Addition of FFRct in the diagnostic pathway of patients with stable chest pain to reduce unnecessary invasive coronary angiography (FUSION) : Rationale and design for the multicentre, randomised, controlled FUSION trial.

BACKGROUND: Coronary computed tomography angiography (CCTA) is widely used in the diagnostic work-up of patients with stable chest pain. CCTA has an excellent negative predictive value, but a moderate positive predictive value for detecting coronary stenosis. Computed tomography-derived fractional flow reserve (FFRct) is a non-invasive, well-validated technique that provides functional assessment of coronary stenosis, improving the positive predictive value of CCTA. However, to determine the value of FFRct in routine clinical practice, a pragmatic randomised, controlled trial (RCT) is required. We will conduct an RCT to investigate the impact of adding FFRct analysis in the diagnostic pathway of patients with a coronary stenosis on CCTA on the rate of unnecessary invasive coronary angiography, cost-effectiveness, quality of life and clinical outcome. METHODS: The FUSION trial is a prospective, multicentre RCT that will randomise 528 patients with stable chest pain and anatomical stenosis of ≥ 50% but < 90% in at least one coronary artery of ≥ 2 mm on CCTA, to FFRct-guided care or usual care in a 1:1 ratio. Follow-up will be 1 year. The primary endpoint is the rate of unnecessary invasive coronary angiography within 90 days. CONCLUSION: The FUSION trial will evaluate the use of FFRct in stable chest pain patients from the Dutch perspective. The trial is funded by the Dutch National Health Care Institute as part of the research programme 'Potentially Promising Care' and the results will be used to assess if FFRct reimbursement should be included in the standard health care package.

Independent prognostic value of coronary artery calcium score and coronary computed tomography angiography in an outpatient cohort of low to intermediate risk chest pain patients.

BACKGROUND: Limited studies report on the additional prognostic value of coronary computed tomography angiography (CCTA) and the coronary artery calcium score (CACS). METHODS: For a median of 637 days, 1551 outpatients with chest pain, without known coronary artery disease (CAD) and low or intermediate pre-test probability of CAD, were followed for major adverse cardiac events (MACE), defined as death, myocardial infarction or late revascularisation. Cox proportional hazard regression was used to evaluate the independent prognostic value of CCTA and CACS. RESULTS: MACE occurred in 23 patients (1.5 %): death (3, 0.2 %), myocardial infarction (4, 0.3 %) and late revascularisation (16, 1.3 %). Multivariate analysis showed an independent prognostic value of CCTA (p < 0.001), CACS of 100-400 (p = 0.035) and CACS of > 400 (p = 0.021). CCTA showed obstructive CAD in 3.1 % of patients with CACS = 0. No events occurred in patients with CACS = 0 without obstructive CAD at CCTA, whereas 2/23 patients (9 %) with CACS = 0 with obstructive CAD had a MACE. CONCLUSIONS: Our study shows that both CCTA and higher CACS categories have independent prognostic value in chest pain patients with low to intermediate pre-test probability of obstructive CAD, in which CCTA is appropriate. Furthermore a non-negligible amount of patients with CACS = 0 have obstructive CAD at CCTA. CCTA can be used in these patients to identify those at risk for MACE.

GRACE and TIMI risk scores but not stress imaging predict long-term cardiovascular follow-up in patients with chest pain after a rule-out protocol.

OBJECTIVE: To determine the long-term prognostic value of stress imaging and clinical risk scoring for cardiovascular mortality in chest pain patients after ruling out acute coronary syndrome (ACS). METHODS: A standard rule-out protocol was performed in emergency room patients with a normal or non-diagnostic admission electrocardiogram (ECG) within 6 h of chest pain onset. ACS patients were identified by troponin T, recurrent angina and serial ECG. Dobutamine stress echocardiography (DSE) was performed after ACS was ruled out. Myocardial perfusion scintigraphy (MPS) was performed within 6 months in an outpatient setting according to the physician's discretion. RESULTS: 524 patients were included. GRACE and TIMI risk scores were 75 (57-96) and 1 (0-2) in the rule-out ACS group, and 89 (74-107) and 2 (1-3) in the ACS group, respectively (median, interquartile range). Follow-up (median 9.4 (8.9-10.0) years) was complete in 96%. 350 of 379 rule-out ACS patients had an interpretable DSE and 52 patients underwent an MPS. 21 of the rule-out ACS patients (6%) died of a cardiovascular cause compared with 24 (17%) ACS patients (p < 0.001). For rule-out ACS patients, C-statistics were 0.829 and 0.803 for the GRACE and TIMI scores. In these patients, DSE and MPS outcome did not predict long-term cardiovascular mortality. In multivariate analysis, known chronic heart failure, ACE inhibitor use, and GRACE score were independent predictors of cardiovascular mortality. CONCLUSIONS: TIMI and GRACE score but not DSE and MPS are accurate predictors of long-term cardiovascular mortality, even in chest pain patients with a normal or non-diagnostic electrocardiogram undergoing a rule-out protocol.

