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.

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.

Scar extent, left ventricular end-diastolic volume, and wall motion abnormalities identify high-risk patients with previous myocardial infarction: a multiparametric approach for prognostic stratification.

AIMS: We sought to investigate whether combining left ventricular (LV) volumes, regional wall motion abnormalities, and scar tissue extent obtained by cardiac magnetic resonance (CMR) improves risk stratification of patients with previous myocardial infarction (MI). METHODS AND RESULTS: In 231 consecutive patients (age 64 ± 11 years, males 89%) with previous MI, we quantified LV volumes and regional wall motion abnormalities by cine CMR, and measured the extent of the infarction scar by late gadolinium enhancement (LGE). During follow-up (median, 3.2 years) cardiac events (cardiac death or appropriate intra-cardiac defibrillator shocks) occurred in 19 patients. After adjustment for age, an extent of LGE >12.7%, an LV end-diastolic volume >105 mL/m(2), and a wall motion score index >1.7 were independent associated with adverse cardiac events at multivariate analysis (P < 0.05, P < 0.001, and P < 0.01, respectively). The patients with none of these factors, and those with one or two factors, showed a lower risk of cardiac events [hazard ratio (HR) = 0.112, P < 0.01 and HR = 0.261, P < 0.05] than those with three factors. The cumulative event-rate estimated at 4 years was 29.6% in patients with all three factors, 7.7% in those with one or two factors, and 3.5% in patients with none of these factors. CONCLUSION: A multiparametric CMR approach, which includes the measure of scar tissue extent, LV end-diastolic volume and regional wall motion abnormalities, improves risk stratification of patients with previous MI.

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.

Abnormal glucose and lipid control in non-ischemic left ventricular dysfunction.

BACKGROUND: Cardiovascular risk factors are classically associated with coronary atherosclerosis. We sought to investigate whether risk factors are also associated with left ventricular (LV) dilatation, contractile impairment and reduced myocardial blood flow (MBF) in patients with non-ischemic LV dysfunction. METHODS: We studied 81 patients (59 males, age 60 ± 9 years) with mild-to-severe LV dysfunction (mean ejection fraction 37%, range 19%-50%), no history of diabetes and normal coronary arteries. Absolute MBF was measured by positron emission tomography and (13)N-ammonia at rest and after dipyridamole (0.56 mg/kg I.V. over 4 min). RESULTS: Overt LV dysfunction (LV end-diastolic diameter >60 mm associated with LV ejection fraction <45%) was present in 42 patients (52%); severely depressed hyperemic MBF (<1.09 mL · min(-1) · g(-1)) was present in 41 patients (51%). Using multivariate logistic regression analysis, low high-density lipoprotein cholesterol (HDL-C, P < .036), newly diagnosed non-insulin-dependent diabetes or insulin-resistance (NIDD/IR, P < .019) and the use of diuretics (P = .001) were independently associated with overt LV dysfunction. Low HDL-C (P = .015) and NIDD/IR (P = .048) were also independently associated with severely depressed hyperemic MBF. CONCLUSIONS: Low HDL-C and NIDD/IR are associated with more severe LV impairment and reduced hyperemic MBF in non-ischemic LV dysfunction.

Religiosity associated with prolonged survival in liver transplant recipients.

