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Biomedical subjects

Raj R Makkar

Publications and source records attributed to Raj R Makkar.

At least 19 recordsLinked to original sources
PubMed2007

Stent fracture associated with drug-eluting stents: clinical characteristics and implications.

OBJECTIVE: To evaluate the clinical characteristics and implications of stent fracture in drug-eluting stents. BACKGROUND: Approximately 2.5 million drug-eluting stents are implanted every year worldwide. In 10 randomized controlled trials involving 2,602 patients, no incidence of stent fracture was recognized or reported. METHODS: From April 2003 to December 2005, 2,728 patients underwent drug-eluting stenting. The angiograms of all 530 patients who underwent repeat angiography were analyzed to identify the presence of stent fracture. We then documented the incidence of adverse events associated with drug-eluting stent fracture and systematically analyzed the clinical, procedural, and structural factors, which might predispose to stent fracture. RESULTS: Stent fracture was identified in 10 patients. None of these fractures were detectable at the time of stent placement. The median time interval from stent implantation to detection of fracture at repeat angiography was 226 days (range, 7-620 days). Adverse clinical outcomes associated with stent fracture occurred in 7 patients (6 patients had binary restenosis and 1 patient had stent thrombosis), all necessitating repeat intervention. Analysis of potential predisposing clinical, procedural, and structural factors revealed that 4 patients had excessive tortuosity in the proximal segment, and overlapping stents were used in 5 cases. All fractures occurred in sirolimus-eluting stents. CONCLUSIONS: Stent fracture may represent a new potential mechanism of restenosis and stent thrombosis in drug-eluting stents. Predisposing clinical and procedural factors may be vessel tortuosity and use of overlapping stents. The most important predisposing factor, however, may be stent structure, since all fractures occurred in sirolimus-eluting stents.

Adult↗
PubMed2006

The effect of granulocyte colony stimulating factor on regional and global myocardial function in the porcine infarct model.

BACKGROUND: Stem cell therapy has been shown to attenuate the reduction of left ventricular function following myocardial infarction. Most studies have utilized either a direct injection or intra-coronary infusion of cells, but cytokine mobilization of stem cells in the murine model of acute myocardial infarction has been reported to induce similar improvement in cardiac function. METHODS: An antero-apical infarction was induced in swine by balloon occlusion, followed by the daily administration of granulocyte colony stimulating factor (G-CSF) or placebo for 5 days. We used left ventricular angiograms and 2D echocardiograms to assess global function, and 3D echocardiograms to assess regional function prior to infarction, immediately following infarction, and at 8 weeks. Histologic evaluation was performed after sacrifice at 8 weeks. RESULTS: There was no significant difference in early or late post-infarction left ventricular ejection fraction or in myocardial histology between the two groups. Following G-CSF therapy, however, 3D echocardiography demonstrated that the regional ejection fractions of the infarcted segments showed a 50.3% improvement in the G-CSF pigs compared to a 7.4% deterioration in the untreated pigs (p=0.005). CONCLUSIONS: Global left ventricular ejection fraction remained unchanged, and there is no histologic evidence for infarct attenuation following G-CSF infusion in the porcine infarct-reperfusion model. There was recovery of regional function in the infarcted segment in the G-CSF pigs. These data suggest that bone marrow mobilization in larger species has limited potential as a therapy designed to replace infarcted myocardium or to improve overall cardiac function, although further studies are needed to examine regional effect in the infarct area.

Animals↗
PubMed2006

Comparison of coronary artery bypass surgery with percutaneous coronary intervention with drug-eluting stents for unprotected left main coronary artery disease.

