Early direct coronary angioplasty in survivors of out-of-hospital cardiac arrest.
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Adult↗
Biomedical subjects
David R Holmes
Publications and source records attributed to David R Holmes.
Enhanced external counterpulsation for ischemic heart disease: what's behind the curtain?
Enhanced external counterpulsation (EECP) has been shown to reduce angina and to improve objective measures of myocardial ischemia in patients with refractory angina. Prospective clinical studies and large treatment registries suggest that a course of EECP is associated with prolongation of the time to exercise-induced ST-segment depression and resolution of myocardial perfusion defects, as well as with enhanced exercise tolerance and quality of life. With a growing knowledge base supporting the safety and beneficial clinical effects associated with EECP, this therapy can be considered a valuable treatment option, particularly in patients who have exhausted traditional revascularization methods and yet remain symptomatic despite optimal medical care. However, although the concept of external counterpulsation was introduced almost four decades ago, and despite growing evidence supporting the clinical benefit and safety of this therapeutic modality, little is firmly established regarding the mechanisms responsible for the beneficial effects associated with this technique. Suggested mechanisms contributing to the clinical benefit of EECP include improvement in endothelial function, promotion of coronary collateralization, enhancement of ventricular function, peripheral effects similar to those observed with regular physical exercise, and nonspecific placebo effects. This review summarizes the current evidence for a contribution of these mechanisms to the clinical benefit associated with EECP.
Counterpulsation↗
Coronary endothelial dysfunction is associated with an increased risk of cerebrovascular events.
BACKGROUND: Stroke, mainly attributable to atherothrombotic disease, represents a leading cause of disability and death in the Western world. Endothelial dysfunction, which is considered a key factor in atherogenesis, is associated with an increased risk of cardiovascular events. However, the magnitude of the association between coronary endothelial dysfunction (CED) and cerebrovascular events is unknown. This study was performed to investigate the association between CED and cerebrovascular events. METHODS AND RESULTS: We studied 503 patients without obstructive coronary artery disease (CAD) who underwent coronary endothelial function testing by intracoronary acetylcholine infusion. Patients were divided according to the presence (n=305) or absence (n=198) of CED, and medical records were examined for the occurrence of ischemic or hemorrhagic stroke or transient ischemic attack either before (prevalent) or after (incident) coronary endothelial function testing. Among the study population, a total of 25 cerebrovascular events were documented, 22 in patients with CED (15 prevalent) and 3 in patients without (all prevalent) (P=0.008). Multivariable logistic regression, which included traditional cerebrovascular disease-related risk factors, identified the presence of CED as the single strongest factor associated with cerebrovascular events (OR, 4.32; 95% CI, 1.26 to 14.83). Kaplan-Meier analysis indicated that patients with CED had a significantly higher cumulative cerebrovascular event rate than those without (P=0.04). CONCLUSIONS: Presence of CED in patients without obstructive CAD is independently associated with an increased risk of cerebrovascular events. Thus, detection of this early stage of atherosclerosis may provide important information to identify patients who benefit from aggressive preventive strategies.
Acetylcholine↗
Enhanced external counterpulsation improves endothelial function in patients with symptomatic coronary artery disease.
