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1.
ESC Heart Fail ; 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38627992

ABSTRACT

AIMS: This study aimed to examine the diagnostic pathways and outcomes of patients with heart failure (HF), stratified by left ventricular ejection fraction (EF), and to highlight deficiencies in real-world HF diagnosis and management. METHODS AND RESULTS: We conducted a retrospective cohort study in Salford, United Kingdom, utilizing linked primary and secondary care data for HF patients diagnosed between January 2010 and November 2019. We evaluated characteristics, diagnostic patterns, healthcare resource utilization, and outcomes. Patients were categorized according to baseline (the latest measure prior to or within 90 days post-diagnosis) as having HF with reduced EF (HFrEF), mildly reduced EF (HFmrEF), or preserved EF (HFpEF). The data encompassed a 2 year period before diagnosis and up to 5 years post-diagnosis. A total of 3227 patients were diagnosed with HF between January 2010 and November 2019. The mean follow-up time was 2.6 [±1.9 standard deviation (SD)] years. The mean age at diagnosis was 74.8 (±12.7 SD) years, and 1469 (45.5%) were female. HFpEF was the largest cohort (46.6%, npEF = 1505), HFmrEF constituted 16.1% (nmrEF = 520), and HFrEF 18.5% (nrEF = 596) of the population, while 18.8% (nu = 606) of patients remained unassigned due to insufficient evidence to support categorization. At baseline, measurement of natriuretic peptide (NP; brain NP and N-terminal pro-B-type NP) and echocardiographic report data were available for 592 (18.3%) and 2621 (81.2%) patients, respectively. A total of 2099 (65.0%) of the HF cohort had access to a cardiology-led outpatient clinic prior to the HF diagnosis, and 602 (18.7%) attended cardiac rehabilitation post-diagnosis. The 5 year crude survival rate was 37.8% [95% confidence interval (CI) (35.2-40.7%)], 42.3% [95% CI (38.0-47.2%)], and 45.5% [95% CI (41.0-50.4%)] for HFpEF, HFrEF, and HFmrEF, respectively. CONCLUSIONS: Low survival rates were observed across all HF groups, along with suboptimal rates of NP testing and specialist assessments. These findings suggest missed opportunities for timely and accurate HF diagnosis, a pivotal first step in improving outcomes for HF patients. Addressing these gaps in diagnosis and management is urgently needed.

2.
BMJ Open ; 13(10): e070028, 2023 10 29.
Article in English | MEDLINE | ID: mdl-37899155

ABSTRACT

OBJECTIVE: The aim of this study was to evaluate the potential real-world application of a machine learning (ML) algorithm, developed and trained on heart failure (HF) cohorts in the USA, to detect patients with undiagnosed wild type cardiac amyloidosis (ATTRwt) in the UK. DESIGN: In this retrospective observational study, anonymised, linked primary and secondary care data (Clinical Practice Research Datalink GOLD and Hospital Episode Statistics, respectively, were used to identify patients diagnosed with HF between 2009 and 2018 in the UK. International Classification of Diseases (ICD)-10 clinical modification codes were matched to equivalent Read (primary care) and ICD-10 WHO (secondary care) diagnosis codes used in the UK. In the absence of specific Read or ICD-10 WHO codes for ATTRwt, two proxy case definitions (definitive and possible cases) based on the degree of confidence that the contributing codes defined true ATTRwt cases were created using ML. PRIMARY OUTCOME MEASURE: Algorithm performance was evaluated primarily using the area under the receiver operating curve (AUROC) by comparing the actual versus algorithm predicted case definitions at varying sensitivities and specificities. RESULTS: The algorithm demonstrated strongest predictive ability when a combination of primary care and secondary care data were used (AUROC: 0.84 in definitive cohort and 0.86 in possible cohort). For primary care or secondary care data alone, performance ranged from 0.68 to 0.78. CONCLUSION: The ML algorithm, despite being developed in a US population, was effective at identifying patients that may have ATTRwt in a UK setting. Its potential use in research and clinical care to aid identification of patients with undiagnosed ATTRwt, possibly enabling earlier diagnosis in the disease pathway, should be investigated.


Subject(s)
Amyloid Neuropathies, Familial , Cardiomyopathies , Heart Failure , Humans , Prealbumin/metabolism , Amyloid Neuropathies, Familial/diagnosis , Amyloid Neuropathies, Familial/complications , Heart Failure/diagnosis , Heart Failure/complications , Cardiomyopathies/diagnosis , Cardiomyopathies/complications , United Kingdom
3.
Allergy Asthma Proc ; 44(4): 275-282, 2023 07 16.
Article in English | MEDLINE | ID: mdl-37328263

