Abstract: AIMS: Microvascular damage (MD) occurring soon after primary percutaneous coronary intervention (PPCI) may reverse or remain sustained within the first week after ST-elevation myocardial infarction (STEMI). We investigated the incidence, determinants, and long-term clinical relevance of MD reversal after PPCI. METHODS AND RESULTS: Serial two-dimensional echocardiograms (2DE) and a myocardial contrast study were obtained within 24 h of PPCI (T1) and at pre-discharge (T2) in 110 successfully re-perfused STEMI patients. Six months 2DE and 2-year clinical follow-up were obtained. After PPCI myocardial re-perfusion was normal at T1 only in 40 patients (36%, 'normal reflow'), recovered at T2 in 33 (30%, 'reversible MD'), and remained abnormal in 37 (34%, 'sustained MD'). At follow-up, normal reflow and reversible MD were coupled with a significant reduction in the infarct area, decrease in cardiac volumes, and a slight non-significant improvement in systolic function. Conversely, in the sustained MD group, the infarct area did not change and cardiac volumes significantly increased with a parallel worsening in systolic function. By multivariate analysis, independent predictors of reversible MD were: absence of family history of coronary artery disease (CAD), younger age, shorter time to re-perfusion, and absence of diabetes. The 2-year combined events rate was significantly lower in reversible MD (log-rank test P= 0.03) compared with sustained MD patients. CONCLUSIONS: In STEMI patients treated according to the current guidelines, MD frequently occurs soon after re-perfusion but it is reversible in �50% of cases and it is associated with a favourable functional and clinical outcome. Family history of CAD, aging, time to re-perfusion, and diabetes are independent predictors of MD reversibility.
Abstract: 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.
Abstract: 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.
Abstract: BACKGROUND: Recent data show that percutaneous coronary intervention (PCI) in patients with stable postthrombolytic ST-segment elevation myocardial infarction (STEMI) is better than no PCI or ischemia-guided PCI. These results still have to find a pathophysiologic explanation. We hypothesized that complete mechanical recanalization of infarct-related artery improves clinical benefits of thrombolysis as a result of more preserved and better perfused coronary microcirculation. To test this hypothesis, we studied a selected STEMI population presenting very early after symptom onset in whom successful infarct-related artery reperfusion was obtained by thrombolysis followed or not by elective PCI within 24 hours, and we compared these 2 groups with those underwent primary PCI. METHODS: This study analyzed 96 patients with STEMI randomized within 3 hours from symptom onset to primary PCI (group A, n = 36), tenecteplase followed within 24 hours by PCI (group B, n = 30), or to tenecteplase alone (group C, n = 30). Microvascular perfusion was assessed by myocardial contrast echocardiography. Regional contrast score, endocardial length and area of contrast defect on day 2 (T1) and at predischarge (T2), left ventricular end-diastolic volume, regional wall motion score, extent of wall motion abnormalities, and ejection fraction at T1, T2, and at 3 months' follow-up were calculated. RESULTS: Baseline clinical and angiographic characteristics were not statistically different between groups. The extent of microvascular damage and of myocardial salvage was similar in primary PCI-treated or in invasively treated patients after lytic administration. Conversely, group C patients, although treated very early with fibrinolytic therapy, showed higher extent of microvascular damage and infarct size and a more depressed left ventricular function after reperfusion and at follow-up. CONCLUSIONS: Our data suggest that early PCI after lysis is more effective in preserving myocardial perfusion and function than lysis alone and may be a helpful alternative when primary PCI is not available.
Abstract: 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).
Abstract: 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.
