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  • 1
    In: The Lancet, Elsevier BV, Vol. 400, No. 10369 ( 2022-12), p. 2199-2209
    Type of Medium: Online Resource
    ISSN: 0140-6736
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
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    detail.hit.zdb_id: 3306-6
    detail.hit.zdb_id: 1476593-7
    SSG: 5,21
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  • 2
    In: Endocrinology, Diabetes & Metabolism, Wiley, Vol. 4, No. 3 ( 2021-07)
    Abstract: This study examined the effect of experimentally‐induced hypoglycaemia on measures of myocardial blood flow and myocardial injury in adults with, and without, type 1 diabetes. Methods In a prospective, randomised, open‐label, blinded, endpoint cross‐over study, 17 young adults with type 1 diabetes with no cardiovascular risk factors, and 10 healthy non‐diabetic volunteers, underwent hyperinsulinaemic‐euglycaemic (blood glucose 4.5–5.5 mmol/L) and hypoglycaemic (2.2–2.5 mmol/L) clamps. Myocardial blood flow was assessed using transthoracic echocardiography Doppler coronary flow reserve (CFR) and myocardial injury using plasma high‐sensitivity cardiac troponin I (hs‐cTnI) concentration. Results During hypoglycaemia, coronary flow reserve trended non‐significantly lower in those with type 1 diabetes than in the non‐diabetic participants (3.54 ± 0.47 vs. 3.89 ± 0.89). A generalised linear mixed‐model analysis examined diabetes status and euglycaemia or hypoglycaemia as factors affecting CFR. No statistically significant difference in CFR was observed for diabetes status ( p  = .23) or between euglycaemia and hypoglycaemia ( p  = .31). No changes in hs‐cTnI occurred during hypoglycaemia or in the recovery period ( p  = .86). Conclusions A small change in CFR was not statistically significant in this study, implying hypoglycaemia may require more than coronary vasomotor dysfunction to cause harm. Further larger studies are required to investigate this putative problem.
    Type of Medium: Online Resource
    ISSN: 2398-9238 , 2398-9238
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
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  • 3
    Online Resource
    Online Resource
    Portland Press Ltd. ; 2021
    In:  Clinical Science Vol. 135, No. 23 ( 2021-12-10), p. 2661-2663
    In: Clinical Science, Portland Press Ltd., Vol. 135, No. 23 ( 2021-12-10), p. 2661-2663
    Abstract: Dramatic improvements in cancer survival have arisen because of the rapid development of novel anti-cancer therapies. The potential for cardiovascular toxicity associated with these drugs often reflects overlap between pathogenic cancer mechanisms and physiological pathways required for normal cardiovascular function. Clinical Science has, therefore, compiled a themed collection on Cardiovascular-Oncology. This collection examines the intersection between cancer treatments and their potentially harmful cardiovascular effects. By defining the mechanisms underlying unwanted cardiovascular effects of anti-cancer therapies, cardioprotective strategies can be developed. Only by doing so, will patients be able to achieve optimal cancer treatment at the minimum cost to cardiovascular health.
    Type of Medium: Online Resource
    ISSN: 0143-5221 , 1470-8736
    Language: English
    Publisher: Portland Press Ltd.
    Publication Date: 2021
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  • 4
    Online Resource
    Online Resource
    Portland Press Ltd. ; 2021
    In:  Clinical Science Vol. 135, No. 1 ( 2021-01-15), p. 71-100
    In: Clinical Science, Portland Press Ltd., Vol. 135, No. 1 ( 2021-01-15), p. 71-100
    Abstract: The development of new therapies for cancer has led to dramatic improvements in survivorship. Angiogenesis inhibitors represent one such advancement, revolutionising treatment for a wide range of malignancies. However, these drugs are associated with cardiovascular toxicities which can impact optimal cancer treatment in the short-term and may lead to increased morbidity and mortality in the longer term. Vascular endothelial growth factor inhibitors (VEGFIs) are associated with hypertension, left ventricular systolic dysfunction (LVSD) and heart failure as well as arterial and venous thromboembolism, QTc interval prolongation and arrhythmia. The mechanisms behind the development of VEGFI-associated LVSD and heart failure likely involve the combination of a number of myocardial insults. These include direct myocardial effects, as well as secondary toxicity via coronary or peripheral vascular damage. Cardiac toxicity may result from the ‘on-target’ effects of VEGF inhibition or ‘off-target’ effects resulting from inhibition of other tyrosine kinases. Similar mechanisms may be involved in the development of VEGFI-associated right ventricular (RV) dysfunction. Some VEGFIs can be associated with QTc interval prolongation and an increased risk of ventricular and atrial arrhythmia. Further pre-clinical and clinical studies and trials are needed to better understand the impact of VEGFI on the cardiovascular system. Once mechanisms are elucidated, therapies can be investigated in clinical trials and surveillance strategies for identifying VEGFI-associated cardiovascular complications can be developed.
