Valentina Lorenzoni

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.

Relationship between location and size of myocardial infarction and their reciprocal influences on post-infarction left ventricular remodelling

AIMS To assess the intricate relationship between myocardial infarction (MI) location and size and their reciprocal influences on post-infarction left ventricular (LV) remodelling. METHODS AND RESULTS A cohort of 260 reperfused ST-segment elevation MI patients was prospectively studied with cardiovascular magnetic resonance at 1 week (baseline) and 4 months (follow-up). Area at risk (AAR) and MI size were quantified by T2-weighted and late-gadolinium enhancement imaging, respectively. Adverse LV remodelling was defined as an increase in LV end-systolic volume ≥15% at follow-up. One hundred and twenty-seven (49%) patients had anterior MI and 133 (51%) patients had non-anterior MI. Although the degree of myocardial salvage was similar between groups (P = 0.74), anterior MI patients had larger AAR and MI size than non-anterior MI patients yielding worse regional and global LV function at baseline and follow-up. At univariable analysis, anterior MI was associated with increased risk of adverse LV remodelling (P = 0.017) and lower LV ejection fraction (EF) at follow-up (P = 0.001), but not when accounted for baseline MI size. Accordingly, at multivariable analysis, baseline MI size but not its location was an independent predictor of adverse LV remodelling (odds ratio = 1.061, P < 0.001) and EF at follow-up (β-coefficient = -0.255, P < 0.001). CONCLUSION Anterior MI patients experience more pronounced post-infarction LV remodelling and dysfunction than non-anterior MI patients due to a greater magnitude of irreversible ischaemic LV damage without any independent contribution of MI location.

Prognostic Value of High-Dose Dipyridamole Stress Myocardial Contrast Perfusion Echocardiography

Background— The addition of myocardial perfusion (MP) imaging during dipyridamole real-time contrast echocardiography improves the sensitivity to detect coronary artery disease, but its prognostic value to predict hard cardiac events in large numbers of patients with known or suspected coronary artery disease remains unknown. Methods and Results— We studied 1252 patients with the use of dipyridamole real-time contrast echocardiography and followed them for a median of 25 months. The prognostic value of MP imaging regarding death and nonfatal myocardial infarction was determined and related to wall motion (WM), clinical risk factors, and rest ejection fraction by the use of Cox proportional-hazards models, C index, and risk reclassification analysis. A total of 59 hard events (4.7%) occurred during the follow-up (24 deaths, 35 myocardial infarctions). The 2-year event-free survival was 97.9% in patients with normal MP and WM, 91.9% with isolated reversible MP defects but normal WM, and 67.4% with both reversible MP and WM abnormalities (P<0.001). By multivariate analysis the independent predictors of events were age (hazard ratio 1.05, 95% confidence interval [CI], 1.02–1.08), sex (hazard ratio, 2.36; 95% CI, 1.32–4.23), reversible MP defects (hazard ratio, 3.88; 95% CI, 1.83–8.21), and reversible WM abnormalities with reversible MP defects (hazard ratio, 4.51; 95% CI, 2.25–9.07). Reversible MP defects added incremental predictive value and reclassification benefit over WM response and clinical factors (P=0.001). Conclusions— MP imaging using real-time perfusion echocardiography during dipyridamole real-time contrast echocardiography provides independent, incremental prognostic information regarding hard cardiac events in patients with known or suspected coronary artery disease. Patients with normal MP responses have better outcome than patients with normal WM; patients with both reversible WM and MP abnormalities have the worst outcome.

Incremental Prognostic Value of Myocardial Fibrosis in Patients With Non–Ischemic Cardiomyopathy Without Congestive Heart Failure

Background—We conducted a prospective longitudinal study to investigate the yet unknown clinical significance of myocardial fibrosis in patients with non–ischemic cardiomyopathy without history of congestive heart failure (CHF). Methods and Results—At 3 tertiary referral centers, 228 patients with non–ischemic cardiomyopathy without history of CHF were studied with cardiovascular magnetic resonance for late gadolinium enhancement (LGE) detection and quantification and prospectively followed up for a median of 23 months. The end point was a composite of cardiac death, onset of CHF, and aborted sudden cardiac death. LGE was detected in 61 (27%) patients. Thirty-one of 61 (51%) patients with LGE reached combined end point when compared with 18 of 167 (11%) patients without LGE (hazard ratio, 5.10 [2.78–9.36]; P<0.001). Patients with LGE had greater risk of developing CHF than patients without LGE (hazard ratio, 5.23 [2.61–10.50]; P<0.001) and higher rate of aborted sudden cardiac death (hazard ratio, 8.31 [1.66–41.55]; P=0.010). Multivariate analysis showed that LGE was associated with high likelihood of composite end point independent of other prognostic determinants, including age; duration of cardiomyopathy; and left ventricular volumes, mass, and ejection fraction (hazard ratio, 4.02 [2.08–7.76]; P<0.001). Improvement &khgr;2 analysis disclosed that LGE addition to models, including clinical data alone or in combination with parameters of left ventricular remodeling and function, yielded an improvement in outcome prediction (P<0.001). Addition of LGE to age and left ventricular ejection fraction improved risk stratification for composite end point (net reclassification improvement, 29.6%) and onset of CHF (net reclassification improvement, 25.4%; both P<0.001). Conclusions—In patients with non–ischemic cardiomyopathy without history of CHF, myocardial fibrosis is a strong and independent predictor of outcome, providing incremental prognostic information and improvement in risk stratification beyond clinical data and degree of left ventricular dysfunction.

