Claudio Reverberi

Tako-Tsubo cardiomyopathy with coronary artery stenosis: A case-series challenging the original definition

We report a case-series of seven patients with Tako-Tsubo cardiomyopathy (TTC) and at least one concomitant >or=50% coronary stenosis. Each case involves a female patient who presented symptoms and an electrocardiogram compatible with acute coronary syndrome, mild troponin I elevation, a ventriculogram showing left ventricle (LV) apical or midventricular ballooning (classical or variant TTC), an angiogram showing at least one >or=50% stenosis and a cardiac magnetic resonance showing no myocardial late Gadolinium enhancement. Full recovery of normal LV contractility after the event was required to confirm TTC. Our report presents the case for the opportunity to modify the TTC definition, removing the requirement for absence of coronary stenosis not to exclude patients with bystander coronary lesions, who are probably under diagnosed as per the original TTC definition.

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.

Detection of coronary artery disease by combined assessment of wall motion, myocardial perfusion and coronary flow reserve: a multiparametric contrast stress-echocardiography study.

BACKGROUND Wall motion (WM), Doppler-derived measurement of the coronary flow reserve (CFR) in the left anterior descending coronary artery (LAD), and myocardial perfusion imaging (MPI) can be sequentially assessed during dipyridamole stress echocardiography. Data regarding the relative diagnostic value of each of these parameters when assessed during the same examination in patients with suspected coronary artery disease (CAD) are lacking. METHODS Dipyridamole stress echocardiography was performed in 400 patients at two centers, before the performance of clinically indicated coronary angiography. The diagnostic accuracy of WM, CFR-LAD, combined WM and CFR-LAD, and MPI was measured in comparison with quantitative angiographic results. RESULTS For CAD defined as ≥ 1 stenosis >50%, MPI had the highest sensitivity (96%), lowest specificity (66%), and highest accuracy (86%); WM and CFR-LAD had the highest specificities (85% and 80%), lowest sensitivities (63% and 66%), and lowest overall accuracies (70% and 71%). Combined WM and CFR-LAD obtained intermediate values for both sensitivity (84%) and specificity (71%) and the second best accuracy (80%). For CAD defined as >70% stenosis, MPI, combined WM and CFR-LAD, and WM obtained similar accuracies (P = NS), but WM showed the best balance of sensitivity (73%) and specificity (73%), with the highest Youden index. CONCLUSIONS MPI had the highest sensitivity and accuracy for the detection of CAD > 50% during dipyridamole stress echocardiography, despite showing the lowest specificity among tested parameters. Standalone WM and combined WM and CFR-LAD were not significantly inferior in terms of overall accuracy when CAD > 70% was the diagnostic end point. The addition of MPI or CFR-LAD to standard WM assessment allows the detection of milder CAD.

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.

64-slice computed tomography coronary angiography: diagnostic accuracy in the real world