ABSTRACT

Background: New hereditary angioedema (HAE) treatments have become available in recent years for the treatment of HAE due to C1-inhibitor (C1-INH) deficiency, including two subcutaneous (SC) options: a monoclonal antibody (lanadelumab) and a plasma-derived C1-INH concentrate (SC-C1-INH). Limited real-world data on these therapies have been reported. Objective: The objective was to describe new users of lanadelumab and SC-C1-INH, including demographics, healthcare resource utilization (HCRU), costs, and treatment patterns before and after beginning treatment. Methods: This was a retrospective cohort study that used an administrative claims data base. Two mutually exclusive cohorts of adult (ages ≥18 years) new users of lanadelumab or SC-C1-INH with ≥180 days of continuous use were identified. HCRU, costs, and treatment patterns were assessed in the 180-day period before the index date (new treatment use) and up to 365 days after the index date. HCRU and costs were calculated as annualized rates. Results: Forty-seven patients who used lanadelumab and 38 patients who used SC-C1-INH were identified. The most frequently used on-demand HAE treatments at baseline were the same for both cohorts: bradykinin B2 antagonists (48.9% of the patients on lanadelumab, 52.6% of the patients on SC-C1-INH) and C1-INHs (40.4% of the patients on lanadelumab, 57.9% of the patients on SC-C1-INH). More than 33% of the patients continued to fill on-demand medications after treatment initiation. Annualized angioedema-associated emergency department visits and hospitalizations decreased after initiation of treatment, from 1.8 to 0.6 for the patients on lanadelumab and from 1.3 to 0.5 for the patients on SC-C1-INH. Annualized total healthcare costs after treatment initiation in the database were $866,639 and $734,460 for the lanadelumab and SC-C1-INH cohorts, respectively. Pharmacy costs accounted for >95% of these total costs. Conclusion: Although HCRU decreased after the initiation of treatment, angioedema-associated emergency department visits and hospitalizations and on-demand treatment fills were not completely eliminated. This indicates ongoing disease and treatment burden despite use of modern HAE medicines.


Subject(s)
Angioedema , Angioedemas, Hereditary , Adult , Humans , Angioedemas, Hereditary/drug therapy , Retrospective Studies , Complement C1 Inhibitor Protein/adverse effects , Angioedema/chemically induced , Patient Acceptance of Health Care
5.
ANZ J Surg ; 92(9): 2261-2268, 2022 09.
Article in English | MEDLINE | ID: mdl-36097420

ABSTRACT

BACKGROUND: To determine the prevalence of opioid use in Australian hip (THA) or knee (TKA) cohort, and its association with outcomes. METHODS: About 837 primary THA or TKA subjects prospectively completed Oxford Scores, and Knee or Hip Osteoarthritis Outcomes Score(KOOS/HOOS) and opioid use in the previous week before arthroplasty. Subjects repeated the baseline survey at 6 months, with additional questions regarding satisfaction. RESULTS: Opioid use was reported by 19% preoperatively and 7% at 6 months. Opioid use was 46% at 6 weeks and 10% at 6 months after TKR, and 16% at 6 weeks and 4% at 6 months after THR. Preoperative opioid use was associated with back pain(OR 2.2, P = 0.006), anxiety or depression(OR 1.8, P = 0.001) and Oxford knee scores <30(OR 5.6, P = 0.021) in TKA subjects, and females in THA subjects(OR 1.7, P = 0.04). There was no difference between preoperative opioid users and non-users for satisfaction, or KOOS or HOOS scores at 6 months. 77% of patients taking opioids before surgery had ceased by 6 months, and 3% of preoperative non users reported opioid use at 6 months. Opioid use at 6 months was associated with preoperative use (OR 6.6-14.7, P < 0.001), and lower 6 month oxford scores (OR 4.4-83.6, P < 0.01). CONCLUSION: One in five used opioids before arthroplasty. Pre-operative opioid use was the strongest risk factor for opioid use at 6 months, increasing odds 7-15 times. Prolonged opioid use was rarely observed in the opioid naïve (<5% TKA and 1% THA). Preoperative opioid use was not associated with inferior outcomes or satisfaction.


Subject(s)
Arthroplasty, Replacement, Hip , Arthroplasty, Replacement, Knee , Opioid-Related Disorders , Analgesics, Opioid/therapeutic use , Australia/epidemiology , Female , Humans
6.
Haemophilia ; 28(4): 588-609, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35438818

