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Coronary artery disease (CAD) is a leading cause of death and morbidity globally. Myocardial perfusion scintigraphy (MPS) is commonly used for the diagnosis of CAD, necessitating hyperaemia achieved either by physical exertion or by pharmacological stress, most commonly through use of a coronary arteriolar dilator. This is challenging in patients with respiratory conditions because exercise may be submaximal and adenosine is contraindicated because of the risk of bronchoconstriction. Regadenoson is the only selective adenosine A 2A receptor agonist approved as a vasodilator in MPS. The risk of bronchospasm with regadenoson has been investigated in large, randomised trials; however, patients with the most severe respiratory conditions were not included. In this case series, we present the use of regadenoson MPS in five patients with moderate-to-severe lung conditions, including patients requiring lung volume reduction surgery and lung transplant. In all cases, regadenoson MPS provided valuable information for risk assessment and treatment optimisation. Although dyspnoea occurred in all patients, regadenoson was well tolerated without serious adverse events or bronchospasm; in no case was intervention required to treat dyspnoea.

In 2012, the American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) Task Force on Practice Guidelines jointly with the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons produced a set of recommendations intended to assist physicians in the diagnosis and management of patients with stable ischemic heart disease. Two years later, a focused update on the 2012 guidelines was published. A year before this update, The Task Force on the management of stable coronary artery disease (CAD) of the European Society of Cardiology (ESC) issued a guideline on the management of stable CAD. This document brings together European and American recommendations that include the use of stress testing and non-invasive imaging for the diagnosis and management of patients with known or suspected stable CAD.

Background: There is emerging evidence of the central role of neutrophils in both atherosclerotic plaque formation and rupture. Patients with lower neutrophil counts following acute coronary syndromes tend to have a greater coronary flow reserve, which is a strong predictor of long-term cardiovascular health. But so far, no data are available regarding the impact of neutrophil inhibition on cardiovascular clinical or surrogate endpoints. Therefore, the aim of this study is to investigate the effects of AZD5069, a cysteine-X-cysteine chemokine receptor 2 (CXCR2) inhibitor, on coronary flow reserve and coronary structure and function in patients with coronary artery disease., Methods/design: Ninety subjects with coronary artery disease undergoing percutaneous coronary intervention will be included in this investigator-driven, randomised, placebo-controlled, double-blind, phase IIa, single-centre study. Participants will be randomised to receive either AZD5069 (40 mg) administered orally twice daily or placebo for 24 weeks. Change in coronary flow reserve as determined by 13 N-ammonia positron emission tomography-computed tomography will be the primary outcome. Change in the inflammatory component of coronary plaque structure and the backward expansion wave, an invasive coronary physiological measure of diastolic function, will be assessed as secondary outcomes., Discussion: Cardiovascular surrogate parameters, such as coronary flow reserve, may provide insights into the potential mechanisms of the cardiovascular effects of CXCR2 inhibitors. Currently, ongoing trials do not specifically focus on neutrophil function as a target of intervention, and we therefore believe that our study will contribute to a better understanding of the role of neutrophil-mediated inflammation in coronary artery disease., Trial Registration: EudraCT, 2016-000775-24 . Registered on 22 July 2016. International Standard Randomised Controlled Trial Number, ISRCTN48328178 . Registered on 25 February 2016.

In 2014, the Task Force on Myocardial Revascularization of the European Society of Cardiology and the European Association for Cardio-Thoracic Surgery with the special contribution of the European Association of Percutaneous Cardiovascular Interventions published a comprehensive set of recommendations on myocardial revascularization in patients presenting with acute or chronic coronary artery disease. In the United States, pertinent guidance on this topic has been published by the American College of Cardiology, American Heart Association and other relevant societies in multiple guideline documents that have been published in recent years. This document brings together European and American recommendations on myocardial revascularization with a focus on the role of cardiac imaging.

Pharmacological stress is an alternative method to dynamic exercise that combined with noninvasive imaging allows the detection of flow-limiting coronary artery disease (CAD). It represents the stress procedure of choice in patients who cannot exercise appropriately. In women, pharmacological stress combined with myocardial perfusion scintigraphy (MPS) has demonstrated to be highly accurate for the detection of obstructive CAD and a valuable tool that helps separate patients at low cardiac risk from those with an adverse prognosis. Pharmacological stress with positron emission tomographic (PET) imaging is increasingly used in the investigation of suspected obstructive CAD; available evidence shows that the diagnostic profile and prognostic value of stress PET imaging is similar to that of stress MPS in women.