PurposeThis study was done to evaluate the diagnostic accuracy of 64-slice computed tomography coronary angiography (CTCA) for the detection of significant coronary artery stenosis in the real clinical world.Materials and methodFrom the CTCA database of our institution, we enrolled 145 patients (92 men, 52 women, mean age 63.4 ± 10.2 years) with suspected coronary artery disease. All patients presented with atypical or typical chest pain and underwent CTCA and conventional coronary angiography (CA). For the CTCA scan (Sensation 64, Siemens, Germany), we administered an IV bolus of 100 ml of iodinated contrast material (Iomeprol 400 mgI/ml, Bracco, Italy). The CTCA and CA reports used to evaluate diagnostic accuracy adopted ≥50% and ≥70%, respectively, as thresholds for significant stenosis.ResultEleven patients were excluded from the analysis because of the nondiagnostic quality of CTCA. The prevalence of disease demonstrated at CA was 63% (84/134). Sensitivity, specificity and positive and negative predictive values for CTCA on a per-segment, per-vessel, and per-patient basis were 75.6%, 85.1%, 97.6%; 86.9%, 81.8%, 58.0%; 48.2%, 68.1%, 79.6%; and 95.7%, 92.3%, 93.5%, respectively. Only two out of 134 eligible patients were false negative. Heart rate did not significantly influence diagnostic accuracy, whereas the absence or minimal presence of coronary calcification improved diagnostic accuracy. The positive and negative likelihood ratios at the per-patient level were 2.32 and 0.041, respectively.ConclusionCTCA in the real clinical world shows a diagnostic performance lower than reported in previous validation studies. The excellent negative predictive value and negative likelihood ratio make CTCA a noninvasive gold standard for exclusion of significant coronary artery disease.RiassuntoObiettivoValutare l’accuratezza diagnostica dell’angiografia coronarica non invasiva con tomografia computerizzata (CT-CA) a 64 strati nell’individuazione delle stenosi coronariche significative (riduzione del lume coronarico ≥50%) basando la valutazione sulla refertazione clinica.Materiali e metodiDal database della CT-CA sono stati arruolati nello studio 145 pazienti (92 maschi, 52 femmine, età media 63,4±10,2 anni) con sospetta malattia coronarica. I pazienti si presentavano con dolore toracico atipico o angina pectoris stabile e hanno poi eseguito CT-CA e coronarografia convenzionale (CAG). Per la scansione CT-CA (Sensation 64, Siemens, Germania) sono stati iniettati endovena 100 ml di mezzo di contrasto. (Iomeprol 400 mgI/ml, Bracco, Italia). I referti della CT-CA e della CAG sono utilizzati per la valutazione dell’accuratezza diagnostica utilizzano la definizione di stenosi ≥50% per la CT-CA e ≥70% per la CAG.RisultatiUndici pazienti sono stati esclusi dall’analisi per CT-CA di qualità insufficiente. La prevalenza di malattia dimostrata alla CAG era del 63% (84/134). Sensibilità, specificità, valore predittivo positivo e negativo della CT-CA nella determinazione delle stenosi significative utilizzando un’analisi per segmento, per vaso e per paziente sono risultate del 75,6%, 85,1%, 97,6%; 86,9%, 81,8%, 58,0%; 48,2%, 68,1%, 79,6%; e 95,7%, 92,3%, 93,5%, rispettivamente. Solo due pazienti su 134 eleggibili per lo studio sono risultati falsi negativi. La frequenza cardiaca non ha mostrato influenzare significativamente l’accuratezza diagnostica, mentre la presenza di scarse o assenti calcificazioni coronariche ha determinato un incremento dei valori di accuratezza diagnostica. I likelihood ratio positivo e negativo nell’analisi per paziente sono risultati 2,32 e 0,041, rispettivamente.ConclusioniLa CT-CA nel mondo reale mostra una performance diagnostica inferiore rispetto agli studi di validazione pubblicati in letteratura. I valori ottimali di valore predittivo negativo e likelihood ratio negativo collocano la CT-CA tra le metodiche non invasive gold standard per l’esclusione di malattia coronarica critica.

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.

Severe coronary tortuosity or myocardial bridging in patients with chest pain, normal coronary arteries, and reversible myocardial perfusion defects.

We reviewed patients with normal or near-normal coronary angiograms enrolled in the SPAM contrast stress echocardiographic diagnostic study in which 400 patients with chest pain syndrome of suspected cardiac origin with a clinical indication to coronary angiography were enrolled. Patients underwent dipyridamole contrast stress echocardiography (cSE) with sequential analysis of wall motion, myocardial perfusion, and Doppler coronary flow reserve before elective coronary angiography. Ninety-six patients with normal or near-normal epicardial coronary arteries were screened for the presence of 2 prespecified findings: severely tortuous coronary arteries and myocardial bridging. Patients were divided in 2 groups based on the presence (false-positive results, n = 37) or absence (true-negative results, n = 59) of reversible myocardial perfusion defects during cSE and compared for history and clinical and angiographic characteristics. Prevalence of severely tortuous coronary arteries (35% vs 5%, p <0.001) or myocardial bridging (13% vs 2%, p <0.05) was 7 times higher in patients who demonstrated reversible perfusion defects at cSE compared to those without reversible perfusion defects. No significant differences were found between the 2 groups for the main demographic variables and risk factors. Patients in the false-positive group more frequently had a history of effort angina (p <0.001) and ST-segment depression at treadmill electrocardiography (p <0.001). In conclusion, we hypothesize that patients with a positive myocardial perfusion finding at cSE but without obstructive epicardial coronary artery disease have a decreased myocardial blood flow reserve, which may be caused by a spectrum of causes other than obstructive coronary artery disease, among which severely tortuous coronary arteries/myocardial bridging may play a significant role.