ABSTRACT

INTRODUCTION: With the development of gene therapy for people with haemophilia (PWH), it is important to understand how people impacted by haemophilia (PIH) and clinicians prioritise haemophilia treatment attributes to support informed treatment decisions. OBJECTIVE: To examine the treatment attribute preferences of PIH and clinical experts in the United Kingdom (UK) and to develop a profile of gene therapy characteristics fit for use in future discrete choice experiments (DCEs). METHODS: Semi-structured interviews were conducted with PIH (n = 14) and clinical experts (n = 6) who ranked pre-defined treatment attributes by importance. Framework analysis was conducted to identify key themes and treatment attributes; points were allocated based on the rankings. Synthesis of results by a multidisciplinary group informed development of a profile of gene therapy characteristics for use in future research. RESULTS: Key themes identified by PIH and clinical experts included patient relevant features and the importance of 'informed decision making'. The six top-ranked treatment attributes were 'effect on factor level' (79 points), 'uncertainty regarding long-term risks' (57 points), 'impact on daily life' (41 points), 'frequency of monitoring' (33 points), 'impact on ability to participate in physical activity' (29 points), and 'uncertainty regarding long-term benefits' (28 points). The final treatment characteristics were categorised as therapeutic option, treatment effectiveness, safety concerns, impact on self-management and quality of life (role limitations). CONCLUSION: We identified several gene therapy characteristics important to PIH and clinicians in the UK. These characteristics will be used in a future DCE to further investigate patient preferences for gene therapy.


Subject(s)
Choice Behavior , Hemophilia A , Genetic Therapy , Hemophilia A/genetics , Hemophilia A/therapy , Humans , Patient Preference , Quality of Life , United Kingdom
7.
Heart ; 108(17): 1383-1391, 2022 08 11.
Article in English | MEDLINE | ID: mdl-34969871

ABSTRACT

AIMS: The population prevalence of cardiomyopathies and the natural history of symptomatic heart failure (HF) and arrhythmia across cardiomyopathy phenotypes is poorly understood. Study aims were to estimate the population-diagnosed prevalence of cardiomyopathies and describe the temporal relationship between a diagnosis of cardiomyopathy with HF and arrhythmia. METHODS: People with cardiomyopathy (n=4116) were identified from linked electronic health records (~9 million individuals; 2000-2018) and categorised into hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), restrictive cardiomyopathy (RCM) and cardiac amyloidosis (CA). Cardiomyopathy point prevalence, rates of symptomatic HF and arrhythmia and timing relative to a diagnosis of cardiomyopathy were determined. RESULTS: In 2018, DCM was the most common cardiomyopathy. DCM and HCM were twice as common among men, with the reverse trend for ARVC. Between 2010 and 2018, prevalence increased for ARVC by 180% and HCM by 9%. At diagnosis, more patients with CA (66%), DCM (56%) and RCM (62%) had pre-existing HF compared with ARVC (29%) and HCM (27%). Among those free of HF at diagnosis of cardiomyopathy, annualised HF incidence was greatest in CA and DCM. Diagnoses of all cardiomyopathies clustered around the time of HF onset. CONCLUSIONS: The recorded prevalence of all cardiomyopathies increased over the past decade. Recognition of CA is generally preceded by HF, whereas individuals with ARVC or HCM more often developed HF after their cardiomyopathy diagnosis suggesting a more indolent course or better asymptomatic recognition. The clustering of HF and cardiomyopathy diagnoses suggests opportunities for presymptomatic or earlier diagnosis.


Subject(s)
Arrhythmogenic Right Ventricular Dysplasia , Cardiomyopathies , Cardiomyopathy, Dilated , Cardiomyopathy, Hypertrophic , Cardiomyopathy, Restrictive , Heart Failure , Cardiomyopathies/diagnosis , Cardiomyopathies/epidemiology , Cardiomyopathies/genetics , Cohort Studies , Heart Failure/diagnosis , Heart Failure/epidemiology , Humans
8.
Orphanet J Rare Dis ; 16(1): 218, 2021 05 13.
Article in English | MEDLINE | ID: mdl-33985575

ABSTRACT

BACKGROUND: In the absence of a framework designed to evaluate medicines for rare diseases in the UK, most orphan medicines are appraised by the National Institute for Health and Care Excellence (NICE) through the Single Technology Appraisal (STA) process. RESULTS: An analysis of STA appraisals of orphan and non-orphan medicines revealed that orphan medicines were subject to a significantly longer mean time in the NICE process than non-orphan medicines [370 days (n = 44) vs. 277 days (n = 118), p = < 0.0001]. A higher proportion of orphan STAs required more than one Appraisal Committee Meeting (ACM) versus non-orphan STAs, and orphan STAs were disadvantaged by worse outcomes with respect to positive recommendations than those orphan medicines assessed by Highly Specialised Technology evaluation (HST). CONCLUSIONS: The uncertainties inherent to developing orphan medicines may contribute to these disadvantages. Improved understanding of the challenges in drug development for orphan medicines and clearer guidance for decision makers on navigating uncertainty in the HTA process may promote greater equity in access to medicines across rare and common conditions.


