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Biomedical subjects

D R Holmes

Publications and source records attributed to D R Holmes.

At least 19 recordsLinked to original sources

An integrated system for real-time image guided cardiac catheter ablation.

Minimally invasive cardiac catheter ablation procedures require effective visualization of the relevant heart anatomy and electrophysiology (EP). In a typical ablation procedure, the visualization tools available to the cardiologist include bi-plane fluoroscopy, real-time ultrasound, and a coarse 3D model which gives a rough representation of cardiac anatomy and electrical activity. Recently, there has been increased interest in incorporating detailed, patient specific anatomical data into the cardiac ablation procedure. We are currently developing a prototype system which both integrates a patient specific, preoperative data model into the procedure as well as fuses the various visualization modalities (i.e. fluoroscopy, ultrasound, EP) into a single display. In this paper, we focus on two aspects of the prototype system. First, we describe the framework for integrating the various system components, including an efficient communication protocol. Second, using a simple two-chamber phantom of the heart, we demonstrate the ability to integrate preoperative data into the ablation procedure. This involves the registration and visualization of tracked catheter points within the cardiac chambers of the preoperative model.

Cardiac Catheterization↗

Quantitative characterization of lung disease.

The increase in prevalence, incidence and variety of pulmonary diseases has precipitated the need for more non-invasive quantitative assessment of structure/function relationships in the lung. This need requires concise description not only of lung anatomy but also of associated underlying mechanics of pulmonary function, as well as deviation from normal in specific diseases. This can be facilitated through the use of adaptive deformable surface models of the lung at end inspiratory and expiratory volumes. Lung surface deformation may be used to represent tissue excursion, which can characterize both global and regional lung mechanics. In this paper, we report a method for robust determination and visualization of pulmonary structure and function using clinical CT scans. The method provides both intuitive 3D parametric visualization and objective quantitative assessment of lung structure and associated function, in both normal and pathological cases.

Humans↗

Comparative outcomes of percutaneous coronary interventions in diabetics vs non-diabetics with prior coronary artery bypass grafting.

AIMS: To determine the influence of diabetes on outcome after percutaneous coronary intervention in patients with prior coronary artery bypass grafting. METHODS AND RESULTS: Patients with prior coronary artery bypass grafting undergoing percutaneous coronary intervention from 1 January 1996, to 31 August 2000, were divided into two groups based on whether or not they had diabetes, excluding patients with acute infarction or shock. Cox proportional hazards models were utilized to estimate the association between diabetes and adverse events. One thousand one hundred and fifty-three post-coronary artery bypass grafting percutaneous coronary intervention patients were identified (326 diabetics and 827 non-diabetics). Diabetics were younger, more likely to have hypertension, heart failure, and lower ejection fraction. Procedural characteristics and angiographic and procedural success rates were similar. Diabetes was associated with increased mortality (hazard ratio 1.58, 95% confidence intervals 1.10-2.27). Diabetes did not have a significant effect on mortality in patients treated for single-territory coronary disease (hazard ratio 1.44, 95% confidence intervals 0.69-3.02), but did in patients with multi-territory disease (hazard ratio 1.79, 95% confidence intervals 1.16-2.76). However, in diabetics with multi-territory disease who were completely revascularized with percutaneous coronary intervention, mortality was comparable to non-diabetics (hazard ratio 1.32, 95% confidence intervals 0.57-3.03). CONCLUSION: Among percutaneous coronary intervention patients with prior coronary artery bypass grafting, diabetes portends an adverse prognosis.

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Influence of coronary thrombus on outcome of percutaneous coronary angioplasty in the current era (the Mayo Clinic experience).

