Gradus-Pizlo, Irmina

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269www.fc.viamedica.plEDITORIALFolia Cardiol.2006, Vol. 13, No. 4, pp. 269–271Copyright © 2006 Via MedicaISSN 1507–4145Address for correspondence: Irmina Gradus-Pizlo, MD, FACCAssociate Professor of CardiologyKrannert Institute of CardiologyIndiana University School of Medicine1800 N. Capitol Ave, Suite 4000Indianapolis, IN 46202, USAe-mail: igradus@iupui.eduEvolving diagnostic and therapeuticapplications of ultrasound contrast agentsIrmina Gradus-PizloKrannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, USAArticle p. 293Ultrasound contrast agents have been prima-rily used for improving left ventricular opacification,but there are emerging applications that could si-gnificantly increase their utilization. In addition toenhancement of endocardial border detection andDoppler assessment of LV function, contrast echo-cardiography may be utilized to assess myocardialperfusion and viability. Until now, detection of my-ocardial perfusion has been almost exclusively donewith radionuclide tracers. However, since the my-ocardial contrast echocardiography (MCE) is safe,less expensive and it can be performed at the pa-tient’s bedside there is growing interest in this ap-plication. In addition MCE has increased resolutionwhen compared with radionuclide imaging (2 mmvs. 8–12 mm) which permits detection of subendo-cardial perfusion defects with improved precision.New data indicate that MCE may be used in theemergency department to assist in ruling out acu-te coronary syndromes [1] and that myocardial per-fusion imaging with ultrasound contrast agents du-ring dobutamine stress echocardiography is signi-ficantly better than wall motion analysis alone inpredicting patient’s outcome [2].MCE has also been used to detect the no-re-flow phenomenon. The defect detected before pri-mary PCI can define the region at risk, and the de-fect detected after successful coronary reperfusionconstitute the area of no-reflow. The improvementof myocardial perfusion on MCE was predictive ofsubsequent improvement in left ventricular func-tion [3]. Assessment of myocardial perfusion andthe coronary microcirculation with MCE correspon-ded to evaluation using coronary flow reserve me-asurements obtained with a coronary artery Dop-pler wire. MCE may also provide prognostic infor-mation. In one study of 50 patients with a firstmyocardial infarction who received thrombolytictherapy, the presence of reduced opacification onMCE, performed on day two, predicted a highermajor cardiac event rate (death, nonfatal infarction,or admission for congestive heart failure) duringa mean follow up of 22 months (28% vs. 4% in tho-se with adequate opacification) [4]. In another stu-dy, patients with a persistent defect in the infarctzone due to the no-reflow phenomenon, despite therestoration of TIMI grade 3 flow, had a deteriora-tion of regional and global systolic dysfunction [5].Current study published by Wita et al. in this issueof Folia Cardiologica contributes significant data.It demonstrates that MCE has high prognostic va-lue for prediction of functional left ventricular im-provement in patients with first myocardial infarc-tion and restored patency of target artery. In fact,MCE turned out to be significantly better than cur-rently utilized methods, raising the possibility ofMCE becoming the new “gold standard” for evalu-ation of no-reflow phenomenon.The role of myocardial contrastechocardiography in evaluationof infarcted, stunned and hibernatingmyocardiumDysfunctional segments of the LV following anischemic insult may represent either necrotic, in-farcted tissue, temporary effect of hypoperfusioncalled stunning or chronically hypoperfused, but still270Folia Cardiol. 2006, Vol. 13, No. 4www.fc.viamedica.plviable tissue called hibernating myocardium. Pro-longed occlusion of coronary artery leads to myocar-dial necrosis which may be easily detected as wallmotion abnormality on echocardiography. However,if the coronary flow is restored before the onset ofmyocardial necrosis, the persistent wall motionabnormalities may represent viable but not contrac-tile thus “stunned” myocardium. Since there isa substantial variability in the time course overwhich myocardium recovers from stunning, rangingfrom weeks to months, it is good to know that MCEmay be helpful in differentiating these two patternsof myocardial dysfunction. Stunned myocardium hashomogeneous myocardial contrast, representingnormal blood flow with an intact microvasculature.Such a pattern implies either that the decrease inperfusion was not lethal or that reperfusion (eitherspontaneous or as a result of intervention) occur-red prior to necrosis. In this setting, systolic func-tion is likely to return over the next several weeks[6–9]. In one study of 96 patients, the positive andnegative predictive value of homogeneous opacifi-cation for recovery of contractile function at sixmonths was 47% and 84%, respectively; the positi-ve predictive value for predicting functional reco-very was 78% in those who were revascularized [8].Chronically reduced blood flow may also leadto a state of persistently