Subject(s)
Biomedical Technology , Technology Assessment, Biomedical , Cost-Benefit Analysis , Humans , Rare Diseases/drug therapy
9.
Clin Endocrinol (Oxf) ; 95(1): 143-152, 2021 07.
Article in English | MEDLINE | ID: mdl-33749903

ABSTRACT

CONTEXT: A lack of consensus remains about the relative importance of insulin-like growth factor-1 (IGF-1) and growth hormone (GH) in predicting adverse outcomes in patients with acromegaly. OBJECTIVE: To describe the differing association between IGF-1 and GH and major disease outcomes in acromegaly. DESIGN: Retrospective cohort study. PATIENTS: United Kingdom National Health Service patients with acromegaly who had an IGF-1 and/or a GH measurement recorded following diagnosis, prior to December 2019. MEASUREMENTS: A composite endpoint including all-cause mortality (ACM), type 2 diabetes (DM), major adverse cardiovascular events (MACE) or cancer was the primary outcome. These outcomes were also analysed individually. Follow-up period was capped at 5 years. RESULTS: A maximum of 417 cases and 332 cases were eligible for the IGF-1 and GH analyses, respectively, comprising 1041.5 and 938.9 years of follow-up. There was a direct association between increased IGF-1 concentration and adjusted event risk for the composite endpoint (hazard ratio [HR] = 1.2; 95% confidence interval [CI] = 1.02-1.5); in GH, the HR was 1.1 (1.0-1.2). For the individual endpoints in relation to IGF-1 level, the HRs were ACM (1.2; 0.93-1.5), MACE (1.2; 0.64-2.1), DM (1.53; 1.09-2.2) and cancer (1.3; 0.95-1.7). For GH, the HRs were ACM (1.1; 0.97-1.2), MACE (0.99; 0.73-1.3), DM (1.1; 0.99-1.2) and cancer (0.90; 0.66-1.2). CONCLUSIONS: In this contemporary data set with extended follow-up, IGF-1 and GH concentrations showed an association with major adverse outcomes from acromegaly.


Subject(s)
Acromegaly , Diabetes Mellitus, Type 2 , Human Growth Hormone , Growth Hormone , Humans , Insulin-Like Growth Factor I , Retrospective Studies , State Medicine
10.
ESC Heart Fail ; 6(5): 1041-1051, 2019 10.
Article in English | MEDLINE | ID: mdl-31487121

ABSTRACT

AIMS: The study aims to systematically assess the diagnostic performance of cardiac magnetic resonance (CMR) and nuclear scintigraphy (index tests) for the diagnosis and differentiation of subtypes of cardiac amyloidosis. METHODS AND RESULTS: MEDLINE and Embase electronic databases were searched for studies evaluating the diagnostic performance of CMR or nuclear scintigraphy in detecting cardiac amyloidosis and subsequently in differentiating transthyretin amyloidosis (ATTR) from immunoglobulin light-chain (AL) amyloidosis. In this meta-analysis, histopathological examination of tissue from endomyocardial biopsy (EMB) or extra-cardiac organs were reference standards. Pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were calculated, and a random effects meta-analysis was used to estimate diagnostic odds ratios. Methodological quality was assessed using a validated instrument. Of the 2947 studies identified, 27 met the criteria for inclusion. Sensitivity and specificity of CMR in diagnosing cardiac amyloidosis was 85.7% and 92.0% against EMB reference and 78.9% and 93.9% with any organ histology reference. Corresponding sensitivity and specificity of nuclear scintigraphy was 88.4% and 87.2% against EMB reference and 82.0% and 98.8% with histology from any organ. CMR was unable to reliably differentiate ATTR from AL amyloidosis (sensitivity 28.1-99.0% and specificity 11.0-60.0%). Sensitivity and specificity of nuclear scintigraphy in the differentiation of ATTR from AL amyloidosis ranged from 90.9% to 91.5% and from 88.6% to 97.1%. Pooled negative likelihood ratio and positive likelihood ratio for scintigraphy in this setting were 0.1 and 8, with EMB reference standard. Study quality assessed by QUADAS-2 was generally poor with evidence of bias. CONCLUSIONS: Cardiac magnetic resonance is a useful test for diagnosing cardiac amyloidosis but is not reliable in further classifying the disease. Nuclear scintigraphy offers strong diagnostic performance in both the detection of cardiac amyloidosis and differentiating ATTR from AL amyloidosis. Our findings support the use of both imaging modalities in a non-invasive diagnostic algorithm that also tests for the presence of monoclonal protein.