    Type of Medium: Online Resource
    ISSN: 0143-5221 , 1470-8736
    Language: English
    Publisher: Portland Press Ltd.
    Publication Date: 2021
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  • 5
    In: Circulation, Ovid Technologies (Wolters Kluwer Health)
    Abstract: We investigated the usefulness of invasive coronary function testing to diagnose the cause of angina in patients with no obstructive coronary arteries. METHODS: Outpatients referred for coronary computed tomography angiography in 3 hospitals in the United Kingdom were prospectively screened. After coronary computed tomography angiography, patients with unobstructed coronary arteries, and who consented, underwent invasive endotyping. The diagnostic assessments included coronary angiography, fractional flow reserve (patient excluded if ≤0.80), and, for those without obstructive coronary artery disease, coronary flow reserve (abnormal 〈 2.0), index of microvascular resistance (abnormal ≥25), and intracoronary infusion of acetylcholine (0.182, 1.82, and 18.2 μg/mL; 2 mL/min for 2 minutes) to assess for microvascular and coronary spasm. Participants were randomly assigned to disclosure of the results of the coronary function tests to the invasive cardiologist (intervention group) or nondisclosure (control group, blinded). In the control group, a diagnosis of vasomotor angina was based on medical history, noninvasive tests, and coronary angiography. The primary outcome was the between-group difference in the reclassification rate of the initial diagnosis on the basis of coronary computed tomography angiography versus the final diagnosis after invasive endotyping. The Seattle Angina Questionnaire summary score and Treatment Satisfaction Questionnaire for Medication were secondary outcomes. RESULTS: Of 322 eligible patients, 250 (77.6%) underwent invasive endotyping; 19 (7.6%) had obstructive coronary disease, 127 (55.0%) had microvascular angina, 27 (11.7%) had vasospastic angina, 17 (7.4%) had both, and 60 (26.0%) had no abnormality. A total of 231 patients (mean age, 55.7 years; 64.5% women) were randomly assigned and followed up (median duration, 19.9 [12.6–26.9] months). The clinician diagnosed vasomotor angina in 51 (44.3%) patients in the intervention group and in 55 (47.4%) patients in the control group. After randomization, patients in the intervention group were 4-fold (odds ratio, 4.05 [95% CI, 2.32–7.24] ; P 〈 0.001) more likely to be diagnosed with a coronary vasomotor disorder; the frequency of this diagnosis increased to 76.5%. The frequency of normal coronary function (ie, no vasomotor disorder) was not different between the groups before randomization (51.3% versus 50.9%) but was reduced in the intervention group after randomization (23.5% versus 50.9%, P 〈 0.001). At 6 and 12 months, the Seattle Angina Questionnaire summary score in the intervention versus control groups was 59.2±24.2 (2.3±16.2 change from baseline) versus 60.4±23.9 (4.6±16.4 change) and 63.7±23.5 (4.7±14.7 change) versus 66.0±19.3 (7.9±17.1 change), respectively, and not different between groups (global P =0.36). Compared with the control group, global treatment satisfaction was higher in the intervention group at 12 months (69.9±22.8 versus 61.7±26.9, P =0.013). CONCLUSIONS: For patients with angina and no obstructive coronary arteries, a diagnosis informed by invasive functional assessment had no effect on long-term angina burden, whereas treatment satisfaction improved. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03477890
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
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  • 6
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 143, No. 6 ( 2021-02-09), p. 516-525
    Abstract: Sodium-glucose cotransporter 2 inhibitors reduce the risk of heart failure hospitalization and cardiovascular death in patients with heart failure and reduced ejection fraction (HFrEF). However, their effects on cardiac structure and function in HFrEF are uncertain. Methods: We designed a multicenter, randomized, double-blind, placebo-controlled trial (the SUGAR-DM-HF trial [Studies of Empagliflozin and Its Cardiovascular, Renal and Metabolic Effects in Patients With Diabetes Mellitus, or Prediabetes, and Heart Failure]) to investigate the cardiac effects of empagliflozin in patients in New York Heart Association functional class II to IV with a left ventricular (LV) ejection fraction ≤40% and type 2 diabetes or prediabetes. Patients were randomly assigned 1:1 to empagliflozin 10 mg once daily or placebo, stratified by age ( 〈 65 and ≥65 years) and glycemic status (diabetes or prediabetes). The coprimary outcomes were change from baseline to 36 weeks in LV end-systolic volume indexed to body surface area and LV global longitudinal strain both measured using cardiovascular magnetic resonance. Secondary efficacy outcomes included other cardiovascular magnetic resonance measures (LV end-diastolic volume index, LV ejection fraction), diuretic intensification, symptoms (Kansas City Cardiomyopathy Questionnaire Total Symptom Score, 6-minute walk distance, B-lines on lung ultrasound, and biomarkers (including N-terminal pro-B-type natriuretic peptide). Results: From