Earlier studies documented an increased risk of percutaneous coronary intervention (PCI) in patients with angiographic evidence of thrombus. With newer antiplatelet agents and stents, it is not known whether thrombus is a risk factor after PCI. This study examines whether outcome of PCI in patients with thrombus has improved, and whether thrombus is associated with adverse outcome after PCI in the current era. This single-institution retrospective analysis of PCI in 7,184 patients was divided into 2 periods: group I, 1990 to 1995 (n = 3,640), and group II, 1996 to 1999 (n = 3,544). The groups were subdivided according to the presence or absence of angiographic thrombus before PCI. We compared the outcome of PCI for patients with and without thrombus in group II. A comparison was made in the 2 groups in patients with angiographic thrombus. Procedural success improved in group II compared with group I patients with thrombus (93% vs 88%, p <0.001). There was significant reduction in abrupt closure in the recent era in patients with thrombus (4% vs 7%, p = 0.01). In group II, procedural success remained lower in patients with (93% vs 96%) than without thrombus (p <0.001). After adjusting for the significant univariate characteristics of group II patients, thrombus remained an independent predictor of Q-wave infarction (odds ratio 3.78; 95% confidence interval [CI], 1.8 to 8.0; p <0.0013) and the composite end point of death, Q-wave infarction, and emergency bypass surgery (odds ratio 2.37; 95% CI 1.4 to 4.1; p = 0.002). There was a trend toward increased in-hospital death among patients with thrombus (odds ratio 2.06; 95% CI 0.9 to 4.8; p = 0.09). The 1-year outcome after successful PCI was similar for those with and without thrombus. Despite improvement in the outcome of patients with thrombus undergoing PCI in recent years, thrombus is still an independent predictor of adverse in-hospital outcomes after PCI.

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Pregnancy-associated plasma protein A as a marker of acute coronary syndromes.

BACKGROUND: Circulating markers indicating the instability of atherosclerotic plaques could have diagnostic value in unstable angina or acute myocardial infarction. We evaluated pregnancy-associated plasma protein A (PAPP-A), a potentially proatherosclerotic metalloproteinase, as a marker of acute coronary syndromes. METHODS: We examined the level of expression of PAPP-A in eight culprit unstable coronary plaques and four stable plaques from eight patients who had died suddenly of cardiac causes. We also measured circulating levels of PAPP-A, C-reactive protein, and insulin-like growth factor I (IGF-I) in 17 patients with acute myocardial infarction, 20 with unstable angina, 19 with stable angina, and 13 controls without atherosclerosis. RESULTS: PAPP-A was abundantly expressed in plaque cells and extracellular matrix of ruptured and eroded unstable plaques, but not in stable plaques. Circulating PAPP-A levels were significantly higher in patients with unstable angina or acute myocardial infarction than in patients with stable angina and controls (P<0.001). A PAPP-A threshold value of 10 mlU per liter identified patients who had acute coronary syndromes with a sensitivity of 89.2 percent and a specificity of 81.3 percent. PAPP-A levels correlated with levels of C-reactive protein and free IGF-I, but not with markers of myocardial injury (troponin I and the MB isoform of creatine kinase). CONCLUSIONS: PAPP-A is present in unstable plaques, and circulating levels are elevated in acute coronary syndromes; these increased levels may reflect the instability of atherosclerotic plaques. PAPP-A is a new candidate marker of unstable angina and acute myocardial infarction.

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Long-term clinical outcomes after unprotected left main trunk percutaneous revascularization in 279 patients.

BACKGROUND: Percutaneous coronary revascularization (PCI) has been increasingly applied to unprotected left main trunk (LMT) lesions, with varied long-term success. This study attempts to define the predictors of outcome in this population. METHODS AND RESULTS: Two hundred seventy-nine consecutive patients who had LMT PCI at 1 of 25 sites between 1993 and 1998 were studied. Forty-six percent of these patients were deemed inoperable or at high surgical risk. Thirty-eight patients (13.7%) died in hospital, and the rest were followed up for a mean of 19 months. The 1-year incidence was 24.2% for all-cause mortality, 20.2% for cardiac mortality, 9.8% for myocardial infarction, and 9.4% for CABG. Independent correlates of all-cause mortality were left ventricular ejection fraction </=30%, mitral regurgitation grade 3 or 4, presentation with myocardial infarction and shock, creatinine >/=2.0 mg/dL, and severe lesion calcification. For the 32% of patients <65 years old with left ventricular ejection fraction >30% and without shock, the prevalence of these adverse risk factors was low. No periprocedural deaths were observed in this low-risk subset, and the 1-year mortality was only 3.4%. CONCLUSIONS: Patients undergoing unprotected LMT PCI have frequent serious comorbidities and consequently have high event rates. PCI may be an alternative to CABG for a select proportion of elective patients and may also be appropriate for highly symptomatic inoperable patients. Meticulous follow-up of hospital survivors is required because of the rather high mortality during the first few months after treatment.