Subject(s)
Amyloid Neuropathies, Familial/diagnostic imaging , Amyloidosis/diagnostic imaging , Immunoglobulin Light-chain Amyloidosis/diagnostic imaging , Magnetic Resonance Imaging/methods , Radionuclide Imaging/methods , Amyloid Neuropathies, Familial/complications , Amyloid Neuropathies, Familial/epidemiology , Amyloid Neuropathies, Familial/pathology , Amyloidosis/pathology , Biopsy/standards , Diagnosis, Differential , Heart Diseases/diagnostic imaging , Heart Diseases/pathology , Heart Failure/diagnostic imaging , Heart Failure/epidemiology , Heart Failure/etiology , Heart Failure/mortality , Humans , Immunoglobulin Light-chain Amyloidosis/complications , Immunoglobulin Light-chain Amyloidosis/epidemiology , Immunoglobulin Light-chain Amyloidosis/pathology , Prevalence , Radionuclide Imaging/trends , Sensitivity and Specificity
11.
JAMA Netw Open ; 1(8): e185554, 2018 12 07.
Article in English | MEDLINE | ID: mdl-30646277

ABSTRACT

Importance: Both adherence and treatment intensity can alter the effectiveness of lipid-lowering therapy in routine clinical practice. Objective: To evaluate the association of adherence and treatment intensity with cardiovascular outcomes in patients with documented cardiovascular disease (CVD), type 2 diabetes without CVD or chronic kidney disease (CKD), and CKD without CVD. Design, Setting, and Participants: Retrospective cohort study using the Clinical Practice Research Datalink from January 2010 through February 2016. United Kingdom primary care was the setting. Participants were newly treated patients who received their first statin and/or ezetimibe prescription between January 1, 2010, and December 31, 2013, plus an additional prescription for statins and/or ezetimibe during the following year. Exposures: Adherence was assessed annually using the proportion of days covered, with adherent defined as a proportion of days covered of 80% or higher. Treatment intensity was classified according to guidelines based on the expected percentage of low-density lipoprotein cholesterol (LDL-C) reduction as low (<30% reduction), moderate (30% to <50% reduction), or high (≥50% reduction). Adherence and treatment intensity were multiplied to create a combined measure, reflecting treatment intensity after accounting for adherence. Main Outcomes and Measures: Composite end point of cardiovascular death or hospitalization for myocardial infarction, unstable angina, ischemic stroke, heart failure, or revascularization. Hazard ratios (HRs) were estimated against patients not treated for 1 year or longer. Results: Among a total of 29 797 newly treated patients, there were 16 701, 12 422, and 674 patients with documented CVD, type 2 diabetes without CVD or CKD, and CKD without CVD, respectively; mean (SD) ages were 68.3 (13.2), 59.3 (12.4), and 67.3 (15.1) years, and male proportions were 60.6%, 55.0%, and 47.0%. In the documented CVD cohort, patients receiving high-intensity therapy were more likely to be adherent over time (84.1% in year 1 and 72.3% in year 6) than patients receiving low-intensity therapy (57.4% in year 1 and 48.4% in year 6). Using a combined measure of adherence and treatment intensity, a graded association was observed with both LDL-C reduction and CVD outcomes: each 10% increase in the combined measure was associated with a 10% lower risk (HR, 0.90; 95% CI, 0.86-0.94). Adherent patients receiving a high-intensity regimen had the lowest risk (HR, 0.60; 95% CI, 0.54-0.68) vs patients untreated for 1 year or longer. Findings in the other 2 cohorts were similar. Conclusions and Relevance: Results of this study demonstrate that the lowest cardiovascular risk was observed among adherent patients receiving high-intensity therapy, and the highest cardiovascular risk was observed among nonadherent patients receiving low-intensity therapy. Strategies that improve adherence and greater use of intensive therapies could substantially improve cardiovascular risk.


Subject(s)
Anticholesteremic Agents/therapeutic use , Atherosclerosis , Cardiovascular Diseases , Ezetimibe/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Medication Adherence/statistics & numerical data , Aged , Atherosclerosis/complications , Atherosclerosis/drug therapy , Atherosclerosis/epidemiology , Atherosclerosis/mortality , Cardiovascular Diseases/complications , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/mortality , Diabetes Mellitus, Type 2/complications , Female , Humans , Male , Middle Aged , Renal Insufficiency, Chronic/complications , Retrospective Studies , Risk Factors
12.
Vasc Endovascular Surg ; 51(6): 417-428, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28656809

ABSTRACT

BACKGROUND: Current surveillance protocols after endovascular aneurysm repair (EVAR) are ineffective and costly. Stratifying surveillance by individual risk of reintervention requires an understanding of the factors involved in developing post-EVAR complications. This systematic review assessed risk factors for reintervention after EVAR and proposals for stratified surveillance. METHODS: A systematic search according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was performed using EMBASE and MEDLINE databases to identify studies reporting on risk factors predicting reintervention after EVAR and proposals for stratified surveillance. RESULTS: Twenty-nine studies reporting on 39 898 patients met the primary inclusion criteria for reporting predictors of reintervention or aortic complications with or without suggestions for stratified surveillance. Five secondary studies described external validation of risk scores for reintervention or aortic complications. There was great heterogeneity in reporting risk factors identified at the pre-EVAR, intraoperative, and post-EVAR stages of treatment, although large preoperative abdominal aortic aneurysm diameter was the most commonly observed risk factor for reintervention after EVAR. CONCLUSION: Existing data on predictors of post-EVAR complications are generally of poor quality and largely derived from retrospective studies. Few studies describing suggestions for stratified surveillance have been subjected to external validation. There is a need to refine risk prediction for EVAR failure and to conduct prospective comparative studies of personalized surveillance with standard practice.