We tested the hypothesis that religiosity (ie, seeking God's help, having faith in God, trusting in God, and trying to perceive God's will in the disease) is associated with improved survival in patients with end-stage liver disease who have undergone orthotopic liver transplantation. We studied a group of 179 candidates for liver transplantation who responded to a questionnaire on religiosity during the pretransplant psychological evaluation and underwent transplantation between 2004 and 2007. The demographic data, educational level, employment status, clinical data, and results of the questionnaire were compared with the survival of patients during follow-up, regardless of the cause of any deaths. Factorial analysis of responses to the questionnaire revealed 3 main factors: searching for God (active), waiting for God (passive), and fatalism. The consistency of the matrix was very high (consistency index = 0.92). Eighteen patients died during follow-up (median time = 21 months). In multivariate analysis, only the searching for God factor [hazard ratio (HR) = 2.95, 95% confidence interval (CI) = 1.05-8.32, χ(2) = 4.205, P = 0.040] and the posttransplant length of stay in the intensive care unit (HR = 1.05, 95% CI = 1.01-1.08, χ(2) = 8.506, P = 0.035) were independently associated with survival, even after adjustments for the waiting for God factor, fatalism, age, sex, marital status, employment, educational level, viral etiology, Child-Pugh score, serum creatinine level, time from the questionnaire to transplantation, donor age, and intraoperative bleeding. Patients who did not present the searching for God factor were younger than those who did, but they had shorter survival times (P = 0.037) and a 3-fold increased relative risk of dying (HR = 3.01, 95% CI = 1.07-8.45). In conclusion, religiosity is associated with prolonged survival in patients undergoing liver transplantation.

Different substrates of non-sustained ventricular tachycardia in post-infarction patients with and without left ventricular dilatation.

BACKGROUND: We investigated the relationship between nonsustained ventricular tachycardia (NSVT) and left ventricular (LV) dilatation, function, remodeling, and scar tissue extent in patients with previous myocardial infarction (MI). METHODS AND RESULTS: Eighty-two patients (ages 64+/-10 years) with first previous MI were referred for 24-hour electrocardiogram recording and cine and delayed enhancement (DE) cardiac magnetic resonance (CMR). LV volumes, ejection fraction, systolic wall thickening, sphericity index, and core and peri-infarctual areas of scar tissue by CMR were evaluated. LV dilatation was observed in 39 patients. Episodes of NSVT were recorded in 32 patients: 23 with LV dilatation and 9 without. In the entire population, NSVT was related to ejection fraction, LV volumes, LV mass, and sphericity index; end-systolic volume (P=.001) resulted in the only independent predictor at multivariate analysis. In patients without LV dilatation, the occurrence of NSVT was only positively related with percentage of contracting segments with DE (P=.008). Conversely, in patients with LV dilatation, increase in LV mass (P=.020) and end-systolic volume (P=.038) were independent predictors of NSVT. CONCLUSIONS: Necrotic and viable myocardium coexistence within the same wall segments predicted occurrence of NSVT in patients without LV dilatation, whereas LV mass and end-systolic volume were predictors of NSVT in those with LV dilatation.

Stress/Rest Myocardial Perfusion Abnormalities by Gated SPECT: Still the Best Predictor of Cardiac Events in Stable Ischemic Heart Disease.

UNLABELLED: The prognostic power of myocardial perfusion imaging in patients with ischemic heart disease (IHD) has been demonstrated since planar imaging. We aimed to investigate whether gated SPECT retains this value in current cardiology if compared with a complete diagnostic work-up and with more recent prognostic indicators. METHODS: We selected from our database a cohort of 676 consecutive inpatients who underwent a complete diagnostic work-up that included gated SPECT and coronary arteriography for known or suspected IHD. Patients with acute myocardial infarction (MI), previous coronary artery bypass surgery, or overt hyperthyroidism and patients who were undergoing dialysis treatment were excluded. During follow-up (median, 37 mo), 24 patients died from cardiac causes and 19 experienced a nonfatal MI. RESULTS: The following were determined to be independent predictors of event-free survival (cardiac death and nonfatal MI) in the different phases of diagnostic work-up using Cox proportional hazards regression analysis: among clinical variables, a previous MI; among laboratory examinations, serum creatinine and low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels; among electrocardiographic and echocardiographic variables, left ventricular ejection fraction; and among SPECT variables, summed rest score (SRS) and summed difference score (SDS). In addition, a score of coronary stenoses at angiography was an independent predictor. When the above predictors were tested together, SRS (P < 0.0001), SDS (P = 0.0108), and serum creatinine (P = 0.0186) and LDL and HDL cholesterol levels (P = 0.0222) were the final independent predictors of event-free survival. When gated SPECT was added to the clinical, laboratory, electrocardiographic, and echocardiographic variables, the prognostic stratification significantly improved (P < 0.05); when coronary arteriography was added to gated SPECT, prognostic stratification did not further improve (P > 0.25). If the information provided by gated SPECT was made available after clinical, laboratory, electrocardiographic, echocardiographic, and angiographic variables, the prognostic stratification still improved significantly (P < 0.05). In 492 of these patients with ascertained IHD, SRS and SDS were the final independent predictors of survival. Medical treatment and coronary revascularization did not affect the prognostic information of gated SPECT. CONCLUSION: Myocardial perfusion abnormalities at rest and after stress are still the best predictors of cardiac event-free survival in patients with known or suspected IHD, even when compared with an extensive diagnostic work-up.