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Clinical risk stratification correlates with the angiographic extent of coronary artery disease in unstable angina.

OBJECTIVES: We sought to determine whether clinical risk stratification correlates with the angiographic extent of coronary artery disease (CAD) in patient with unstable angina. BACKGROUND: The Agency for Health Care Policy and Research (AHCPR) guidelines stratify patients with unstable angina according to short-term risk of myocardial infarction or death. Whether these guidelines are useful in predicting the extent of CAD is unknown. METHODS: All residents of Olmsted County, Minnesota, undergoing emergency department evaluation from January 1, 1985 through December 31, 1992 for unstable angina without a history of prior coronary artery bypass grafting, and who underwent early angiography (within seven days of presentation) were classified into low, intermediate and high risk subgroups based on AHCPR criteria. RESULTS: Seven hundred ninety-five patients underwent early angiography: 159 high risk, 572 intermediate risk and 64 low risk patients. Logistic regression analysis demonstrated that low risk patients had a greater likelihood of normal or mild CAD relative to intermediate risk (odds ratio [OR], 4.67; 95% confidence interval [CI], 2.70-8.06; p < 0.001) and high risk (OR, 11.1; 95% CI, 5.71-22.2; p < 0.001). Significant 1-, 2-, 3-vessel coronary disease or left main coronary disease was more likely in high relative to low risk (OR, 8.09; 95% CI, 4.22-15.5; p < 0.001), intermediate relative to low risk (OR, 4.11; 95% CI, 2.34-7.22; p < 0.001), and high relative to intermediate risk (OR, 1.97; 95% CI, 1.31-2.96; p = 0.0012). CONCLUSIONS: Among patients with unstable angina undergoing early coronary angiography, risk stratification according to the AHCPR guidelines correlates with the angiographic extent of CAD.

Adult↗

Point-of-care measured platelet inhibition correlates with a reduced risk of an adverse cardiac event after percutaneous coronary intervention: results of the GOLD (AU-Assessing Ultegra) multicenter study.

BACKGROUND: The optimal level of platelet inhibition with a glycoprotein (GP) IIb/IIIa antagonist necessary to minimize thrombotic complications in patients undergoing a percutaneous coronary intervention (PCI) is currently unknown. METHODS AND RESULTS: Five hundred patients undergoing a PCI with the planned use of a GP IIb/IIIa inhibitor had platelet inhibition measured at 10 minutes, 1 hour, 8 hours, and 24 hours after the initiation of therapy with the Ultegra Rapid Platelet Function Assay (Accumetrics). Major adverse cardiac events (MACES: composite of death, myocardial infarction, and urgent target vessel revascularization) were prospectively monitored, and the incidence correlated with the measured level of platelet function inhibition at all time points. One quarter of all patients did not achieve >/=95% inhibition 10 minutes after the bolus and experienced a significantly higher incidence of MACEs (14.4% versus 6.4%, P=0.006). Patients whose platelet function was <70% inhibited at 8 hours after the start of therapy had a MACE rate of 25% versus 8.1% for those >/=70% inhibited (P=0.009). By multivariate analysis, platelet function inhibition >/=95% at 10 minutes after the start of therapy was associated with a significant decrease in the incidence of a MACE (odds ratio 0.46, 95% CI 0.22 to 0.96, P=0.04). CONCLUSIONS: Substantial variability in the level of platelet function inhibition is achieved with GP IIb/IIIa antagonist therapy among patients undergoing PCI. The level of platelet function inhibition as measured by a point-of-care assay is an independent predictor for the risk of MACEs after PCI.

Abciximab↗

Immediate and one-year outcome in patients with coronary bifurcation lesions in the modern era (NHLBI dynamic registry).

