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Biomedical subjects

Charles J Davidson

Publications and source records attributed to Charles J Davidson.

At least 19 recordsLinked to original sources

Prevention of contrast induced nephropathy: recommendations for the high risk patient undergoing cardiovascular procedures.

Contrast induced nephropathy (CIN) is the third leading cause of hospital acquired renal failure and is associated with significant morbidity and mortality. Chronic kidney disease is the primary predisposing factor for CIN. As estimated glomerular filtration rate<60 ml/1.73 m2 represents significant renal dysfunction and defines patients at high risk. Modifiable risk factors for CIN include hydration status, the type and amount of contrast, use of concomitant nephrotoxic agents and recent contrast administration. The cornerstone of CIN prevention, in both the high and low risk patients, is adequate parenteral volume repletion. In the patient at increased risk for CIN it is often appropriate to withhold potentially nephrotoxic medications, and consider the use of n-acetylcysteine. In patients at increased risk for CIN the use of low or iso-osomolar contrast agents should be utilized and strategies employed to minimize contrast volume. In these patients serum creatinine should be obtained forty-eight hours post procedure and it is often appropriate to continue withholding medications such as metformin or non steroidal anti-inflammatories until renal function returns to normal.

Contrast Media↗

Cardiac hemodynamic and coronary angiographic characteristics of patients being evaluated for liver transplantation.

With improved survival after liver transplantation (LT), the referral of older candidates has increased. The increasing demand for, and the decreased supply of, liver donors makes careful preoperative cardiac risk assessment imperative. There is a paucity of information regarding the cardiac characteristics of patients being referred for LT in the current era. This study aimed to describe the cardiac hemodynamic and coronary angiographic characteristics of a cohort of patients with end-stage liver disease without known coronary artery disease (CAD) being evaluated for LT. One hundred sixty-one consecutive patients aged>or=45 years with end-stage liver disease who were referred for right- and left-sided cardiac catheterization as part of a liver transplant evaluation were identified. There was a high prevalence of atherosclerotic risk factors; half had hypertension or diabetes, and more than half had >or=2 coronary risk factors other than age. There was a high prevalence of CAD, with 26% having unknown moderate to severe coronary narrowing. Patients with moderate to severe CAD were older, were more likely to be men, and were more likely to have hypertension or diabetes mellitus. Right- and left-sided filling pressures were elevated, suggesting abnormalities in left ventricular diastolic compliance. In conclusion, this study showed a high prevalence of coronary risk factors and unknown moderate to severe CAD in patients with end-stage liver disease being referred for LT.

Aged↗

Quantitative assessment of in-stent dimensions: a comparison of 64 and 16 detector multislice computed tomography to intravascular ultrasound.

OBJECTIVES: To determine the utility of multislice computed tomography (MSCT) technology to evaluate coronary stent luminal diameter. BACKGROUND: Stent metal induced "blooming" artifact makes quantitative coronary angiography by MSCT difficult. There is a paucity of data on the efficacy of using 64 and 16 detector MSCT in evaluating coronary stents. METHODS: We evaluated four commercially available bare metal and polymer coated drug eluting stents using 64 and 16 detector MSCT for the following: (1) Strut density in Hounsfield's Units (Hu) using a 2 mm MIP; (2) In-stent luminal diameter (ISLD) measured by MSCT compared to intravascular ultrasound (IVUS). RESULTS: Increased strut thickness did not correlate with greater strut density as measured in Hu (R(2) = 0.05, P = 0.29). The ISLD by 16 MSCT vs. IVUS is: Vision 1.63 +/- 0.58 mm vs. 2.8 +/- 0.0; Cypher 1.80 +/- 0.00 vs. 2.9 +/- 0.0; Taxus 1.87 +/- 0.58 vs. 2.9 +/- 0.0; Liberté 1.80 +/- 0.10 vs. 3.0 +/- 0.1 (P < 0.01). ISLD determined by 64 MSCT vs. IVUS is: Vision 1.73 +/- 0.06 mm vs. 2.8 +/- 0.0; Cypher 1.87 +/- 0.12 vs. 2.9 +/- 0.0; Taxus 1.77 +/- 0.06 vs. 2.9 +/- 0.0; Liberté 1.80 +/- 0.10 vs. 3.0 +/- 0.1 (P < 0.01). CONCLUSIONS: When compared to IVUS measurements, MSCT results in a significant, underestimation of ISLD. This consistent underestimation (even with 64 MSCT) limits the applicability of CT angiography to quantify in-stent restenosis.