OBJECTIVES: The goal of this study was to examine the effect of enhanced external counterpulsation (EECP) on endothelial function. BACKGROUND: Enhanced external counterpulsation improves symptoms and exercise tolerance in patients with symptomatic coronary artery disease (CAD). However, the exact mechanisms by which this technique exerts its clinical benefit are unclear. METHODS: Reactive hyperemia-peripheral arterial tonometry (RH-PAT), a noninvasive method to assess peripheral endothelial function by measuring reactive hyperemic response in the finger, was performed in 23 patients with refractory angina undergoing a 35-h course of EECP. In each patient RH-PAT measurements were performed before and after the first, at midcourse, and the last EECP session. In addition, RH-PAT response was assessed one month after completion of EECP therapy; RH-PAT index, a measure of reactive hyperemia, was calculated as the ratio of the digital pulse volume during reactive hyperemia divided by that at rest. RESULTS: Enhanced external counterpulsation led to symptomatic improvement (>/=1 Canadian Cardiovascular Society class) in 17 (74%) patients; EECP was associated with a significant immediate increase in average RH-PAT index after each treatment (p < 0.05). In addition, average RH-PAT index at one-month follow-up was significantly higher than that before EECP therapy (p < 0.05). When patients were divided by their clinical response, RH-PAT index at one-month follow-up increased only in those patients who experienced clinical benefit. CONCLUSIONS: Enhanced external counterpulsation enhances peripheral endothelial function with beneficial effects persisting at one-month follow-up in patients with a positive clinical response. This suggests that improvement in endothelial function may contribute to the clinical benefit of EECP in patients with symptomatic CAD.
Aged↗
Comparison of in-hospital and one-year outcomes in patients with left ventricular ejection fractions or=50% having percutaneous coronary revascularization.
Outcome studies of percutaneous coronary intervention (PCI) with conventional balloon angioplasty have established increased in-hospital and 1-year mortality in patients with left ventricular (LV) dysfunction compared with others. It is unclear whether recent PCI practice innovations, including stents and adjunctive pharmacotherapy, have made PCI safer and more effective in patients with LV dysfunction. We evaluated the influence of LV ejection fraction (EF) indexes on in-hospital and 1-year outcomes in 1,458 patients within the National Heart, Lung, and Blood Institute-sponsored Dynamic Registry. Patients (n = 300) with acute myocardial infarction were excluded. The remaining 1,158 patients were subdivided into 3 categories: group 1, EF or=50% (n = 866). We determined the frequency of individual and composite adverse events (death/myocardial infarction [MI]/coronary artery bypass grafting) at discharge and 1 year. In the Dynamic Registry patients, mean EF in the 3 groups was 32%, 45%, and 62% and in-hospital mortality was 3.0%, 1.6%, and 0.1%, respectively (p <0.001). The composite end point of death/MI was also significant, but other in-hospital adverse events did not differ between groups. The respective mortality rates were 11.0%, 4.5%, and 1.9% (p <0.001) after 1 year. The composite end points of death/MI and death/MI/coronary artery bypass grafting also occurred more frequently in group 1 patients. Thus, significant LV dysfunction was still associated with increased in-hospital and 1-year mortality in patients having contemporary PCI.
Aged↗
Treatment of saphenous vein bypass grafts with ultrasound thrombolysis: a randomized study (ATLAS).
BACKGROUND: Percutaneous coronary interventions (PCIs) in saphenous vein grafts (SVGs) with thrombus have a high frequency of distal embolization. Acolysis (therapeutic ultrasound) can break up thrombus in vitro in animal models and humans. Whether this is beneficial during percutaneous SVG interventions is unknown. METHODS AND RESULTS: We performed a trial of coronary ultrasound thrombolysis in which patients with an acute coronary syndrome undergoing PCI in SVGs were randomly assigned to receive acolysis or abciximab. The primary end point was a successful procedure, defined as final luminal diameter stenosis 30% or less with Thrombolysis In Myocardial Infarction grade 3 flow and freedom from major adverse cardiac events (composite of death, Q-wave, and non-Q-wave myocardial infarction [MI], emergency bypass procedure, disabling stroke, and target lesion revascularization). Of 181 enrolled, 92 received acolysis and 89 abciximab. Angiographic procedural success was achieved in 63% of acolysis patients and 82% of abciximab patients (P=0.008). Incidence of major adverse cardiac events at 30 days was 25% with acolysis and 12% with abciximab (P=0.036), attributable mainly to a greater frequency of non-Q-wave MI with acolysis (19.6% versus 7.9%, P=0.03). The incidence of Q-wave MI was also higher with acolysis (5.4% versus 2.2%, P=nonsignificant). The primary end point was achieved in 53.8% of acolysis patients and 73.1% of abciximab patients (P=0.014). CONCLUSIONS: Use of therapeutic ultrasound in vein graft lesions in patients with acute coronary syndrome had poor angiographic outcome and increased the incidence of acute ischemic complications.
