Multicentre multi-device hybrid imaging study of coronary artery disease: results from the EValuation of INtegrated Cardiac Imaging for the Detection and Characterization of Ischaemic Heart Disease (EVINCI) hybrid imaging population.

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.

Effect of Coronary Atherosclerosis and Myocardial Ischemia on Plasma Levels of High-Sensitivity Troponin T and NT-proBNP in Patients With Stable Angina.

OBJECTIVE: Circulating levels of high-sensitivity cardiac troponin T (hs-cTnT) and N terminal pro brain natriuretic peptide (NT-proBNP) are predictors of prognosis in patients with coronary artery disease (CAD). We aimed at evaluating the effect of coronary atherosclerosis and myocardial ischemia on cardiac release of hs-cTnT and NT-proBNP in patients with suspected CAD. APPROACH AND RESULTS: Hs-cTnT and NT-proBNP were measured in 378 patients (60.1±0.5 years, 229 males) with stable angina and unknown CAD enrolled in the Evaluation of Integrated Cardiac Imaging (EVINCI) study. All patients underwent stress imaging to detect myocardial ischemia and coronary computed tomographic angiography to assess the presence and characteristics of CAD. An individual computed tomographic angiography score was calculated combining extent, severity, composition, and location of plaques. In the whole population, the median (25-75 percentiles) value of plasma hs-cTnT was 6.17 (4.2-9.1) ng/L and of NT-proBNP was 61.66 (31.2-132.6) ng/L. In a multivariate model, computed tomographic angiography score was an independent predictor of the plasma hs-cTnT (coefficient 0.06, SE 0.02; P=0.0089), whereas ischemia was a predictor of NT-proBNP (coefficient 0.38, SE 0.12; P=0.0015). Hs-cTnT concentrations were significantly increased in patients with CAD with or without myocardial ischemia (P<0.005), whereas only patients with CAD and ischemia showed significantly higher levels of NT-proBNP (P<0.001). CONCLUSIONS: In patients with stable angina, the presence and extent of coronary atherosclerosis is related with circulating levels of hs-cTnT, also in the absence of ischemia, suggesting an ischemia-independent mechanism of hs-cTnT release. Obstructive CAD causing myocardial ischemia is associated with increased levels of NT-proBNP.

T wave abnormalities identify patients with previous lateral wall myocardial infarction and circumflex artery disease.

BACKGROUND: The diagnosis of previous lateral myocardial infarction is based on QRS morphology. OBJECTIVES: To explore the diagnostic role of T wave abnormalities. METHODS: We studied 166 patients with known or suspected ischemic heart disease who underwent a 12-lead electrocardiogram, myocardial perfusion scintigraphy, and coronary arteriography within 90days. We excluded patients with bundle-branch block, hypertrophy, or paced rhythm. RESULTS: Only one patient had a prominent R wave in V1, no patient showed lateral Q waves of necrosis. T wave amplitude in V2-V6 ≥0.6mV, and T wave amplitude in lead 1+V6 ≤0mV detected a lateral infarction (sensitivity 33 and 44%, specificity 83 and 80%). T wave amplitude in lead 1+V6 ≤0mV was the only independent predictor of infarction or LCx occlusion (AUC 0.72 and 0.74). Serum potassium values were not associated with T wave abnormalities. CONCLUSION: T wave abnormalities identify previous lateral infarction and LCx disease.

Limitations of Chest Pain Categorization Models to Predict Coronary Artery Disease.

We aimed to evaluate how chest pain categorization, currently used to assess the pretest probability of coronary artery disease (CAD), predicts the actual presence of CAD in a population of patients with stable symptoms. We studied 475 consecutive patients enrolled in the Evaluation of Integrated Cardiac Imaging for the Detection and Characterization of Ischemic Heart Disease study based on possible symptoms of CAD. Chest pain or discomfort was categorized as typical angina, atypical angina, or as nonanginal according to the guidelines. Exertional dyspnea and fatigue suspected to be angina equivalents were classified as atypical angina. Patients with a probability of CAD <20 or >90% based on age, gender, and symptoms were excluded. The end points of this substudy were significant CAD (defined by invasive coronary angiography as >50% reduction in lumen diameter in the left main stem or >70% stenosis in a major coronary vessel or 30% to 70% stenosis with fractional flow reserve ≤0.8), inducible myocardial ischemia at noninvasive stress imaging, and their association. Patients' symptoms had limited ability to predict the presence of significant CAD, global chi-square being 5.0. The inclusion of age increased global chi-square to 18.7 and gender increased it further to 51.1. Using inducible myocardial ischemia or the association of CAD with inducible ischemia as end points, the ability to predict these end points was again better for patient demographics than for patient symptoms. Thus, the ability of current models based on symptoms, age, and gender to predict the presence of CAD is mainly based on patient demographics as opposed to symptoms.