Abstract: Recent studies have demonstrated the usefulness of myocardial contrast echocardiography (MCE) in studying myocardial perfusion. Several first and second generation contrast agent such as Levovist, Sonovue, Optison, Definity and Imagent are commercially available or close to be introduced into the market. Use of MCE allowed the clinical demonstration of no-reflow phenomenon in patients with acute myocardial infarction (AMI) after recanalization of the infarct related artery (IRA). Coronary angiography is unable to assess the microvascular damage as showed by the poor correlation between TIMI grading and perfusion score evaluated by MCE. Furthermore, the use of MCE is important to determine coronary stenosis, to identify microvascular damage during ischaemia-reperfusion and to evaluate the presence of collateral circulation in the area at risk. MCE seems to be the most effective technique for assessing microvascular integrity after reperfusion as compared to TIMI myocardial perfusion grade, nuclear myocardial perfusion imaging and magnetic resonance imaging. These techniques are expensive, invasive and not available in most of the hospitals. Furthermore, as compared to nuclear medicine and echo-dobutamine, MCE has greater specificity and higher accuracy in detecting coronary artery disease. Recent studies showed that not only primary percutaneous coronary intervention (PCI) but also rescue and delayed PCI reduced microvascular damage and that MCE play a key role in assessing myocardial salvage after reperfusion. The most exciting aspect of MCE is the independent role in predicting left ventricular (LV) remodelling and functional recovery. The extent on no-reflow is an important predictor of LV dysfunction and remodelling at follow-up. Several studies have demonstrated that the extent of infarct-zone viability is a powerful independent predictor of LV dilation. There is a close relationship between the extent of microvascular damage, the extension of necrosis, the site of AMI and LV remodelling. We demonstrated that MCE performed 24 hours after reperfusion, at 1 week and 6 months appears to provide important prognostic information. These data support the daily use of MCE in coronary care unit and could establish a strategy for clinical decision making in patients with AMI.
Abstract: After many years of study and research, the noninvasive assessment of myocardial perfusion by echo contrast agents is becoming a clinical reality. The fast technological progress of echocardiographic imaging and the approval for human use in Europe and the United States of some first and second generation contrast agents explains the growing interest in this new methodology. Recently, a new second generation contrast agent, SonoVue, made of microbubbles stabilized by phospholipids and containing sulphur hexafluoride, has been introduced on the European market. We describe the role of intravenous myocardial contrast echocardiography with second-generation contrast agents such as SonoVue in the tailored reperfusion strategies in acute myocardial infarction.
Abstract: OBJECTIVES: The implantation of a transjugular intrahepatic portosystemic shunt (TIPS) has been shown to exacerbate the hyperdynamic circulation and might induce a significant cardiac overload. We investigated cardiac function before and 1, 3, 6, and 12 months after the TIPS procedure in cirrhotic patients. METHODS: Eleven patients with nonalcoholic cirrhosis were evaluated. Cardiovascular parameters were assessed by two-dimensional Doppler echocardiography. RESULTS: After TIPS, the left ventricular diastolic diameter increased from 26.5 +/- 1.8 mm (basal) to 30.0 +/- 2.8 mm (6 months) (p < 0.05), whereas the ejection fraction showed a slight increase (basal, 64.5 +/- 3.3; 6 months, 68.1 +/- 3.2). The left ventricular pre-ejection period and the isovolumetric relaxation time decreased transiently at 1 month (p < 0.05). An increased velocity in all of the components of pulmonary venous flow (systolic, diastolic, and atrial) documented the accelerated fluxes induced by the procedure. The estimated pulmonary systolic arterial pressure also increased at 1 month (29.5 +/- 1.4 vs 44.1 +/- 1.4 mm Hg, p < 0.05). All of these modifications reverted after 6 months. CONCLUSIONS: Our study demonstrates that nonalcoholic cirrhotic patients, without cardiovascular pathologies, show transient modifications in cardiac dimension and function for 3-6 months after TIPS caused by the increased volume load shunted to the heart.