Diagnostic accuracy of 64-slice CT in the assessment of coronary stents

PurposeThe purpose of this study was to assess the diagnostic accuracy of 64-slice computed tomography (64-CT) coronary angiography in the detection of coronary in-stent restenosis.Materials and methodsNinety-five patients (72 men and 23 women, mean age 58±8 years) with previous percutaneous coronary intervention with stenting and suspected restenosis underwent 64-CT (Sensation 64, Siemens). The mean time between stent deployment and 64-CT was 6.1±4.2 months. The scan parameters were: slices 32×2, individual detector width 0.6 mm, rotation time 0.33 s, feed 3.84 mm/rotation, 120 kV, 900 mAs. After the intravenous administration of iodinated contrast material (Iomeprol 400 mgI/ml, Iomeron, Bracco) and a bolus chaser (40 ml of saline), the scan was completed in <12 s. All coronary segments with a stent were assessed on 64-CT by two observers in consensus and judged as: patent, with intimal hyperplasia (lumen reduction of <50%), with in-stent restenosis (≥50%), or with in-stent occlusion (100%). The consensus reading was compared with conventional coronary angiography.ResultsFour patients were excluded because of insufficient image quality. In the remaining 91, we assessed 102 stents (31 RCA; 10 LM; 54 LAD; 7 CX). In 14 (13.7%) stents, in-stent restenosis (n=8) or in-stent occlusion (n=6) was found. Intimal hyperplasia was detected in 11 (10.8%) stents. The sensitivity and negative predictive value of 64-CT for in-stent occlusion were 100% and 100%, respectively, whereas for all stenoses, >50% they were 92.9% and 98.7%, respectively.ConclusionsWe found that 64-CT has a high diagnostic accuracy for the detection of in-stent restenosis in a selected patient population.RiassuntoObiettivoValutare l’accuratezza diagnostica dell’angiografia coronarica con TC a 64 strati (64-TC) nella re-stenosi degli stent coronarici.Materiali e metodiIn 95 pazienti (72 maschi e 23 femmine, età media 58±8 anni) precedentemente sottoposti a posizionamento di stent intra-coronarico e con sospetta re-stenosi, è stata effettuata una 64-TC (Sensation 64, Siemens). Il tempo medio tra il posizionamento dello stent e l’esame 64-TC è stato 6,1±4,2 mesi. I parametri di scansione erano: strati 32×2 (sovracampionamento sull’asse z mediante flying focal spot), collimazione individuale 0,6 mm, tempo di rotazione 0,33 s, avanzamento 3,84 mm/rot, kV 120, mA 900. Dopo la somministrazione di mezzo di contrasto iodato (Iomeprolo 400 mgI/ml, Iomeron; 100 ml a 5 ml/s) e bolus chaser (40 ml di soluzione fisiologica a 5 ml/s), la scansione è stata completata in meno di 12 s. Tutti i segmenti coronarici con uno stent sono stati valutati da due osservatori in consenso e giudicati come segue: pervi, con iperplasia intimale intra-stent (IIS; riduzione del lume <50%), con re-stenosi intra-stent (RIS; ≥50%), o con occlusione intra-stent (OIS; 100%). La lettura in consenso è stata confrontata con i risultati della coronarografia convenzionale.Risultati4 pazienti sono stati esclusi dall’analisi per insufficiente Qualityà della scansione. Nei rimanenti 91 pazienti sono stati valutati 102 stent (31 in arteria coronaria destra; 10 del tronco comune sinistro; 54 della arteria discendente anteriore; 7 nell’arteria circonflessa). In 14 (13,7%) stent era presente una RIS (8) o una OIS (6). In 11 (10,8%) stent è stata, invece, rilevata una IIS. La Sensibilityà ed il valore predittivo negativo per la rilevazione di OIS sono state rispettivamente, 100% e 100%, mentre quelle per la rilevazione di RIS+OIS sono state, rispettivamente, 92,9% e 98,7%.ConclusioniLa 64-TC fornisce una accuratezza diagnostica elevata nella rilevazione della re-stenosi intrastent in una popolazione selezionata di pazienti.

Usefulness of Contrast Stress-Echocardiography or Exercise-Electrocardiography to Predict Long-Term Acute Coronary Syndromes in Patients Presenting With Chest Pain Without Electrocardiographic Abnormalities or 12-Hour Troponin Elevation

The evaluation of patients presenting to the hospital with a recent episode of chest pain suggestive of myocardial ischemia, nondiagnostic electrocardiographic findings, and normal 12-hour cardiac troponin levels remains a challenge for the clinician. We selected 1,081 consecutive patients who presented to the emergency department during 2008 for a chest pain complaint of suspected cardiac origin without significant electrocardiographic abnormalities or troponin elevation. These patients underwent either contrast-enhanced stress-echocardiography with myocardial perfusion imaging or exercise-electrocardiography within 5 days of the index admission. We analyzed their 1-year cardiac outcome (i.e., unstable angina, myocardial infarction, or cardiac death). A post test likelihood of cardiac events was determined on the basis of the results of the provocative testing. Significantly better event-free survival (log-rank p <0.0001) was found for both hard (cardiac death and nonfatal myocardial infarction) and combined (acute coronary syndrome) end points in patients with normal contrast-enhanced stress-echocardiographic findings. However, this was not the case for patients in the exercise-electrocardiographic group, for whom event-free survival was not significantly different among the 3 possible result categories (normal, indeterminate, and abnormal test findings; log-rank p = NS). In conclusion, inducible ischemia detected by contrast-enhanced stress-echocardiography predicted the 1-year incidence of acute coronary syndrome (11.3% for positive vs 0.8% for negative results). However, this was not the case for exercise-electrocardiography, with a 2.7%, 2.3%, and 2.9% 1-year incidence of acute coronary syndromes for positive, negative, and indeterminate results, respectively.

