In ischemic LV dysfunction, adding PCI to medical therapy did not reduce a composite of death or aborted sudden death.

SOURCE CITATION: Perera D, Morgan HP, Ryan M, et al; REVIVED-BCIS2 Investigators. Arrhythmia and death following percutaneous revascularization in ischemic left ventricular dysfunction: prespecified analyses from the REVIVED-BCIS2 trial. Circulation. 2023;148:862-871. 37555345.

A novel genetic marker of decreased inflammation and improved survival after acute myocardial infarction.

The CHRNA5 gene encodes a neurotransmitter receptor subunit involved in multiple processes, including cholinergic autonomic nerve activity and inflammation. Common variants in CHRNA5 have been linked with atherosclerotic cardiovascular disease. Association of variation in CHRNA5 and specific haplotypes with cardiovascular outcomes has not been described. The aim of this study was to examine the association of CHRNA5 haplotypes with gene expression and mortality among patients with acute myocardial infarction (AMI) and explore potential mechanisms of this association. Patients (N = 2054) hospitalized with AMI were genotyped for two common variants in CHRNA5. Proportional hazard models were used to estimate independent association of CHRNA5 haplotype with 1-year mortality. Both individual variants were associated with mortality (p = 0.0096 and 0.0004, respectively) and were in tight LD (D' = 0.99). One haplotype, HAP3, was associated with decreased mortality one year after AMI (adjusted HR = 0.42, 95% CI 0.26, 0.68; p = 0.0004). This association was validated in an independent cohort (N = 637) of post-MI patients (adjusted HR = 0.23, 95% CI 0.07, 0.79; p = 0.019). Differences in CHRNA5 expression by haplotype were investigated in human heart samples (n = 28). Compared with non-carriers, HAP3 carriers had threefold lower cardiac CHRNA5 mRNA expression (p = 0.023). Circulating levels of the inflammatory marker hsCRP were significantly lower in HAP3 carriers versus non-carriers (3.43 ± 4.2 versus 3.91 ± 5.1; p = 0.0379). Activation of the inflammasome, an important inflammatory complex involved in cardiovascular disease that is necessary for release of the pro-inflammatory cytokine IL-1 ß, was assessed in bone marrow-derived macrophages (BMDM) from CHRNA5 knockout mice and wild-type controls. In BMDM from CHRNA5 knockout mice, IL-1ß secretion was reduced by 50% compared to wild-type controls (p = 0.004). Therefore, a common haplotype of CHRNA5 that results in reduced cardiac expression of CHRNA5 and attenuated macrophage inflammasome activation is associated with lower mortality after AMI. These results implicate CHRNA5 and the cholinergic anti-inflammatory pathway in survival following AMI.

Left Ventricular Unloading by Impella Device Versus Surgical Vent During Extracorporeal Life Support.

BACKGROUND: Patients supported with extracorporeal life support (ECLS) can experience severe complications from increased left ventricular (LV) afterload. The Impella (Abiomed, Danvers, MA) percutaneous ventricular assist device (PVAD) may offer an attractive option for unloading the LV in these patients. This study describes the efficacy and outcomes of PVAD use during ECLS compared with surgically placed LV vent. METHODS: In this retrospective study, we reviewed patients supported by ECLS with PVAD or surgical LV vent for cardiogenic shock between April 2010 and May 2016. Included were 23 patients with PVADs and 22 with surgical vents. Patients' baseline characteristics, hemodynamic data, and outcomes were collected immediately preceding combined support initiation, at 48 hours, intensive care unit discharge, and 30 days. RESULTS: After 48 hours, pulmonary artery diastolic pressure was significantly reduced in the PVAD (23.3 ± 8.4 vs 15.6 ± 4.2, p = 0.02) and surgical vent groups (20.1 ± 5.9 vs 15.6 ± 5.4, p = 0.01), and radiographic evidence of pulmonary edema was reduced or unchanged in 90% of PVAD patients and in 76% of surgical vent patients. The primary end points of survival to 30 days (43% vs 32%, p = 0.42) and intensive care unit discharge (35% vs 23%, p = 0.37) were not different between the two methods of support. The PVAD and surgical vent groups were also not significantly different in the rate of vascular complications or in the number decannulated from ECLS and transitioned to durable LV assist device. CONCLUSIONS: PVAD use in ECLS patients is an effective means of LV unloading and preventing worsened pulmonary edema, with outcomes and complications that are comparable to surgical LV vent.

Variation in Practice Regarding Pretreatment With Dual Antiplatelet Therapy for Patients With Non-ST Elevation Myocardial Infarction.

