Maintenance of geometric alterations associated with percutaneous mitral valve repair: real-time three-dimensional echocardiographic assessment in an ovine model.

BACKGROUND AND AIM OF THE STUDY: Percutaneous catheter-based mitral annuloplasty (PTMA) exploits the anatomic proximity of the coronary sinus (CS) to the mitral valve apparatus. Acute results of PTMA have been favorable, but the durability of the geometric alterations associated with PTMA has not been reported. The study aim was to assess the three-dimensional (3D) geometry of the mitral annulus (MA) in normal sheep at 20 weeks after PTMA implantation. METHODS: A PTMA device was implanted percutaneously in the CS of 10 normal sheep without mitral regurgitation. All animals were followed for 20 weeks with real-time 3D echocardiography (RT3DE). The MA area, the diagonal diameters in four directions, and the angle alpha, representing the degree of the saddle shape of MA, were determined. RESULTS: No significant hemodynamic, pathologic or mechanical complications were observed during implantation or follow up. Both, the MA area (from 4.8 +/- 0.9 cm2 to 3.7 +/- 0.9 cm2) and anterior-posterior (A-P) diameter (from 21.4 +/- 3.0 mm to 17.6 +/- 2.4 mm) were reduced immediately after the procedure (both p <0.05). The angle alpha decreased after the procedure (from 142.0 +/- 11.5 degrees to 128.3 +/- 15.6 degrees; p <0.05). These changes remained stable over the 20-week follow up period. CONCLUSION: RT3DE demonstrates that PTMA reduces the MA area and A-P diameter and maintains the physiologic curved or saddle shape of the MA. These changes remained stable for 20 weeks after device implantation.

Intraplaque hemorrhage and progression of coronary atheroma.

BACKGROUND: Intraplaque hemorrhage is common in advanced coronary atherosclerotic lesions. The relation between hemorrhage and the vulnerability of plaque to disruption may involve the accumulation of free cholesterol from erythrocyte membranes. METHODS: We stained multiple coronary lesions from 24 randomly selected patients who had died suddenly of coronary causes with an antibody against glycophorin A (a protein specific to erythrocytes that facilitates anion exchange) and Mallory's stain for iron (hemosiderin), markers of previous intraplaque hemorrhage. Coronary lesions were classified as lesions with pathologic intimal thickening, fibrous-cap atheromas with cores in an early or late stage of necrosis, or thin-cap fibrous atheromas (vulnerable plaques). The arterial response to plaque hemorrhage was further defined in a rabbit model of atherosclerosis. RESULTS: Only traces of glycophorin A and iron were found in lesions with pathologic intimal thickening or fibrous-cap atheromas with cores in an early stage of necrosis. In contrast, fibroatheromas with cores in a late stage of necrosis or thin caps had a marked increase in glycophorin A in regions of cholesterol clefts surrounded by iron deposits. Larger amounts of both glycophorin A and iron were associated with larger necrotic cores and greater macrophage infiltration. Rabbit lesions with induced intramural hemorrhage consistently showed cholesterol crystals with erythrocyte fragments, foam cells, and iron deposits. In contrast, control lesions from the same animals had a marked reduction in macrophages and lipid content. CONCLUSIONS: By contributing to the deposition of free cholesterol, macrophage infiltration, and enlargement of the necrotic core, the accumulation of erythrocyte membranes within an atherosclerotic plaque may represent a potent atherogenic stimulus. These factors may increase the risk of plaque destabilization.

Comparison of nonuniform rotational distortion between mechanical IVUS and OCT using a phantom model.