Stress-ECG vs. CT coronary angiography for the diagnosis of coronary artery disease: a “real-world” experience

PurposeThis study aimed to evaluate the diagnostic accuracy of stress electrocardiogram (ECG) and computed tomography coronary angiography (CTCA) for the detection of significant coronary artery stenosis (≥50%) in the real world using conventional CA as the reference standard.Materials and methodsA total of 236 consecutive patients (159 men, 77 women; mean age 62.8±10.2 years) at moderate risk and with suspected coronary artery disease (CAD) were enrolled in the study and underwent stress ECG, CTCA and CA. The CTCA scan was performed after i.v. administration of a 100-ml bolus of iodinated contrast material. The stress ECG and CTCA reports were used to evaluate diagnostic accuracy compared with CA in the detection of significant stenosis ≥50%.ResultsWe excluded 16 patients from the analysis because of the nondiagnostic quality of stress ECG and/or CTCA. The prevalence of disease demonstrated at CA was 62% (n=220), 51% in the population with comparable stress ECG and CTCA (n=147) and 84% in the population with equivocal stress ECG (n=73). Stress ECG was classified as equivocal in 73 cases (33.2%), positive in 69 (31.4%) and negative in 78 (35.5%). In the per-patient analysis, the diagnostic accuracy of stress ECG was sensitivity 47%, specificity 53%, positive predictive value (PPV) 51% and negative predictive value (NPV) 49%. On stress ECG, 40 (27.2%) patients were misclassified as negative, and 34 (23.1%) patients with nonsignificant stenosis were overestimated as positive. The diagnostic accuracy of CTCA was sensitivity 96%, specificity 65%, PPV 74% and NPV 94%. CTCA incorrectly classified three (2%) as negative and 25 (17%) as positive. The difference in diagnostic accuracy between stress ECG and CTCA was significant (p<0.01).ConclusionsCTCA in the real world has significantly higher diagnostic accuracy compared with stress ECG and could be used as a first-line study in patients at moderate risk.RiassuntoObiettivoScopo del presente lavoro è stato valutare l’accuratezza diagnostica dell’elettrocardiogramma sotto stress (stress-ECG) e dell’angiografia coronarica con tomografia computerizzata (CT-CA) nell’individuazione delle stenosi coronariche significative (riduzione del lume coronarico ≥50%) vs l’angiografia coronaria convenzionale (CAG) basando la valutazione sulla refertazione clinica.Materiali e metodiDuecentotrentasei pazienti consecutivi (159 maschi, 77 femmine, età media 62,8±10,2 anni) a rischio intermedio con sospetta malattia coronarica sono stati arruolati per lo studio e sottoposti a stress-ECG, CT-CA e CAG. Per la scansione CT-CA sono stati iniettati endovena 100 ml di mezzo di contrasto. Tutti i pazienti sono stati quindi sottoposti a CAG. I referti dello stress-ECG e della CT-CA sono stati confrontati con la CAG quantitativa per la valutazione dell’accuratezza diagnostica.RisultatiSedici pazienti sono stati esclusi dall’analisi per stress-ECG e/o CT-CA di qualità inadeguata. La prevalenza di malattia è risultata del 62% nella popolazione complessiva (n=220), del 51% nella popolazione con stress-ECG e CT-CA confrontabili (n=147), e dell’84% nella popolazione con stress-ECG dubbio (n=73). Settantatre (33,2%) stress-ECG sono stati classificati come dubbi, 69 (31,4%) sono stati classificati come positivi e 78 (35,5%) sono stati classificati come negativi. Nell’analisi per paziente i valori dell’accuratezza diagnostica dello stress-ECG sono risultati: sensibilità 47%, specificità 53%, valore predittivo positivo 51%, valore predittivo negativo 49%. Quaranta (27,2%) pazienti sono stati erroneamente classificati come negativi. Trentaquattro (23,1%) pazienti che non avevano stenosi significative sono stati incorrettamente classificati come positivi. I valori dell’accuratezza diagnostica della CT-CA sono risultati: sensibilità 96%, specificità 65%, valore predittivo positivo 74%, valore predittivo negativo 94%. Tre (2%) pazienti sono stati erroneamente classificati come negativi. Venticinque (17%) pazienti che non avevano stenosi significative sono stati incorrettamente classificati come positivi. La differenza di accuratezza diagnostica è risultata significativa (p<0,01).ConclusioniLa CT-CA nel mondo reale mostra una accuratezza diagnostica significativamente superiore allo stress-ECG e potrebbe essere utilizzata in prima istanza nei pazienti a rischio intermedio.