Aims: Hybrid imaging provides a non-invasive assessment of coronary anatomy and myocardial perfusion. We sought to evaluate the added clinical value of hybrid imaging in a multi-centre multi-vendor setting., Methods and Results: Fourteen centres enrolled 252 patients with stable angina and intermediate (20-90%) pre-test likelihood of coronary artery disease (CAD) who underwent myocardial perfusion scintigraphy (MPS), CT coronary angiography (CTCA), and quantitative coronary angiography (QCA) with fractional flow reserve (FFR). Hybrid MPS/CTCA images were obtained by 3D image fusion. Blinded core-lab analyses were performed for CTCA, MPS, QCA and hybrid datasets. Hemodynamically significant CAD was ruled-in non-invasively in the presence of a matched finding (myocardial perfusion defect co-localized with stenosed coronary artery) and ruled-out with normal findings (both CTCA and MPS normal). Overall prevalence of significant CAD on QCA (>70% stenosis or 30-70% with FFR≤0.80) was 37%. Of 1004 pathological myocardial segments on MPS, 246 (25%) were reclassified from their standard coronary distribution to another territory by hybrid imaging. In this respect, in 45/252 (18%) patients, hybrid imaging reassigned an entire perfusion defect to another coronary territory, changing the final diagnosis in 42% of the cases. Hybrid imaging allowed non-invasive CAD rule-out in 41%, and rule-in in 24% of patients, with a negative and positive predictive value of 88% and 87%, respectively., Conclusion: In patients at intermediate risk of CAD, hybrid imaging allows non-invasive co-localization of myocardial perfusion defects and subtending coronary arteries, impacting clinical decision-making in almost one every five subjects., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Noninvasive functional imaging plays a major role in the diagnosis of hemodynamically significant coronary artery disease (CAD) by means of the detection of abnormal myocardial perfusion. For this, cardiac stressors are essential as they induce hypoperfusion in the presence of flow-limiting coronary stenosis. Several pharmacological stressors are currently available and it is important that clinicians who are involved in the care and management of patients with CAD become familiar with their indications, contraindications and protocols. Among the primary coronary vasodilator agents, regadenoson is increasingly used as the default stressor or as an alternative to other modalities of stress. This article provides an updated review of regadenoson stress for the assessment of patients with suspected or known CAD and describes its pharmacological properties, stress protocol, efficacy and safety profile.

Background: The choice of imaging techniques in patients with suspected coronary artery disease (CAD) varies between countries, regions, and hospitals. This prospective, multicenter, comparative effectiveness study was designed to assess the relative accuracy of commonly used imaging techniques for identifying patients with significant CAD., Methods and Results: A total of 475 patients with stable chest pain and intermediate likelihood of CAD underwent coronary computed tomographic angiography and stress myocardial perfusion imaging by single photon emission computed tomography or positron emission tomography, and ventricular wall motion imaging by stress echocardiography or cardiac magnetic resonance. If ≥1 test was abnormal, patients underwent invasive coronary angiography. Significant CAD was defined by invasive coronary angiography as >50% stenosis of the left main stem, >70% stenosis in a major coronary vessel, or 30% to 70% stenosis with fractional flow reserve ≤0.8. Significant CAD was present in 29% of patients. In a patient-based analysis, coronary computed tomographic angiography had the highest diagnostic accuracy, the area under the receiver operating characteristics curve being 0.91 (95% confidence interval, 0.88-0.94), sensitivity being 91%, and specificity being 92%. Myocardial perfusion imaging had good diagnostic accuracy (area under the curve, 0.74; confidence interval, 0.69-0.78), sensitivity 74%, and specificity 73%. Wall motion imaging had similar accuracy (area under the curve, 0.70; confidence interval, 0.65-0.75) but lower sensitivity (49%, P<0.001) and higher specificity (92%, P<0.001). The diagnostic accuracy of myocardial perfusion imaging and wall motion imaging were lower than that of coronary computed tomographic angiography (P<0.001)., Conclusions: In a multicenter European population of patients with stable chest pain and low prevalence of CAD, coronary computed tomographic angiography is more accurate than noninvasive functional testing for detecting significant CAD defined invasively., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT00979199., (© 2015 American Heart Association, Inc.)