Artifacts↗

Contrast-Induced Nephropathy (CIN) Consensus Working Panel: executive summary.

With the advances made in radiology and cardiology, greater numbers of patients are expected to undergo exposure to iodinated contrast media in the years to come. Contrast-induced nephropathy (CIN) accounts for a significant number of cases of hospital-acquired renal failure, with adverse effects on prognosis and healthcare costs. The CIN Consensus Working Panel is an international multidisciplinary group convened to address the challenges of CIN. The group reviewed 865 published papers, chosen for potential relevance from a comprehensive literature search that identified over 4000 references. The results were used to compile reviews covering the epidemiology and pathogenesis of CIN, baseline renal function measurement, risk assessment, identification of high-risk patients, contrast medium use, and preventive strategies. In this executive summary, consensus statements and an algorithm for the risk stratification and management of CIN are presented.

Contrast Media↗

Hypersensitivity cases associated with drug-eluting coronary stents: a review of available cases from the Research on Adverse Drug Events and Reports (RADAR) project.

OBJECTIVES: We undertook the review of all available cases of hypersensitivity reactions after placement of a drug-eluting stent (DES) and classified potential causes. BACKGROUND: Six months after the approval of the first DES, the Food and Drug Administration (FDA) reported 50 hypersensitivity reactions after stent placement but later concluded these were due to concomitantly prescribed medications such as clopidogrel. Nevertheless, the FDA continued to receive reports of hypersensitivity. METHODS: Reports available from April 2003 through December 2004 for hypersensitivity-like reactions associated with the sirolimus-eluting stent (CYPHER, Cordis Corp., Miami Lakes, Florida) and paclitaxel-eluting stent (TAXUS, Boston Scientific Corp., Natick, Massachusetts) were reviewed. Sources of reports included the FDA's adverse-device-event database, the published literature, and investigators from the Research on Adverse Drug/Device events And Reports (RADAR) project. Causality was assessed using standardized World Health Organization criteria. RESULTS: Of 5,783 reports identified for the DES in the FDA database, 262 unique events included hypersensitivity symptoms. Of these reports, 2 were certainly and 39 unlikely caused by clopidogrel and 1 was certainly, 9 probably, and 13 unlikely caused by the DES. From all sources, we identified 17 distinct cases that were probably or certainly caused by the stent, of which 9 had symptoms that lasted longer than four weeks. Four autopsies confirmed intrastent eosinophilic inflammation, thrombosis, and lack of intimal healing. CONCLUSIONS: The FDA reports and autopsy findings suggest that DES may be a cause of systemic and intrastent hypersensitivity reactions that, in some cases, have been associated with late thrombosis and death.

Coronary Vessels↗

The Research on Adverse Drug Events and Reports (RADAR) project.