Abciximab↗
Modeling and risk prediction in the current era of interventional cardiology: a report from the National Heart, Lung, and Blood Institute Dynamic Registry.
BACKGROUND: Validation of in-hospital mortality models after percutaneous coronary interventions using multicenter data remains limited. METHODS AND RESULTS: This study evaluated whether multivariable mortality models developed during the pre-stent era by New York State, American College of Cardiology (ACC)-National Cardiovascular Data Registry, Northern New England Cooperative Group, Cleveland Clinic Foundation, and the University of Michigan are relevant in patients undergoing percutaneous coronary intervention in the 1997 to 1999 National Heart, Lung, and Blood Institute Dynamic Registry. Of 4448 Dynamic Registry patients, 73% received > or =1 stent and 28% received a IIB/IIIA receptor inhibitor. In-hospital mortality occurred in 64 patients (1.4%). The New York state model predicted mortality in 69 patients (1.5%; 95% confidence bounds [CI], 0.89% to 1.70%); Northern New England predicted mortality in 60 patients (1.3%; 95% CI, 1.0% to 1.7%); and Cleveland Clinic predicted mortality in 76 patients (1.7%; 95% CI, 1.3% to 2.1%). Among high-risk subgroups, with these 3 models, observed and predicted in-hospital mortality rates in general were not different. The other 2 models yielded different results. The University of Michigan predicted fewer deaths (n=47; 1.1%; 95% CI, 0.7% to 1.3%), and the ACC Registry model predicted 603 deaths (13.5%; 95% CI, 12.6% to 14.4%). Using the ACC Registry model, predicted mortality was higher than observed in each subgroup. CONCLUSIONS: Application of 5 mortality risk models developed from different data sets to patients undergoing percutaneous coronary intervention in the Dynamic Registry predicted, in 3 models, mortality rates that were not significantly different than those observed. In both high and low risk subgroups, the University of Michigan slightly underpredicted mortality, and the ACC Registry predicted significantly higher mortality than that observed.
Angioplasty, Balloon, Coronary↗
Relation of Thrombolysis in Myocardial Infarction (TIMI) frame count to coronary flow parameters.
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Acetylcholine↗
Association of body mass index with outcome after percutaneous coronary intervention.
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Aged↗
State of the art in coronary intervention.
Issues related to restenosis have been known since the beginning of coronary intervention, and by now, restenosis has been characterized in terms of its time course, pathophysiology, clinical presentation, and some of its histology. In 1984, the initial National Heart, Lung, and Blood Institute's percutaneous transluminal coronary angioplasty registry reported a restenosis rate of 33.6% and identified male gender, new unstable angina, diabetes mellitus, and treatment of bypass graft stenoses as risk factors. Today restenosis still occurs in 33% of patients, is still associated with recurrent angina, and occurs usually within several months after a successful intervention. These current conclusions are very interesting because we now treat a clearly different patient population. Clinical trials have documented that restenosis results in adverse clinical consequences. In recent large clinical trials involving patients with class B or C lesions, pharmacologic intervention with such agents as tranilast was still associated with a 33% restenosis rate and had no significant effect on major adverse cardiac events. More recently, drug-coated stents have been introduced and are undergoing testing in large clinical trials to definitively establish the long-term efficacy and safety suggested in their early promising experience. Thus, whether the solution for restenosis is at hand or whether we will continue to see patients who undergo successful intervention and develop restenosis only months later in the some position as the initial lesion remains an open issue.
Angioplasty, Balloon↗
An invasive strategy is associated with decreased mortality in patients with unstable angina and non-ST-elevation myocardial infarction: GUSTO IIb trial.