Abstract: Myocardial contrast echocardiography (intracoronary application) has emerged as an accurate method to detect the "no-reflow phenomenon." To investigate the diagnostic value of harmonic angiography after intravenous infusion of Levovist in assessing "no-reflow," both intracoronary and intravenous contrast injections were performed in a group of patients with acute myocardial infarction. Seventeen consecutive patients with a successfully reperfused acute myocardial infarction within 6 hours of symptom onset were selected for this study. All patients underwent contrast echocardiography with harmonic angiography with Levovist (400 mg/mL, intravenous pump infusion, trigger intervals 1:4 to 1:8) and sonicated albumin (0.5 to 1 mL, intracoronary bolus) on day 1 after the achievement of a sustained coronary reflow. Myocardial perfusion was qualitatively assessed with a 12-segment model. The endocardial length of the residual contrast defect after reflow was also calculated. Forty-four of 204 segments were not analyzed after intravenous contrast echocardiography and 37 after intracoronary contrast echocardiography because of artifacts. Intracoronary and intravenous injections showed a perfusion defect in 31 (19%) segments, with a concordance of 89% (kappa coefficient, 0.72). Concordance in anteroseptal, anterolateral, and inferolateral segments was 95% (kappa = 0.92), 88% (kappa = 0.66), and 83% (kappa = 0.57), respectively. With intracoronary injection used as the reference method, intravenous injection had a sensitivity of 74% and a specificity of 93% for diagnosing contrast defects. The endocardial extent of no-reflow was 18 +/- 19 after intravenous and 21 +/- 17 after intracoronary contrast echocardiography (P = not significant). Intravenous contrast echocardiography with Levovist reliably identifies the no-reflow phenomenon after successful reperfusion, especially in acute anteroseptal myocardial infarction.
Abstract: Many technical problems, related to both imaging instrumentation and contrast agents, have to be taken into account before attempting non-invasive evaluation of myocardial perfusion by intravenous contrast media injection. Potentials and pitfalls of first generation contrast agents (i.e. Levovist, Schering AG, Berlin, Germany) using intermittent harmonic angio imaging and of second generation contrast media (i.e. SonoVue, Bracco SpA, Milan, Italy) using real-time perfusion imaging in the non-invasive assessment of myocardial perfusion were described and discussed. We still need more solid data before introducing intravenous myocardial echocardiography into the clinical arena. However, convincing data from several research laboratories are paving the way for the widespread use of this new method in clinical practice.
Abstract: OBJECTIVES: The goals of this study were to analyze temporal changes in cardiac cyclic variation of integrated backscatter (CVIB) in acute myocardial infarction (AMI) and to investigate the predictive value of CVIB normalization compared with that of dobutamine stress echocardiography (DSE) in the assessment of functional recovery after revascularization. BACKGROUND: The normal CVIB is blunted by ischemia and recovers early after reperfusion, faster than wall motion improvement. Analysis of CVIB has been widely investigated for its potential to detect viable myocardium in the early stage of infarction. No studies have compared CVIB analysis with other techniques for viability assessment in patients with acute ischemic. Methods and Results: Integrated backscatter images were obtained in 12 patients with AMI on days 1, 3, and 7 after admission and 1 month after revascularization. On day 7, DSE was performed in all patients. On admission, 22 of 144 segments were dyssynergic. On day 1, CVIB was abnormal in all 22 infarcted segments, on day 3, in 16, and on day 7, in only 10 infarcted segments. Eight of 10 segments nonviable by CVIB (CVIB-nonviable) were also nonrespondent by DSE; whereas 12 of 14 segments viable by DSE (DSE-viable) were also CVIB-viable. At follow-up, 10 CVIB-viable segments and 1 CVIB-nonviable segment showed functional recovery; whereas 10 of 14 DSE-viable segments showed functional recovery. Thus the positive predictive value of CVIB and DSE was 83% and 72%, respectively, with a diagnostic agreement between techniques in 77% of segments. CONCLUSIONS: Our data suggest that the normalization in CVIB in the first week after AMI accurately predicts residual tissue viability within the infarct zone. We also observed that the initial pattern of cyclic variation may be predictive of functional recovery. Finally, we found a good correlation between the recovery of a normal CVIB in segments that were still dysfunctional and a more validated method to assess tissue viability, such as the dobutamine test.
