Biomedical subjects
Publications and source records attributed to W W O'Neill.
This report describes the management of a patient with severe symptomatic mitral stenosis and a large mobile thrombus extending from the left atrial appendage that was resistant to warfarin therapy. Percutaneous balloon mitral valvuloplasty was performed with cerebral protection using bilateral internal carotid artery filters to minimize the risk of embolic stroke.
AIMS: To investigate the clinical and angiographic outcome of patients with mild coronary lesions treated with balloon angioplasty or coronary stenting (coronary plaque sealing, i.e. dilatation of angiographically non-significant lesions) compared to moderate and severe stenoses. METHODS AND RESULTS: Patients with chronic stable angina and a single de novo lesion in a native coronary vessel scheduled to undergo percutaneous coronary intervention (PCI) were selected from 14 different studies. Off-line analysis of angiographic outcomes was assessed in all patients using identical and standardised methods of data acquisition, analysis and definitions. Clinical endpoints were adjudicated by independent clinical events committees. All quantitative coronary angiographic (QCA) analyses were performed in the same core laboratory. Stenosis severity prior to PCI was categorised into three groups: <50% diameter stenosis (DS), 50-99%DS and >99%DS pre. A total of 3812 patients were included in this study; 1484 patients (39%) were successfully treated with balloon angioplasty (BA) only and stented angioplasty was performed in 2328 patients (61%).One-year mortality and rate of non-fatal myocardial infarction (MI) (Kaplan-Meier) did not differ between BA and stented angioplasty for any of the stenosis severity categories. Following BA, the combined event rate (death and non-fatal MI) was 4.8, 4.6 and 0% in the <50, 50-99 and >99%DS categories, respectively. Following stented angioplasty, the combined event rate was 3.1, 4.4 and 4.8% in the same categories. The need for repeat revascularisation corrected for stenosis severity in the Cox proportional-hazards regression model was reduced by 20% after stented angioplasty (hazard ratio (HR) 0.80, 95%CI 0.69-0.93). CONCLUSION: The concept of plaque sealing is appealing from the theoretical point of view. However, with current technology, plaque sealing cannot prevent death and future non-fatal MIs in the long-term because 1-year event rates after PCI of non-significant stenoses remain unacceptably elevated when compared with the estimated 1-year probability of a non-fatal MI in lesions with a <50%DS. Moreover, major adverse cardiac events at 1-year after PCI are not directly related to the degree of pre-procedural stenosis severity.
BACKGROUND: Angiographic flow measurements do not define perfusion accurately at a microvascular level, so other techniques which assess flow at a tissue level are to be preferred. OBJECTIVES: To compare intravenous myocardial contrast echocardiography (MCE) with other methods of assessing microvascular reperfusion for their ability to predict left ventricular function at one month after acute myocardial infarction. DESIGN: 15 patients underwent primary percutaneous coronary angioplasty for acute myocardial infarction, with restoration of TIMI grade 3 flow. Corrected TIMI frame count (cTFC), myocardial blush grade (MBG), and percentage ST segment resolution at 90 and 180 minutes were recorded. Baseline regional wall motion score index (WMSI) and regional contrast score index (RCSI) were obtained 12-24 hours after the procedure, with a final regional WMSI assessment at one month. RESULTS: Mean (SD) cTFC was 27 (9.4), and ST segment resolution was 69 (22)% at 90 minutes and 77 (20)% at 180 minutes. MBG values were 0 in six patients, 2 in two, and 3 in seven. Baseline regional WMSI, RCSI, and follow up WMSI were 2.7 (0.71), 1.5 (0.71), and 1.6 (0.73), respectively. The correlation coefficient between RCSI and follow up WMSI was 0.82 (p = 0.0012). Peak CK correlated with follow up WMSI (R = 0.80). None of the other reperfusion assessment techniques correlated significantly with follow up WMSI. Multiple regression analysis showed that a perfused hypokinetic or akinetic segment was 50 times more likely to recover function than a non-perfused segment. MCE predicted segmental myocardial recovery with a sensitivity of 88%, a specificity of 74%, and positive and negative predictive values of 83% and 81%, respectively. CONCLUSIONS: MCE is currently the best and most accurate measure of reperfusion at a microvascular level and an excellent predictor of left ventricular function at one month following acute myocardial infarction.