Right-sided invasive metastatic thymoma of the heart.

Cardiac tumours may display diverse symptoms through potential involvement of any structure of the heart. We describe a case of a highly malignant thymoma with involvement of different cardiac structures with important haemodynamic compromise. With the high sensitivity of transthoracic echocardiography for detection of intracardiac masses, computed tomography and magnetic resonance add essential structural preoperative information on the tumour and surrounding tissue as vessels, pleura, lung and mediastinum.

C-reactive protein in myocardial infarction binds to circulating microparticles but is not associated with complement activation.

BACKGROUND: C-reactive protein (CRP) is elevated in patients with acute myocardial infarction (AMI). When CRP binds to membrane phospholipids or Fc receptors, it activates the complement system. Recent studies show that CRP can be exposed on cell-derived microparticles (MP) and is associated complement activation. OBJECTIVES: We studied complement activation on circulating MP in AMI patients and healthy controls. METHODS: MP were isolated from plasma of AMI patients (n=21) and sex- and age-matched healthy individuals (n=10), and analyzed by flow cytometry for bound complement components (C1q, C4, C3) and complement inhibitor and activator molecules (C4bp, CRP, serum amyloid P component, immunoglobulins IgM and IgG). Concurrently, the levels of fluid phase complement activation products and inhibitor and activator molecules were determined. RESULTS: Fluid phase CRP, MP with bound CRP (CRP + MP), and C3 activation products were elevated in AMI patients compared to controls (P=0.032, P=0.031 and P=0.023, respectively), and fluid phase CRP correlated with CRP+ MP (r=0.84, P<0.001). Although CRP+ MP were elevated, they were not associated with C1q+ MP (r=0.32, P=0.174). In contrast, IgG+ MP were associated with C1q+ MP (r=0.73, P<0.001), C4+ MP and C3+ MP (r=0.78 and r=0.87, respectively; both P<0.001), and C4bp (r=0.63, P=0.004). In healthy individuals, CRP+ MP were strongly associated with C1q+ MP (r=0.82, P=0.007), which in turn were associated with C4+ MP and C3+ MP (r=0.68, P=0.032 and r=0.68, P=0.031, respectively). CONCLUSIONS: Despite CRP-associated complement activation on the surface of MP in healthy individuals and a strong correlation between MP-bound CRP and fluid phase CRP in AMI patients, the MP-associated complement activation is IgG- but not CRP-dependent in AMI patients.

Increases in myeloperoxidase levels after exercise in myocardial perfusion scintigraphy are not induced by myocardial ischemia.

BACKGROUND: Increased systemic levels of myeloperoxidase (MPO) have been reported in patients with acute myocardial ischemia. We studied the association between exercise-induced myocardial ischemia measured by myocardial perfusion scintigraphy (MPS) and the magnitude and time course of changes in MPO levels in humans. METHODS: One hundred and twenty six patients underwent symptom limited exercise MPS. Myocardial ischemia was assessed semi-quantitatively. Plasma samples were taken before the start of exercise (baseline), at maximum exercise and every hour up to 6 h after maximum exercise. RESULTS: Myocardial ischemia was present in 42 (33%) patients. MPO levels rapidly increased during exercise in patients with and without ischemia (to 131% (106-172%) and 145% (121-199%) of baseline, respectively). MPO levels and absolute changes in MPO did not differ between patients with and without ischemia at any time point. None of the patient characteristics, including presence of ischemia, was independently predictive of the absolute increase in MPO levels during exercise. CONCLUSIONS: Exercise related immediate increases in MPO levels do not reflect myocardial ischemia.