Dynamic Changes in High-Sensitivity Cardiac Troponin I in Response to Anthracycline-Based Chemotherapy.

AIMS: Treatment advances have improved cancer-related outcomes and shifted interest towards minimising long-term iatrogenic complications, particularly chemotherapy-related cardiotoxicity. High-sensitivity cardiac troponin I (hs-cTnI) assays accurately quantify very low concentrations of plasma troponin and enable early detection of cardiomyocyte injury prior to the development of myocardial dysfunction. The profile of hs-cTnI in response to anthracycline-based treatment has not previously been described. MATERIALS AND METHODS: This was a multicentre prospective observational cohort study. Female patients with newly diagnosed invasive breast cancer scheduled to receive anthracycline-based (epirubicin) chemotherapy were recruited. Blood sampling was carried out before and 24 h after each cycle. Hs-cTnI concentrations were measured using the Abbott ARCHITECTSTAT assay. RESULTS: We recruited 78 women with a median (interquartile range) age of 52 (49-61) years. The median baseline troponin concentration was 1 (1-4) ng/l and the median cumulative epirubicin dose was 394 (300-405) mg/m2. Following an initial 33% fall 24 h after anthracycline dosing (P < 0.001), hs-cTnI concentrations increased by a median of 50% (P < 0.001) with each successive treatment cycle. In total, 45 patients had troponin measured immediately before the sixth treatment cycle, 21 (46.6%) of whom had hs-cTnI concentrations ≥16 ng/l, indicating myocardial injury. Plasma hs-cTnI concentrations before the second treatment cycle were a strong predictor of subsequent myocardial injury. CONCLUSIONS: Cardiotoxicity arising from anthracycline therapy is detectable in the earliest stages of breast cancer treatment and is cumulative with each treatment cycle. This injury is most reliably determined from blood sampling carried out before rather than after each treatment cycle.

Staphylococcus aureus endocarditis associated with injecting new psychoactive substances.

BACKGROUND: Staphylococcus aureus infective endocarditis (IE) associated with injection of new psychoactive substances (NPS) in Edinburgh from 2014 to 2016 was observed. We compared these infections with a series of S. aureus IE cases in a non-injecting population within Edinburgh. METHODS: NPS-associated S. aureus IE diagnosed between 1 January 2014 and 31 May 2016 in persons who inject drugs (PWID) were compared with a series of S. aureus IE cases from non-PWID. RESULTS: There was a fourfold increase in the annual incidence of S. aureus IE, mainly due to NPS use in PWID. A larger vegetation diameter was seen on echocardiogram in PWID vs non-PWID (median 1.7 cm vs 0.65 cm; p = 0.009) with more embolic complications in PWID (15 PWID vs 1 non-PWID; p = 2.1 x 10-7) but no difference in 90-day mortality (2 PWID vs 4 non-PWID; p = 0.39). CONCLUSIONS: NPS-associated S. aureus IE correlated with complications, such as deep organ embolic abscesses, that were different from non-PWID S. aureus IE. The alarming increase in incidence resolved with targeted public health and legislative measures.

Perioperative elafin for ischaemia-reperfusion injury during coronary artery bypass graft surgery: a randomised-controlled trial.

BACKGROUND: Elafin is a potent endogenous neutrophil elastase inhibitor that protects against myocardial inflammation and injury in preclinical models of ischaemic-reperfusion injury. We investigated whether elafin could inhibit myocardial ischaemia-reperfusion injury induced during coronary artery bypass graft (CABG) surgery. METHODS AND RESULTS: In a randomised double-blind placebo-controlled parallel group clinical trial, 87 patients undergoing CABG surgery were randomised 1:1 to intravenous elafin 200 mg or saline placebo administered after induction of anaesthesia and prior to sternotomy. Myocardial injury was measured as cardiac troponin I release over 48 h (area under the curve (AUC)) and myocardial infarction identified with MRI. Postischaemic inflammation was measured by plasma markers including AUC high-sensitive C reactive protein (hs-CRP) and myeloperoxidase (MPO). Elafin infusion was safe and resulted in >3000-fold increase in plasma elafin concentrations and >50% inhibition of elastase activity in the first 24 h. This did not reduce myocardial injury over 48 h (ratio of geometric means (elafin/placebo) of AUC troponin I 0.74 (95% CI 0.47 to 1.15, p=0.18)) although post hoc analysis of the high-sensitive assay revealed lower troponin I concentrations at 6 h in elafin-treated patients (median 2.4 vs 4.1 µg/L, p=0.035). Elafin had no effect on myocardial infarction (elafin, 7/34 vs placebo, 5/35 patients) or on markers of inflammation: mean differences for AUC hs-CRP of 499 mg/L/48 h (95% CI -207 to 1205, p=0.16), and AUC MPO of 238 ng/mL/48 h (95% CI -235 to 711, p=0.320). CONCLUSIONS: There was no strong evidence that neutrophil elastase inhibition with a single-dose elafin treatment reduced myocardial injury and inflammation following CABG-induced ischaemia-reperfusion injury. TRIAL REGISTRATION NUMBER: (EudraCT 2010-019527-58, ISRCTN82061264).