The mortality benefit of thrombolytic therapy for acute myocardial infarction (AMI) is strongly dependent on time to treatment. Recent observations suggest that time to treatment may be less important with primary percutaneous transluminal coronary angioplasty (PTCA). Patients with AMI of <12 hours duration, without cardiogenic shock, who were treated with primary PTCA from the Stent PAMI Trial (n = 1,232) were evaluated to assess the effect of time to reperfusion on outcomes. Thrombolysis In Myocardial Infarction grade 3 flow was achieved in a high proportion of patients regardless of time to treatment. Improvement in ejection fraction from baseline to 6 months was substantial with reperfusion at <2 hours but was modest and relatively independent of time to reperfusion after 2 hours (<2 hours, 12.3% vs > or =2 hours, 4.2%, p = 0.004). There were no differences in 1- or 6-month mortality by time to reperfusion (6-month mortality: <2 hours [5.5%], 2 to <4 hours [4.6%], 4 to <6 hours [4.5%], >6 hours [4.2%], p = 0.97). There were also no differences in other clinical outcomes by time to reperfusion, except that reinfarction and infarct artery reocclusion at 6 months were more frequent with later reperfusion. The lack of correlation between time to treatment and mortality in patients without cardiogenic shock suggests that the survival benefit of primary PTCA may be related principally to factors other than myocardial salvage. These data may also have implications regarding the triage of patients with AMI for primary PTCA.
BACKGROUND: Whereas survival after lytic therapy for myocardial infarction is strongly dependent on early administration, it is unknown whether the otherwise excellent outcomes in patients undergoing primary PTCA for acute myocardial infarction, in whom TIMI-3 flow rates of >90% may be achieved, can be further improved by early reperfusion. METHODS AND RESULTS: Among 2507 patients enrolled in 4 PAMI trials undergoing primary PTCA, spontaneous reperfusion (TIMI-3 flow) was present in 16% at initial angiography. Compared with patients without TIMI-3 flow, those with TIMI-3 flow before PTCA had greater left ventricular ejection fraction (57+/-10% versus 53+/-11%, P=0.003) and were less likely to present in heart failure (7.0% versus 11.6%, P=0.009). Patients with initial TIMI-3 flow had significantly lower in-hospital rates of mortality, new-onset heart failure, and hypotension and had a shorter hospital stay. Cumulative 6-month mortality was 0.5% in patients with initial TIMI-3 flow, 2.8% with TIMI-2 flow, and 4.4% with initial TIMI-0/1 flow (P=0.009). By multivariate analysis, TIMI-3 flow before PTCA was an independent determinant of survival (odds ratio 2.1, P=0.04), even when corrected for by postprocedural TIMI-3 flow. CONCLUSIONS: Patients undergoing primary PTCA in whom TIMI-3 flow is present before angioplasty present with greater clinical and angiographic evidence of myocardial salvage, are less likely to develop complications related to left ventricular failure, and have improved early and late survival. These data warrant prospective randomized trials of pharmacological strategies to promote early reperfusion before definitive mechanical intervention in acute myocardial infarction.
Previous studies have shown higher levels of Chlamydia pneumoniae (C. pneumoniae, CP) antibody titers (CPIgG), C-reactive protein (CRP), and fibrinogen in patients with coronary artery disease. The role of these infectious and inflammatory markers in precipitating acute coronary syndrome (ACS) is unclear. We conducted a cross-sectional study on patients (n = 830, mean age 63 +/- 15 years, 57% male) admitted to the chest pain center of our institution. The differences in the CPIgG, CRP, and fibrinogen levels in patients who were diagnosed with ACS versus those who were not (non-ACS) were evaluated. CPIgG titers tended to be higher in the ACS group than in the non-ACS group. However, when different titers were used to define seropositivity, the difference achieved statistical significance only at the titer of > or =1:1,024 (35% vs 26%, p = 0.004). CRP (median 0.48 vs 0.33 mg/dl, p <0.0001), fibrinogen (median 317 vs 293 mg/dl, p <0.0001), and leukocyte count (median 7.7 vs 6.9 10(9)/L, p <0.0001) were higher in the ACS group. On multivariate analysis, CPIgG > or =1:1,024 (odds ratio [OR] 1.62), diabetes (OR 1.91), hypertension (OR 1.46), prior myocardial infarction (OR 1.78), smoking (OR 1.70), Caucasian race (OR 1.7), high-density lipoprotein (OR 0.98), and elevated troponin-T (OR 12.44) were the only factors independently associated with ACS. Thus, we found a strong association between high level seropositivity to CP and ACS. This may indicate recent re-infection or an exaggerated immune response to CP as an etiologic factor for ACS. This study also suggests that therapeutic interventions may need to be specifically targeted to these patients.
