Paul A. Hudson

Cytokines regulate matrix metalloproteinases and migration in cardiac fibroblasts

We sought to define the relationship between cytokine stimulated release of matrix metalloproteinases (MMPs) and cell migration using adult rat cardiac fibroblasts. Interleukin-1beta (IL-1beta) increased release of MMP-2, -3, and -9, and TIMP-1, by 3-6-fold, measured by immunoblotting and gel zymography. Tumor necrosis factor-alpha (TNFalpha) augmented IL-1beta stimulated release of MMP-9, but not MMP-2 or -3. Transforming growth factor-beta1 (TGFbeta1) attenuated all the responses to IL-1beta. IL-1beta was also the most robust stimulus of adult rat cardiac fibroblast migration, measured in Boyden chamber assays. The combination of IL-1beta plus TNFalpha substantially enhanced migration, whereas TGFbeta1 strongly inhibited the migratory response to IL-1beta. The pan-selective MMP inhibitor GM 6001 effectively blocked IL-1beta stimulated migration. Pharmacologic inhibitors selective for ERK, JNK, and p38 MAP kinase pathways inhibited the IL-1beta regulation of individual MMPs. Increased MMP activity associated with migration of cardiac fibroblasts may be important determinants of cytokine-directed remodeling of injured myocardium.

Safety and efficacy of dual-axis rotational coronary angiography vs. standard coronary angiography.

Objective: To determine the safety and efficacy of dual‐axis rotational coronary angiography (DARCA) by directly comparing it to standard coronary angiography (SA). Background: Standard coronary angiography (SA) requires numerous fixed static images of the coronary tree and has multiple well‐documented limitations. Dual‐axis rotational coronary angiography (DARCA) is a new rotational acquisition technique that entails simultaneous LAO/RAO and cranial/caudal gantry movement. This technological advancement obtains numerous unique images of the left or right coronary tree with a single coronary injection. We sought to assess the safety and efficacy of DARCA as well as determine DARCAs adequacy for CAD screening and assessment. Methods: Thirty patients underwent SA following by DARCA. Contrast volume, radiation dose (DAP) and procedural time were recorded for each method to assess safety. For DARCA acquisitions, blood pressure (BP), heart rate (HR), symptoms and any arrhythmias were recorded. All angiograms were reviewed for CAD screening adequacy by two independent invasive cardiologists. Results: Compared to SA, use of DARCA was associated with a 51% reduction in contrast, 35% less radiation exposure, and 18% shorter procedural time. Both independent reviewers noted DARCA to be at least equivalent to SA with respect to the ability to screen for CAD. Conclusion: DARCA represents a new angiographic technique which is equivalent in terms of image quality and is associated with less contrast use, radiation exposure, and procedural time than SA.

Association of prior coronary artery bypass graft surgery with quality of care of patients with non-ST-segment elevation myocardial infarction: a report from the National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With the Guidelines.

BACKGROUND The American College of Cardiology/American Health Association guidelines recommend both an early invasive strategy and administration of antiplatelet/anticoagulant therapy for high-risk patients in the absence of contraindications. Little is known about adherence to guideline recommendations in patients with prior coronary artery bypass graft (CABG) surgery presenting with non-ST-segment elevation myocardial infarction (NSTEMI). METHODS We analyzed 47,557 patients with NSTEMI in the 2007-2008 National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With The Guidelines. Treatment patterns were compared between patients with and without prior CABG surgery. Multivariable regression with generalized estimating equations evaluated the association between prior CABG and in-hospital outcomes. RESULTS In this study, 8,790 NSTEMI patients (18.5%) had a history of CABG surgery. Prior CABG surgery was associated with a significantly lower adjusted likelihood of early cardiac catheterization (adjusted odds ratio [OR] 0.88, 95% CI 0.83-0.92), higher rates of short-term clopidogrel use (adjusted OR 1.08, 95% CI 1.02-1.14), and comparable use of anticoagulant therapy (adjusted OR 0.96, 95% CI 0.88-1.04). Adjusted risks of bleeding and in-hospital mortality did not differ significantly between the 2 groups (adjusted ORs 1.00, 95% CI 0.92-1.11 and 0.99, 95% CI 0.87-1.11, respectively). CONCLUSIONS Patients with prior CABG surgery presenting with NSTEMI are often felt to be at high risk for adverse outcomes and therefore require aggressive treatment. Our study indicates that they are less likely to undergo guideline-recommended early cardiac catheterization but equally or more likely to receive guideline-recommended antiplatelet and anticoagulant therapy. This risk-treatment paradox, however, does not appear to negatively influence short-term clinical outcomes.