There has been much debate concerning an invasive versus a conservative strategy for patients with acute coronary syndromes. The purpose of this study was to determine whether early in-hospital catheterization reduced mortality in patients with unstable angina and non-ST-elevation myocardial infarction. We performed a retrospective analysis of data collected in the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) IIb trial, which compared hirudin and heparin in patients with acute coronary syndromes. We identified 8011 patients with non-ST-segment elevation myocardial infarction and unstable angina who were enrolled in the trial. The primary endpoints were all-cause mortality at 30 days and 1 year. Data were analyzed with multivariate hazards models and propensity scores.After accounting for inception time bias, there were 7897 patients identified, of whom 4536 patients (57%) underwent invasive therapy and 3361 (43%) underwent conservative therapy. Adjusting for propensity scores, the adjusted 30-day mortality for the invasive group was 2.5% compared with 2.7% in the conservative group (P = 0.92); at 1 year, the invasive group had a 6.2% mortality, versus 8.6% in the conservative group (P = 0.005). In a multivariate analysis that adjusted for other clinical factors, an invasive strategy was associated with lower 1-year mortality (hazard ratio = 0.46; 95% confidence interval: 0.10 to 0.84). In patients presenting with acute coronary syndromes, an invasive strategy is associated with improved survival at 1 year even after adjusting for baseline differences.
Aged↗
How did we get here from there?
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Angioplasty, Balloon, Coronary↗
Role of incremental doses of intracoronary adenosine for fractional flow reserve assessment.
BACKGROUND: The achievement of maximal vasodilatation of the coronary microvessels is mandatory for the accurate determination of fractional flow reserve (FFR); the optimal dosing to achieve maximal vasodilation is unclear. This study was designed to address the hypothesis that incremental doses of intracoronary adenosine are necessary to ensure complete vasodilatation of the coronary microcirculation and accurate assessment of FFR. We also examined the relationship between FFR and coronary artery disease risk factors. METHODS: A total of 191 patients (215 vessels) with intermediate coronary lesions were examined. FFR was measured during cardiac catheterization with a pressure monitoring wire. Incremental doses of intracoronary adenosine (12-42 microg, left coronary artery; 12-48 microg, right coronary artery) were administered. RESULTS: Diabetes mellitus was present in 23% of patients, hypertension was present in 65% of patients, and prior myocardial infarction had occurred in 25% of patients. The average percent stenosis in vessels was 57% +/- 15%. Vessels were subdivided on the basis of initial FFR (group 1, <0.75; group II, 0.75-0.79; group III, 0.80-0.89; group IV, >or=0.9). Five of the 24 (21%) vessels with an initial FFR in the 0.75 to 0.80 range had a subsequent FFR of <0.75. There was no difference in FFR or doses of adenosine in the patients with coronary artery disease risk factors. The average adenosine dose given at the achievement of minimal FFR was 26 microg in the right coronary artery (RCA) and 34 microg in the left coronary artery (LCA). The average maximum dose of intracoronary adenosine administered was 29 microg for the RCA and 37 microg for the LCA. The maximum dose of adenosine ever required to achieve minimum FFR was 42 microg in both the LCA and RCA. CONCLUSION: This study suggests that a single high dose of 42 microg of intracoronary adenosine for both the RCA and LCA is sufficient to achieve maximum hyperemia and accurate FFR in most patients, independent of risk factors. Alternatively, when a lower initial dose is administered and FFR is in the 0.75 to 0.90 range, incremental doses of adenosine should be administered to ensure maximal hyperemia.
Adenosine↗
Safety of abciximab in patients with chronic renal insufficiency who are undergoing percutaneous coronary interventions.