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The predictive value of Killip classification of acute myocardial infarction (AMI) in patients undergoing percutaneous coronary intervention (PCI) is not well established. We performed a pooled analysis of 2,654 patients with AMI enrolled in 3 primary angioplasty trials. Of these, 2,305 patients were class I, 302 were class II, and 47 were class III (class IV patients were excluded). Univariate and multivariate analyses were performed to determine if Killip class at admission was a predictor of in-hospital and 6-month mortality. Higher Killip classification was associated with greater in-hospital (2.4%, 7%, and 19% for class I, II, and III, respectively) and 6-month mortality (4%, 10%, and 28% for class I, II, and III, respectively). Higher Killip class was associated with increased age (p <0.001), history of diabetes (p <0.02), lower systolic blood pressure and higher heart rate at presentation (p <0.0001 for both), more 3-vessel disease (p <0.001), lower left ventricular ejection fraction (p <0.0001), and higher peak creatine phosphokinase (p <0.0001). With each increasing Killip class, there was an increased need for an intra-aortic balloon counterpulsation (p <0.001) and greater incidence of renal failure (p <0.001), major arrhythmia (p <0.001), and major bleeding (p <0.001). After controlling for potential confounding variables, Killip classification remained a multivariate predictor of mortality at both time end points. Killip classification at hospital admission remains a simple and useful independent predictor of in-hospital and 6-month mortality in patients with AMI who are undergoing primary PCI.
Experimental data suggest that myocardial revascularization with a high-energy laser may cause a significant reduction in left ventricular (LV) function immediately after creation of myocardial channels. We sought to determine if percutaneous myocardial laser revascularization (PMR) causes immediate deterioration in hemodynamic parameters or regional LV systolic function. PMR was performed in 40 patients (mean age 62.9 +/- 10.8 years) using the Eclipse Holmium laser (26 had PMR alone; 14 patients underwent PMR plus percutaneous coronary intervention). Intracardiac pressures and left ventriculograms were recorded before and after PMR. Regional wall motion was assessed using the centerline method. A mean of 18 +/- 5 channels were created per patient. There was no significant change in LV ejection fraction immediately after PMR (56 +/- 9% vs 55 +/- 10%, p = 0.25). No deterioration in regional wall motion was demonstrated in the lased region (mean chord motion for anterior wall PMR: -1.5 +/- 0.8 before vs -1.5 +/- 0.8 after the procedure, p = 0.93; inferior wall PMR: -1.5 +/- 0.9 before vs - 1.6 +/- 0.8 after the procedure, p = 0.43). Similarly, there was no change in the number of hypokinetic chords in the treated region. Systemic blood pressure, LV end-diastolic pressure, heart rate, and right-sided heart pressures were not significantly different after laser revascularization. In patients with refractory angina, PMR did not cause immediate deterioration in hemodynamic status or regional LV function.
Mechanical rotational atherectomy with the Rotablator is widely used for percutaneous coronary revascularization, but the ideal debulking strategy remains unknown. The purpose of this study was to compare the immediate and late results after Rotablator using two treatment strategies: Large burrs (burr/artery ratio of >0.7) to achieve maximal debulking (lesion debulking strategy) or small burrs (burr/artery ratio < or = 0.7) to modify lesion compliance (lesion modification strategy). Two hundred twenty-two patients at six centers were prospectively enrolled in this study and randomly assigned to large (n = 104 patients with 118 lesions) or small (n = 118 patients with 136 lesions) burrs. The primary endpoint was final diameter stenosis at the end of the procedure, and secondary endpoints included inhospital angiographic and clinical complications, and target lesion revascularization at 6 months. Baseline demographic and angiographic characteristics were similar. There were no differences in procedural success, the extent of immediate lumen enlargement, inhospital ischemic complications, or late target vessel revascularization. However, compared with small burrs, patients randomized to large burrs were more likely to experience serious angiographic complications (5.1% vs. 12.7%, P < 0.05) immediately after atherectomy. This study suggests that a routine lesion modification strategy employing small burrs (burr/artery ratio < or = 0.7) achieves similar immediate lumen enlargement and late target vessel revascularization compared with a more aggressive debulking strategy (burr/artery ratio >0.7), but with fewer angiographic complications.