Subject(s)
Aortic Aneurysm/surgery , Blood Vessel Prosthesis Implantation/adverse effects , Endovascular Procedures/adverse effects , Postoperative Complications/therapy , Aortic Aneurysm/diagnostic imaging , Decision Support Techniques , Humans , Postoperative Complications/diagnostic imaging , Postoperative Complications/etiology , Predictive Value of Tests , Retreatment , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome
13.
J Am Heart Assoc ; 6(4)2017 Apr 11.
Article in English | MEDLINE | ID: mdl-28400366

ABSTRACT

BACKGROUND: Small artery pathophysiology is frequently invoked as a cause of obesity-related diastolic heart failure. However, evidence to support this hypothesis is scant, particularly in humans. METHODS AND RESULTS: To address this, we studied human small artery structure and function in obesity and looked for correlations between vascular parameters and diastolic function. Seventeen obese patients with metabolic syndrome and 5 control participants underwent echocardiography and subcutaneous gluteal fat biopsy. Small arteries were isolated from the biopsy and pressure myography was used to study endothelial function and wall structure. In comparison with the control group, small arteries from obese participants exhibited significant endothelial dysfunction, assessed as the vasodilatory response to acetylcholine and also pathological growth of the wall. For the obese participants, multiple regression analysis revealed an association between left atrial volume and both the small artery wall thickness (ß=0.718, P=0.02) and wall-to-lumen ratio (ß=0.605, P=0.02). Furthermore, the E:E' ratio was associated with wall-to-lumen ratio (ß=0.596, P=0.02) and inversely associated with interleukin-6 (ß=-0.868, P=0.03). By contrast, endothelial function did not correlate with any of the echocardiographic parameters studied. CONCLUSIONS: Although the small arteries studied were not cardiac in origin, our results support a role for small artery remodeling in the development of diastolic dysfunction in humans. Further direct examination of the structure and function of the myocardial resistance vasculature is now warranted, to elucidate the temporal association between metabolic risk factors, small artery injury, and diastolic impairment.


Subject(s)
Arteries/physiopathology , Metabolic Syndrome/physiopathology , Obesity/physiopathology , Subcutaneous Fat/blood supply , Vascular Remodeling , Ventricular Dysfunction, Left/physiopathology , Ventricular Function, Left , Adult , Aged , Arteries/pathology , Biopsy , Buttocks , Case-Control Studies , Diastole , Echocardiography, Doppler , Humans , Metabolic Syndrome/diagnosis , Middle Aged , Obesity/diagnosis , Risk Factors , Vasodilation , Ventricular Dysfunction, Left/diagnostic imaging
14.
Vascular ; 25(1): 74-79, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27136950

ABSTRACT

Approximately 40-50% of patients undergoing thoracic endovascular aortic repair require left subclavian artery coverage for adequate proximal landing zone. Many of these patients undergo left subclavian artery revascularisation. However, outcomes data for left subclavian artery revascularisation in the context of thoracic endovascular aortic repair remain limited. In this study, 70 left subclavian artery revascularisation procedures, performed on thoracic endovascular aortic repair patients at a tertiary hospital, were retrospectively reviewed. Particular emphasis was placed on revascularisation-related outcomes during staging interval between revascularisation and thoracic endovascular aortic repair. Forty-six (66%) carotid-subclavian bypass, 17 (24%) carotid-carotid-subclavian bypass and 7 (10%) aorto-inominate-carotid-subclavian bypass procedures were performed. There were no strokes or mortalities following left subclavian artery revascularisation procedures alone. Three (10%) minor complications occurred including a seroma, a haematoma and a temporary neuropraxia. Separation of complications following left subclavian artery revascularisation from those of the associated thoracic endovascular aortic repair can be difficult. Early outcomes data from patients who underwent left subclavian artery revascularisation in isolation indicate that the procedure is safe with low complication rates.


Subject(s)
Aorta, Thoracic/surgery , Aortic Aneurysm, Thoracic/surgery , Aortic Dissection/surgery , Blood Vessel Prosthesis Implantation , Endovascular Procedures , Subclavian Artery/surgery , Aged , Aortic Dissection/diagnostic imaging , Aortic Dissection/mortality , Aorta, Thoracic/diagnostic imaging , Aortic Aneurysm, Thoracic/diagnostic imaging , Aortic Aneurysm, Thoracic/mortality , Blood Vessel Prosthesis , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis Implantation/instrumentation , Blood Vessel Prosthesis Implantation/mortality , Endovascular Procedures/adverse effects , Endovascular Procedures/instrumentation , Endovascular Procedures/mortality , Female , Humans , London , Male , Middle Aged , Postoperative Complications/etiology , Prosthesis Design , Retrospective Studies , Stents , Subclavian Artery/diagnostic imaging , Tertiary Care Centers , Treatment Outcome
16.
Lancet Diabetes Endocrinol ; 4(7): 588-97, 2016 07.
Article in English | MEDLINE | ID: mdl-27216886