[Dilated cardiomyopathy post-chemotherapy]. / Cardiomiopatia post-chemioterapia: curare oggi pensando al domani.

We describe the case of a dilated cardiomyopathy with angiographically normal coronary arteries in a 32-year-old man who underwent head and spine radiotherapy and high dose antracicline chemotherapy at the age of 5 year for acute lymphoblastic leukemia. The long-term detrimental cytotoxic effect of remote life-saving chemotherapy should be considered in survivals of leukemia.

[Cardiotoxicity induced by chemo- and radiotherapy]. / Cardiotossicità da chemio- e radioterapia.

The authors describe the case of a 55-year old patient, with dyslipidemia as single cardiovascular risk factor, who previously underwent chemo and radiotherapy for Hodgkin lymphoma (stage 2b). The patient developed early coronary atherosclerosis followed by aortic and mitral valve disease and initial constrictive pericarditis. The role of chemo and radiotherapy in the development of cardiovascular disease, in particular valvular and pericardial disease, is discussed.

[The mysterious case of an intracardiac mass]. / Il caso di una massa intra-cardiaca.

The authors describe the case of a 73-year old patient, with multiple cardiovascular risk factors and severe renal insufficiency, presenting with an intracardiac mass, as shown at echocardiography. Differential diagnosis and use of different imaging tests are discussed.

Paucity of anginal symptoms and stress-induced perfusion abnormalities in ischemic cardiomyopathy.

BACKGROUND: We sought to investigate whether the paucity of anginal symptoms in patients with ischemic cardiomyopathy reflects a reduction in the severity of stress-induced myocardial ischemia. METHODS AND RESULTS: We selected 38 patients with coronary artery disease and severe left ventricular dysfunction (ejection fraction [EF]

Echocardiography and the clinical diagnosis of left ventricular dysfunction.

INTRODUCTION: The added value of routine echocardiography, in respect to clinical examination and ECG, has received little attention. We sought to evaluate the contribution of two-dimensional echocardiography, in respect to clinical examination and ECG, in detecting left ventricular (LV) dilatation and systolic dysfunction. METHOD: A group of 100 patients, scheduled for cardiac magnetic resonance imaging (MRI), was prospectively studied. RESULTS: Clinical examination identified moderate-to-severe LV dysfunction, defined as a LV ejection fraction (EF) < 45% at MRI, with a sensitivity of 62% and a specificity of 68%. After ECG, sensitivity and specificity slightly improved (71 and 70%, respectively). After the echocardiographic report, sensitivity reached 84% and specificity 90%. LV EF by echocardiography (routine studies) was closely related with that by MRI (r = 0.84). LV function was scored as undefined in 17% of patients after clinical examination, in 5% of patients after ECG and in no patient after echocardiography (P < 0.0001). Clinical examination identified patients with LV dilatation (LV end-diastolic volume > or = 110 ml/m2) with a poor sensitivity (33%) but a good specificity (88%). After ECG, sensitivity was 39% and specificity 87%; after echocardiography, sensitivity reached 53% and specificity 92%. CONCLUSION: Echocardiography provides information on LV function and dimensions that vastly exceeds that obtained by clinical examination and ECG. This study supports the use of echocardiography to improve patient diagnosis and management after history and physical examination.

Relation of pain-to-balloon time and myocardial infarct size in patients transferred for primary percutaneous coronary intervention.

