patients with FD treated with agalsidase alfa and beta at their registered dose after correction for phenotype and sex. Results 387 patients (192 women) were included, 248 patients received agalsidase alfa. Mean age at start of enzyme replacement therapy was 46 (±15) years. Propensity score matched analysis revealed a similar event rate for both enzymes (HR 0.96, P=0.87). The decrease in plasma lysoGb3 was more robust following treatment with agalsidase beta, specifically in men with classical FD (β: −18 nmol/L, P Conclusions Treatment with agalsidase beta at higher dose compared with agalsidase alfa does not result in a difference in clinical events, which occurred especially in those with more advanced disease. A greater biochemical response, also in the presence of antibodies, and better reduction in left ventricular mass was observed with agalsidase beta.

Characteristic optical coherence tomography findings in patients with primary vitreoretinal lymphoma: a novel aid to early diagnosis

Abstract: Background The diagnosis of primary vitreoretinal lymphoma (PVRL) poses significant difficulties; presenting features are non-specific and confirmation usually necessitates invasive vitreoretinal biopsy. Diagnosis is often delayed, resulting in increased morbidity and mortality. Non-invasive imaging modalities such as spectral domain optical coherence tomography (SD-OCT) offer simple and rapid aids to diagnosis. We present characteristic SD-OCT images of patients with biopsy-positive PVRL and propose a number of typical features, which we believe are useful in identifying these lesions at an early stage. Methods Medical records of all patients attending Moorfields Eye Hospital between April 2010 and April 2016 with biopsy-positive PVRL were reviewed. Pretreatment SD-OCT images were collected for all eyes and were reviewed independently by two researchers for features suggestive of PVRL. Results Pretreatment SD-OCT images of 32 eyes of 22 patients with biopsy-proven PVRL were reviewed. Observed features included hyper-reflective subretinal infiltrates (17/32), hyper-reflective infiltration in inner retinal layers (6/32), retinal pigment epithelium (RPE) undulation (5/32), clumps of vitreous cells (5/32) and sub-RPE deposits (3/32). Of these, the hyper-reflective subretinal infiltrates have an appearance unique to PVRL, with features not seen in other diseases. Conclusion We have identified a range of SD-OCT features, which we believe to be consistent with a diagnosis of PVRL. We propose that the observation of hyper-reflective subretinal infiltrates as described is highly suggestive of PVRL. This case series further demonstrates the utility of SD-OCT as a non-invasive and rapid aid to diagnosis, which may improve both visual outcomes and survival of patients with intraocular malignancies such as PVRL.

Catheter ablation for ventricular tachycardia in patients with cardiac sarcoidosis: a systematic review.

Abstract: AIMS: Cardiac sarcoidosis (CS) is associated with a poor prognosis. Important features of CS include heart failure, conduction abnormalities, and ventricular arrhythmias. Ventricular tachycardia (VT) is often refractory to antiarrhythmic drugs (AAD) and immunosuppression. Catheter ablation has emerged as a treatment option for recurrent VT. However, data on the efficacy and outcomes of VT ablation in this context are sparse. METHODS AND RESULTS: A systematic search was performed on PubMed, EMBASE, and Cochrane database (from inception to September 2016) with included studies providing a minimum of information on CS patients undergoing VT ablation: age, gender, VT cycle length, CS diagnosis criteria, and baseline medications. Five studies reporting on 83 patients were identified. The mean age of patients was 50 ± 8 years, 53/30 (males/females) with a maximum of 56 patients receiving immunosuppressive therapy, mean ejection fraction was 39.1 ± 3.1% and 94% had an implantable cardioverter defibrillator in situ. The median number of VTs was 3 (2.6–4.9)/patient, mean cycle length of 360 ms (326–400 ms). Hundred percent of VTs received endocardial ablation, and 18% required epicardial ablation. The complication rates were 4.7–6.3%. Relapse occurred in 45 (54.2%) patients with an incidence of relapse 0.33 (95% confidence interval 0.108–0.551, P < 0.004). Employing a less stringent endpoint (i.e. freedom from arrhythmia or reduction of ventricular arrhythmia burden), 61 (88.4%) patients improved following ablation. CONCLUSIONS: These data support the utilization of catheter ablation in selected CS cases resistant to medical treatment. However, data are derived from observational non-controlled case series, with low-methodological quality. Therefore, future well-designed, randomized controlled trials, or large-scale registries are required.