Cardiovascular Effects of Urocortin 2 and Urocortin 3 in Patients with Chronic Heart Failure

Aims: Urocortin 2 and urocortin 3 may play a role in the pathophysiology of heart failure and are emerging therapeutic targets. We aimed to examine the local and systemic cardiovascular effects of urocortin 2 and urocortin 3 in healthy subjects and patients with heart failure. Methods: Patients with heart failure (n = 8) and age and gender-matched healthy subjects (n = 8) underwent bilateral forearm arterial blood flow measurement using forearm venous occlusion plethysmography during intra-arterial infusions of urocortin 2 (3.6–36 pmol min−1), urocortin 3 (360–3600 pmol min−1) and substance P (2–8 pmol min−1). Heart failure patients (n = 9) and healthy subjects (n = 7) underwent non-invasive impedance cardiography during incremental intravenous infusions of sodium nitroprusside (573–5730 pmol kg−1 min−1 ), urocortin 2 (36–360 pmol min−1 ), urocortin 3 (1.2–12 nmol min−1) and saline placebo. Results: Urocortin 2, urocortin 3 and substance P induced dose-dependent forearm arterial vasodilatation in both groups (P < 0.05 for both) with no difference in magnitude of vasodilatation between patients and healthy subjects. During systemic intravenous infusions, urocortin 3 increased heart rate and cardiac index and reduced mean arterial pressure and peripheral vascular resistance index in both groups (P < 0.01 for all). Urocortin 2 produced similar responses to urocortin 3, although increases in cardiac index and heart rate were only significant in heart failure (P < 0.05) and healthy subjects (P < 0.001), respectively. Conclusion: Urocortins 2 and 3 cause vasodilatation, reduce peripheral vascular resistance and increase cardiac output in both health and disease. These data provide further evidence to suggest that urocortins 2 and 3 continue to hold promise for the treatment of heart failure

Ferumoxytol-enhanced magnetic resonance imaging in acute myocarditis

Objectives Ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced MRI can detect tissue-resident macrophage activity and identify cellular inflammation within tissues. We hypothesised that USPIO-enhanced MRI would provide a non-invasive imaging technique that would improve the diagnosis and management of patients with acute myocarditis. Methods Ten volunteers and 14 patients with suspected acute myocarditis underwent T2, T2* and late gadolinium enhancement (LGE) 3T MRI, with further T2* imaging at 24 hours after USPIO (ferumoxytol, 4 mg/kg) infusion, at baseline and 3 months. Myocardial oedema and USPIO enhancement were determined within areas of LGE as well as throughout the myocardium. Results Myocarditis was confirmed in nine of the 14 suspected cases of myocarditis. There was greater myocardial oedema in regions of LGE in patients with myocarditis when compared with healthy volunteer myocardium (T2 value, 57.1±5.3 vs 46.7±1.6 ms, p0.05). Imaging after 3 months in patients with myocarditis revealed a reduction in volume of LGE, a reduction in oedema measures within regions displaying LGE and improvement in ejection fraction (mean −19.7 mL, 95% CI (−0.5 to −40.0)), −5.8 ms (−0.9 to −10.7) and +6% (0.5% to 11.5%), respectively, p<0.05 for all). Conclusion In patients with acute myocarditis, USPIO-enhanced MRI does not provide additional clinically relevant information to LGE and T2 mapping MRI. This suggests that tissue-resident macrophages do not provide a substantial contribution to the myocardial inflammation in this condition. Clinical trial registration NCT02319278; Results

Systematic hand-held echocardiography in patients hospitalized with acute coronary syndrome

