NC100100, a new echo contrast agent for the assessment of myocardial perfusion—safety and comparison with technetium‐99m sestamibi single‐photon emission computed tomography in a randomized multicenter study

• Published in: Clinical cardiology (Mahwah, N.J.) Vol. 22; no. 4; pp. 273 - 282
• Main Authors: Binder, Thomas, Assayag, Patrick, Baer, Frank, Flachskampf, Frank, Kamp, Otto, Nienaber, Christoph, Nihoyannopoulos, Petros, Pi érard, Luc, Steg, Gabriel, Vanoverschelde, Jean‐Louis, Wouw, Poll Van Der, Meland, Nils, Marelli, Claudio, Lindvall, Kaj
• Format: Journal Article Web Resource
• Language: English
• Published: New York Wiley Periodicals, Inc 01-04-1999; Wiley-Blackwell
• Subjects: Aged; Cardiovascular & respiratory systems; Clinical Investigation; Clinical Investigations; Contrast Media - administration & dosage; coronary artery disease; Dose-Response Relationship, Drug; Echocardiography - methods; Female; Ferric Compounds - administration & dosage; Ferric Compounds - adverse effects; Ferric Compounds/administration & dosage/adverse effects/diagnostic use; harmonic imaging; Human health sciences; Humans; Iron - administration & dosage; Iron - adverse effects; Iron/administration & dosage/adverse effects/diagnostic use; Male; Middle Aged; myocardial contrast echocardiography; myocardial infarction; Myocardial Infarction - diagnostic imaging; Myocardial Infarction/radionuclide imaging/ultrasonography; myocardial perfusion; Myocardial Reperfusion; Oxides - administration & dosage; Oxides - adverse effects; Oxides/administration & dosage/adverse effects/diagnostic use; Prospective Studies; Sciences de la santé humaine; Sensitivity and Specificity; Systèmes cardiovasculaire & respiratoire; Technetium Tc 99m Sestamibi; Technetium Tc 99m Sestamibi/diagnostic use; Tomography, Emission-Computed, Single-Photon - methods
• ISSN: 0160-9289; 1932-8737; 1932-8737
• DOI: 10.1002/clc.4960220405

Background and hypothesis: Myocardial contrast echocardiography using second‐generation agents has been proposed to study myocardial perfusion. A placebo‐controlled, multi‐center trial was conducted to evaluate the safety, optimal dose, and imaging mode for NC100100, a novel intravenous second‐generation echo contrast agent, and to compare this technique with technetium ‐ 99m sestamibi (MIBI) single‐photon emission computed tomography (SPECT).
Methods: In a placebo‐controlled, multicenter trial, 203 patients with myocardial infarction > 5 days and < 1 year previously underwent rest SPECT and MCE. Fundamental and harmonic imaging modes combined with continuous and electrocardiogram‐ (ECG) triggered intermittent imaging were used. Six dose groups (0.030, 0.100, and 0.300 μl particles/kg body weight for fundamental imaging; and 0.006, 0.030, and 0.150 μl particles/kg body weight for harmonic imaging) were tested. A saline group was also included. Safety was followed for 72 h after contrast injection. Myocardial perfusion by MCE was compared with myocardial rest perfusion imaging using MIBI as a tracer.
Results: NC100100 was well tolerated. No serious adverse events or deaths occurred. No clinically relevant changes in vital signs, laboratory parameters, and ECG recordings were noted. There was no significant difference between adverse events in the NC100100 (25.7%) and in the placebo group (17.9%, p=0.3). Intermittent harmonic imaging using the intermediate dose was superior to all other modalities, allowing the assessment of perfusion in 76% of all segments. Eighty segments (96%) with normal perfusion by SPECT imaging also showed myocardial perfusion with MCE. However, a substantial percentage of segments (61–80%) with perfusion defects by SPECT imaging also showed opacification by MCE. This resulted in an overall agreement of 66–81% and a high specificity (80–96%), but in low sensitivity (20–39%) of MCE for the detection of perfusion defects.
Conclusion: NC100100 is safe in patients with myocardial infarction. Intermittent harmonic imaging with a dose of 0.03 μl particles/kg body weight can be proposed as the best imaging protocol. Myocardial contrast echocardiography with NC 100100 provides perfusion information in approximately 76% of segments and results in myocardial opacification in the vast majority of segments with normal perfusion as assessed by SPECT. Although the discrepancies between MCE and SPECT with regard to the definition of perfusion defects requires further investigation, MCE with NC 100100 is a promising technique for the noninvasive assessment of myocardial perfusion.