Angiogenesis gene therapy: phase I assessment of direct intramyocardial administration of an adenovirus vector expressing VEGF121 cDNA to individuals with clinically significant severe coronary artery disease.

BACKGROUND: Therapeutic angiogenesis, a new experimental strategy for the treatment of vascular insufficiency, uses the administration of mediators known to induce vascular development in embryogenesis to induce neovascularization of ischemic adult tissues. This report summarizes a phase I clinical experience with a gene-therapy strategy that used an E1(-)E3(-) adenovirus (Ad) gene-transfer vector expressing human vascular endothelial growth factor (VEGF) 121 cDNA (Ad(GV)VEGF121.10) to induce therapeutic angiogenesis in the myocardium of individuals with clinically significant coronary artery disease. METHODS AND RESULTS: Ad(GV)VEGF121.10 was administered to 21 individuals by direct myocardial injection into an area of reversible ischemia either as an adjunct to conventional coronary artery bypass grafting (group A, n=15) or as sole therapy via a minithoracotomy (group B, n=6). There was no evidence of systemic or cardiac-related adverse events related to vector administration. In both groups, coronary angiography and stress sestamibi scan assessment of wall motion 30 days after therapy suggested improvement in the area of vector administration. All patients reported improvement in angina class after therapy. In group B, in which gene transfer was the only therapy, treadmill exercise assessment suggested improvement in most individuals. CONCLUSIONS: The data are consistent with the concept that direct myocardial administration of Ad(GV)VEGF121.10 to individuals with clinically significant coronary artery disease appears to be well tolerated, and initiation of phase II evaluation of this therapy is warranted.

Pheochromocytoma of the heart.

This is a presentation of a unique case of cardiac pheochromocytoma during pregnancy. The case is significant because pheochromocytoma is a difficult diagnosis and its rarity during pregnancy may lead to this important diagnosis being overlooked, even though treatment is specific and highly successful.

Cardiac motion of coronary arteries: variability in the rest period and implications for coronary MR angiography.

PURPOSE: To measure the duration of the rest period in the cardiac cycle, a parameter vital to data acquisition in coronary magnetic resonance (MR) angiography. MATERIALS AND METHODS: Motion of coronary arteries was measured in 13 patients by using breath-hold, biplane, conventional angiography, with frontal and lateral projections of the left and right coronary arteries acquired at 30 frames per second. The time courses of the coordinates of bifurcations of proximal parts of the coronary arteries were measured, from which the rest period (motion < 1 mm in orthogonal axes), velocity, displacement range, motion correlation, and reproducibility from heartbeat to heartbeat were estimated. RESULTS: Both the motion pattern and the amplitude varied substantially from patient to patient. The rest period varied from 66 to 333 msec (mean, 161 msec) for the left coronary artery and from 66 to 200 msec (mean, 120 msec) for the right coronary artery. CONCLUSION: The rest period for coronary arteries in the cardiac cycle varies substantially from patient to patient, which may cause quality to be inconsistent in current coronary MR angiography. A cardiac motion image prior to coronary data acquisition (preimage) may be used to estimate the optimal duration and timing in the cardiac cycle for coronary MR angiography.

Coronary MR angiography: selection of acquisition window of minimal cardiac motion with electrocardiography-triggered navigator cardiac motion prescanning--initial results.

The authors developed an electrocardiography-triggered M-mode navigator-echo technique to help monitor cardiac motion and identify the period of minimal cardiac motion in the cardiac cycle. Coronary magnetic resonance angiography was performed in eight healthy adult volunteers and one patient with heart disease. To minimize cardiac motion effects, trigger delays were estimated with the navigator-echo technique and two empirical formulas. The quality of images obtained with the different delay times was compared for clarity of depiction of the coronary arteries. Image quality was best with the delay calculated with the navigator-echo technique.

Breath-hold three-dimensional contrast-enhanced coronary MR angiography: motion-matched k-space sampling for reducing cardiac motion effects.

A view order that matches k-space sampling to cardiac motion within the acquisition window was developed for breath-hold three-dimensional contrast material-enhanced coronary magnetic resonance angiography. In vivo experiments in seven volunteers demonstrated that blurring was substantially reduced with this motion-matched view order as compared with the standard centric view order. Coronary arteries were well delineated.

Novel distal occluder washout method for prevention of no-reflow during stenting of saphenous vein grafts.

This study assessed safety of the distal occlusion washout (DOW) method for prevention of no-reflow during stenting of degenerated saphenous vein grafts (SVGs). The DOW method involves protection of distal native coronary circulation with an occlusive balloon during the pretreatment and washout steps prior to stenting. Outcomes of stenting of 23 grafts in 21 patients after pretreatment with the DOW method were evaluated. The mean graft age was 7.4 +/- 4.3 years. The mean treated lesion length was 53 +/- 28 mm. Total occlusions were treated in 6 grafts and thrombotic lesions in 10 nontotally occluded grafts. One non-Q-wave MI and one acute stent thrombosis were observed. No deaths, Q-wave MIs, or subacute thromboses occurred. Follow-up in 18/21 (85.7%) patients at 28 +/- 8 weeks demonstrated target graft revascularization in 1 (5%) patient. The DOW method prevented clinically significant no-reflow in all 23 degenerated SVGs stented.