Optical coherence tomography (OCT) is an optical analog of mechanical intravascular ultrasound (M-IVUS) with much higher spatial resolution. However, no data exist regarding the nonuniform rotational distortion (NURD) with OCT. The aim of the study was to investigate whether OCT generates less NURD relative to M-IVUS. A coronary artery phantom model was constructed with a rubber ring (3.68 mm in diameter), located at the distal end of the phantom. This model was also composed of eight equally spaced steel wires and an additional marker-wire. Two types of vascular phantoms were used, mild curve (90 degrees ) and acute curve (near 180 degrees ). Subsequent M-IVUS (n = 6) and OCT (n = 6) imaging was performed. Eight angles between eight wires, except the marker-wire, were measured from each image. These angles, measured with M-IVUS and OCT, were compared with those of high-resolution optical photography as a gold standard. The average in angle differences was significantly smaller in OCT compared with M-IVUS in the mild curve model (3.2 +/- 1.0 degrees vs, 6.9 +/- 2.1 degrees , p < 0.01). Compared with the latter model, the average in angle differences was exaggerated in the acute curve model with M-IVUS (9.1 +/- 0.9 degrees vs. 6.9 +/- 2.1 degrees , p < 0.05) but not with OCT (3.5 +/- 0.8 degrees vs. 3.2 +/- 1.0 degrees , p= not significant). OCT generates significantly less NURD compared with M-IVUS, especially in tortuous situation.

Percutaneous mitral valve repair for chronic ischemic mitral regurgitation: a real-time three-dimensional echocardiographic study in an ovine model.

BACKGROUND: Although surgical annuloplasty is the standard repair for ischemic mitral regurgitation (IMR), its application is limited by high morbidity and mortality. Using 2D and real-time 3D echocardiography in an ovine model of chronic IMR, we evaluated the geometric impact and short-term efficacy of a percutaneous transvenous catheter-based approach for mitral valve (MV) repair using a novel annuloplasty device placed in the coronary sinus. METHODS AND RESULTS: Six sheep developed IMR 8 weeks after induced posterior myocardial infarction. An annuloplasty device optimized to reduce anterior-posterior (A-P) mitral annular dimension and MR was placed percutaneously in the coronary sinus. Mitral annular A-P and commissure-commissure dimensions and MV tenting area (MVTa) in 3 parallel A-P planes (medial, central, and lateral) were assessed by real-time 3D echocardiography with 3D software. The annuloplasty device reduced MR jet area from 5.4+/-2.6 to 1.3+/-0.9 cm2 (P<0.01), mitral annular A-P dimension in both systole and diastole (24.3+/-2.5 to 19.7+/-2.4 mm; P<0.03; 31.0+/-3.9 to 24.7+/-2.1 mm; P<0.001), and MVTa at mid systole in all 3 planes (153+/-46 to 93+/-24 mm2, P<0.01; 140+/-47 to 88+/-23 mm2, P<0.03; and 103+/-23 to 87+/-26 mm2, P<0.03). CONCLUSIONS: Percutaneous coronary sinus-based mitral annuloplasty reduces chronic IMR by reducing mitral annular A-P diameter and MVTa. This suggests the potential clinical application of a new nonsurgical therapeutic approach in patients with IMR.

Will a partial posterior annuloplasty ring prevent acute ischemic mitral regurgitation?

BACKGROUND: Acute posterolateral ischemia in sheep results in ischemic mitral regurgitation (IMR). While complete ring annuloplasty prevents acute IMR, partial annuloplasty rings may offer a more physiologic repair, but are untested in animal models of IMR. METHODS: Radiopaque markers were placed on the LV, mitral annulus (MA), and leaflets in 13 sheep. Seven sheep served as controls, and 6 had a St. Jude Tailor partial flexible ring implanted (29 mm in 5, 31 mm in 1). After 8+/-1 day, the animals were studied with biplane videofluoroscopy and echocardiography before and during acute posterolateral LV ischemia (balloon occlusion of circumflex artery). Mitral annular area (MAA), septal-lateral annular diameter (SL), annular perimeters, and leaflet edge separation were calculated from 3-D marker coordinates. RESULTS: The average degree of mitral regurgitation increased from 0.0+/-0.0 to 2.1+/-0.7 (P=0.0006) in the control group during acute ischemia but remained unchanged in the Tailor group (0.1+/-0.2 for both conditions). The change in MAA throughout the cardiac cycle before ischemia was 17+/-4% in control animals, but only 5+/-2% (P=0.0002) in the Tailor ring group. Unlike the control animals, there was no increase in MAA (5.4+/-0.8 and 5.5+/-0.7 cm(2), respectively; p=NS) nor dilatation of the muscular annulus (6.2+/-0.3 and 6.2+/-0.4, respectively; p=NS) during ischemia with the Tailor ring. Mitral SL dimension increased slightly with ischemia (2.3+/-0.2 versus 2.2+/-0.2 cm, P=0.03). Although posterior leaflet motion was limited, as observed with complete rings, normal annular flexion was maintained with the Tailor ring before and during acute ischemia. CONCLUSIONS: The Tailor partial annuloplasty ring prevented acute IMR probably by limiting SL diameter dilatation during acute ischemia. In this animal model of acute IMR, a partial, flexible posterior annuloplasty ring is as effective as a complete ring.