Nanoparticle enhanced MRI scanning to detect cellular inflammation in experimental chronic renal allograft rejection.

Objectives. We investigated whether ultrasmall paramagnetic particles of iron oxide- (USPIO-) enhanced magnetic resonance imaging (MRI) can detect experimental chronic allograft damage in a murine renal allograft model. Materials and Methods. Two cohorts of mice underwent renal transplantation with either a syngeneic isograft or allograft kidney. MRI scanning was performed prior to and 48 hours after USPIO infusion using T2(∗)-weighted protocols. R2(∗) values were calculated to indicate the degree of USPIO uptake. Native kidneys and skeletal muscle were imaged as reference tissues and renal explants analysed by histology and electron microscopy. Results. R2(∗) values in the allograft group were higher compared to the isograft group when indexed to native kidney (median 1.24 (interquartile range: 1.12 to 1.36) versus 0.96 (0.92 to 1.04), P < 0.01). R2(∗) values were also higher in the allograft transplant when indexed to skeletal muscle (6.24 (5.63 to 13.51)) compared to native kidney (2.91 (1.11 to 6.46) P < 0.05). Increased R2(∗) signal in kidney allograft was associated with macrophage and iron staining on histology. USPIO were identified within tissue resident macrophages on electron microscopy. Conclusion. USPIO-enhanced MRI identifies macrophage.

Granulomatosis with polyangiitis and constrictive pericarditis--a case report.

Polyangiitis with granulomatosis, previously known as Wegener's granulomatosis, is a systemic necrotising granulomatous vasculitis. It predominantly affects the upper and lower respiratory tracts and the kidneys, but can potentially affect any organ system. It is diagnosed by clinical features, immunology (anti-neutrophil cytoplasmic antibodies) and histology. Cardiac involvement occurs in 6 to 44% of cases. We present a case of polyangiitis with granulomatosis and constrictive pericarditis, which occurred despite vigorous immunosuppression and which required surgical pericardectomy.

Urgent in-patient coronary angiography: a comparison of centres with and without cardiac catheter facilities.

OBJECTIVES: To review the referral of patients to a tertiary centre for urgent angiography and to determine if there are differences in invasive treatment strategies for patients with acute coronary syndrome (ACS). METHODS: There were 2 parts to the study, a retrospective part over 3.5 years from a computerised cardiac laboratory booking data base and a prospective part over 3 months. RESULTS: There were 1190 urgent in-patient angiograms performed with 499 (42%) admitted initially to the tertiary centre while the remaining 691 (58%) were admitted to district general hospitals (DGH), with no on-site access to a cardiac laboratory, and subsequently transferred to the tertiary centre. Once referred, DGH patients waited longer for their angiogram (2.7 +/- 3.2 vs 2.0 +/- 2.8 days, p < 0.0001). Interestingly, DGH patients appear to spend an average of 4 days in hospital prior to referral for angiography. DGH patients were more likely to have a higher Thrombosis in Myocardial Infarction (TIMI) risk score at presentation and following angiography were more likely to have coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI) and less likely to have angiographically normal arteries. CONCLUSIONS: Our findings are consistent with previous studies demonstrating that access to coronary angiography varies considerably between hospitals. However, we have demonstrated that patients in DGHs wait on average 4 days before referral for coronary angiography suggesting that there may be triage based on initial responses to medical therapy. Further research is needed to determine whether this has a direct effect on outcomes.

Therapeutic inhibition of tumour necrosis factor alpha in patients with heart failure: cooling an inflamed heart.

Heart failure is a systemic disorder characterised by tissue hypoxia and secondary organ dysfunction which occurs in response to various myocardial insults that include ischaemia, viral infections, and toxins. In addition to maladaptive neurohumoral activation, heart failure is associated with an inflammatory state that appears to have a detrimental effect on cardiac function and prognosis. This has led to the suggestion that anti-inflammatory interventions may have therapeutic potential in the symptomatic and prognostic treatment of patients with heart failure. This review considers the role of inhibition of the cytokine tumour necrosis factor alpha in the treatment of heart failure.

Application of gene expression profiling to cardiovascular disease.

The number of cardiovascular publications featuring gene expression profiling technologies is growing rapidly. This article introduces four profiling techniques; serial analysis of gene expression, differential display, subtractive hybridisation and DNA microarrays. Illustrations of their application towards cardiovascular research are given and their potential for gene discovery and improving our understanding of gene function is discussed.