CONTEXT: In 1998, a multidisciplinary team of investigators initiated RADAR (Research on Adverse Drug events And Reports), a clinically based postmarketing surveillance program that systematically investigates and disseminates information describing serious and previously unrecognized adverse drug and device reactions (ADRs). OBJECTIVE: To describe the structure, operations, and preliminary findings from the RADAR project and related dissemination efforts by pharmaceutical suppliers and the US Food and Drug Administration (FDA). DESIGN: After identifying a serious and unexpected clinical event suitable for further investigation, RADAR collaborators postulated clinical hypotheses and derived case series and incidence estimates from physician queries, published and unpublished clinical trials, published case reports, FDA databases, and manufacturer sales figures. RESULTS: RADAR investigators identified 16 types of serious ADRs among 1699 patients, of whom 169 (10%) died as a result of the reaction. Initial cases were identified by 7 RADAR investigators, 4 collaborating physicians, 2 attorneys, and by reviewing 3 published reports. Additional sources included queries of occupational health programs and medical directors of interventional cardiology laboratories (3 types of ADRs), published manuscripts and clinical trials (11 types of ADRs), review of medical records at a RADAR site (2 types of ADRs), unpublished clinical trial reports (3 types of ADRs), and reports from attorneys, family members, or patients (4 types of ADRs). Incidence estimates, ranging from 0.4% to 33%, were derived from 5 clinical trial reports, 2 physician queries, and 2 observational databases. Laboratory support for hypotheses included identification of 3 neutralizing antibodies and 3 histopathological findings. ADR reports were disseminated as 8 revised package inserts, 7 "dear doctor" letters, and 9 peer-reviewed articles. CONCLUSION: A new, clinically based, hypothesis-driven approach to postmarketing surveillance may supplement existing regulatory surveillance systems and improve patient safety.

Adverse Drug Reaction Reporting Systems↗

Diabetes and coronary revascularization.

CONTEXT: Patients with diabetes mellitus account for approximately 25% of the nearly 1.5 million coronary revascularization procedures performed each year in the United States and experience worse outcomes compared with nondiabetic patients. OBJECTIVES: To summarize the current state of evidence comparing the effectiveness and safety of coronary artery bypass graft (CABG) surgery and percutaneous coronary intervention (PCI) in diabetic patients and to examine developments that may affect future outcomes in this high-risk group. EVIDENCE ACQUISITION: Using the key terms diabetes mellitus, revascularization, coronary artery bypass, angioplasty, and coronary intervention, we searched MEDLINE from 1985 to 2004 for all randomized controlled trials (RCTs) comparing CABG surgery and PCI that reported outcomes in diabetic patients. Bibliographies and the Web sites of cardiology conferences were also reviewed. Studies comparing drug-eluting stents and bare-metal stents were identified in a similar fashion. The literature was reviewed to identify clinical measures that may impact revascularization outcomes in diabetic patients. EVIDENCE SYNTHESIS: We identified 6 RCTs comparing CABG surgery and PCI in a total of 950 diabetic patients. A mortality benefit for CABG over balloon-only PCI has been demonstrated in diabetic patients with multivessel coronary artery disease but has not been clearly established against stent-assisted PCI or in high-risk CABG patients. Use of glycoprotein IIb/IIIa receptor inhibitors has improved survival in diabetic patients undergoing PCI. Restenosis after PCI in diabetic patients has led to substantially higher repeat revascularization rates than after CABG. The use of drug-eluting stents has led to dramatic reductions in restenosis in diabetic patients. Ongoing RCTs comparing CABG and PCI using drug-eluting stents in diabetic patients will clarify the impact of these advances on outcomes. CONCLUSIONS: There is a relative lack of data from RCTs specifically comparing CABG surgery and PCI as currently practiced in diabetic patients. The mortality advantage and decreased rates of revascularization seen with CABG in subgroups from early trials may not be applicable in the era of drug-eluting stents, glycoprotein IIb/IIIa inhibitors, and the latest medical therapies.

Angioplasty, Balloon, Coronary↗

Clopidogrel-associated TTP: an update of pharmacovigilance efforts conducted by independent researchers, pharmaceutical suppliers, and the Food and Drug Administration.