In vivo volumetric analysis of coronary stent using optical coherence tomography with a novel balloon occlusion-flushing catheter: a comparison with intravascular ultrasound.

Optical coherence tomography (OCT) is limited as an intravascular imaging tool because of interference with blood. This study tested a new balloon occlusion-flushing catheter for OCT scanning of stented coronary arteries and compared stent measurements between OCT and intravascular ultrasound (IVUS). Motorized pullback with OCT and IVUS was examined in coronary stents deployed in swine. Quantitative measurements were obtained and compared between both groups. In addition, stent strut thickness was compared among OCT, IVUS and actual measurement. The occlusion catheter successfully provided motorized pullback OCT images in the stented coronary arteries without any complications. There were no differences in calculated lumen volume. However, stent volumes were significantly smaller with OCT than with IVUS (p < 0.05). OCT significantly underestimated the stent strut thickness compared with the actual measurement. Although OCT underestimates the stent strut thickness, motorized pullback OCT imaging with the occlusion catheter can provide appropriate in-stent images in the porcine coronary arteries.

Impact of deep vessel wall injury and vessel stretching on subsequent arterial remodeling after balloon angioplasty: a serial intravascular ultrasound study.

BACKGROUND: Arterial remodeling has been shown to be responsible for lumen narrowing after nonstent interventions. METHODS: To examine the impact of deep vessel wall injury (DI) after balloon angioplasty on the subsequent vessel remodeling process, we performed serial intravascular ultrasound (IVUS) analysis in 47 native coronary artery lesions that underwent balloon angioplasty. An IVUS study was performed before and after balloon angioplasty and repeated at follow-up. Vessel and lumen area were measured at the narrowest site before intervention. Plaque area was calculated as vessel area minus lumen area. DI was defined as the presence of plaque/vessel wall fracture deep in the medial layer (sonolucent zone by IVUS) after angioplasty. RESULTS: After angioplasty, DI was present in 18 (38%, DI group) and absent in 29 (62%, non-DI group) of lesions. During follow-up, changes in vessel area in the DI group were significantly larger than in the non-DI group (P =.007). There were no significant differences in changes in plaque area. A trend toward greater late lumen loss was observed in the non-DI group (P =.05). In the DI group, changes in lumen area correlated better with changes in vessel area (r = 0.81, P <.0001) than with changes in plaque area (r = 0.32, P =.20). However, in the non-DI group, changes in lumen area correlated with changes in plaque area (r = -0.55, P =.002), but not with changes in vessel area (r = 0.30, P =.11). CONCLUSIONS: Deep vessel wall injury after balloon angioplasty is associated with the magnitude of the subsequent vessel remodeling process. The differences in the remodeling process may have implications regarding adjunctive therapies to prevent restenosis after balloon angioplasty.

Effects of percutaneous coronary arterial thrombectomy during acute myocardial infarction on left ventricular remodeling.