BACKGROUND: Patients with chronic renal insufficiency (CRI) have worse outcomes during and after percutaneous coronary interventions (PCI). Abciximab reduces complications, but may cause excessive bleeding in patients with CRI. Therefore, we sought to determine the safety of abciximab in patients with CRI. METHODS: Patients (n = 4158) undergoing PCI at the Mayo Clinic since abciximab became available were analyzed according to their estimated creatinine clearance (> or =70, 50-69, or <50 mL/min) or need for dialysis. Major bleeding was defined as a cerebrovascular bleed or a decrease in the hematocrit level >15%. Minor bleeding was defined as a decrease in the hematocrit level of 10% to 15% with an identifiable site of bleeding. RESULTS: CRI was associated with increased bleeding in patients who received abciximab and patients who did not. However, there was only a trend toward an interaction between creatinine clearance and major bleeding with abciximab (odds ratio [OR], 1.18; P =.06) and no interaction with minor bleeding (OR, 1.01; P =.94) or any bleeding (OR, 1.10; P =.15). CONCLUSION: CRI is associated with an increased risk of bleeding complications after PCI. Although abciximab increases the risk of bleeding in all patients, the increase in relative risk is not significantly greater in patients with CRI. Thus, abciximab may be given safely in patients with CRI who are undergoing PCI.
Abciximab↗
Impact of age on procedural and 1-year outcome in percutaneous transluminal coronary angioplasty: a report from the NHLBI Dynamic Registry.
BACKGROUND: Older age has been associated with adverse outcomes in patients undergoing percutaneous coronary intervention (PCI). As PCI technology evolves and the US population becomes proportionally older, assessment of PCI in older age groups is essential. METHODS: From the National Heart, Lung, and Blood Institute Dynamic Registry, 4620 PCI-treated patients (1997 to 1999) were studied. Differences in clinical presentation, treatment strategy, and inhospital and 1-year outcomes were compared between patient age groups: younger (<65 years, n = 2537); older (65 to 79 years, n = 1776); and elderly (> or =80 years, n = 307). RESULTS: Older and elderly patients had more cardiac and comorbid noncardiac conditions and more extensive and complex arteriosclerosis, including stenoses in bypass grafts. Stent use was similar as age increased (72% vs 73% vs 73%), as was the use of IIb/IIIa receptor antagonists (29% vs 26% vs 28%). Rates of successful treatment of all attempted lesions were 93%, 92%, and 89%, respectively. Adjusted relative risks of inhospital death (1.0 vs 2.91 vs 3.64) and myocardial infarction (1.0 vs 1.35 vs 2.57) increased by age group, as did 1-year mortality rates (1.0 vs 1.87 vs 3.02). However, the relative magnitude of excess mortality rates at 1 year was comparable to that observed by age in the US general population. Age was not associated with 1-year risk of myocardial infarction or coronary artery bypass grafting. CONCLUSIONS: Although new technologies may allow for treatment of complex disease in older and elderly patients with comorbid disease, the increased procedural risk remains substantial in these patients. After PCI, the long-term relative risk of death is similar to that expected among persons of similar ages in the general population.
Age Factors↗
Abnormal coronary microvascular endothelial function in humans with asymptomatic left ventricular dysfunction.
BACKGROUND: Coronary endothelial dysfunction may potentially lead to myocardial ischemia and to the progression of heart failure. Though endothelial dysfunction is associated with advanced heart failure in humans, relatively little is known regarding their temporal relationship. Thus, the current study was designed to test the hypothesis that coronary endothelial dysfunction is present in patients with asymptomatic left ventricular dysfunction. METHODS AND RESULTS: Three hundred patients without symptoms of heart failure, with normal or mildly diseased coronary arteries at angiography underwent coronary vascular reactivity evaluation using intracoronary adenosine, acetylcholine (ACH) and nitroglycerin. Patients were divided into 2 groups based on the left ventricular ejection fraction (EF): patients with asymptomatic left ventricular dysfunction (ALVD), EF <45% (n = 11); and patients with EF > or =45% (n = 289, controls). Except for a lower high-density lipoprotein level in patients with ALVD, there were no significant differences between the groups in regards to conventional cardiovascular risk factors. There was no difference in the change (mean +/- SE) in epicardial diameter in response to ACH (-21.7% +/- 7.2% vs -13.8% +/- 1.5%, P =.3). The change in coronary blood flow in response to ACH was significantly attenuated in the patients with ALVD when compared to the controls (-18.5% +/- 14.9% vs 74.0% +/- 7.2%, P <.013). By multivariate analysis, EF was an independent predictor of coronary microvascular dilation with ACH (P <.001). CONCLUSION: The current study demonstrates that coronary microvascular endothelial dysfunction is present in ALVD. Thus, coronary endothelial dysfunction may be an early event in the pathophysiology of heart failure.