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OBJECTIVES: The purpose of this study was to examine the long-term clinical outcome after percutaneous intervention of saphenous vein grafts (SVG) and to identify the predictors of major adverse cardiac events (MACE). BACKGROUND: Percutaneous interventions of SVGs have been associated with more procedural complications and higher restenosis rates compared with interventions on native vessels. METHODS: From 1993 to 1997, 1,062 patients underwent percutaneous intervention on 1,142 SVG lesions. Procedural, in-hospital and long-term clinical outcomes were recorded in a database and analyzed. RESULTS: In-hospital MACE occurred in 137 patients (13%) including death (8%), Q-wave myocardial infarction (MI) (2%) and coronary artery bypass surgery (3%). Late MACE occurred in 565 patients (54%) including death (9%), Q-wave MI (9%) and target vessel revascularization (36%). Any MACE occurred in 457 (43%) patients. Follow-up was available in 1,056 (99%) patients at 3 +/- 1 year. Univariate predictors were restenotic lesion (odds ratio [OR]: 2.47, confidence interval [CI]: 1.13 to 3.85, p = 0.0003), unstable angina (OR: 1.99, CI: 1.27 to 2.91, p = 0.04) and congestive heart failure (CHF) (OR: 1.97, CI: 1.14 to 3.24, p = 0.02) for in-hospital MACE, and peripheral vascular disease (PVD) (OR: 2.18, CI: 1.34 to 3.44, p = 0.002), intra-aortic balloon pump placement (OR: 2.08, CI: 1.13 to 3.85, p = 0.02) and previous MI (OR: 1.97, CI: 1.14 to 3.25, p = 0.007) for late MACE. Independent multivariate predictors for late MACE were restenotic lesion (relative risk [RR] 1.33, p = 0.02), PVD (RR: 1.31, p = 0.01), CHF (RR: 1.42, p = 0.01) and multiple stents (RR: 1.47, p = 0.004). Angiographic follow-up was available for 422 patients. Angiographic restenosis occurred in 122 (29%) of stented SVGs and 181 (43%) of nonstented SVGs (p = 0.04). Stent implantation did not confer a survival benefit. CONCLUSIONS: Despite the use of new interventional devices, SVG interventions are associated with significant morbidity and mortality; SVG stenting is not associated with better three-year event-free survival. This may be due to progressive disease at nonstented sites.
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BACKGROUND: Diabetic patients are at increased risk for both macrovascular and microvascular disease compared with nondiabetic patients. METHODS: We conducted a prospective observational study to assess the control of multiple predetermined cardiovascular risk factors in 235 treated diabetic patients undergoing elective cardiac catheterization at our institution between December 20, 1997, and February 15, 2000. The following parameters were used to define optimal treatment in these patients: hemoglobin (Hgb) A1c <7%, low-density lipoprotein cholesterol (LDL-c) <100 mg/dL, high-density lipoprotein cholesterol (HDL-c) >/=45 mg/dL for men and >/=55 mg/dL for women, triglyceride (TG) level <200 mg/dL, blood pressure (BP) <130/85 mm Hg, body mass index (BMI) <25, daily aspirin therapy, and current nonsmoking status. The use of b-blockers and angiotensin-converting enzyme inhibitors was also evaluated. RESULTS: The average patient age was 64 +/- 11 years; 155 (65%) were male. One hundred ninety-one (81%) patients had documented coronary artery disease at cardiac catheterization. The mean Hgb A1c level for all diabetic patients was 8.2% +/- 1.6%. Overall, 49 (21%) had an Hgb A1c level <7%. The fasting cholesterol panel for all patients revealed a mean LDL-c level of 103 +/- 41 mg/dL, a mean HDL level of 39 +/- 11 mg/dL, and a mean TG level of 164 +/- 128 mg/dL. One hundred sixteen (52%) patients had an LDL-c <100 mg/dL. Only 32 of 147 (22%) male patients and 14 of 80 (18%) female patients achieved an HDL-c >/=45 mg/dL or >/=55 mg/dL, respectively. One hundred seventy-seven of 232 (76%) patients had a TG level <200 mg/dL. Only 23 of 233 (10%) diabetics were controlled to a BP of <130/85 mm Hg, and 25 (11%) achieved a BMI <25. Only one patient (0.4%) had optimal control of all modifiable risk factors. CONCLUSIONS: These data demonstrate the poor control of numerous cardiovascular risk factors in treated diabetics undergoing elective cardiac catheterization.
Patients with acute coronary syndromes who are considered ineligible for thrombolytic therapy are at high risk of recurrent ischemia and death. This trial randomized 201 patients to triage angiography in the first 24 hours of hospital admission versus conventional medical care. Of the 165 patients who underwent angiography that was either protocol-driven or on the basis of physician preference, those who underwent angiography within 6 hours of symptom onset had a reduction in early and late adverse events. The rates of in-hospital recurrent ischemia were 15.4%, 15.4%, 17.5%, 32.4%, and 38.5%, respectively (P = 0.01 for trend), and rates of cumulative recurrent myocardial infarction or death were 0%, 12.8%, 10.0%, 11.8%, and 7.7%, respectively (P = 0.48 for trend) for patients who underwent angiography at 0-6, 6-12, 12-24, 24-48, and over 48 hours, respectively from symptom onset. Future trials of invasive versus conservative therapy should focus on performing angiography within 6 hours of symptom onset.