The benefit of primary angioplasty for acute myocardial infarction (AMI) is limited by the no-reflow phenomenon, resulting in chronic left ventricular (LV) remodeling. The aim of this study was to evaluate the impact of thrombectomy with the Rescue percutaneous thrombectomy catheter on LV function after AMI. We performed a retrospective study comparing conventional angioplasty with the combination of angioplasty and thrombectomy using the Rescue catheter. The study population was comprised of 109 consecutive patients with AMI who underwent angioplasty and thrombectomy and 86 controls treated with conventional angioplasty. Baseline clinical and lesion characteristics were similar in the 2 groups. Postprocedural restoration of normal flow (Thrombolysis In Myocardial Infarction grade 3) was more frequent in the thrombectomy group (82% vs 69%, p = 0.03). No differences were observed in cardiac events, including death, reinfarction, and target vessel revascularization (thrombectomy vs controls, 27% vs 33%; p = 0.44) or changes in ejection fraction (p = 0.22) during 6-month follow-up. The incidence of LV remodeling, defined as an increase in LV end-diastolic volume index of >20%, was significantly lower in the thrombectomy group (22% vs 44%; p = 0.01). Multiple logistic regression analysis revealed that thrombectomy with the Rescue catheter contributed significantly to reduction of both no-reflow and LV remodeling. In the setting of primary angioplasty, adjunctive pretreatment with a rescue catheter reduces the no-reflow phenomenon and protects against LV remodeling.

Effect of local delivery of L-arginine on in-stent restenosis in humans.

To determine whether intramural administration of L-arginine reduces intimal thickening after optimal Palmaz-Schatz stent deployment in humans, 50 patients with native coronary artery disease who received a single Palmaz-Schatz stent were enrolled in this pilot study. Patients were randomized into 2 treatment groups: an L-arginine group (n = 25) and a saline group (n = 25). After stent deployment, L-arginine (600 mg/6 ml) or saline (6 ml) was locally delivered via the Dispatch catheter (Scimed) over 15 minutes. Serial angiography and intravascular ultrasound examinations (motorized pull-back at 0.5 mm/s) were performed before and after the procedure, and at 6-month follow-up. Measurements of stent area, lumen area, and neointimal area were computed within the stents at 1-mm intervals, by technicians who were blinded to the treatment assignment. Using Simpson's rule, stent, plaque, and lumen volumes, neointimal volume within the stent, and percent neointimal volume were measured before and after the procedure, and at 6-month follow-up. The 6-month volume data in quantitative coronary ultrasound showed that neointimal volume in the L-arginine group was significantly less than in the saline group (25 vs 39 mm(3); p = 0.049). Similarly, percent neointimal volume was significantly less in the L-arginine group at 6-month follow-up (17 +/- 13% vs 27 +/- 21%; p = 0.048). Thus, these results showed that local delivery of L-arginine reduces in-stent neointimal hyperplasia in humans, indicating that this approach may be a novel strategy to prevent in-stent restenosis.

3D coronary motion tracking in swine models with MR tracking catheters.

PURPOSE: To develop MR-tracked catheters to delineate the three-dimensional motion of coronary arteries at high spatial and temporal resolution. MATERIALS AND METHODS: Catheters with three tracking microcoils were placed into nine swine. During breath-holds, electrocardiographic (ECG)-synchronized 3D motion was measured at varying vessel depths. 3D motion was measured in American Heart Association left anterior descending (LAD) segments 6-7, left circumflex (LCX) segments 11-15, and right coronary artery (RCA) segments 2-3, at 60-115 beats/min heart rates. Similar-length cardiac cycles were averaged. Intercoil cross-correlation identified early systolic phase (ES) and determined segment motion delay. RESULTS: Translational and rotational motion, as a function of cardiac phase, is shown, with directionality and amplitude varying along the vessel length. Rotation (peak-to-peak solid-angle RCA approximately 0.10, LAD approximately 0.06, LCX approximately 0.18 radian) occurs primarily during fast translational motion and increases distally. LCX displacement increases with heart rate by 18%. Phantom simulations of motion effects on high-resolution images, using RCA results, show artifacts due to translation and rotation. CONCLUSION: Magnetic resonance imaging (MRI) tracking catheters quantify motion at 20 fps and 1 mm(3) resolution at multiple vessel depths, exceeding that available with other techniques. Imaging artifacts due to rotation are demonstrated. Motion-tracking catheters may provide physiological information during interventions and improve imaging spatial resolution.