OBJECTIVES: This study evaluated the clinical outcomes of consecutive, selected patients treated with coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI) with drug-eluting stents (DES) for unprotected left main coronary artery (ULMCA) disease. BACKGROUND: Although recent data suggest that PCI with DES provides better clinical outcomes compared to bare-metal stenting for ULMCA disease, there is a paucity of data comparing PCI with DES to CABG. METHODS: Since April 2003, when DES first became available at our institution, 123 patients underwent CABG, and 50 patients underwent PCI with DES for ULMCA disease. RESULTS: High-risk patients (Parsonnet score >15) comprised 46% of the CABG group and 64% of the PCI group (p = 0.04). The 30-day major adverse cardiac and cerebrovascular event (MACCE) rate for CABG and PCI was 17% and 2% (p < 0.01), respectively. The mean follow-up was 6.7 +/- 6.2 months in the CABG group and 5.6 +/- 3.9 months in the PCI group (p = 0.26). The estimated MACCE-free survival at six months and one year was 83% and 75% in the CABG group versus 89% and 83% in the PCI group (p = 0.20). By multivariable Cox regression, Parsonnet score, diabetes, and CABG were independent predictors of MACCE. CONCLUSIONS: Despite a higher percentage of high-risk patients, PCI with DES for ULMCA disease was not associated with an increase in immediate or medium-term complications compared with CABG. Our data suggest that a randomized comparison between the two revascularization strategies for ULMCA may be warranted.

Aged↗
PubMed2006

Coronary sinus is dilated and outwardly displaced in patients with mitral regurgitation: quantitative angiographic analysis.

OBJECTIVES: Our aim was to define the anatomy of the coronary sinus (CS) by venography. These measurements are essential in the selection of physical characteristics of percutaneous annuloplasty devices for mitral regurgitation (MR). BACKGROUND: Clinical trials of percutaneous annuloplasty of the CS for MR are now underway. Although the CS is in close proximity to the mitral annulus, there is as yet no published quantitative data defining the magnitude of change in CS dimensions in MR, and how these changes might reflect the magnitude of MR. METHODS: We studied 57 patients (27 patients with MR and 30 patients with no MR) who were referred for cardiac resynchronization therapy and underwent CS venography. Echocardiography was used to assess the degree of MR, cardiac dimensions, and right heart filling pressures. The diameter of the ostial and proximal CS and perimeter of the CS-great cardiac vein (GCV) were assessed by quantitative coronary analysis. RESULTS: Patients with MR had a larger ostial CS diameter (19.4+/-3.9 mm vs. 16.9+/-4.6 mm, P=0.02) and proximal CS diameter (8.2+/-1.7 mm vs. 7.4+/-2.3 mm, P=0.05) and larger CS-GCV perimeter (104.4+/-15.6 mm vs. 86.5+/-15.3 mm, P=0.005) compared with patients with no MR. The CS-GCV perimeter is positively correlated to the severity of MR (P=0.02) and pulmonary artery pressure (r=0.32, P<0.05). CONCLUSIONS: Patients with MR have a dilated and outward displacement of the CS. The CS-GCV perimeter is positively correlated with the degree of MR and pulmonary artery pressure.

Analysis of Variance↗
PubMed2006

Percutaneous left ventricular support devices.

Patients undergoing percutaneous coronary intervention (PCI) who have severely compromised left ventricular systolic function and complex coronary lesions including multivessel disease, left main disease, or bypass graft disease are at higher risk of adverse outcomes from hemodynamic collapse. The TandemHeart percutaneous left ventricular assist device and the Impella Recover LP 2.5 System may provide rapid circulatory support in high-risk PCI patients and in those who have cardiogenic shock. Identification of patients who are at high risk for severe hemodynamic compromise and most likely to benefit from mechanical circulatory support is crucial to derive the most benefit from this therapy. Multicenter randomized clinical trials are needed to clearly define the role of these two devices in providing circulatory support in a variety of clinical settings.

Cardiac Output, Low↗
PubMed2005

Intravenous mesenchymal stem cell therapy early after reperfused acute myocardial infarction improves left ventricular function and alters electrophysiologic properties.