Abstract: OBJECTIVES: Abnormalities in cardiac function have been reported in liver cirrhosis, suggesting a latent cardiomyopathy in these patients. In this study we investigated cardiac function in cirrhotic patients and in controls. METHODS: A total of 20 cirrhotic patients without previous or ongoing ascites, 20 cirrhotic patients with moderate-to-severe ascites, and 10 healthy controls were studied by two-dimensional Doppler echocardiography. Cardiac dimensions and left and right ventricular function were evaluated. The left ventricular geometric pattern was calculated according to Ganau's criteria. Diastolic function was evaluated by the peak filling velocity of E wave and A wave, E/A ratio, and deceleration time of E wave. The pulmonary systolic arterial pressure was also estimated in patients with tricuspid insufficiency. RESULTS: Right and left atrium and right ventricle diameters were significantly enlarged in cirrhotic patients versus controls. E/A ratio was decreased (p < 0.05) in patients with ascites (0.9 +/- 0.2) versus those without ascites (1.3 +/- 0.4) and controls (1.3 +/- 1). The estimated pulmonary systolic arterial pressure was slightly elevated in patients with ascites (35 +/- 5 mm Hg, six patients) versus those with no ascites (28 +/- 5, 10 patients) and controls (27 +/- 8, 6 controls, analysis of variance, p < 0.05). The pattern of left ventricular geometry was normal in the majority of patients. Nitrite and nitrate levels were increased in cirrhotics irrespective of the presence of ascites. CONCLUSIONS: Liver cirrhosis is associated with enlarged right cardiac chambers. Diastolic dysfunction and mild pulmonary hypertension are evident in cirrhotic patients with ascites. These changes do not depend on variations in the left ventricular geometry.
Abstract: Although angiotensin-converting enzyme inhibitors have been shown to affect left ventricular (LV) remodeling favorably in several conditions, it remains unclear whether they can influence LV geometric pattern in hypertension. To address this issue, 122 patients (71 men and 51 women; mean age = 51 +/- 10 years) with mild to moderate hypertension were studied prospectively. All underwent clinical evaluation and Doppler echocardiography at entry and more than 2 years of quinapril therapy (10-40 mg/day). According to either LV mass (normal if < 131 g/m2 for men or < 100 g/m2 for women) or the ratio of LV posterior wall thickness to diastolic diameter (RWT; normal if < 0.45) at baseline, 58 patients had normal mass and RWT, 18 patients had concentric remodelling (i.e., normal mass but increased RWT), 24 patients had eccentric hypertrophy (i.e., increased mass but normal RWT), and 22 patients had concentric hypertrophy (i.e., increase in both mass and RWT). After 6 months of quinapril therapy, all patients with normal left ventricles showed the maintenance of mass and RWT within normal limits. Patients with concentric remodeling showed no increase in mass but had a significant decrease in RWT. Patients with eccentric hypertrophy exhibited a significant reduction in mass with no substantial change in RWT. Patients with concentric hypertrophy had a significant reduction in both mass and RWT. Changes in LV mass and geometry were maintained during the 2-year period of treatment and were paralleled by improvements in Doppler indices of LV diastolic function in each group. It is concluded that quinapril, with its well-known effects on LV hypertrophy, modifies the LV geometric pattern of hypertensive patients favorably, regardless of the presence of an abnormal LV mass or RWT.
Abstract: Multiple sclerosis is the most common cause of neurologic disability in young adults. Recent reports have suggested that Mitoxantrone might be a candidate for clinical trials in multiple sclerosis patients. The authors studied 20 patients with relapsing remitting multiple sclerosis to evaluate cardiac toxicity during a one-year follow-up period. Patients were divided into 2 groups: group A, mitoxantrone treated patients (cumulative dose of 96 mg/m2); group B, placebo patients. The clinical course of multiple sclerosis was assessed using the Expanded Disability Status Scale and the number of relapses during the follow-up. Each patient had an electrocardiogram and a spectral and color flow Doppler echocardiographic examination at enrollment, and 6 and 12 months later, to investigate cardiac toxicity. The mean exacerbation rate was reduced significantly in group A patients. No significant differences in the electrocardiograms or the echocardiographic parameters of systolic and diastolic function were noted between the two groups or in group A during the follow-up. Mitoxantrone treatment seems able to improve the clinical course of relapsing remitting multiple sclerosis patients. It does not show any cardiac toxicity in selected patients at this dosage.