Development of a novel calcified total occlusion model in porcine coronary arteries.

OBJECTIVE: The objective of this study was to create a calcified total occlusion model in porcine coronary arteries using a catheter-based technique. BACKGROUND: Chronic total occlusion (CTO) represents 10-20% of all angioplasty cases and remains a challenge for interventional cardiologists. One of the limitations to successful recanalization is the failure to cross the wire through the CTOs. METHODS: Twenty swine underwent total occlusion creations in the coronary arteries. Via a carotid artery, previously prepared bone chips with absorbable sponge were delivered into the coronary arteries using catheter-based techniques. Twenty-eight days post creation, coronary angiography and histology were performed. RESULTS: Twelve animals survived and 10/12 had successful total occlusions. There were successful total occlusions in 100% (8/8) of the left anterior descending coronary arteries in the animals that survived. Angiography showed visible calcified total occlusions under fluoroscopy and also showed bridge collaterals distal to the occlusions (4/8) or contralateral collaterals from the right coronary arteries (4/8). The histology showed calcified nodules and abundant microchannels within the occlusions, media, and adventitia. CONCLUSIONS: We could successfully create a reliable and repeatable porcine coronary model of calcified total occlusions. This method can be utilized in many preclinical evaluations of CTO technologies.

The evolving role of coronary angiography and fluoroscopy in cardiac diagnosis and intervention.

In the era of drug-eluting stents that have dramatically reduced the re-stenosis rate, and in the context of the development of emerging modalities like magnetic resonance imaging (MRI) and multislice computed tomography that allow precise and non-invasive diagnosis, it becomes important to question whether and how fluoroscopic-based evaluation of cardiac structure and function shall evolve. Indeed, this widely used technique is also known for its invasiveness, risk of ionising radiation effects, and projection imaging limitations.In order to answer this question it is important to understand the technological advances under development for fluoroscopy and link them with the unmet clinical needs of today in the field of both diagnostic and interventional coronary procedures. It can then be understood how fluoroscopic-based technologies can meet these needs. This discussion shall review the emerging technologies available in the cath lab and, in doing so, portray a concept for the next generation catheterisation laboratory.

Dynamic change in mitral annular area and motion during percutaneous mitral annuloplasty for ischemic mitral regurgitation: preliminary animal study with real-time 3-dimensional echocardiography.

We used a novel 3-dimensional (3D) echocardiographic technique to evaluate the impact of a coronary sinus-based percutaneous transvenous mitral annuloplasty (PTMA) on dynamic changes in mitral annular geometry and motion during the cardiac cycle in 8 sheep with ischemic mitral regurgitation. Using real-time 3D echocardiographic data before and after PTMA, 10 points along the saddle-shaped annulus were identified. For every 3D volume/frame during a cardiac cycle, we assessed mitral annular area and excursion defined as the traveling distance of the annular center. The PTMA device reduced both minimum and maximal mitral annular area (9.5 +/- 0.9-7.0 +/- 0.6 and 12.8 +/- 1.3-9.8 +/- 1.5 cm(2), P < .001 for both, respectively) with reduction of mitral regurgitation jet area (5.1 +/- 2.3-1.2 +/- 0.8 cm(2), P < .001), whereas it did not significantly impair mitral annular excursion amplitude (8.3 +/- 1.1-7.0 +/- 1.9 mm, P = .13). This 3D echocardiographic method noninvasively enabled dynamic study of mitral annular geometry and motion with quantitative analysis of the impact of PTMA.