April 2018 to August 2019, 105 patients were randomly assigned: mean age 68.7 (SD, 11.1) years, 77 (73.3%) male, 82 (78.1%) diabetes and 23 (21.9%) prediabetes, mean LV ejection fraction 32.5% (9.8%), and 81 (77.1%) New York Heart Association II and 24 (22.9%) New York Heart Association III. Patients received standard treatment for HFrEF. In comparison with placebo, empagliflozin reduced LV end-systolic volume index by 6.0 (95% CI, –10.8 to –1.2) mL/m 2 ( P =0.015). There was no difference in LV global longitudinal strain. Empagliflozin reduced LV end-diastolic volume index by 8.2 (95% CI, –13.7 to –2.6) mL/m 2 ( P =0.0042) and reduced N-terminal pro-B-type natriuretic peptide by 28% (2%–47%), P =0.038. There were no between-group differences in other cardiovascular magnetic resonance measures, diuretic intensification, Kansas City Cardiomyopathy Questionnaire Total Symptom Score, 6-minute walk distance, or B-lines. Conclusions: The sodium-glucose cotransporter 2 inhibitor empagliflozin reduced LV volumes in patients with HFrEF and type 2 diabetes or prediabetes. Favorable reverse LV remodeling may be a mechanism by which sodium-glucose cotransporter 2 inhibitors reduce heart failure hospitalization and mortality in HFrEF. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03485092.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 1466401-X
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  • 7
    Online Resource
    Online Resource
    SAGE Publications ; 2020
    In:  Scottish Medical Journal Vol. 65, No. 1 ( 2020-02), p. 24-27
    In: Scottish Medical Journal, SAGE Publications, Vol. 65, No. 1 ( 2020-02), p. 24-27
    Abstract: Testicular germ cell tumours are the most common malignancy in men aged 20 to 40 years. They are subdivided into seminoma and non-seminomatous germ cell tumours (NSGCTs). Both seminoma and NSGCT occur at about the same rate, however some tumours contain a combination of both. Cisplatin-based chemotherapy is used adjuvantly in high-risk stage 1 mixed and NSGCT patients and contributes towards oncological cure in almost all metastatic cases, regardless of histology. However, cardiovascular toxicity is a major concern. In addition to acute endothelial toxicity and associated risk of arterial thrombosis, accelerated atherosclerosis may be the result of chemotherapy-associated latent cardio-metabolic dysfunction. A 45-year-old man began treatment with cisplatin-based chemotherapy for testicular cancer. On day 9, he suffered an anterior ST segment elevation myocardial infarction (STEMI). There was proximal occlusion of the left anterior descending (LAD) artery but otherwise normal coronary arteries. Ten months following chemotherapy, he had another STEMI. There was a fresh obstructive lesion in the previously angiographically normal mid LAD, new diffuse coronary atheroma elsewhere and a deterioration in lipid profile despite statin therapy. Acute and longer-term cardiovascular risks of cisplatin-based chemotherapy may have different underlying pathophysiological mechanisms. These issues are of growing relevance in a population of patients expected to have excellent cancer-related outcomes.
    Type of Medium: Online Resource
    ISSN: 0036-9330 , 2045-6441
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2020
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  • 8
    In: Pulmonary Circulation, Wiley, Vol. 3, No. 3 ( 2013-09), p. 675-691
    Abstract: Circulating levels of asymmetric dimethylarginine (ADMA), a nitric oxide synthase inhibitor, are increased in patients with idiopathic pulmonary hypertension (IPAH). We hypothesized that ADMA abrogates gap junctional communication, required for the coordinated regulation of endothelial barrier function and angiogenesis, and so contributes to pulmonary endothelial dysfunction. The effects of ADMA on expression and function of gap junctional proteins were studied in human pulmonary artery endothelial cells; pulmonary endothelial microvascular cells from mice deficient in an enzyme metabolizing ADMA, dimethylarginine dimethylaminohydrolase I (DDAHI); and blood‐derived endothelial‐like cells from patients with IPAH. Exogenous and endogenous ADMA inhibited protein expression and membrane localization of connexin 43 (Cx43) in a nitric oxide/soluble guanosine monophosphate/c‐jun‐dependent manner in pulmonary endothelial cells, resulting in the inhibition of gap junctional communication, increased permeability, and decreased angiogenesis. The effects of ADMA were prevented by overexpression of DDAHI or Cx43 and by treatment with rotigaptide. Blood‐derived endothelial‐like cells from IPAH patients displayed a distinct disease‐related phenotype compared to cells from healthy controls, characterized by reduced DDAHI expression, increased ADMA production, and abnormal angiogenesis. In summary, we show that ADMA induces pulmonary endothelial dysfunction via changes in expression and activity of Cx43. Cells from IPAH patients exhibit abnormal DDAHI/Cx43 signaling as well as differences in gap junctional communication, barrier function, and angiogenesis. Strategies that promote DDAHI/Cx43 signaling may have an endothelium‐protective effect and be beneficial in pulmonary vascular disease.