BACKGROUND AND PURPOSE: Since the 1999 identification of clopidogrel-associated thrombotic thrombocytopenic purpura (TTP) through independent active surveillance, subsequent cases have been identified by pharmaceutical suppliers of clopidogrel and the Food and Drug Administration (FDA). For cases of clopidogrel-associated TTP reported between 1998 to 2002, we evaluated the quality and timeliness of data from 3 reporting systems-independent active surveillance (n=13), pharmaceutical suppliers (n=24), and the FDA (n=13)-and identified prognostic factors associated with mortality. METHODS: This study assessed the completeness of information on TTP diagnosis, treatment response, and causality from the 3 reporting systems. In addition, predictors of mortality were identified through classification tree analysis. RESULTS: Completeness, timeliness, and certainty of diagnosis were best for cases obtained by active surveillance, intermediate for cases reported to the pharmaceutical supplier, and poorest for cases reported directly to the FDA. Clopidogrel had been used for </=2 weeks by 65%. The survival rate for patients with clopidogrel-associated TTP was 71.2%. Receipt of therapeutic plasma exchange within 3 days of onset of TTP increased the likelihood of survival (100% versus 27.3%, P<0.001). CONCLUSIONS: Compared with reports submitted by suppliers or the FDA, reports obtained through active surveillance provided timelier and more complete information. Clopidogrel-associated TTP often occurs within 2 weeks of drug initiation, occasionally relapses, and has a high mortality if not treated promptly.

Adult↗

Myonecrosis following stent placement: association between impaired TIMI myocardial perfusion grade and MRI visualization of microinfarction.

Contrast-enhanced cardiac MRI (ceMRI) and TIMI myocardial perfusion grade analysis (TMPG) are proven methods for visualization of microinfarction and assessment of microvascular perfusion, respectively. To determine whether microvascular obstruction accounts for procedure-related myonecrosis, 14 poststent patients, 9 with procedural CK-MB elevation and 5 controls, underwent ceMRI and TMPG. All had TIMI 3 flow pre- and poststent. TMPG was normal in 12/14 pre- and 7/14 poststent. Those with poststent decline in TMPG had higher CK-MB (median, 41.0 vs. 7.4 ng/mL; P = 0.01) and larger infarct mass (median, 3.1 vs. 0.89 g; P = 0.04). More extensive myonecrosis (CK-MB > 3 x normal; infarct mass > 3 g) was observed more frequently if there was a poststent decline in TMPG (3/3, 100%, vs. 2/11, 18.2%; P = 0.03). These data support the theory that distal embolization and microvascular obstruction are associated with myonecrosis following otherwise successful coronary stent placement and provide further insight into its pathophysiology.

Adult↗

Primary coronary intervention in acute myocardial infarction.

Percutaneous coronary intervention (PCI) with stent implantation has become the standard of care for acute myocardial infarction <12 hours from symptom onset. This has led to decreased morbidity and mortality both short and long term compared to thrombolytic therapy. Stent implantation has been demonstrated to be superior to balloon PCI for mechanical reperfusion of acute myocardial infarction. Intravenous antiplatelet glycoprotein IIb/IIIa inhibitors may have a role in improving TIMI flow prior to PCI and decreasing morbidity and mortality. The role of thrombolytics vs. IIb/IIIa inhibitors in "facilitated reperfusion" is unclear at this time and further research is needed to define the indication of adjunctive pharmacology.

Angioplasty, Balloon, Coronary↗

Antirestenotic effects of a locally delivered caspase inhibitor in a balloon injury model.

BACKGROUND: The precise role of arterial barotrauma-mediated apoptosis in causing restenosis is unclear. The purpose of this study was to determine if a link exists between angioplasty-mediated medial smooth muscle cell apoptosis and subsequent neointimal hyperplasia. METHODS AND RESULTS: Bilateral iliac artery angioplasty was performed in 25 male New Zealand White rabbits. Simultaneous with balloon injury, each artery was treated locally with either the caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp(Ome)-fluoromethylketone (ZVAD-fmk) or control. In the acute cohort that was survived to 4 hours (n=10, 7 high dose and 3 low dose), an apoptotic index was calculated using the terminal deoxynucleotidyl TUNEL method. In the intermediate cohort that was survived to 2 weeks (n=5), luminal reendothelialization was measured via CD-31 staining. In the chronic cohort that was survived to 4 weeks (n=10), neointimal area was measured. In the acute cohort, there was a 40% reduction in the apoptotic index with high-dose ZVAD-fmk (P=0.008) and a 33% reduction with low-dose ZVAD-fmk (P=0.08). At 2 weeks, there was no significant difference in the degree of luminal reendothelialization. However, at 4 weeks, there was a 33% (0.33+/-0.23 versus 0.22+/-0.20 mm2) (P<0.005) reduction in neointimal area in ZVAD-fmk-treated arteries. CONCLUSIONS: The local delivery of ZVAD-fmk during balloon injury inhibits smooth muscle cell apoptosis. This corresponds to a significant reduction in neointimal proliferation seen at 4 weeks without a significant change in the degree of reendothelialization at 2 weeks.