Magnetic resonance assessment of myocardial perfusion via catheter-based ventricle-coronary vein bypass in porcine myocardial infarction model.

OBJECTIVE: The goal of this study was to investigate the efficacy of VPASS with physiological measurements, magnetic resonance imaging (MRI), and histology in a porcine model of myocardial infarction. BACKGROUND: A catheter-based ventricle-to-coronary vein bypass (VPASS) has been proposed as a potential treatment strategy for refractory coronary artery disease patients. METHODS: In an acute setting, the VPASS implant was deployed percutaneously in three swine. The partial pressure of oxygen (PO(2)) in the anterior interventricular vein (AIV) and left ventricle (LV) were measured before and after VPASS implant with various combinations of balloon occlusion in the AIV and left anterior descending artery (LAD). In a separate chronic study, the VPASS procedure was completed on three swine with a mid-LAD occlusion. Thirty days post-VPASS procedure, angiography, contrast-enhanced MRI, and histology were performed to assess myocardial viability. Perfusion was analyzed using the average percent signal intensity change (APSIC) in the anterior walls (AW) and inferior walls (IW). RESULTS: The VPASS implant was performed without complication. Post-VPASS implantation, the distal AIV PO(2) increased up to the LV PO(2) level during simultaneous AIV and LAD blockage (432 +/- 24 mmHg). At day 30, quantitative perfusion analysis demonstrated no difference in APSIC between AW and IW (125 +/- 26% vs. 137 +/- 38%, P = 0.46). Delayed enhancement and histology showed focal subendomyocardial infarction. CONCLUSIONS: VPASS implant with simultaneous AIV and LAD occlusion allows perfusion of oxygenated blood to the distal AIV, which in the setting of an acute myocardial infarction model was capable of rescuing most of the myocardium at risk.

Catheter-based ventricle-coronary vein bypass.

The goal of this study was to investigate the feasibility of a catheter-based ventricle-to-coronary vein bypass (VPASS) in order to achieve retrograde myocardial perfusion by a conduit (VSTENT) from the left ventricle (LV) to the anterior interventricular vein (AIV). Percutaneous coronary venous arterialization has been proposed as a potential treatment strategy for otherwise untreatable coronary artery disease. In an acute setting, the VSTENT implant was deployed percutaneously using the VPASS procedure in five swine. Coronary venous flow and pressure patterns were measured before and after VSTENT implant deployment with and without AIV and left anterior descending artery (LAD) occlusion. In a separate chronic pilot study, the VPASS procedure was completed on two animals that had a mid-LAD occlusion or LAD stenosis. At day 30 post-VPASS procedure, left ventriculography and magnetic resonance imaging (MRI) were performed to assess the patency and myocardial viability of the VSTENT implants. Pre-VSTENT implantation, the mid-AIV systolic wedge pressure was significantly lower than LV systolic pressure during AIV blockage (46 +/- 19 vs. 90 +/- 16 mm Hg; P < 0.01). The VSTENT implant deployment was performed without complication and achieved equalization of the AIV and LV systolic pressures and creation of retrograde flow in the distal AIV (maximal flow velocity: 37 +/- 7 cm/sec). At day 30 post-VPASS procedure, left ventriculography showed VSTENT implant patency. MRI perfusion images demonstrated myocardial viability even with an LAD occlusion. Coronary retrograde perfusion using the VPASS procedure is feasible and may represent a potential technique for end-stage myocardial ischemia.

Left ventricular functional recovery with percutaneous, transvascular direct myocardial delivery of bone marrow-derived cells.