A New Integrated Clinical-Biohumoral Model to Predict Functionally Significant Coronary Artery Disease in Patients With Chronic Chest Pain.

BACKGROUND: In patients with chronic angina-like chest pain, the probability of coronary artery disease (CAD) is estimated by symptoms, age, and sex according to the Genders clinical model. We investigated the incremental value of circulating biomarkers over the Genders model to predict functionally significant CAD in patients with chronic chest pain. METHODS: In 527 patients (60.4 years, standard deviation, 8.9 years; 61.3% male participants) enrolled in the European Evaluation of Integrated Cardiac Imaging (EVINCI) study, clinical and biohumoral data were collected. RESULTS: Functionally significant CAD-ie, obstructive coronary disease seen at invasive angiography causing myocardial ischemia at stress imaging or associated with reduced fractional flow reserve (FFR < 0.8), or both-was present in 15.2% of patients. High-density lipoprotein (HDL) cholesterol, aspartate aminotransferase (AST) levels, and high-sensitivity C-reactive protein (hs-CRP) were the only independent predictors of disease among 31 biomarkers analyzed. The model integrating these biohumoral markers with clinical variables outperformed the Genders model by receiver operating characteristic curve (ROC) (area under the curve [AUC], 0.70 [standard error (SE), 0.03] vs 0.58 [SE, 0.03], respectively, P < 0.001) and reclassification analysis (net reclassification improvement, 0.15 [SE, 0.07]; P = 0.04). Cross-validation of the ROC analysis confirmed the discrimination ability of the new model (AUC, 0.66). As many as 56% of patients who were assigned to a higher pretest probability by the Genders model were correctly reassigned to a low probability class (< 15%) by the new integrated model. CONCLUSIONS: The Genders model has a low accuracy for predicting functionally significant CAD. A new model integrating HDL cholesterol, AST, and hs-CRP levels with common clinical variables has a higher predictive accuracy for functionally significant CAD and allows the reclassification of patients from an intermediate/high to a low pretest likelihood of CAD.

HDL cholesterol, leptin and interleukin-6 predict high risk coronary anatomy assessed by CT angiography in patients with stable chest pain.

OBJECTIVES: Coronary computed tomography angiography (CTA) describes several features of coronary plaques, i.e. location, severity, and composition. Integrated CTA scores are able to identify individual patterns of higher risk. We sought to test whether circulating biomarkers related with metabolism and inflammation could predict high risk coronary anatomy at CTA in patients with stable chest pain. METHODS: We evaluated a panel of 17 biomarkers in 429 patients (60.3 ± 0.4 years, 268 males) with stable chest pain who underwent coronary CTA having been enrolled in the Evaluation of Integrated Cardiac Imaging (EVINCI) study. The individual CTA risk score was calculated combining plaque extent, severity, composition, and location. The presence and distribution of non-calcified, mixed and calcified plaques were analyzed in each patient. RESULTS: After adjustment for age, sex and medical treatment, high-density lipoprotein (HDL) cholesterol, leptin, and interleukin-6 (IL-6) were independent predictors of CTA risk score at multivariate analysis (P = 0.050, 0.002, and 0.007, respectively). Integrating these biomarkers with common clinical variables, a model was developed which showed a better discriminating ability than the Framingham Risk Score and the Euro-SCORE in identifying the patients with higher CTA risk score (area under the receiver-operating characteristics curve = 0.81, 0.63 and 0.71, respectively, P < 0.001). These three biomarkers were significantly altered in patients with mixed or non-calcified plaques. CONCLUSIONS: In patients with stable chest pain, low HDL cholesterol, low leptin and high IL-6 are independent predictors of high risk coronary anatomy as defined by an integrated CTA risk score.

Prominent T wave in V2 with respect to V6 as a sign of lateral myocardial infarction.

BACKGROUND: In the absence of confounding electrocardiographic features, a prominent R wave in leads V1-V2 reflects a lateral myocardial infarction (MI). We hypothesized that repolarization abnormalities in V1-V2 could also reflect a lateral MI. METHODS: We retrospectively selected a group of 57 patients with a recent or previous first Q-wave MI involving left ventricular (LV) inferior and/or lateral wall at contrast-enhanced cardiac magnetic resonance (CMR). The location and extent of the MI at CMR were compared with electrocardiographic features. RESULTS: The infarction was located in the inferior wall in 12 patients (21%), in the lateral wall in 8 (14%), and in both walls in 37 patients (65%). Infarct size corresponded to 16.8 (SD 9.0%) of LV myocardium. Infarct extent in the inferior and lateral wall (8.3%, SD 7.2% vs. 8.4%, SD 7.5% of LV myocardium) did not differ significantly. Using multiple linear regression analysis, inferior Q-waves and inferior negative T waves were directly associated with infarct extent in the inferior wall (p = 0.014 and p = 0.010, respectively). A prominent R wave in V1 and a prominent anterior T wave (expressed by the T wave amplitude in V2 minus its amplitude in V6) were directly associated with MI extent in the lateral wall (p = 0.008 and p = 0.018), while inferior negative T waves were negatively associated (p = 0.006). CONCLUSIONS: In patients with MI of the inferior and/or lateral wall, a prominent T wave in V2 with respect to V6 reflects greater infarct extent in the lateral wall.

