Bleeding during percutaneous intervention: tailoring the approach to minimise risk.

The incidence of ischaemic complications during percutaneous intervention (PCI) has reduced over recent years. As a result, bleeding has now emerged as one of the most common complications of PCI in contemporary practice. In addition, measures intended to minimise ischaemic complications--such as balloon pumps or glycoprotein inhibitors--may actually increase bleeding frequency. Recent studies have not only highlighted the incidence with which major bleeding occurs but also demonstrated the profound effect of bleeding on mortality. Thus bleeding can no longer be considered an irritation that can simply be ignored or transfused. This review summarises the major trial and registry data obtained in a PubMed search combining the terms "bleeding" and "percutaneous coronary intervention" and then proposes strategies to minimise bleeding occurrence.

Clinical review: gastrointestinal bleeding after percutaneous coronary intervention: a deadly combination.

BACKGROUND: Managing gastrointestinal bleeding in a patient who has undergone recent percutaneous coronary intervention requires balancing the risk of stent thrombosis against further catastrophic bleeding. Stent thrombosis and severe gastrointestinal bleeding are life-threatening complications. AIMS: To evaluate the risks of gastrointestinal bleeding in patients undergoing percutaneous coronary intervention in relation to anti-platelet therapy and to discuss management of gastrointestinal bleeding in these patients. DESIGN: Review of published studies comparing anti-platelet and ulcer healing therapy. A review of the evidence surrounding the management of gastrointestinal bleeding and the need for anti-platelet therapy in patients undergoing percutaneous coronary intervention. FINDINGS: Gastrointestinal bleeding is relatively common after percutaneous coronary intervention. In one study it complicated 2.3% of primary angioplasty, and these patients had a mortality of 10%. Recent registry data of patients experiencing a gastrointestinal bleed reported a mortality of 5.4%. Cessation of anti-platelet therapy carries a high risk of acute stent thrombosis, which has a high mortality. CONCLUSION: Individualized specialist gastrointestinal and cardiological management of these patients in a high dependency environment is recommended. Supportive care and proton pump inhibition in combination with judicious use of anti-platelet therapy is likely to provide the best balance of risk.

Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms.

BACKGROUND: Bone marrow cell therapy is reported to contribute to collateral formation through cell incorporation into new or remodeling vessels. However, the possible role of a paracrine contribution to this effect is less well characterized. METHODS AND RESULTS: Murine marrow-derived stromal cells (MSCs) were purified by magnetic bead separation of cultured bone marrow. The release of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), placental growth factor (PlGF), and monocyte chemoattractant protein-1 (MCP-1) was demonstrated by analysis of MSC conditioned media (MSC-CM). MSC-CM enhanced proliferation of endothelial cells and smooth muscle cells in a dose-dependent manner; anti-VEGF and anti-FGF antibodies only partly attenuated these effects. Balb/C mice (n=10) underwent distal femoral artery ligation, followed by adductor muscle injection of 1x10(6) MSCs 24 hours later. Compared with controls injected with media (n=10) or mature endothelial cells (n=8), distal limb perfusion improved, and mid-thigh conductance vessels increased in number and total cross-sectional area. MSC injection improved limb function and appearance, reduced the incidence of auto-amputation, and attenuated muscle atrophy and fibrosis. After injection, labeled MSCs were seen dispersed between muscle fibers but were not seen incorporated into mature collaterals. Injection of MSCs increased adductor muscle levels of bFGF and VEGF protein compared with controls. Finally, colocalization of VEGF and transplanted MSCs within adductor tissue was demonstrated. CONCLUSIONS: MSCs secrete a wide array of arteriogenic cytokines. MSCs can contribute to collateral remodeling through paracrine mechanisms.

Marrow-derived stromal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms.