BACKGROUND: The optimal timing of coronary angioplasty in unstable angina patients is controversial. Early reports suggested using 3-5 days of intravenous heparin and aspirin for plaque stabilization before angioplasty. There is no clearcut data in this regard from the published literature. The purpose of this study was to evaluate whether delaying the angioplasty in order to stabilize the plaque affected the outcome. METHODS: We reviewed the hospital course of patients who were admitted with unstable angina through the emergency room and ruled out for myocardial infarction, and who required angioplasty during the index hospitalization. To diminish the influence of coronary stenting and glycoprotein IIb/IIIa receptor blockade, we reviewed all patients admitted during 1994. RESULTS: Of the 305 patients, 166 patients received < or = 48 hours and 139 patients received > 48 hours of intravenous heparin infusion before angioplasty. Both groups were well-matched. The procedural success was similar in both the groups (98% vs 97%, P = 0.72). The complication rate was similar in both groups, including abrupt closure, emergency bypass surgery, myocardial infarction and death. Length of hospital stay was significantly prolonged in the group with > 48 hours of heparin infusion (4.4 +/- 3.0 vs 7.4 +/- 3.6 days; P < 0.001). CONCLUSION: In patients with unstable angina undergoing angioplasty, prolonged duration of heparin infusion influenced the procedural outcome or postprocedural complications, but prolonged the hospital stay. These data suggest that early angioplasty of unstable angina patients is safe and may be cost-effective, even in the absence of stenting and potent antiplatelet agents. However, prospective, randomized trials are needed to clarify the need for and duration of heparin infusion prior to angioplasty in unstable angina patients.
Acute myocardial infarct (MI) results in ischemia distal to lesions which puts heart muscle at risk for reperfusion injury (RI). Neutrophils, platelets and complement are putative mediators of RI. Recent advances in filtration technology provide integrated neutrophil and platelet removal together with complement-attenuating properties in a single blood-conditioning device. The present study characterizes the properties of a blood-conditioning filter and describes its clinical effect when used in conjunction with active hemoperfusion for acute MI. The filter reduces leukocytes by 99.9998 +/- 0.0002% (p<0.0001) and platelets by 99.9934 +/- 0.0069% (p<0.0001). Human plasma, derived from heparinized blood that was 'conditioned' by filtration, was studied using the Langendorff isolated rabbit heart preparation. The deposition of membrane attack complex and the resultant functional myocardial impairments [reflected in hemodynamic and biochemical measurements, including developed pressure, coronary blood flow, lymph-derived myocardial creatine kinase (CK)] are significantly attenuated by blood conditioning. Integration of the blood-conditioning filter into an active hemoperfusion system during primary percutaneous transluminal coronary angioplasty (PTCA) for acute MI (n=8) did not delay the procedure or cause any complications. Reperfusion of occluded coronary arteries with 300 cm3 of conditioned blood led to significant improvement in echocardiographic global wall motion scores (in standard deviations) following treatment (-1.64 +/- 0.18 to -1.45 +/- 0.15, p=0.02). Initial reperfusion of totally occluded coronary arteries with conditioned blood leads to acutely improved ventricular function. Collectively, these data provide a strong indication for continued investigation of conditioned blood reperfusion in angioplasty following acute MI for the long-term effect upon recovery of salvagable myocardium.
Radiocontrast-induced nephropathy develops in approximately 10% to 20% of patients following administration of iodine-based dye and is one of the most prognostically detrimental complications that invasive cardiologists and radiologists encounter. Preexisting renal dysfunction and diabetes mellitus are two of the most powerful predictors of the likelihood of developing acute renal insufficiency after contrast delivery. To date, only adequate preprocedural hydration and postprocedural hydration to offset dehydration from contrast-induced diuresis have been shown to be effective in preventing this condition. Fenoldopam mesylate, a systemic vasodilator currently FDA-approved for short-term, in-hospital management of severe hypertension, has been shown to increase renal plasma flow in patients with and without chronic renal insufficiency. As a selective agonist of the dopamine-1 receptor, fenoldopam may preserve outer medullary renal blood flow and thereby attenuate radiocontrast-induced nephropathy. Small studies with fenoldopam prior to iodine-based dye administration have demonstrated low rates of radiocontrast nephropathy, and a larger, randomized trial has found that renal blood flow 1 hour after angiography rose in the fenoldopam group compared to a decline in the placebo group. The CONTRAST study has been designed to determine whether fenoldopam is indeed effective in diminishing the occurrence of radiocontrast-induced nephropathy.