ABSTRACT

BACKGROUND: Diabetes confers a two times excess risk of cardiovascular disease, yet predicting individual risk remains challenging. The effect of total microvascular disease burden on cardiovascular disease risk among individuals with diabetes is unknown. METHODS: A population-based cohort of patients with type 2 diabetes from the UK Clinical Practice Research Datalink was studied (n=49 027). We used multivariable Cox models to estimate hazard ratios (HRs) for the primary outcome (the time to first major cardiovascular event, which was a composite of cardiovascular death, non-fatal myocardial infarction, or non-fatal ischaemic stroke) associated with cumulative burden of retinopathy, nephropathy, and peripheral neuropathy among individuals with no history of cardiovascular disease at baseline. FINDINGS: During a median follow-up of 5·5 years, 2822 (5·8%) individuals experienced a primary outcome. After adjustment for established risk factors, significant associations were observed for the primary outcome individually for retinopathy (HR 1·39, 95% CI 1·09-1·76), peripheral neuropathy (1·40, 1·19-1·66), and nephropathy (1·35, 1·15-1·58). For individuals with one, two, or three microvascular disease states versus none, the multivariable-adjusted HRs for the primary outcome were 1·32 (95% CI 1·16-1·50), 1·62 (1·42-1·85), and 1·99 (1·70-2·34), respectively. For the primary outcome, measures of risk discrimination showed significant improvement when microvascular disease burden was added to models. In the overall cohort, the net reclassification index for USA and UK guideline risk strata were 0·036 (95% CI 0·017-0·055, p<0·0001) and 0·038 (0·013-0·060, p<0·0001), respectively. INTERPRETATION: The cumulative burden of microvascular disease significantly affects the risk of future cardiovascular disease among individuals with type 2 diabetes. Given the prevalence of diabetes globally, further work to understand the mechanisms behind this association and strategies to mitigate this excess risk are warranted. FUNDING: Circulation Foundation.


Subject(s)
Cardiovascular Diseases/mortality , Diabetes Mellitus, Type 2/complications , Diabetic Angiopathies/complications , Aged , Aged, 80 and over , Cardiovascular Diseases/etiology , Cohort Studies , Diabetes Mellitus, Type 2/epidemiology , Female , Heart Failure/etiology , Humans , Male , Middle Aged , United Kingdom/epidemiology
18.
J Endovasc Ther ; 22(3): 283-7, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25904491

ABSTRACT

PURPOSE: To assess the feasibility and report preliminary results of ruptured abdominal aortic aneurysm (rAAA) repair with endovascular aneurysm sealing (EVAS), a novel therapeutic alternative whose feasibility has not been established in rAAAs due to the unknown effects of the rupture site on the ability to achieve sealing. CASE REPORT: Between December 2013 and April 2014, 5 patients (median age 71 years, range 57-90; 3 men) with rAAAs were treated with the Nellix EVAS system at a single institution. Median aneurysm diameter was 70 mm (range 67-91). Aneurysm morphology in 4 of the 5 patients was noncompliant with instructions for use (IFU) for both EVAS and standard stent-grafts; the remaining patient was outside the IFU for standard stent-grafts but treated with EVAS under standard IFU for the Nellix system. Median Hardman index was 2 (range 0-3). Two patients died of multiorgan failure after re-laparotomy and intraoperative cardiac arrest, respectively. Among survivors, all devices were patent with no signs of endoleak or failed aneurysm sac sealing at 6 months (median follow-up 9.2 months). CONCLUSION: EVAS for the management of infrarenal rAAAs appears feasible. The use of EVAS in emergency repairs may broaden the selection criteria of the current endovascular strategy to include patients with more complex aneurysm morphology.


Subject(s)
Aortic Aneurysm, Abdominal/surgery , Aortic Rupture/surgery , Blood Vessel Prosthesis Implantation/instrumentation , Blood Vessel Prosthesis , Endovascular Procedures/instrumentation , Stents , Aged , Aged, 80 and over , Aortic Aneurysm, Abdominal/diagnostic imaging , Aortic Aneurysm, Abdominal/mortality , Aortic Rupture/diagnostic imaging , Aortic Rupture/mortality , Aortography/methods , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis Implantation/mortality , Endovascular Procedures/adverse effects , Endovascular Procedures/mortality , Feasibility Studies , Female , Humans , London , Male , Middle Aged , Patient Selection , Postoperative Complications/mortality , Postoperative Complications/surgery , Prosthesis Design , Risk Factors , Time Factors , Tomography, X-Ray Computed , Treatment Outcome
19.
Circulation ; 130(24): 2136-42, 2014 Dec 09.
Article in English | MEDLINE | ID: mdl-25378548