Amino Acid Chloromethyl Ketones↗

Angiographically silent left main disease detected by intravascular ultrasound: a marker for future adverse cardiac events.

BACKGROUND: Concomitant moderate obstructive left main (LM) disease is associated with future cardiac events and poor prognosis in patients undergoing percutaneous intervention (PCI). Whether prognosis is similarly effected by LM disease not detected by angiography, but evident on intravascular ultrasound (IVUS) imaging, is not known. The purpose of this study was to evaluate the long-term prognosis of patients with angiographically insignificant LM coronary artery disease undergoing PCI. METHODS AND RESULTS: One hundred and seven consecutive patients undergoing PCI with angiographically normal or mild LM disease had 2- and 3-dimensional IVUS imaging. IVUS images were digitized, and 3-dimensional reconstruction was performed. Percent diameter and area stenosis by angiography were 4.8% +/- 3.5% and 18.2% +/- 9.8%, respectively. IVUS mean luminal area and area stenosis were 17.9 +/- 5.6 mm2 and 30.2% +/- 14.7%, respectively. Long-term follow-up was available in 102 (95%) patients at a median of 29 (range 8-52) months. Major adverse cardiac events, defined as death (6), myocardial infarction (4), repeat PCI (13), or CABG (16), were associated with female sex (P =.04), diabetes (P =.02), angiographic minimum lumen diameter (P =.04), and IVUS minimum (P =.01) and mean (P =.01) lumen area. Multivariate predictors of late cardiac events were diabetes (hazard ratio 2.69, P =.014) and minimum lumen area by IVUS (hazard ratio 0.59, P =.015). CONCLUSIONS: Despite being angiographically silent, LM disease detected by IVUS is an independent predictor of cardiac events and may serve as a marker for such events. These data extend the spectrum of LM disease severity and its relationship to cardiac prognosis in patients undergoing PCI.

Aged↗

Troponin I elevation and cardiac events after percutaneous coronary intervention.

BACKGROUND: Serum troponins are sensitive markers of myonecrosis and ischemia and are now widely used in clinical practice. Although percutaneous coronary intervention (PCI)-related creatine kinase-myocardial band isoenzyme (CK-MB) elevation has been associated with future cardiac events, the significance of troponin elevation in this setting is unknown. We sought to determine whether serum troponin I (Tn-I) elevation after PCI is associated with future cardiac events. Methods and Results Consecutive patients undergoing elective PCI underwent systematic postprocedure measurement of Tn-I and CK-MB levels. Serum levels were correlated with demographic, angiographic, and procedural characteristics and the development of major adverse cardiac events (MACE; defined as death, MI, or need for PCI or coronary bypass graft surgery) at 30 days, 6 months, and 1 year. In 286 consecutive procedures, postintervention myonecrosis-specific Tn-I was elevated in 13.6% of patients, and CK-MB was elevated in 12.9% of patients. Multivariable predictors of Tn-I elevation were procedural side branch occlusion and thrombus formation. Peak Tn-I and CK-MB values were well correlated (r = 0.81, P <.0001). Three-fold elevation of Tn-I after successful PCI was independently predictive of MACE (P =.01). CONCLUSIONS: Tn-I elevation after elective PCI is relatively common and is associated with procedural complications such as incidental side branch occlusion and thrombus formation. In addition, this study demonstrates that a 3-fold elevation of Tn-I after successful elective PCI is predictive of future cardiac events, especially the need for early repeat revascularization.