Detection of significant coronary artery disease by noninvasive anatomical and functional imaging.

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.

Mind injuries after cardiac surgery.

After cardiac surgery, delirium, cognitive dysfunction, depression, or anxiety disorders frequently occur, and profoundly affect patients' prognosis and quality of life. This narrative review focuses on the main clinical presentations of cognitive and psychological problems ('mind injuries') that occur postoperatively in absence of ascertainable focal neurologic deficits, exploring their pathophysiological mechanisms and possible strategies for prevention and treatment. Postoperative cognitive dysfunction is a potentially devastating complication that can involve several mechanisms and several predisposing, intraoperative, and postoperative risk factors, which can result in or be associated to cerebral microvascular damage. Postoperative depression is influenced by genetic or psychosocial predisposing factors, by neuroendocrine activation, and by the release of several pro-inflammatory factors. The net effect of these changes is neuroinflammation. These complex biochemical alterations, along with an aspecific response to stressful life events, might target the function of several brain areas, which are thought to represent a trigger factor for the onset of depression.

Right ventricular dysfunction: an independent and incremental predictor of cardiac deaths late after acute myocardial infarction.

Prognostic implication of right ventricular dysfunction and infarction scar in the chronic phase of the myocardial infarction has been little analyzed. In 299 consecutive patients (age 63 ± 11 years) with >3 months old myocardial infarction, we quantified right and left ventricular volumes and ejection fractions by cine cardiac magnetic resonance, and right and left ventricular scar tissue by late gadolinium enhancement. During follow-up (median, 2.4 years) cardiac events (cardiac-related deaths or appropriate intra-cardiac defibrillator shocks) occurred in 21 patients. Right ventricular systolic dysfunction (ejection fraction lower the reference mean values-2 SD) was present in 67 patients (22 %), right ventricular late gadolinium enhancement was observed in 15 patients (5 %). After adjustment for left ventricular end-diastolic volume, wall motion score index, and global extent of late gadolinium enhancement, right ventricular dysfunction was an independent and incremental predictor of cardiac events (p = 0.0053), while right ventricular scar tissue extent was not. Right ventricular dysfunction is an independent and incremental predictor of cardiac events also in the chronic phase of the myocardial infarction. In these patients, right ventricular dysfunction does not necessarily mean right ventricular infarction scar, but likely reflects the effects of hemodynamic and biohumoral factors.

Myocardial bridging: a review with emphasis on electrocardiographic findings.

BACKGROUND: Myocardial bridging (MB) occurs when a segment of an epicardial coronary artery takes an intra- myocardial course, thus leading to systolic compression. Most myocardial bridges involve the left anterior descending artery and are observed in 14-35% of patients. Different pathophysiological mechanisms can induce symptoms secondary to myocardial ischemia: systolic coronary compression, diastolic dysfunction associated with aging and coronary atherosclerosis, LV hypertrophy, vasospasm, microvascular and endothelial dysfunction, plaque development proximal to the bridge. METHODS: We performed a literature review of MB, with a particular emphasis on electrocardiographic manifestations. RESULTS: Stable angina-like chest pain is the usual presentation and MB should be suspected in patients at low risk for coronary atherosclerosis which refer this symptom or which present myocardial ischemia at instrumental examinations. ECG changes are not specific for MB and resting ECG is often normal or presents ST segment anomalies. Exercise stress test often shows non specific signs of ischemia, conduction disturbances or arrhythmias which do not allow the distinction between myocardial bridging and other causes of myocardial ischemia; angina often appears during exercise, even in the absence of ECG changes. Myocardial perfusion deficits at scintigraphy are neither obligatory nor specific. Although the clinical significance of MB is still debated, MB has been associated with acute coronary syndrome, coronary vasospasm, and even sudden cardiac death. CONCLUSION: Although MB may lead to myocardial ischemia during stress, its clinical presentation and electrocardiographic findings are not specific.

Calcified apical cardiomyopathy: a rare form of endomyocardial fibrosis.

Endomyocardial fibrosis is a rare cardiomyopathy characterized by thickening of the endocardium, which leads to a restrictive phenotype. Differential diagnosis with other forms of cardiomyopathy may not always be straightforward and various imaging modalities are frequently necessary. In the present case, we report a patient with heart failure of uncertain origin, in whom, after an in-depth instrumental evaluation, a rare variant of endomyocardial fibrosis was diagnosed.