    Type of Medium: Online Resource
    ISSN: 2045-8940 , 2045-8940
    Language: English
    Publisher: Wiley
    Publication Date: 2013
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  • 9
    In: Circulation: Heart Failure, Ovid Technologies (Wolters Kluwer Health), Vol. 15, No. 7 ( 2022-07)
    Abstract: Anthracyclines are effective cytotoxic drugs used in the treatment of breast cancer and lymphoma but are associated with myocardial injury, left ventricular dysfunction, and heart failure. Anthracycline-induced cardiotoxicity is highly variable in severity and without a proven therapeutic intervention. β-Adrenergic receptor blockers and renin-angiotensin-system inhibitor therapies have been associated with modest cardioprotective effects in unselected patients. Methods: The Cardiac CARE trial is a multicentre prospective randomized open-label blinded end point trial of combination β-adrenergic receptor blocker and renin-angiotensin-system inhibitor therapy in patients with breast cancer and non-Hodgkin lymphoma receiving anthracycline chemotherapy that is associated with myocardial injury. Patients at higher risk of cardiotoxicity with plasma high-sensitivity cTnI (cardiac troponin I) concentrations in the upper tertile at the end of chemotherapy are randomized to standard of care plus combination candesartan and carvedilol therapy or standard of care alone. All patients undergo cardiac magnetic resonance imaging before and 6 months after anthracycline treatment. The primary end point is the change in left ventricular ejection fraction at 6 months after chemotherapy. In low-risk nonrandomized patients, left ventricular ejection fraction before and 6 months after anthracycline will be compared with define the specificity of the high-sensitivity cTnI assay for identifying low-risk participants who do not develop left ventricular systolic dysfunction. Discussion: Cardiac CARE will examine whether cardiac biomarker monitoring identifies patients at risk of left ventricular dysfunction following anthracycline chemotherapy and whether troponin-guided treatment with combination candesartan and carvedilol therapy prevents the development of left ventricular dysfunction in these high-risk patients.
    Type of Medium: Online Resource
    ISSN: 1941-3289 , 1941-3297
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 2428100-1
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  • 10
    In: Clinical Kidney Journal, Oxford University Press (OUP), Vol. 16, No. 3 ( 2023-02-28), p. 512-520
    Abstract: Lymphocyte ratios reflect inflammation and have been associated with adverse outcomes in a range of diseases. We sought to determine any association between neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) and mortality in a haemodialysis cohort, including a coronavirus disease 2019 (COVID-19) infection subpopulation. Methods A retrospective analysis was performed of adults commencing hospital haemodialysis in the West of Scotland during 2010–21. NLR and PLR were calculated from routine samples around haemodialysis initiation. Kaplan–Meier and Cox proportional hazards analyses were used to assess mortality associations. Results In 1720 haemodialysis patients over a median of 21.9 (interquartile range 9.1–42.9) months, there were 840 all-cause deaths. NLR but not PLR was associated with all-cause mortality after multivariable adjustment [adjusted hazard ratio (aHR) for in participants with baseline NLR in quartile 4 (NLR ≥8.23) versus quartile 1 (NLR & lt;3.12) 1.63, 95% confidence interval (CI) 1.32–2.00]. The association was stronger for cardiovascular death (NLR quartile 4 versus 1 aHR 3.06, 95% CI 1.53–6.09) than for non-cardiovascular death (NLR quartile 4 versus 1 aHR 1.85, 95% CI 1.34–2.56). In the COVID-19 subpopulation, both NLR and PLR at haemodialysis initiation were associated with risk of COVID-19-related death after adjustment for age and sex (NLR: aHR 4.69, 95% CI 1.48–14.92 and PLR: aHR 3.40, 95% CI 1.02–11.36; for highest vs lowest quartiles). Conclusions NLR is strongly associated with mortality in haemodialysis patients while the association between PLR and adverse outcomes is weaker. NLR is an inexpensive, readily available biomarker with potential utility in risk stratification of haemodialysis patients.
    Type of Medium: Online Resource
    ISSN: 2048-8505 , 2048-8513
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2656786-6
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