ABSTRACT

BACKGROUND: Mycotic aortic aneurysm (MAA) is a rare and life-threatening disease. The aim of this European multicenter collaboration was to study the durability of endovascular aortic repair (EVAR) of MAA, by assessing late infection-related complications and long-term survival. METHODS AND RESULTS: All EVAR treated MAAs, between 1999 and 2013 at 16 European centers, were retrospectively reviewed. One hundred twenty-three patients with 130 MAAs were identified. Mean age was 69 years (range 39-86), 87 (71%) were men, 58 (47%) had immunodeficiency, and 47 (38%) presented with rupture. Anatomic locations were ascending/arch (n=4), descending (n=34), paravisceral (n=15), infrarenal aorta (n=63), and multiple (n=7). Treatments were thoracic EVAR (n=43), fenestrated/branched EVAR (n=9), and infrarenal EVAR (n=71). Antibiotic was administered for mean 30 weeks. Mean follow-up was 35 months (range 1 week to 149 months). Six patients (5%) were converted to open repair during follow-up. Survival was 91% (95% confidence interval, 86% to 96%), 75% (67% to 83%), 55% (44% to 66%), and 41% (28% to 54%) after 1, 12, 60, and 120 months, respectively. Infection-related death occurred in 23 patients (19%), 9 after discontinuation of antibiotic treatment. A Cox regression analysis demonstrated non-Salmonella-positive culture as predictors for late infection-related death. CONCLUSIONS: Endovascular treatment of MAA is feasible and for most patients a durable treatment option. Late infections do occur, are often lethal, and warrant long-term antibiotic treatment and follow-up. Patients with non-Salmonella-positive blood cultures were more likely to die from late infection.


Subject(s)
Aneurysm, Infected/microbiology , Aneurysm, Infected/therapy , Aortic Aneurysm/microbiology , Aortic Aneurysm/therapy , Endovascular Procedures/methods , Adult , Aged , Aged, 80 and over , Aneurysm, Infected/epidemiology , Anti-Bacterial Agents/therapeutic use , Aortic Aneurysm/epidemiology , Europe/epidemiology , Feasibility Studies , Female , Follow-Up Studies , Humans , Incidence , Male , Middle Aged , Regression Analysis , Retrospective Studies , Surgical Wound Infection/epidemiology , Surgical Wound Infection/microbiology , Surgical Wound Infection/mortality , Survival Rate , Time Factors , Treatment Outcome
20.
Heart ; 100(23): 1837-43, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25095826

ABSTRACT

AIMS: Identifying individuals with diabetes at high risk of cardiovascular disease (CVD) remains challenging. We aimed to establish whether peripheral neuropathy (PN) is associated with incident CVD events and to what extent information on PN may improve risk prediction among individuals with type 2 diabetes. METHODS: We obtained data for individuals with type 2 diabetes, and free of CVD, from a large primary care patient cohort. Incident CVD events were recorded during a 30-month follow-up period. Eligible individuals had complete ascertainment of cardiovascular risk factors and PN status at baseline. The association between PN and incident CVD events (non-fatal myocardial infarction, coronary revascularisation, congestive cardiac failure, transient ischaemic attack and stroke) was evaluated using Cox regression, adjusted for standard CVD risk factors. We assessed the predictive accuracy of models including conventional CVD risk factors with and without information on PN. RESULTS: Among 13 043 eligible individuals, we recorded 407 deaths from any cause and 399 non-fatal CVD events. After adjustment for age, sex, ethnicity, systolic blood pressure, cholesterol, body mass index, HbA1c, smoking status and use of statin or antihypertensive medication, PN was associated with incident CVD events (HR 1.33; 95% CI 1.02 to 1.75, p=0.04). The addition of information on PN to a model based on standard CVD risk factors resulted in modest improvements in discrimination for CVD risk prediction and reclassified 6.9% of individuals into different risk categories. CONCLUSIONS: PN is associated with increased risk for a first cardiovascular event among individuals with diabetes.


Subject(s)
Cardiovascular Diseases/etiology , Diabetes Mellitus, Type 2/complications , Diabetic Neuropathies/etiology , Peripheral Nervous System Diseases/etiology , Adult , Aged , Aged, 80 and over , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/mortality , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/mortality , Diabetic Neuropathies/diagnosis , Diabetic Neuropathies/mortality , England/epidemiology , Female , Humans , Incidence , Kaplan-Meier Estimate , Male , Middle Aged , Peripheral Nervous System Diseases/diagnosis , Peripheral Nervous System Diseases/mortality , Prognosis , Proportional Hazards Models , Risk Assessment , Risk Factors , Time Factors , Young Adult
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