Background: The extent and severity of ischemia on myocardial perfusion scintigraphy (MPS) is commonly used to risk-stratify patients with coronary artery disease. Estimation of ischemic burden by cardiovascular magnetic resonance (CMR) with conventional 2-dimensional myocardial perfusion methods is limited by incomplete cardiac coverage. More recently developed 3-dimensional (3D) myocardial perfusion CMR, however, provides whole-heart coverage. The aim of this study was to compare ischemic burden on 3D myocardial perfusion CMR with (99m)Tc-tetrofosmin MPS., Methods and Results: Forty-five patients who had undergone clinically indicated MPS underwent rest and adenosine stress 3D myocardial perfusion and late gadolinium enhancement CMR. Summed stress and rest scores were calculated for MPS and CMR using a 17-segment model and expressed as a percentage of the maximal possible score. Ischemic burden was defined as the difference between stress and rest scores. 3D myocardial perfusion CMR and MPS agreed in 38 of the 45 patients for the detection of any inducible ischemia. The mean ischemic burden for MPS and CMR was similar (7.5±8.9% versus 6.8±9.5%, respectively, P=0.82) with a strong correlation between techniques (rs=0.70, P<0.001). In a subset of 33 patients who underwent clinically indicated invasive coronary angiography, sensitivities and specificities of the 2 techniques to detect angiographic coronary artery disease were similar (McNemar P=0.45)., Conclusions: 3D myocardial perfusion CMR is an alternative to MPS for detecting the presence and rating the severity of ischemia., (© 2014 American Heart Association, Inc.)

Stress radionuclide myocardial perfusion single-photon emission computed tomography (SPECT) imaging (MPI) is a well-validated diagnostic procedure for the assessment of patients with suspected coronary artery disease (CAD). It has a high sensitivity for the detection of flow-limiting coronary stenosis and provides incremental prognostic information that contributes to risk stratification and guides clinical-decision making with regard to management and therapeutic interventions. The diagnostic accuracy and predictive value of MPI in patients with three-vessel and left main stem (LMS) disease is less well-documented. There is evidence suggesting that assessment of myocardial perfusion on MPI is less effective at identifying significant three-vessel CAD as well as LMS disease. This limitation can be overcome, to a certain extent, by incorporating other imaging findings as well as clinical and stress testing parameters that help identify individuals at an increased risk of adverse cardiac events and hence those with severe and extensive coronary disease. Quantification of myocardial perfusion reserve using currently available radiotracers as well as simultaneous non-invasive assessment of coronary anatomy and atheromatous plaque may enhance the diagnostic performance of MPI in this subset of high-risk patients.

Objectives: We studied whether an increase in adenosine dose overcomes caffeine antagonism on adenosine-mediated coronary vasodilation., Background: Caffeine is a competitive antagonist at the adenosine receptors, but it is unclear whether caffeine in coffee alters the actions of exogenous adenosine, and whether the antagonism can be surmounted by increasing the adenosine dose., Methods: Myocardial perfusion scintigraphy (MPS) was used to assess adenosine-induced hyperemia in 30 patients before (baseline) and after coffee ingestion (caffeine). At baseline, patients received 140 microg/kg/min of adenosine combined with low-level exercise. For the caffeine study, 12 patients received 140 microg/kg/min of adenosine (standard) and 18 patients received 210 microg/kg/min (high dose) after caffeine intake (200 mg). Myocardial perfusion was assessed semiquantitatively and quantitatively, and perfusion defect was characterized according to the presence of reversibility., Results: Caffeine reduced the magnitude of perfusion abnormality induced by standard adenosine as measured by the summed difference score (SDS) (12.0 +/- 4.4 at baseline vs. 4.1 +/- 2.1 after caffeine, p < 0.001) as well as defect size (18% [3% to 38%] vs. 8% [0% to 22%], p < 0.01), whereas it had no effect on the abnormalities caused by high-dose adenosine (SDS, 7.7 +/- 4.0 at baseline vs. 7.8 +/- 4.2 after caffeine, p = 0.7). There was good agreement between baseline and caffeine studies for segmental defect category (kappa = 0.72, 95% confidence interval: 0.65 to 0.79) in the high-dose group. An increase in adenosine after caffeine intake was well tolerated., Conclusions: Caffeine in coffee attenuates adenosine-induced coronary hyperemia and, consequently, the detection of perfusion abnormality by adenosine MPS. This can be overcome by increasing the adenosine dose without compromising test tolerability.

Mortality rates due to coronary arterial disease (CAD) have declined as result of improved prevention, diagnosis and management, but CAD remains the leading cause of death. Myocardial perfusion scintigraphy (MPS) provides a cost-effective tool for early detection of CAD in symptomatic individuals and can stratify patients according to risk of cardiac events. MPS also provides valuable information to assist clinical decision-making. A large body of evidence supports the current applications of MPS, which has become integral to several guidelines for clinical practice.