UNLABELLED: Direct intramyocardial injection of mesenchymal stem cells (MSCs) improves left ventricular ejection fraction (LVEF) and may increase ventricular arrhythmia in hearts with myocardial infarction (MI). We hypothesized that intravenous MSCs given early after acute MI would engraft in injured myocardium, improve LV function, and result in pro-arrhythmic electrical remodeling. We created an apical infarction in swine by balloon occlusion/reperfusion, administered diI-labeled allogeneic bone marrow derived MSCs intravenously 30 min post-reperfusion and measured LVEF and wall thickness at baseline, 1 month, and 3 months. Epicardial effective refractory periods (ERPs) were determined before sacrifice. At 3 months, treated pigs [n=7] had significantly higher LVEF than controls [n=8] (49+/-2% vs. 44+/-3%, P=0.015) and significantly less wall thickening of non-infarcted myocardium. ERPs were significantly shorter than controls at all pacing cycle lengths (P<or=0.002), suggesting a pro-arrhythmic potential. DiI was found in the lungs, in infarct, and peri-infarct myocardium. CONCLUSION: IV infusion of MSCs soon after acute MI in swine improves LVEF and limits wall thickening in the remote non-infarcted myocardium, consistent with a beneficial effect on post-MI ventricular remodeling. Since there is no need for immune suppression or clinical expertise, IV infusion of MSCs may expand the potential clinical application of stem cell therapy.

Animals↗
PubMed2005

Percutaneous left ventricular assist device: "TandemHeart" for high-risk coronary intervention.

Patients undergoing percutaneous coronary intervention (PCI) with severely compromised left ventricular systolic function and complex coronary lesions, including multivessel disease, left main disease, or bypass graft disease, are at higher risk of adverse outcomes from hemodynamic collapse. The TandemHeart percutaneous ventricular assist device may provide circulatory support during high-risk PCI. We implanted the TandemHeart device in eight patients who underwent high-risk PCI. The patients were considered to be at exceptionally high risk for decompensation due to procedural complexity combined with underlying LV dysfunction. The mean ejection fraction was 30% +/- 9% and five patients were turned down for surgical revascularization. Seven patients underwent multivessel PCI, including three patients who underwent unprotected left main coronary artery PCI. There was 100% procedural success. The TandemHeart was removed immediately post-PCI with no groin complications. Six patients are event- and symptom-free at 189 +/- 130 days; one patient died 10 days post-PCI after lower extremity bypass surgery and another developed acute renal failure postprocedure, requiring hemodialysis. Our initial clinical experience with the TandemHeart ventricular assist device demonstrates that hemodynamic support can be rapidly achieved percutaneously during high-risk PCI, with excellent procedural success in highly complex and critically ill patients.

Adult↗
PubMed2005

Drug-eluting stenting is superior to bare metal stenting in saphenous vein grafts.

This study compared the outcomes of percutaneous coronary intervention (PCI) of saphenous vein grafts (SVGs) with drug-eluting stents (DES) with bare metal stents (BMS). PCI of degenerated SVG is associated with worse outcomes and high incidence of in-stent restenosis compared with PCI of native coronary arteries. There is a paucity of data on the outcomes of PCI of SVG with DES. Data from 223 consecutive patients who underwent PCI of SVG were imputed into a dedicated clinical database. We assessed the clinical outcomes at a mean follow-up of 9.1+/-2.1 months. A total of 139 patients underwent PCI of SVG with DES and 84 patients with BMS. The mean age of the SVG was 7.6+/-3.8 years in the DES group and 7.7+/-2.8 years in the BMS group (P=0.38). Procedural success was achieved in all patients except for one patient in the BMS group who underwent emergent coronary artery bypass graft surgery for SVG dissection. There were no other in-hospital cardiac events in both groups. There was one cardiac death in the DES group and three deaths in the BMS group (P=0.03). When compared to the BMS, PCI of SVG with DES was associated with a lower incidence of myocardial infarction (4.3% vs. 20.2%; P=0.04) and target vessel revascularization (10.1% vs. 36.9%; P=0.035). When compared with BMS, PCI of SVG with DES was associated with a lower incidence of death, myocardial infarction, and target vessel revascularization.

Aged↗
PubMed2005

Intramyocardial injection of allogenic bone marrow-derived mesenchymal stem cells without immunosuppression preserves cardiac function in a porcine model of myocardial infarction.