Rhabdomyolysis in an HIV-infected patient following coronary angiography: case report and literature review.

Rhabdomyolysis is a rare, but possible, complication of combination antiretroviral therapy (cART). We report a unique case of an HIV-positive patient on cART who came to our attention for suspected ischaemic heart disease. Coronary angiography was carried out and complicated in the following days by rhabdomyolysis. We discuss the possible links between rhabdomyolysis, iodinated contrast media and HAART.

Insulin resistance is a major determinant of myocardial blood flow impairment in anginal patients.

PURPOSE: In patients with chest pain, stress-induced myocardial perfusion abnormalities are often the result of depressed myocardial blood flow (MBF) reserve. We investigated the relative contribution of cardiovascular risk factors and coronary atherosclerosis to MBF abnormalities in anginal patients. METHODS: We studied 167 patients with typical (n = 100) or atypical (n = 67) chest pain who underwent quantitative evaluation of MBF by PET at rest and after dipyridamole infusion, and quantitative coronary angiography (invasive or by 64-slice CT). Patients with left ventricular (LV) dysfunction (ejection fraction <45 %) were excluded. Coronary atherosclerosis of ≥50 % was defined as obstructive. RESULTS: At rest median MBF was 0.60 ml min-1 g-1, and after dipyridamole infusion median MBF was 1.22 ml min-1 g-1. MBF reserve was <2 in 77 of 167 patients (46 %). Coronary atherosclerosis was present in 67 patients (40 %), 26 with obstructive disease. In a univariate analysis several variables were associated with reduced MBF at rest, including male gender, coronary atherosclerosis and elevated LV end-diastolic diameter, and during hyperaemia, including male gender, insulin resistance (IR), smoking habit, LV ejection fraction and end-diastolic diameter. In a multivariate analysis, after adjustment for LV function and for pharmacological treatments, male gender was the only independent predictor of reduced MBF at rest (P < 0.001), while male gender (P = 0.003), IR (P = 0.033) and coronary atherosclerosis (P < 0.001) remained the only independent predictors of reduced hyperaemic MBF. IR (P = 0.043) and coronary atherosclerosis (P = 0.005) were the only predictors of depressed MBF reserve. Coronary atherosclerosis, male gender and IR showed additive effects on hyperaemic MBF. CONCLUSION: In patients with chest pain and normal LV systolic function, IR, male gender and coronary atherosclerosis are independent and additive determinants of impaired hyperaemic MBF.

Surgical correction of left coronary artery origin from the right coronary artery.

We describe the case of a patient with limiting angina pectoris and anomalous origin of the left coronary artery from the right coronary artery, with a retroaortic course. Myocardial ischemia in the left anterior descending territory was documented by positron emission tomography, confirmed by fractional flow reserve, and relieved by surgical coronary reimplantation. This patient did not have coronary atherosclerosis or any other significant anatomic abnormality, such as myocardial bridging or compression between the aorta and the pulmonary artery. We attempt to describe the mechanisms of myocardial ischemia that contributed to the clinical manifestations in our patient.

Routine laboratory tests to risk-stratify patients with chronic coronary artery disease.

BACKGROUND: Several biohumoral variables, taken individually, are predictors of prognosis in patients with chronic coronary artery disease (CAD). We hypothesized that taken together, laboratory tests provide prognostic information that is additive to a complete diagnostic work-up. METHODS: We prospectively examined 2370 consecutive patients with chronic CAD, as shown by a >50% coronary stenosis (in 95% of patients), previous coronary revascularization (in 31% of patients), and/or previous myocardial infarction (MI, in 54% of patients). We tested the ability of laboratory and clinical variables to predict future cardiac events (cardiac death and non-fatal MI). RESULTS: During follow-up (median, 46 months), 147 patients (6.2%) died from cardiac causes and 81 (3.4%) experienced a non-fatal MI. Using multivariate analysis, after adjustment for clinical variables (including left ventricular ejection fraction and angiographic extent of coronary stenoses), a high-density lipoprotein cholesterol (HDLc) concentration<35 mg/dL (p<0.0001), a neutrophil-to-lymphocyte ratio >2.4 (p=0.0014), and an fT3 serum level<2.1 pg/mL with normal thyrotropin (low-T3 syndrome) (p=0.0260) showed an independent and incremental prognostic value, and were associated with an increase in the rate of cardiac events of 86%, 57% and 41%, respectively. When these variables were added to clinical and instrumental variables, the prognostic power of the model increased significantly (global chi-square improvement: from 157.01 to 185.07, p<0.0001). CONCLUSION: Low HDLc, high neutrophil-to-lymphocyte ratio and low-T3 syndrome, both individually and taken together, provide prognostic information that is independent of and incremental to the main clinical and instrumental findings.