Background: Cardiac computed tomography (CCT) has the potential to assess both coronary anatomy and ventricular function in a single study. We examined the agreement between CCT and myocardial perfusion scintigraphy (MPS) for the assessment of global and regional ventricular function., Methods and Results: Research CCT was performed in 52 patients with a low to intermediate likelihood of coronary artery disease referred for MPS. Left ventricular end-diastolic volume, left ventricular end-systolic volume, left ventricular ejection fraction (LVEF), and myocardial wall motion and thickening were compared between techniques. In addition, myocardial contrast attenuation on CCT was compared with radiotracer uptake on MPS. LVEF values agreed well (mean difference, 4.1%; SD, 15.13%), but CCT left ventricular end-diastolic volume was greater compared with MPS (mean difference, 46.0 mL; SD, 33.34 mL) (P < .001). There was moderate agreement for segmental myocardial motion and thickening, with kappa values of 0.57 (95% confidence interval, 0.51-0.63) and 0.47 (95% confidence interval, 0.41-0.53), respectively. Seventeen patients had hypoattenuation in at least 1 myocardial segment on CCT. Three of four patients with concomitant abnormalities of wall motion and thickening on CCT had infarction in the same territory on MPS., Conclusions: There was good agreement for LVEF between CCT and MPS but myocardial volumes differed, and these modalities cannot be used interchangeably. Mild abnormalities of regional function are detected more commonly by CCT than by MPS. Myocardial hypoattenuation on CCT is highly specific for myocardial infarction when associated with reduction of systolic wall thickening and regional wall motion abnormality.

Background: Multislice computed tomography coronary angiography (CTA) was proposed as a method for investigating possible coronary artery disease (CAD) in patients who present with chest pain but with a low to intermediate likelihood of CAD. Sixty-four-channel CTA was compared prospectively with (99m)Tc-tetrofosmin myocardial perfusion scintigraphy (MPS) (as the gold standard in the detection of flow-limiting stenoses) for the detection of functionally significant CAD., Methods and Results: Fifty-two consecutive symptomatic patients with a low to intermediate likelihood of coronary artery disease, and who were referred for MPS, also underwent CTA. The CTA datasets were analyzed by two experienced observers who were blinded to the MPS data, and coronary artery segments were reported as < 50%, 50% to 69%, 70% to 99% stenoses, or occluded. The MPS images were similarly analyzed for inducible perfusion abnormalities, and coronary territories were identified. At the patient level, agreement between CTA and MPS for CTA lesions at >/= 50% was 87% (sensitivity, 100%; specificity, 84%; positive predictive value, 50%; negative predictive value, 100%). For CTA lesions, agreement at >/= 70% was 96% (sensitivity, 86%; specificity, 98%; positive predictive value, 86%; negative predictive value, 98%)., Conclusions: In patients with a low to intermediate likelihood of CAD, there is good correlation between MPS and CTA for the detection of functionally significant coronary artery stenoses when CTA detects a narrowing of >/= 70% severity. Computed tomography coronary angiography stenoses of 70% should be used to determine functional significance, and not 50%, as is the usual practice at present.

Mortality rates due to coronary artery disease (CAD) have declined in recent years as result of improved prevention, diagnosis, and management. Nonetheless, CAD remains the leading cause of death worldwide with most casualties expected to occur in developing nations. Myocardial perfusion scintigraphy (MPS) provides a highly cost-effective tool for the early detection of obstructive CAD in symptomatic individuals and contributes substantially to stratification of patients according to their risk of cardiac death or nonfatal myocardial infarction. MPS also provides valuable information that assists clinical decision-making with regard to medical treatment and intervention. A large body of evidence supports the current applications of MPS, which has become integral to several guidelines for clinical practice.

Background: Adenosine may cause bronchoconstriction in subjects with asthma or chronic obstructive pulmonary disease (COPD). Recent evidence suggests that this effect may be dependent on the severity of disease. This study investigates the tolerability of adenosine stress in patients with mild asthma or COPD undergoing myocardial perfusion scintigraphy., Methods and Results: In this case-control study patients with known or suspected mild asthma or COPD were pretreated with an inhaled beta(2)-adrenergic agonist and adenosine titrated up to the maximal dose of 140 microg x kg(-1) x min(-1) over a period of 6 minutes. The occurrence of side effects and test tolerability were compared between the airway disease group and 72 control subjects. Of 1261 patients, 124 had known or suspected airway disease; of these, 72 (58%) were suitable for adenosine stress. The proportion of tests completed as per protocol in the asthma/COPD group was similar to that of control subjects (93% vs 100%, P = .06). Dyspnea (n = 38 [53%] in asthma/COPD group vs n = 25 [35%] in control group, P = .03) and chest pain (n = 14 [19%] in asthma/COPD group vs n = 16 [22%] in control group, P = .7) were the most common side effects, and these were mostly mild and well tolerated. Bronchospasm occurred in 5 patients with asthma/COPD but reverted shortly after discontinuation of the adenosine infusion. Aminophylline was not required in any case., Conclusions: A stepwise 6-minute adenosine infusion with prophylactic beta(2)-adrenergic agonist is safe and well tolerated in patients with mild asthma or COPD.