BACKGROUND: The potential for cellular cardiomyoplasty to provide functional left ventricular recovery in the chronically injured heart remains unclear. METHODS: Yorkshire swine (n = 10; 35-50 kg) had anterolateral myocardial infarction (MI) induced by coil embolization of the left anterior descending artery. Approximately 5 weeks post-MI, a composite, intravascular ultrasound-guided catheter system (TransAccess) was used to deliver an autologous, labeled, bone marrow-derived cell sub-population (approximately 3 x 10(8) cells) or saline control (approximately 50 injections/arm) through coronary veins directly into infarct and peri-infarct myocardium. Two months post-transplant, the animals had blinded endocardial and epicardial left ventricular electrical scar mapping and biventricular electrical stimulation. Coronary angiography and quantitative biplane ventriculography were performed at baseline, transplant, and sacrifice time-points. RESULTS: Robust, viable, predominantly desmin-negative cell grafts were demonstrated post-mortem in all treatment animals. Baseline and pre-transplant global and regional wall motion was similar between groups. The cell treatment group demonstrated functional recovery with a left ventricular ejection fraction of 38.1% at the time of transplant increasing to 48.5% (p = 0.005) at sacrifice, whereas the control arm was unchanged (38.0% vs 34.3%, respectively; p = NS). The regional improvement corresponded with a reduction in percentage of hypokinetic (52.1%-42.9%, p = 0.002) and percentage of akinetic (24.8%-17.7%, p = 0.04) segments in the cell-treated animals. Epicardial scar area was not different (37 cm2 vs 23 cm2, p = 0.37) between groups. CONCLUSIONS: Percutaneous, transvascular, direct intramyocardial bone marrow cell transplantation is safe and feasible in chronically infarcted tissue. In this pilot study, cell therapy improved overall left ventricular systolic function by recruiting previously hypokinetic or akinetic myocardial tissue.

Catheter-based antegrade intracoronary viral gene delivery with coronary venous blockade.

The purpose of this study is to evaluate the feasibility of percutaneous antegrade myocardial gene transfer (PAMGT). A consistent and safe technique for in vivo gene transfer is required for clinical application of myocardial gene therapy. PAMGT with concomitant coronary venous blockade was performed in 12 swine. The myocardium was preconditioned with 1 min of occlusion of the left anterior descending and left circumflex arteries. The anterior interventricular vein was occluded during left anterior descending artery delivery, and the great cardiac vein at the entrance of the middle cardiac vein was occluded during left circumflex artery delivery. With arterial and venous balloons inflated (3 min) and after adenosine (25 mug) injection, PAMGT was performed by antegrade injection of an adenoviral solution (1 ml of 10(11) plaque-forming units in each coronary artery) carrying beta-galactosidase or saline through the center lumen of the angioplasty balloon. In one set of animals, PAMGT was performed with selective coronary vein blockade (n = 9); in another set of animals, PAMGT was performed without coronary vein blockade (n = 5). At 1 wk after gene delivery, the animals were killed. Quantitative beta-galactosidase analysis was performed in the left and right ventricular walls. PAMGT was successfully performed in all animals with and without concomitant occlusion of the coronary veins. Quantitative beta-galactosidase analysis showed that PAMGT with coronary blockade was superior to PAMGT without coronary blockade. beta-Galactosidase activity increased significantly in the beta-galactosidase group compared with the saline group: 1.34 +/- 0.18 vs. 0.81 +/- 0.1 ng (P

Targeting signaling pathways in heart failure by gene transfer.

Congestive heart failure represents an enormous clinical problem demanding effective therapeutic approaches. The varied etiologies of heart failure include abnormalities of ion handling, cellular signaling, neurohormonal control, and apoptosis, all of which are potentially amenable to genetic manipulation. Gene therapy holds the promise of retarding the progression, preventing, and perhaps reversing heart failure. Advances in our knowledge of possible targets, vectors, and delivery techniques have revolutionized this field in recent years, bringing us close to clinical application.

Compression of right ventricular out-flow due to localized hematoma after coronary perforation during PCI.

Although coronary perforation can cause tamponade during percutaneous coronary intervention (PCI), this is unusual for patients previously undergoing coronary artery bypass graft surgery (CABG) due to pericardial adhesions. We report here on a rare case of right ventricular out-flow obstruction complicating PCI in a patient with a previous CABG.