Adult↗

Post-cardiac catheterization access site complications and low-molecular -weight heparin following cardiac catheterization.

The low molecular weight heparin enoxaparin is often administered to patients on long-term anticoagulation regimens who temporarily discontinue warfarin prior to undergoing invasive procedures. The clinical outcome of all enoxaparin-treated patients who underwent cardiac catheterization or coronary artery interventional procedures (n = 119) was evaluated. A total of 5 patients (4.2%) requiring anticoagulation (3 with chronic atrial fibrillation and 2 with ventricular thrombi) developed severe late enoxaparin-associated hemorrhagic or vascular complications at the femoral arterial puncture site between 3 and 11 days post-procedure. Complications included development of femoral arterial pseudoaneurysm (n = 3), hypotension (systolic blood pressure < 90 mmHg) (n = 2), acute decrease in hemoglobin levels to < 8.5 mg/dl (n = 4) and cardiac arrest (n = 1). In patients receiving standard dose enoxaparin after percutaneous invasive cardiac procedures, there is the potential for delayed and severe access site hemorrhagic and vascular complications.

Aged↗

A comparison of arterial closure devices to manual compression in liver transplantation candidates undergoing coronary angiography.

Whether arterial closure devices can be used safely in a coagulopathic population undergoing cardiac catheterization and at high risk for groin complications, such as liver transplant candidates, is unknown. In this prospective, non-randomized consecutive series of 80 liver transplant candidates undergoing coronary angiography, manual compression and arterial closure devices were compared. Ilio-femoral angiography was performed to determine suitability for use of the closure device. Bleeding and vascular complications were recorded along with time to ambulation. Arterial closure devices were used in 31 patients (39%), whereas manual compression was used in 49 patients (50 procedures) (61%). There were no significant differences between the two groups with respect to age, sex, cardiac risk factors, peripheral vascular disease, baseline platelet count or baseline INR. There were 10 total vascular complications out of 50 procedures (20%) in the manual compression group compared to 2 vascular complications out of 31 procedures in the arterial closure device group (6%; p = 0.12). The time to ambulation was significantly less in the group receiving arterial closure devices versus manual compression (4.2 1.8 hours versus 6.6 3.7 hours, respectively; p = 0.0003). In coagulopathic patients at higher risk for groin complications, arterial closure devices can be safely used and decrease time to ambulation compared to manual compression.

Cardiac Catheterization↗

Recent clinical trials of iodixanol.

In patients with well-preserved renal function, the choice of contrast agent appears to have little impact on the development of contrast-induced nephropathy (CIN). However, in patients with underlying renal insufficiency and diabetes mellitus, it has been shown that the use of low-osmolar media is associated with a lower incidence of CIN compared with high-osmolar agents. Previously, it was unknown whether further benefit would be derived from the use of iso-osmolar contrast media. Recent studies, including Nephrotoxicity in High-Risk Patients Study of Iso-osmolar and Low-Osmolar Nonionic Contrast Media (NEPHRIC), have shown a reduction in the incidence of CIN with the iso-osmolar contrast agent iodixanol compared with low-osmolar agents in patients with renal insufficiency and diabetes. The peak rise in serum creatinine was significantly reduced with iodixanol (0.13 mg/dL vs 0.55 mg/dL, P <.001). The incidence of CIN, defined as a peak rise > 0.5 mg/dL, was decreased from 26% to 3%, P <.0002 when iodixanol was used. An ongoing, multicenter, prospective, double-blind, randomized study (Visipaque Angiography/Interventions with Laboratory Outcomes for Renal Insufficiency [VALOR]) is evaluating the potential benefit of iodixanol in reducing CIN in patients with preexisting renal impairment. Accumulating evidence suggests that the use of iso-osmolar contrast agents in conjunction with other proven measures, especially adequate intravenous hydration and contrast dosage limitation, can reduce the morbidity and mortality associated with CIN. These measures have the potential for a significant reduction in health care costs.

Clinical Trials as Topic↗