Stefania Funaro

The Extent of Microvascular Damage During Myocardial Contrast Echocardiography Is Superior to Other Known Indexes of Post-Infarct Reperfusion in Predicting Left Ventricular Remodeling: Results of the Multicenter AMICI Study

OBJECTIVES We sought to evaluate the value of the extent of microvascular damage as assessed with myocardial contrast echocardiography (MCE) in the prediction of left ventricular (LV) remodeling after ST-segment elevation myocardial infarction (STEMI) as compared with established clinical and angiographic parameters of reperfusion. BACKGROUND Early identification of post-percutaneous coronary intervention microvascular dysfunction may help in tailoring appropriate pharmacological interventions in high-risk patients. The ideal method to establish effective microvascular reperfusion after percutaneous coronary intervention remains to be determined. METHODS A total of 110 patients with first successfully reperfused STEMI were enrolled in the AMICI (Acute Myocardial Infarction Contrast Imaging) multicenter study. After reperfusion, peak creatine kinase, ST-segment reduction, and Thrombolysis In Myocardial Infarction (TIMI) and myocardial blush grade were calculated. We evaluated perfusion defects with MCE by using continuous infusion of Sonovue (Bracco, Milan, Italy) in real-time imaging. The endocardial length of contrast defect (CD) on day 1 after reperfusion was calculated. Wall motion score index, the extent of wall motion abnormalities, LV end-diastolic volume, and ejection fraction after reperfusion and at follow-up also were calculated. RESULTS Of 110 patients, 25% evolved in LV remodeling and 75% did not. Although peak creatine kinase, ST-segment reduction >70%, and myocardial blush grade were not different between groups, in patients exhibiting LV remodeling, TIMI flow grade 3 was less frequent (p < 0.001), wall motion score index was greater (p < 0.001), and CD was greater (p < 0.001). At multivariate analysis, only TIMI flow grade <3 and CD with a cutoff of >25% were independently associated with LV remodeling. Among patients with TIMI flow grade 3, CD was the only independent variable associated with LV remodeling. CONCLUSIONS Among patients with TIMI flow grade 3, the extent of microvascular damage, detected and quantitated by MCE, is the most powerful independent predictor of LV remodeling after STEMI as compared with persistent ST-segment elevation and myocardial blush grade.

Incidence, determinants, and prognostic value of reverse left ventricular remodelling after primary percutaneous coronary intervention: results of the Acute Myocardial Infarction Contrast Imaging (AMICI) multicenter study

Aims Few data are available on the extent and prognostic value of reverse left ventricular remodelling (r-LVR) after ST-elevation acute myocardial infarction (STEMI). We sought to evaluate incidence, major determinants, and long-term clinical significance of r-LVR in a group of STEMI patients treated with primary percutaneous coronary intervention (PPCI). In particular, the role of preserved microvascular flow within the infarct zone in inducing r-LVR has been investigated. Methods and results Serial echocardiograms (2DE) and myocardial contrast study were obtained within 24 h of coronary recanalization (T1) and at pre-discharge (T2) in 110 reperfused STEMI patients. Follow-up 2DE was scheduled after 6 months (T3). Two-year clinical follow-up was obtained. Reverse remodelling was defined as a reduction >10% in LV end-systolic volume (LVESV) at 6 months follow-up. r-LVR occurred in 39% of study population. At multivariable analysis, independent predictors of r-LVR were an effective microvascular reflow within the infarct zone, the in-hospital improvement of myocardial perfusion, an initial large LVESV, and a short time to reperfusion. Cox analysis identified r-LVR as the only independent predictor of 2-year event-free survival. Combined events rate was significantly higher among patients without compared to those with r-LVR (log-rank test P < 0.05). Conclusion r-LVR frequently occurs in STEMI patients treated with PPCI and it is an important predictor of favourable long-term outcome. A preserved microvascular perfusion within the infarct zone is the major determinant of r-LVR.

Clinical application of quantitative analysis in real-time MCE

The introduction of stable microbubble contrast agents and technological advances have recently made it feasible to perform quantitative measurements of microvascular damage by myocardial contrast echocardiography (MCE). Qontrast is a new software system far such measurements. It includes physiological filters, global rescale, regional rescale, automatic myocardial tracking, manual ECG trigger and parametric imaging. Qontrast was tested on 5 pigs given sulphur hexafluoride bubbles (I ml/min) and fluorescent microspheres (reference) after the induction of 50% and 100% stenosis of left anterior descending coronary artery. The image sequences were repeated four times using different ultrasound (US) equipment. A close correlation was found between the ratio risk area/control area by microspheres and the equivalent ratio risk area/control area (Sl x beta) by MCE, being approximately 0.9 far any contrast modality tested. Parametric MCE and SPELT were compared in 12 patients with recent myocardial infarction, including 119 segments. Agreement amounted to 83% (kappa: 0.53 far peak SI and 0.55 far SI x beta). The sensitivity and specificity of peak SI far detecting abnormal segmental tracer uptake were 67% and 88%; the values far Sl x beta were 70% and 87%. Parametric MCE is a promising imaging technique far the assessment of myocardial perfusion in patients with suspected or known coronary artery disease.