impaired myocardial func-tion with preservation of viability called hibernatingmyocardium. Hibernating myocardium can be par-tially or completely restored to normal by impro-ving blood flow and/or by reducing demand. Viabi-lity studies performed to detect hibernating but via-ble tissue are usually done in high risk patients withLV dysfunction in order to guide difficult decisionsregarding revascularization. Current techniquesused to determine myocardial viability include sin-gle photon emission computed tomography(SPECT) imaging, positron emission tomographyscanning, nuclear magnetic imaging, and low-dosedobutamine echocardiography. MCE provides si-multaneous LV function and perfusion informationand offers the advantages of improved image reso-lution (over SPECT), portability, cost economy, andpracticality. The identification of subnormal flow(heterogeneous contrast effect) as opposed to noflow (fixed contrast defect) or normal flow (homo-geneous contrast) within dysfunctional myocardiummay predict long-term recovery of function follo-wing the restoration of normal blood supply [10].Microbubbles may also have therapeutic poten-tial. Preclinical trials have demonstrated that ultra-sound-mediated microbubble destruction can be usedto target delivery of genes to the myocardium [11].Phase 1 clinical trials are under way exploringwhether antisense oligonucleotides, which inhi-bit c-myc protooncogene can be safely deliveredto stented coronary artery segment with intrave-nous microbubbles. Microbubbles may also beused in combination with ultrasound to non-in-vasively dissolve intravascular thrombi withoutthe need of a lytic agent [12]. This may be espe-cially useful in the treatment of acute stroke, andpreclinical trials have demonstrated that intra-cranial ultrasound and intravenous target micro-bubbles can successfully recanalize intracranialthrombi [13].Myocardial contrast echocardiography is a newand growing field. It started with the quest for im-proved echocardiographic resolution and left ven-tricular endocardial border detection and grew intothe real time assessment of intracardiac blood flow,myocardial perfusion and viability, and it may pro-vide a future means for drug delivery and other the-rapeutic interventions.References1. Leng Tong K et al. Myocardial contrast echocar-diography versus thrombolysis in myocardial inf-arction score in patients presenting to the emer-gency department with chest pain and nondiagnos-tic electrocardiogram. J Am Coll Cardiol, 2005; 46:920.2. Tsutsui J et al. Prognostic value of dobutamine stressmyocardial contrast perfusion echocardiography. Cir-culation, 2005; 112: 1444.3. Lepper W et al. Assessment of myocardial reperfu-sion by intravenous myocardial contrast echocardio-graphy and coronary flow reserve after primary per-cutaneous transluminal coronary angiography in pa-tients with acute myocardial infarction. Circulation,2000; 101: 2368.4. Sakuma T et al. Prediction of short- and interme-diate-term prognoses of patients with acute myocar-dial infarction using myocardial contrast echocardio-graphy one day after recanalization. J Am Coll Cardiol,1998; 32: 890.5. Porter TR et al. The clinical implications of no re-flow demonstrated with intravenous perfluorocarboncontaining microbubbles following restoration ofthrombolysis in myocardial infarction (TIMI) 3 flowin patients with acute myocardial infarction. Am JCardiol, 1998; 82: 1173.6. Ito H et al. Time course of functional improve-ment in stunned myocardium in risk area in pa-tients with reperfused anterior infarction. Circula-tion, 1993; 87: 355.271Irmina Gradus-Pizlo, Evolving diagnostic and therapeutic applicationswww.fc.viamedica.pl7. Main ML et al. Full-motion pulse inversion powerDoppler contrast echocardiography differentiatesstunning from necrosis and predicts recovery of leftventricular function after acute myocardial infarction.J Am Coll Cardiol, 2001; 38: 1390.8. Swinburn JM et al. Intravenous myocardial contrastechocardiography predicts recovery of dysynergicmyocardium early after acute myocardial infarction.J Am Coll Cardiol, 2001; 38: 19.9. Balcells E et al. Detection of myocardial viability bycontrast echocardiography in acute infarction pre-dicts recovery of resting function and contractile re-serve. J Am Coll Cardiol, 2003; 41:827.10. Kenner MD et al. Ability of the no-reflow phenome-non during an acute myocardial infarction to predictleft ventricular dysfunction at one-month follow-up.Am J Cardiol, 1995; 76: 861.11. Korpanty G et al. Targeting VEGF-mediated angio-genesis to rat myocardium using ultrasonic destruc-tion of microbubbles. Gene Therapy, 2005; 1–8.12. Xie F et al. Effectiveness of lipid microbubbles andultrasound in declotting thrombosis. US Med Biol,2005; 31: 979.13. Culp W et al. Intracranial clot lysis with intravenousmicrobubbles and transcranial ultrasound in swine.Stroke, 2004; 35: 2407.

Evolving diagnostic and therapeutic applications of ultrasound contrast agents

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Evolving diagnostic and therapeutic applications of ultrasound contrast agents

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