BACKGROUND: We investigated the efficacy of directly injected allogenic bone marrow-derived mesenchymal stem cells in improving left ventricular function in a porcine model of myocardial infarction. METHODS: Left ventricular infarction was created in 16 adult Yorkshire pigs by coil embolization and thrombotic occlusion distal to the second diagonal artery. One month after myocardial infarction was induced, the animals were randomized to either direct injection of allogenic mesenchymal stem cells or sham treatment (culture medium). Allogenic bromodeoxyuridine-labeled mesenchymal stem cells (2 +/- 0.1 x 10(8)) were directly injected into the infarct and peri-infarct areas during an open chest procedure. No immunosuppressive therapy was used. The left ventricular function was measured using serial biplane left ventricular angiography at baseline, 30, 60, and 90 days before sacrifice. Mesenchymal stem cells were localized using bromodeoxyuridine, and differentiation of mesenchymal stem cells was assessed by confocal microscopic colocalization of bromodeoxyuridine with immunofluorescent antibodies specific for cardiomyocytes (troponin I and MF-20) and endothelial cells (von Willebrand factor). RESULTS: Mesenchymal stem cells labeled with bromodeoxyuridine engrafted the peri-infarct zone and colocalized with both cardiomyocyte-specific and endothelial cell-specific immunofluorescence. No intramyocardial bromodeoxyuridine was observed in sham-treated animals. At the time of the mesenchymal stem cell injection 30 days after myocardial infarction, the left ventricular ejection fraction (LVEF) was 58% +/- 3% in mesenchymal stem cell-treated pigs and 56% +/- 2% in sham-treated pigs (P = NS). LVEF deteriorated progressively thereafter in untreated pigs (8.5% and 10.5% decline at 60 days and 90 days after myocardial infarction, respectively), but was preserved in mesenchymal stem cell-treated pigs (2.1% increase and -2.0% decline at 60 and 90 days post-MI respectively) (P < .05). CONCLUSIONS: Direct intramyocardial injection of mesenchymal stem cells results in successful intramyocardial engraftment and differentiation into cardiomyocytes and endothelial cells and preserves left ventricular function after myocardial infarction in pigs.

Animals↗
PubMed2004

Stem-cell transplantation in myocardial infarction: a status report.

Myocardial infarction is the leading cause of congestive heart failure and death in the industrialized world. Current therapy is limited in preventing the progression of ventricular remodeling and congestive heart failure. Recent interest has focused on stem cells, which are undifferentiated and pluripotent cells that can proliferate, potentially self-renew, and differentiate into cardiomyocytes. Myocardial regeneration with stem-cell transplantation is a possible treatment option to reverse the deleterious hemodynamic and neurohormonal effects that occur after myocardial infarction and can lead to congestive heart failure. Various preclinical animal studies show the potential to regenerate myocardium and improve perfusion to the infarct area to improve cardiac function but also suggest that stem cells may have proarrhythmic effects. Early phase I clinical studies indicate that stem-cell transplantation is feasible and may have beneficial effects on ventricular remodeling after myocardial infarction. Future randomized clinical trials will establish the magnitude of the benefit and the effects on arrhythmias after stem-cell therapy.

Animals↗
PubMed2004

Percutaneous stent-mounted valve for treatment of aortic or pulmonary valve disease.

The objective of this study was to develop a prosthetic cardiac valve designed for percutaneous transcatheter implantation. Percutaneous catheter-based therapies play a limited role in the management of cardiac valve disease. Surgical implantation of prosthetic valves usually requires thoracotomy and cardiopulmonary bypass. The stent-valve is constructed of a rolled sheet of heat-treated nitinol. Although malleable when cooled, once released from a restraining sheath at body temperature the stent unrolls, becomes rigid, and assumes its predetermined cylindrical conformation. A ratcheting lock-out mechanism prevents recoil and external protrusions facilitate anchoring. Valve leaflets are constructed of bovine pericardium. The feasibility of catheter implantation, prosthetic valve function, and survival were investigated in an animal model. In vitro and pulse duplicator testing documented valve durability. Endovascular delivery of the prototype stent-valve to the aortic or pulmonary position was feasible. Accurate positioning was required to ensure exclusion of the native valve leaflets and, in the case of the aortic valve, to avoid compromise of the coronary ostia or mitral apparatus. Oversizing of the stent in relation to the valve annulus was desirable to facilitate anchoring and prevent paravalvular insufficiency. Stent-valve implantation proved feasible and compatible with survival in an animal model. Transcatheter implantation of prosthetic valves is possible. Further evolution of this technology will involve lower-profile devices with design features that facilitate vascular delivery, visualization, positioning, deployment, and valvular function.