Balloon angioplasty of bifurcation lesions has been associated with lower success and higher complication rates than most other lesion types. The development of alternative strategies such as debulking and stenting, either alone or in combination, are currently used relatively often. The relative role of these newer approaches in improving acute or long-term outcome, however, remains uncertain. Of the total of 2,436 patients treated between July 1997 to February 1998 in the National Heart, Lung, and Blood Institute Dynamic Registry, there were 321 patients (group 1) with bifurcation lesions and 2,115 patients without any bifurcation lesions attempted (group 2). Treatment strategies in terms of major devices used were significantly different between the 2 groups (group 1 vs 2): balloon angioplasty alone (23.1% vs 26.5%), balloon angioplasty and rotational atherectomy (6.9% vs 4.4%), balloon angioplasty and stent (55.8% vs 59.9%), and balloon angioplasty, rotational atherectomy, and stent (10.3% vs 7%) with p <0.01. There were no significant differences between the groups in terms of age, gender, and frequency of prior myocardial infarction (MI) or coronary artery bypass graft surgery (CABG). Complete angiographic success was achieved in only 86% of bifurcation lesions versus 93.5% of nonbifurcation lesions (p <0.001). In-hospital complication rates were increased in patients with bifurcation lesions compared with the nonbifurcation group: MI, 3.7% versus 2.6%; CABG, 2.2% versus 1.1%; side branch occlusion, 7.3% versus 2.3% (p <0.001); and the composite of death, MI, and any CABG, 7.2% versus 5.0%. At 1-year follow-up, major adverse cardiac events were 25% higher in group 1 than in group 2 (32.1% vs 25.7%, p <0.05). We conclude that despite the widespread use of newer percutaneous devices, treatment of bifurcation lesions remains difficult and is associated with decreased success and increased complication rates compared with nonbifurcation lesions.

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Changes in the practice of percutaneous coronary intervention: a comparison of enrollment waves in the National Heart, Lung, and Blood Institute (NHLBI) Dynamic Registry.

The National Heart, Lung, and Blood Institute Dynamic Registry includes 15 clinical sites in wave 1, and 16 sites in wave 2 as well as a data-coordinating center. The first wave of enrollment began in July 1997 and was completed in February 1998. The second wave began in February 1999 and ended in June 1999. There were a total of 2,526 patients in wave 1 and 2,109 patients in wave 2. Comprehensive pre-, intra-, and postprocedure (in-hospital) data were analyzed for changes between recruitment waves. Patients in wave 2 were more frequently nonwhite (p < or = 0.001), hypertensive by history (p < or = 0.001), had more significant noncardiac comorbidity (p < or = 0.01), and had more frequently undergone prior percutaneous coronary intervention (p < 0.05). Patients in wave 2 underwent percutaneous coronary intervention in a setting of acute coronary syndromes more frequently than wave 1 patients (p < or = 0.001). However, most interventions in both waves were performed on 1 vessel, irrespective of the extent of disease. Attempted lesions in wave 2 were longer (p < or = 0.001), less frequently totally occluded (p < or = 0.001), and more frequently in vessels with a prior stent (p < or = 0.01). Using the American Heart Association/American College of Cardiology lesion classification scheme, attempted lesions in wave 2 were less complex than those in wave 1 (p < or = 0.001). Stent use increased significantly from wave 1 (67%) to wave 2 (79%, p < or = 0.001) as did the use of platelet glycoprotein IIb/IIIa antagonists (wave 1, 24%; wave 2, 32%: p < 0.001). Procedural outcomes (angiographic success without major in-hospital adverse events) were excellent in both waves 1 (94.6%) and 2 (95.6%) and were not significantly different. However, the frequency of significant procedural coronary dissection and in- and out-of-laboratory abrupt closure were significantly less in wave 2 (p < or = 0.001) Discharge medications were more likely to include angiotensin-converting enzyme inhibitors, beta-adrenergic blocking agents, and hypolipidemic treatment in wave 2 than in wave 1 (p < or = 0.001). These data indicate a continuing aggressive approach to patient care over the time interval analyzed. Although overall procedural outcomes are excellent, procedural safety has been further enhanced. There is also a growing awareness of the importance of secondary prevention among interventional cardiologists.

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Molecular fingerprint of interferon-gamma signaling in unstable angina.