Aims: Transthoracic echocardiography is recommended in all patients with acute coronary syndrome but is time-consuming and lacks an evidence base. We aimed to assess the feasibility, diagnostic accuracy and time-efficiency of hand-held echocardiography in patients with acute coronary syndrome and describe the impact of echocardiography on clinical management in this setting.Methods and results: Patients with acute coronary syndrome underwent both hand-held and transthoracic echocardiography with agreement between key imaging parameters assessed using kappa statistics. The immediate clinical impact of hand-held echocardiography in this population was systematically evaluated.Overall, 262 patients (65±12 years, 71% male) participated. Agreement between hand-held and transthoracic echocardiography was good-to-excellent (kappa 0.60-1.00) with hand-held echocardiography having an overall negative predictive value of 95%. Hand-held echocardiography was performed rapidly (7.7±1.6 min) and completed a median of 5 [interquartile range 3-20] hours earlier than transthoracic echocardiography. Systematic hand-held echocardiography in all patients with acute coronary syndrome identified an important cardiac abnormality in 50% and the clinical management plan was changed by echocardiography in 42%. In 85% of cases, hand-held echocardiography was sufficient for patient decision-making and transthoracic echocardiography was no longer deemed necessary.Conclusions: In patients with acute coronary syndrome, hand-held echocardiography provides comparable results to transthoracic echocardiography, can be more rapidly applied and gives sufficient imaging information for decision-making in the vast majority of patients. Systematic echocardiography has clinical impact in half of patients, supporting the clinical utility of echocardiography in this population, and providing an evidence-base for current guidelines.Keywords: acute coronary syndrome; clinical impact; diagnostic accuracy; hand-held echocardiography

Ferumoxytol-enhanced magnetic resonance imaging methodology and normal values at 1.5 and 3T

Background: Ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) can detect tissue-resident macrophage activity and identify cellular inflammation. Clinical studies using this technique are now emerging. We aimed to report a range of normal R2* values at 1.5 and 3 T in the myocardium and other tissues following ferumoxytol administration, outline the methodology used and suggest solutions to commonly encountered analysis problems. Methods: Twenty volunteers were recruited: 10 imaged each at 1.5 T and 3 T. T2* and late gadolinium enhanced (LGE) MRI was conducted at baseline with further T2* imaging conducted approximately 24 h after USPIO infusion (ferumoxytol, 4 mg/kg). Regions of interest were selected in the myocardium and compared to other tissues. Results: Following administration, USPIO was detected by changes in R2* from baseline (1/T2*) at 24 h in myocardium, skeletal muscle, kidney, liver, spleen and blood at 1.5 T, and myocardium, kidney, liver, spleen, blood and bone at 3 T (p &lt; 0.05 for all). Myocardial changes in R2* due to USPIO were 26.5 ± 7.3 s-1 at 1.5 T, and 37.2 ± 9.6 s-1 at 3 T (p &lt; 0.0001 for both). Tissues showing greatest ferumoxytol enhancement were the reticuloendothelial system: the liver, spleen and bone marrow (216.3 ± 32.6 s-1, 336.3 ± 60.3 s-1, 69.9 ± 79.9 s-1; p &lt; 0.0001, p &lt; 0.0001, p = ns respectively at 1.5 T, and 275.6 ± 69.9 s-1, 463.9 ± 136.7 s-1, 417.9 ± 370.3 s-1; p &lt; 0.0001, p &lt; 0.0001, p &lt; 0.01 respectively at 3 T). Conclusion: Ferumoxytol-enhanced MRI is feasible at both 1.5 T and 3 T. Careful data selection and dose administration, along with refinements to echo-time acquisition, post-processing and analysis techniques are essential to ensure reliable and robust quantification of tissue enhancement

Vascular and plaque imaging with ultrasmall superparamagnetic particles of iron oxide

Cardiovascular Magnetic Resonance (CMR) has become a primary tool for non-invasive assessment of cardiovascular anatomy, pathology and function. Existing contrast agents have been utilised for the identification of infarction, fibrosis, perfusion deficits and for angiography. Novel ultrasmall superparamagnetic particles of iron oxide (USPIO) contrast agents that are taken up by inflammatory cells can detect cellular inflammation non-invasively using CMR, potentially aiding the diagnosis of inflammatory medical conditions, guiding their treatment and giving insight into their pathophysiology. In this review we describe the utilization of USPIO as a novel contrast agent in vascular disease