We recently demonstrated that marrow stromal cells (MSCs) augment collateral remodeling through release of several cytokines such as VEGF and bFGF rather than via cell incorporation into new or remodeling vessels. The present study was designed to characterize the full spectrum of cytokine genes expressed by MSCs and to further examine the role of paracrine mechanisms that underpin their therapeutic potential. Normal human MSCs were cultured under normoxic or hypoxic conditions for 72 hours. The gene expression profile of the cells was determined using Affymetrix GeneChips representing 12 000 genes. A wide array of arteriogenic cytokine genes were expressed at baseline, and several were induced >1.5-fold by hypoxic stress. The gene array data were confirmed using ELISA assays and immunoblotting of the MSC conditioned media (MSC(CM)). MSC(CM) promoted in vitro proliferation and migration of endothelial cells in a dose-dependent manner; anti-VEGF and anti-FGF antibodies only partially attenuated these effects. Similarly, MSC(CM) promoted smooth muscle cell proliferation and migration in a dose-dependent manner. Using a murine hindlimb ischemia model, murine MSC(CM) enhanced collateral flow recovery and remodeling, improved limb function, reduced the incidence of autoamputation, and attenuated muscle atrophy compared with control media. These data indicate that paracrine signaling is an important mediator of bone marrow cell therapy in tissue ischemia, and that cell incorporation into vessels is not a prerequisite for their effects.

Troponin in acute coronary syndrome patients. The interventional cardiologist perspective.

Troponin measurement has now become an integral part of the assessment of patients with acute coronary syndromes (ACS). Obtaining troponin levels have been used effectively as a diagnostic tool with superior sensitivity and specificity compared to creatine kinase MB fraction in identifying high-risk ACS patients. The adverse prognosis of these high-risk patients can be modified by more aggressive treatment strategy including antiplatelet and antithrombotic therapy accompanied, if feasible, by early percutaneous intervention. The current review summarizes available data on troponin measurement as a clinical tool for tailoring therapeutic strategy in non-ST elevation ACS patients. In addition, the data on the potential predictive value of postintervention troponin levels is discussed.

The deceleration [correction of declaration] time of pulmonary venous diastolic flow is more accurate than the pulmonary artery occlusion pressure in predicting left atrial pressure.

OBJECTIVES: This study compared a prediction of mean left atrial pressure (P(LA)) ascertained by Doppler echocardiography of pulmonary venous flow (PVF), with predicted P(LA) using the pulmonary artery occlusion pressure (P(PAO)). BACKGROUND: In select patient groups, PVF variables correlate with P(PAO)) an indirect measure of P(LA). METHODS: In 93 patients undergoing cardiac surgery, we recorded with transesophageal echocardiography mitral valve early (E) and late (A) wave velocities, deceleration time (DT) of E (DT(E)), and pulmonary vein systolic (S) and diastolic (D) wave velocities, DT of D (DT(D)) and systolic fraction. The P(PAO) was measured using a pulmonary artery catheter zeroed to midaxillary level. A further catheter was held at midatrial level to zero a transducer and was then inserted into the left atrium. A prediction rule for P(LA) from DT(D) was developed in 50 patients and applied prospectively to estimate P(LA) in 43 patients. RESULTS: A close correlation (r = -0.92) was found between P(LA) and DT(D). Systolic fraction (r = -0.63), DT(E) (r = -0.61), D wave (r = 0.57), E wave (r = 0.52), and E/A ratio (r = 0.13) correlated less closely with P(LA). The mean difference between predicted and measured P(LA) was 0.58 mm Hg for DT(D) method and 1.72 mm Hg for P(PAO), with limits of agreement (mean +/- 2 SE) of -2.94 to 4.10 mm Hg and -2.48 to 5.92 mm Hg, respectively. A DT(D)) of <175 ms had 100% sensitivity and 94% specificity for a P(LA) of >17 mm Hg. CONCLUSIONS: Deceleration time of pulmonary vein diastolic wave is more accurate than P(PAO) in estimating left atrial pressure in cardiac surgical patients.