Adult↗
Endothelin type A receptor antagonism restores myocardial perfusion response to adenosine in experimental hypercholesterolemia.
Experimental hypercholesterolemia is characterized by increased endothelin-1 (ET-1) activity and is associated with an attenuated myocardial perfusion response and an inappropriate increase in coronary microvascular permeability during episodes of increased myocardial demand. This study was designed to determine the effect of chronic selective ET type A (ET(A)) receptor antagonism on coronary vascular response to simulated cardiac stress in experimental hypercholesterolemia. Twenty-one pigs were randomized to three groups: normal diet (N), high-cholesterol diet (HC), and HC diet plus ABT-627, a selective ET(A) receptor antagonist, (HC+ABT-627). After 12 weeks, cardiac electron beam computed tomography (EBCT) was performed before and during intravenous infusion of adenosine, and myocardial perfusion (ml/min per g) and coronary microvascular permeability index (arbitrary units) were calculated. Basal myocardial perfusion was similar in all groups (N: 0.91+/-0.10; HC: 0.95+/-0.08; HC+ABT-627: 1.03+/-0.09; P=0.64). Adenosine infusion led to a significant increase in myocardial perfusion in the N (1.32+/-0.15; P<0.001) but not in the HC (0.95+/-0.07) group. However, in the HC+ABT-627 group, adenosine also significantly increased myocardial perfusion (1.33+/-0.12; P=0.001). Basal permeability index did not differ between the groups (N: 1.56+/-0.13; HC: 1.34+/-0.19; HC+ABT-627: 1.62+/-0.10; P=0.38). Adenosine infusion significantly increased permeability index in HC pigs (2.29+/-0.22; P<0.001) but not in N (1.71+/-0.21) and HC+ABT-627 (1.82+/-0.08) pigs. We conclude that chronic selective ET(A) receptor antagonism preserves myocardial perfusion response and coronary microvascular integrity during episodes of increased myocardial demand in experimental hypercholesterolemia, indicating an important role for the endogenous endothelin system in this disorder.
Adenosine↗
Current management of non-ST-segment-elevation acute coronary syndrome: reconciling the results of randomized controlled trials.
AIMS: Patients presenting with non-ST-segment-elevation acute coronary syndrome represent a heterogeneous group with regard to the severity of coronary atherosclerosis and prognosis. The conventional approach to their treatment has involved admission to the hospital for pharmacologic stabilization, subsequent mobilization, and management by either a conservative or an invasive strategy. The choice of one approach over another is guided largely by local practice patterns and the availability of invasive facilities. METHODS AND RESULTS: However, recent randomized trials comparing the strategies have demonstrated a superiority of the invasive strategy, particularly in patients at higher risk. Furthermore, randomized trials have provided information on refining risk stratification. On the basis of these data, we outline criteria for assessing risk and recommend that stratification be conducted at presentation using clinical features, the electrocardiogram, and biomarkers. CONCLUSION: Higher-risk patients should be admitted for pharmacologic stabilization and assessed by coronary angiography within 48h with the aim of early revascularization, provided the risk of periprocedural complications is not prohibitive. Glycoprotein IIb/IIIa receptor inhibitors are indicated, particularly in patients requiring percutaneous coronary intervention. The conservative strategy remains appropriate for patients admitted to hospitals without invasive facilities. Patients not at highrisk may be observed in a facility with cardiac monitoring such as a chest pain unit and undergo subsequent stress testing. The adoption of such an early risk stratification and revascularization-based approach is likely to result in a reduction in recurrent myocardial infarction and ischaemia, duration of hospitalization, repeat hospitalization, and mortality.
Anticoagulants↗