BACKGROUND: Activation of circulating monocytes in patients with acute coronary syndromes may reflect exposure to bacterial products or stimulation by cytokines such as IFN-gamma. IFN-gamma induces phosphorylation and nuclear translocation of transcription factor STAT-1, which initiates a specific program of gene induction. To explore whether monocyte activation is IFN-gamma driven, patients with unstable (UA) or stable angina (SA) were compared for nuclear translocation of STAT-1 complexes and upregulation of IFN-gamma-inducible genes CD64 and IP-10. METHODS AND RESULTS: Peripheral blood mononuclear cells were stained for expression of CD64 on CD14(+) monocytes and analyzed by PCR for transcription of IP-10. Expression of CD64 was significantly increased in patients with UA. Monocytes from UA patients remained responsive to IFN-gamma in vitro, with accelerated transcriptional competency of CD64. IP-10-specific sequences were spontaneously detectable in 82% of the UA patients and 15% of SA patients (P<0.001). Most importantly, STAT-1 complexes were found in nuclear extracts prepared from freshly isolated monocytes of patients with UA, which provides compelling evidence for IFN-gamma signaling in vivo. CONCLUSIONS: Monocytes from UA patients exhibit a molecular fingerprint of recent IFN-gamma triggering, such as nuclear translocation of STAT-1 complexes and upregulation of IFN-gamma-inducible genes CD64 and IP-10, which suggests that monocytes are activated, at least in part, by IFN-gamma. IFN-gamma may derive from stimulated T lymphocytes, which implicates specific immune responses in the pathogenesis of acute coronary syndromes.

Active Transport, Cell Nucleus↗

Comparison of immediate and one-year outcome after coronary angioplasty of narrowing < 3 mm with those > or =3 mm ( the National Heart, Lung, and Blood Institute Dynamic Registry).

Balloon angioplasty of small coronary artery lesions has been associated with lower success and higher complication rates than large coronary artery lesions. This study evaluates the in-hospital and 1-year outcome of the treatment of small coronary artery lesions in the modern era of interventional cardiology and compares it with the outcome of treating large coronary artery lesions. Of 1,658 patients with a single lesion treated from July 1997 to February 1998 in the National Heart, Lung, and Blood Institute (NHLBI) Dynamic Registry, there were 587 patients with small coronary artery lesions (<3 mm) and 1,071 patients with large coronary artery lesions (> or =3 mm). Success, in-hospital, and 1-year outcomes between both groups were compared. Patients with lesions in small coronary arteries were more often women, insulin-treated diabetics, and had undergone more prior coronary bypass graft surgery. Conventional angioplasty alone was performed more often and angioplasty with stents was performed less often in the small coronary artery than in the large coronary artery group. Angiographic success was slightly lower in the small coronary artery group (94.2% vs 96.9%, p <0.05). Periprocedural and in-hospital complication rates were similar in both groups. Likewise, at 1-year follow-up, major adverse cardiac events including death, myocardial infarction, and coronary artery bypass graft surgery were relatively low and comparable between the 2 groups, although patients with small coronary arteries were more likely to undergo repeat revascularization (17.4% vs 13.6%, p <0.05). Treatment of lesions in small coronary arteries in the modern era is associated with high success and low complication rates, comparable to the treatment of large coronary artery lesions, although the incidence of repeat revascularization was significantly greater at follow-up even if stents were used.

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Effect of concomitant or very early statin administration on in-hospital mortality and reinfarction in patients with acute myocardial infarction.

In a retrospective analysis, 66 patients identified as having received a statin drug within 24 hours of admission for acute myocardial infarction were matched 3:1 with a control group of 198 patients not treated with a statin agent. End points of in-hospital mortality and in-hospital reinfarction were significantly lower in the statin-treated group, pointing to a benefit from very early statin treatment in acute myocardial infarction.

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Evaluation of long-term survival after successful percutaneous coronary intervention among patients with chronic renal failure.

We studied the long-term outcomes after percutaneous coronary intervention in dialysis patients and in patients with chronic renal failure (CRF) (serum creatinine > or = 3.0 mg/dl). All-cause mortality at 1 year was 2.9% for the control group, 16.2% for the group with CRF, and 14.1% for dialysis patients. Cardiac mortality at 1 year was 1.9% for ther control group, 15.2% for the group with CRF, and 10.0% for dialysis patients.

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