Myocardial Structural, Perfusion, and Metabolic Correlates of Left Bundle Branch Block Mechanical Derangement in Patients With Dilated Cardiomyopathy A Tagged Cardiac Magnetic Resonance and Positron Emission Tomography Study

Background—Left bundle branch block (LBBB) influences on regional left ventricular (LV) structure, perfusion, and metabolism have not yet been thoroughly investigated in dilated cardiomyopathy patients. Methods and Results—Eleven dilated cardiomyopathy patients with LBBB (mean±SD age, 62±11 years; LV ejection fraction, 35±8%) and 7 dilated cardiomyopathy patients without LBBB (mean±SD age, 58±9 years; LV ejection fraction, 37±10%) were studied by cardiac magnetic resonance and positron emission tomography. The left ventricle was divided in 3 regions: septum, adjacent (anterior-inferior walls), and lateral. Regional midwall circumferential strain, maximum shortening, and strain rate were obtained from tagged cardiac magnetic resonance. The systolic stretch index was calculated as positive strain rate (stretching) divided by total strain rate. Myocardial metabolic rate of glucose and resting and hyperemic myocardial blood flow were quantified by 2-[18F]fluoro-2-deoxyglucose and [13N]ammonia positron emission tomography, respectively. Compared with non-LBBB patients, LBBB patients showed a highly inhomogeneous systolic deformation pattern that changed gradually, moving from a discoordinate [(systolic stretch index, 0.485 (0.284)] and poorly contracting (maximum shortening, −1.14±0.96%) septum to a coordinate [systolic stretch index, 0.002 (0.168)] and strongly contracting (maximum shortening, −13.63±2.58%) lateral region (both P<0.0001). This pattern was closely matched to the myocardial metabolic rate of glucose, disclosing lowest, intermediate, and highest values in the septum, adjacent, and lateral regions, respectively (P<0.0001). Septal-to-lateral thickness ratio was lower in LBBB than in non-LBBB patients (P=0.03). In both groups, the LV distribution of resting and hyperemic myocardial blood flow and myocardial blood flow reserve did not differ significantly. Conclusions—In dilated cardiomyopathy patients, the extensive LV contraction abnormalities induced by LBBB cause regional myocardial metabolic and structural remodeling, without consistent changes in blood flow.

Contrast Stress-Echocardiography Predicts Cardiac Events in Patients with Suspected Acute Coronary Syndrome but Nondiagnostic Electrocardiogram and Normal 12-Hour Troponin

BACKGROUND No large study has demonstrated that any stress test can risk-stratify future hard cardiac events (cardiac death or myocardial infarction) in patients with suspected acute coronary syndromes (ACS), nondiagnostic electrocardiographic (ECG) findings, and normal troponin levels. The aim of this study was to test the hypothesis that combined contrast wall motion and myocardial perfusion echocardiographic assessment (cMCE) during stress echocardiography can predict long-term hard cardiac events in patients with suspected ACS, nondiagnostic ECG findings, and normal troponin. METHODS A total of 545 patients referred for contrast stress echocardiography from the emergency department for suspected ACS but nondiagnostic ECG findings and normal troponin levels at 12 hours were followed up for cardiac events. Patients underwent dipyridamole-atropine echocardiography with adjunctive myocardial perfusion imaging using a commercially available ultrasound contrast medium (SonoVue). RESULTS During a median follow-up period of 12 months, 25 cardiac events (4.6%) occurred (no deaths, 12 nonfatal myocardial infarctions, 13 episodes of unstable angina). Abnormal findings on cMCE were the most significant predictor of both hard cardiac events (hazard ratio, 22.8; 95% confidence interval, 2.9-176.7) and the combined (cardiac death, myocardial infarction, or unstable angina requiring revascularization) end point (hazard ratio, 10.7; 95% confidence interval, 3.7-31.3). The inclusion of the cMCE variable significantly improved multivariate models, determining lower Akaike information criterion values and higher discrimination ability. CONCLUSIONS cMCE during contrast stress echocardiography provided independent information for predicting hard and combined cardiac events beyond that predicted by stress wall motion abnormalities in patients with suspected ACS, nondiagnostic ECG findings, and normal troponin levels.

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.