Clinical outcomes following predilation with a novel 1.25-mm diameter angioplasty catheter†

Objective: An unmet need is represented in angioplasty catheters that permit the predilation stage of treating complex coronary anatomy oftentimes not amenable to conventional device therapies. Background: Lesion preparation with balloon angioplasty prior to stent placement remains the most common method of percutaneous coronary revascularization. Methods: Clinical and angiographic outcomes were evaluated following a treatment strategy of coronary artery disease that included predilation with a low‐profile, 1.25‐mm angioplasty catheter prior to stent placement. The study primary end point of procedural success was defined as successful device delivery and lesion treatment, including the absence of clinically significant perforation, arrhythmia, flow‐limiting dissection, or reduction in baseline Thrombolysis In Myocardial Infarction (TIMI) grade with final achievement of TIMI 3 flow. Results: Among 51 patients (54 lesions), predilation using a 1.25 mm angioplasty catheter was associated with procedural and device‐related success rates of 100%. In‐hospital target lesion failure occurred in one patient (2.0%) related to postprocedural myocardial infarction. Patient and angiographic characteristics included diabetes, 43.1%; lesion length ≥20 mm, 20.4%; bifurcation lesion, 31.5%; lesion classification B2/C, 74.1%; and baseline TIMI 0/1 flow, 13.0%. No subsequent in‐hospital adverse events occurred. Conclusions: Percutaneous coronary revascularization involving a predilation strategy with a low profile, 1.25‐mm angioplasty catheter is associated with favorable procedural safety and efficacy and may represent an effective initial treatment for complex coronary anatomy.

Coronary Stent Fracture : Clinical Use of Image Enhancement

Standard angiography and intravascular ultrasound (IVUS) have limited ability to visualize stent struts and their integrity over time. While it is thought that stent fracture is associated with high incidence of restenosis or thrombosis, the true incidence of stent fracture is difficult to ascertain

A Comparison of Echocardiographic Modalities to Guide Structural Heart Disease Interventions

Percutaneous techniques to treat structural heart disease are rapidly evolving based on innovative interventions and the considerable advancement in image guidance technology. While two-dimensional transthoracic and transesophageal echocardiography have been integral to procedural planning and execution, intracardiac and three-dimensional echocardiography supply unique visualization of target structures with a potential improvement in patient safety and procedural efficacy. The choice of image guidance modality is based on specific differences between imaging systems, as well as other variables including cost, patient safety, operator expertise, and complexity of procedure. We will compare the adjunctive imaging tools for structural heart disease interventions, with a focus on intracardiac echocardiography and real-time three-dimensional transesophageal echocardiography.

Coronary ischemia and percutaneous intervention

The interventional treatment of ischemia is a complex issue grounded on an understanding of basic pathophysiology, but translated and implemented in practice by extensive clinical trial data representing patients with a spectrum of ischemia-causing clinical syndromes and anatomical variations of coronary artery disease (CAD). Percutaneous coronary intervention (PCI) has evolved to treat ischemia within this matrix of clinical and anatomical subsets using a wide array of techniques. Initial techniques using balloon angioplasty were promising, but demonstrated significant rates of restenosis due to negative arterial remodeling. The advent of stent technology prevented arterial recoil and provided a viable treatment for flow-limiting coronary dissections, thereby facilitating improved long-term patency of coronary vessels without the need for repeat revascularization. In-stent restenosis has been successfully addressed with drug elution, but late stent thrombosis has emerged as a complex issue involving dual antiplatelet therapy, patient compliance, and reexamination of the delicate balance between reducing restenosis and promoting endothelial proliferation. Finally, complex coronary lesions associated with heavy calcification or extensive plaque/thrombus burden that introduce unique challenges in obtaining ideal angiographic results have led to the development of new debulking devices aimed at optimizing procedural outcomes. This review will describe a variety of percutaneous coronary interventional techniques and technologies that are employed in the invasive treatment of ischemia under the guidance of clinical guidelines and evidence-based medicine.

Spontaneous left main coronary artery dissection and the role of intravascular ultrasonography.

Objective. Spontaneous left main coronary artery (LMCA) dissection is a rare event with an unknown incidence and high risk of sudden cardiac death. The diagnosis of LMCA dissection is often challenging given the limitations of 2‐dimensional angiography. The 3‐dimensional perspective of intravascular ultrasonography (IVUS) is often indispensable in confirming or excluding the diagnosis of spontaneous LMCA dissection. We report 2 cases of spontaneous LMCA dissection with unique angiographic presentations wherein IVUS was essential in defining the extent of LMCA involvement and facilitated the subsequent referral for emergent coronary artery bypass grafting. Methods. Two patients presented to our facility with acute coronary syndrome prompting coronary angiography, which was notable for an unusual angiographic appearance of the LMCA. Intravascular ultrasonography was performed in each case, revealing spontaneous LMCA dissection. Results. Intravascular ultrasonography permitted the prompt diagnosis and aided in definitive surgical intervention in our 2 cases of spontaneous LMCA dissection. Conclusions. Intravascular ultrasonography is a useful adjunctive imaging modality in the diagnosis and management of spontaneous LMCA dissection.