Quantification methods in contrast echocardiography

New technologies and the availability of new echo-contrast agents have resulted in advances of diagnostic and prognostic indications of left ventricular opacification (LVO) and myocardial perfusion. The clinical diagnostic value of ultrasound contrast media for LVO and its impact on the clinical decision-making process has been demonstrated in several studies. Recent research aims at developing new quantitative software to improve the delineation of the endocardial border, to assess 3D myocardial perfusion for more accurate regional/global LV function measurements, and to evaluate 4D intra-cardiac flow dynamics. Furthermore, a general consensus has been reached on the incremental value of myocardial contrast echocardiography (MCE) for obtaining additional information in both chronic and acute coronary artery disease (CAD) patients and on the possibility to make quantitative measurements of microvascular damage. Q-contrast is a new software system which provides quantitative measurements to generate parametric images of microcirculatory flow. In a research project including 120 patients, Q-contrast software has been tested to assess the role of contrast in AMI (Acute Myocardial Infarction Contrast Imaging (A.M.I.C.I. Study); good agreement between parametric MCE and SPECT has been found. Preliminary results further confirm that quantitative MCE may provide additional clinical value over qualitative information for the assessment of LV function and of the effects of coronary artery disease on the myocardial microcirculation (viability, ischemia or infarct).

Tissue viability by contrast echocardiography

Residual tissue viability within the infarct area is one of the major determinants of regional functional recovery after acute myocardial infarction, playing also a protective role against LV remodelling. However, viability and functional recovery are not synonymous: functional recovery is only one of the aspects of viability. Several studies have shown how important it is to maintain perfusion independently from functional recovery. In patients with an extensive endocardial necrosis and a preserved normal perfusion in the middle and epicardial myocardium layers, even though functional recovery does not occur, remodelling processes may be attenuated. Tissue viability may be detected using several different methods. Perfusion-based techniques (i.e. PET, SPECT, MRI and MCE) are more accurate in predicting global function and LV remodelling whereas inotropic reserve-based methods (i.e. DE) are more accurate in predicting functional recovery. Several studies support the hypothesis that either LV remodelling or the possibility of myocardial dysfunction to recover are strictly dependent on the extent of microvascular damage. To date, myocardial contrast echocardiography and magnetic resonance imaging have shown to be very effective techniques for assessing microvascular perfusion. Our initial experience showed a very close correlation between these two perfusional techniques. In particular by MCE, it has been demonstrated that the persistence of residual anterograde or retrograde blood flow within the infarct zone can maintain myocardial viability for a prolonged time span. The incidence of LV remodelling is significantly lower in dysfunctioning but still perfused segments than in non-perfused ones. Therefore MCE can be used to identify viable segments that may help to prevent infarct expansion and remodelling, and thus improve patient outcomes.

626 Determinants of reverse left ventricular remodelling after acute myocardial infarction

and ejection fraction (EF%) at T1 and at 3-months follow-up (T2) were also calculated. R-LVR was defined as >10% reduction of EDV at follow-up. Results: At T2, 54% of patients had r-LVR. At T1, EDV/BSA was similar in patients with r-LVR than in the others. CDL% and WMA% were significantly lower and EF% was significantly higher in patients with r-LVR than the others. At T2, the EDV/BSA decreased in patients with r-LVR and increased in the others, WMA% and EF% improved in patients with r-LVR, while they didn’t change in the others. By ROC curves analysis, sensitivity and specificity of different parameters to predict reverse LVR was calculated and the results are listed in the table. Conclusion: R-LVR frequently occurs in patients successfully reperfused after AMI. A contrast defect extent <7% soon after reperfusion is the best predictor of r- LVR at follow-up. Patients with reverse LVR have the higher improvement in systolic LV function as compared to the others. Table 1. ROC curves analysis

512 Gender and myocardial salvage after reperfusion treatment in acute myocardial infarction. Results of Acute Myocardial Infarction Contrast Imaging (A.M.I.C.I) multicenter trial

Eur J Echocardiography Abstracts Supplement, December 2006 tion velocity (Vp) (42.0±11.5 cm/sec vs 37.5±7.8 cm/sec, p=0.01). The two groups did not differ in incidence of adverse events. Cox regression analysis performed after selecting the best cut-off parameter’s values identified Vp 76 cm/sec (RR 3.35, 95% CI [1.46-7.71], p=0.004). Conclusions: Baseline Vp 76 cm/sec are the best predictors of adverse events after MI and they are superior to systolic parameters.