Comparative prediction of cardiac events by wall motion, wall motion plus coronary flow reserve, or myocardial perfusion analysis: a multicenter study of contrast stress echocardiography

OBJECTIVES This study sought to determine whether the increasing difficulty of assessing wall motion (WM), Doppler coronary flow reserve on the left anterior descending coronary artery (CFR-LAD), and myocardial perfusion (MP) during stress echocardiography (SE) was justified by increasing prognostic information in patients with known or suspected coronary artery disease. BACKGROUND The use of echocardiographic contrast agents during SE permits the assessment of both CFR-LAD and MP, but their relative incremental prognostic value is undefined. METHODS This study followed a multicenter cohort of 718 patients for 16 months after high-dose dipyridamole contrast SE for evaluation of known or suspected coronary artery disease. The ability of WM, CFR-LAD, and MP to predict cardiac events was studied by multivariable models and risk reclassification. RESULTS Abnormal SE was detected as a reversible WM abnormality in 18%, reversible MP defect in 27%, and CFR-LAD <2 in 38% of subjects. Fifty cardiac events occurred (annualized event rate 6.0%). A normal MP stress test had a 1-year hard event rate of 1.2%. The C-index of outcomes prediction based on clinical data was improved with MP (p < 0.001) and WM/CFR-LAD (p = 0.037), and MP (p = 0.003) added to clinical and WM data. Net risk reclassification was improved by adding MP (p < 0.001) or CFR-LAD (net reclassification improvement p = 0.001) in addition to clinical and WM data. The model including clinical data, WM/CFR-LAD, and MP performed better than that without MP did (p = 0.012). CONCLUSIONS The multiparametric assessment of WM, CFR-LAD and MP during stress testing in patients with known or suspected coronary artery disease is feasible. Contrast SE allowed better prognostication, irrespective of the use of CFR-LAD or MP. The addition of either CFR-LAD or MP assessment to standard WM analysis and clinical parameters yielded progressively higher values for the prediction of cardiac events and may be required in todays intensively treated patients undergoing SE, because their average low risk of future cardiac events requires methods with higher predictive sensitivity than that available with standalone WM assessment.

The calculation of the cardiac troponin T 99th percentile of the reference population is affected by age, gender, and population selection: A multicenter study in Italy

BACKGROUND The aim of this study is to determine the 99th upper-reference limit (URL) for cardiac troponin T (cTnT) in Italian apparently healthy subjects. METHODS The reference population was selected from 5 cities: Bolzano (n=290), Milano (CAMELIA-Study, n=287), Montignoso (MEHLP-Study, n=306), Pisa (n=182), and Reggio Calabria (MAREA-Study, n=535). Subjects having cardiac/systemic acute/chronic diseases were excluded. Participants to MEHLP project underwent cardiac imaging investigation. High-sensitive cTnT was measured with Cobas-e411 (Roche Diagnostics). RESULTS We enrolled 1600 healthy subjects [54.6% males; age range 10-90years; mean (SD): 36.4 (21.2) years], including 34.6% aged <20years, 54.5% between 20 and 64years, and 10.9% over 65years. In the youngest the 99th URL was 10.9ng/L in males and 6.8ng/L in females; in adults 23.2ng/L and 10.2ng/L; and in elderly 36.8ng/L and 28.6ng/L. After the exclusion of outliers the 99th URL values were significantly decreased (P<0.05) in particular those of the oldest (13.8ng/L and 14ng/L). MEHLP participants were divided in healthy and asymptomatic, according to known cardiovascular risk factors (HDL, LDL, glucose, C-reactive protein): the 99th URL of cTnT values of these subgroups was significantly different (19.5 vs. 22.7, P<0.05). CONCLUSIONS 99th URL of cTnT values was strongly affected by age, gender, selection of subjects and the statistical evaluation of outliers.

Persistence of Mortality Risk in Patients With Acute Cardiac Diseases and Mild Thyroid Dysfunction

Introduction:There are no studies on the long-term prognostic role of abnormal thyrotropin value in patients with acute cardiac diseases. Aim of the study was to assess the incidence and persistence of risk of cardiac and overall deaths in patients with acute cardiac diseases. Methods:A total of 1026 patients (mean age: 67.7 years) were divided into 4 groups: (1) euthyroid (EU, n=579); (2) subclinical-like hypothyroidism (SLHYPO, n=68); (3) subclinical-like hyperthyroidism (SLHYPER, n=23) and (4) low-triiodothyronine syndrome (LowT3, n=356). Follow-up started from the day of thyroid hormone evaluation (mean follow-up: 30 months). The events considered were cardiac and overall deaths. Results:Survival rate for cardiac death was lower in SLHYPO and in LT3 than in EU (log rank test; &khgr;2=33.6; P < 0.001). Survival rate for overall death was lower in SLHYPO, SLHYPER and LowT3 than in EU (48.3; P < 0.001). After adjustment for several risk factors, the hazard ratio for cardiac death was higher in SLHYPO (3.65; P=0.004) in LowT3 (1.88; P=0.032) and in SLHYPER (4.73; P=0.047). Hazard ratio for overall death was higher in SLHYPO (2.30; P=0.009), in LowT3 (1.63; P=0.017) and in SLHYPER than in EU (3.71; P=0.004). Hazards for SLHYPO, SLHYPER and LowT3 with respect to EU were proportional over the follow-up period. Conclusion:In patients with acute cardiac disease, a mildly altered thyroid status was associated with increased risk of mortality that remains constant during all the follow-up.