Animals↗
PubMed2004

Molecular and cellular basis of restenosis after percutaneous coronary intervention: the intertwining roles of platelets, leukocytes, and the coagulation-fibrinolysis system.

The major limitation of percutaneous coronary intervention (PCI) is restenosis. Restenosis is considered to be an overreaction of the natural healing process after traumatic balloon dilatation. An elaborate web of cellular and molecular responses, including the interaction of platelets, leukocytes, and the coagulation-fibrinolysis system, as well as the secretion of various growth factors and pro-inflammatory cytokines, contributes to neointimal hyperplasia and the development of restenosis. Moreover, platelet and neutrophil activation after stenting appears to be different from that after balloon angioplasty alone. Pharmacotherapy targeting the cell-to-cell interaction between platelets and neutrophils may potentially offer an effective treatment strategy against restenosis after PCI.

Angioplasty, Balloon, Coronary↗
PubMed2004

Partial restoration of myocardial function and perfusion by cell therapy following myocardial infarction.

PURPOSE OF REVIEW: In animals, both skeletal myoblasts and stem cells partially restore myocardial function after MI. This review provides a critical analysis of the initial clinical trials of these two therapeutic strategies. RECENT FINDINGS: Direct injection of autologous skeletal myoblasts into the peri-infarct area has been performed at bypass surgery and by subendocardial injection in the catheterization laboratory. Both approaches appear to improve function significantly. Nonetheless, ventricular arrhythmias occur quite frequently in the first week after myoblast injection. In contrast, stem cells can be delivered to the injured myocardium by direct injection, by IV injection, or by bone marrow stimulation. The incidence of ventricular arrhythmia does not seem to increase. The magnitude of absolute improvement in cardiac ejection fraction, however, is only about 7%. The potential limitations of stem cell therapy are cell fusion, creating genetically abnormal cells, and the ability to deliver sufficient numbers of cells to have an important biologic effect. SUMMARY: Cell replacement therapy after MI has considerable promise for restoration of cardiac function. Nonetheless because important theoretical and practical questions remain unanswered, the methodology is not yet ready for widespread clinical application.

Cell Transplantation↗
PubMed2004

Stem-cell repair of infarcted myocardium: ready for clinical application?

In cell culture, adult bone marrow stem cells can develop the phenotypic characteristics of myocytes and endothelial cells, and express myocyte-specific and endothelium-specific proteins. In subsequent animal laboratory studies and early clinical trials, stem cells have been delivered to infarcted myocardium by direct injection, by intravascular injection, and by bone marrow stimulation. In animals, myocyte apoptosis is reduced, capillary density increases, and regional perfusion increases accompanied by a decrease in infarct size. Early clinical trials indicate that a variety of approaches is technically feasible and safe in the short term. The trials suggest that stem-cell therapy may induce a modest preservation of cardiac function. The methodology for clinical application of stem-cell therapy currently exists in most large heart hospitals. Nonetheless, until theoretical and practical limitations are resolved, it seems prudent to confine this therapy to randomized clinical trials.

Animals↗
PubMed2004

Treatment of coronary aneurysm in acute myocardial infarction with AngioJet thrombectomy and JoStent coronary stent graft.

A 54-year-old male with a history of coronary artery disease with a percutaneous transluminal coronary angioplasty and stenting presented to the emergency with an acute myocardial infarction. The patient underwent angiography which showed in-stent thrombosis of the right coronary artery along with 2 aneurysms proximal to the lesion. The right coronary artery was treated with AngioJet rheolytic thrombectomy and the JoStent coronary stent graft. To our knowledge, this is the first report of the use of the AngioJet rheolytic thrombectomy and the JoStent coronary stent graft in acute myocardial infarction.

Acute Disease↗