The paradigm of a shorter pain-to-balloon time decreasing extent of infarct size may be not completely true in transferred patients. This study evaluated the influence of pain-to-balloon time on infarct size as assessed by delayed enhancement magnetic resonance imaging in patients transferred from a peripheral hospital to a tertiary center for primary coronary angioplasty (percutaneous coronary intervention [PCI]). Sixty patients (40 men, 64 +/- 3 years of age) with first acute myocardial infarction were treated within <168, 168 to 222, 223 to 300, and >300 minutes. A presentation score system including clinical, laboratory, and echocardiographic data was used to classify severity of presentation at admission. Magnetic resonance imaging was performed 6 +/- 3 days after PCI. Group 1 had a higher presentation score than did group 2 (p <0.02) and group 3 (p <0.02). Group 1 had a significantly longer delayed enhancement than did group 2 (p <0.002) and group 3 (p <0.03). In conclusion we found that patients with worse presentation are transferred sooner for primary PCI. This approach in these patients does not decrease infarct size likely because of unavoidable delay to reperfusion. This finding suggests a different therapeutic strategy in these patients.

Clinical diagnosis of left ventricular dilatation and dysfunction in the age of technology.

BACKGROUND: The diagnostic process has become increasingly dependent on instrumental and laboratory investigation. AIM: To evaluate the accuracy of symptoms and signs in identifying left ventricular (LV) dilatation and/or systolic dysfunction. METHODS: A group of 100 patients in stable clinical condition and scheduled for cardiac magnetic resonance imaging was prospectively examined by two cardiologists, who were unaware of the individual patient's condition. Patients were interviewed and underwent physical examination. RESULTS: Several symptoms and signs were associated with LV dilatation and systolic dysfunction at univariate analysis. Using multiple logistic regression, a mitral systolic murmur, a laterally displaced LV impulse, orthopnoea and hepatomegaly were all independent predictors of LV dilatation (end-diastolic volume >or=110 ml/m(2)) (p<0.0001) and LV dysfunction (ejection fraction <45%) (p<0.0001). The combination of the above variables correctly identified 79% of patients with LV dilatation (sensitivity 51%, specificity 92%), and 82% of patients with LV dysfunction (sensitivity 68%, specificity 90%). Considering LV dilatation and dysfunction, 77% of patients were correctly identified after history alone (kappa=0.13), 84% after LV impulse examination (kappa=0.55) and 86% after cardiac auscultation (kappa=0.58). CONCLUSION: Symptoms and signs predict LV dilatation and/or dysfunction with fair sensitivity and excellent specificity.

Q-wave prediction of myocardial infarct location, size and transmural extent at magnetic resonance imaging.

OBJECTIVE: We investigated how pathologic Q waves or equivalents predict location, size and transmural extent of myocardial infarction (MI). METHODS: MI characteristics, detected by contrast-enhanced magnetic resonance imaging, were compared with 12-lead electrocardiogram in 79 patients with previous first MI. RESULTS: Q waves involved only the anterior leads (V1-V4) in 13 patients: in all patients MI involved the anterior and anteroseptal walls and apex; 81% of scar tissue was within these regions. Q waves involved only the inferior leads (II, III, aVF) in 13 patients: in 12 of these patients MI involved the inferior and inferoseptal walls; however, only 59% of scar occupied these regions. Q waves involved only lateral leads (V5, V6, I, aVL) in 11 patients: in nine of these patients MI involved the lateral wall but only 27% of scar tissue was within this wall. Q waves involved two electrocardiogram locations in 42 patients. In the 79 patients as a whole, the number of anterior Q waves was related to anterior MI size (r=0.70); however, the number of inferior and lateral Q waves was only weakly related to MI size in corresponding territories (r=0.35 and 0.33). A tall and broad R wave in V1-V2 was a more powerful predictor of lateral MI size than Q waves. Finally, the number of Q waves accurately reflected the transmural extent of the infarction (r=0.70) only in anterior infarctions. CONCLUSION: Q waves reliably predict MI location, size and transmural extent only in patients with anterior infarction. A tall and broad R wave in V1-V2 reflects a lateral MI.

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.