BACKGROUND: Despite guideline recommendations, a significant number of patients with non-ST elevation myocardial infarction (NSTEMI) do not receive dual antiplatelet therapy (DAPT) before angiography "pretreatment." While there may be valid clinical reasons to not pretreat, such as concern for bleeding or multivessel disease warranting coronary artery bypass graft surgery, the degree of variability and factors associated with DAPT pretreatment are unknown. METHODS AND RESULTS: From the multicenter TRIUMPH registry, 1632 NSTEMI patients were not taking DAPT on admission and were included in the study cohort. Among the study patients, only 22% patients received DAPT pretreatment. A multivariable logistic regression model showed that race other than white or black (odds ratio [OR] 0.41, 95% CI 0.21-0.83), hemoglobin level (OR 1.18, 95% CI 1.08-1.29), patients' bleeding risk (assessed with NCDR CathPCI Bleeding Risk Score) (OR 0.85, 95% CI 0.74-0.99), and severe left ventricular dysfunction (OR 0.3, 95% CI 0.13-0.65) were the main predictors of pretreatment with DAPT, whereas likelihood of needing coronary artery bypass graft surgery (GRACE prediction model) was not (OR 1.09, 95% CI 0.88-1.35). Median ORs were calculated to assess variability of receiving DAPT pretreatment across sites after adjustment for patient characteristics. Receiving DAPT pretreatment varied substantially across sites (range 0-100%, mean OR 3.94, P<0.0001). CONCLUSIONS: While deviating from guideline-recommended DAPT pretreatment in patients with NSTEMI was associated with patient factors (eg, bleeding risk), marked variation was present across sites after accounting for patient-level characteristics. This suggests that site-level interventions are needed to improve concordance with current guidelines.

Predicting Likelihood for Coronary Artery Bypass Grafting After Non-ST-Elevation Myocardial Infarction: Finding the Best Prediction Model.

BACKGROUND: Up to half of patients with non-ST-elevation myocardial infarction (NSTEMI) do not receive dual antiplatelet therapy before angiography "pretreatment" because of the risk of increased bleeding if coronary artery bypass grafting (CABG) operation is needed. Several models have been published that predict the likelihood of CABG after NSTEMI, but they have not been independently validated. The purpose of this study was to validate these models and improve the best one. METHODS: We studied patients with NSTEMI who were enrolled in the 24-center Translational Research Investigating Underlying Disparities in Acute Myocardial Infarction Patients' Health Status (TRIUMPH) registry between 2005 and 2008. Previous CABG prediction models were assessed using c-statistics and calibration assessments to determine the best model. Variables from TRIUMPH likely to be associated with CABG were tested to see whether they could improve the best model's performance. RESULTS: Among 2,473 patients with NSTEMI, 11.8% underwent in-hospital CABG. C-statistics for the Modified Thrombolysis in Myocardial Infarction, Treat Angina With Aggrastat and Determine the Cost of Therapy With an Invasive or Conservative Strategy-Thrombolysis in Myocardial Infarction 18, Poppe, and Global Risk of Acute Coronary Events (GRACE) models were 0.54, 0.61, 0.61, and 0.62, respectively. The GRACE model showed the best discrimination and calibration. From the TRIUMPH registry, preselected variables were added to the GRACE model but did not significantly improve model discrimination. A GRACE model risk score of less than 9 had high sensitivity (96%), thus making it useful for predicting patients with NSTEMI who were at low risk for requiring CABG, which included approximately 21% of patients with NSTEMI. CONCLUSIONS: This study could not improve on the GRACE model, which had the best predictive value for identifying a need for CABG after NSTEMI with a broader range of predicted risk levels and high sensitivity, especially in patients with scores lower than 9.

Impact of Bleeding on Quality of Life in Patients on DAPT: Insights From TRANSLATE-ACS.

BACKGROUND: Prolonged dual antiplatelet therapy (DAPT) is recommended after an acute myocardial infarction (AMI) to reduce ischemic events but is associated with increased rates of major and minor bleeding. OBJECTIVES: This study sought to determine the incidence of post-percutaneous coronary intervention (PCI) bleeding that occurs on contemporary DAPT and its impact on quality of life (QOL). METHODS: We studied 9,290 AMI patients treated with PCI and discharged alive between April 2010 and September 2012. Post-discharge bleeding was categorized according to the Bleeding Academic Research Consortium (BARC) definition. The primary outcome was the 6-month Euro QOL-5 Dimension (EQ-5D) index score (a measure of health utility); a secondary outcome was the EQ-5D visual analog scale (VAS) at 6 months. RESULTS: Of the 9,290 patients with AMI, bleeding events occurred as follows: any BARC bleeding: 24.2%; BARC 1: 9.1%; BARC 2: 13.8%; BARC 3: 1.1%; BARC 4: 0.03%; and BARC 5: 0%. Those who experienced any BARC bleeding had lower scores across all 5 EQ-5D domains (mobility, self-care, usual activities, pain, and anxiety), as well as lower EQ-5D VAS and EQ-5D index scores. After clinical risk adjustment, any BARC bleeding was independently associated with 6-month EQ-5D index score (p < 0.0001) and lower QOL (p < 0.001). Both the EQ-5D index and the VAS score declined in a stepwise fashion with increasing BARC severity. CONCLUSIONS: Among patients undergoing PCI for AMI, bleeding during follow-up was associated with worse 6-month utility and QOL. Although even minor bleeding was associated with impaired health status and QOL, the degree of impairment increased in a stepwise fashion with bleeding severity.

Repeat revascularisation outcomes after percutaneous coronary intervention in patients with rheumatoid arthritis.

OBJECTIVE: To investigate repeat revascularisation outcomes in patients with rheumatoid arthritis(RA) after percutaneous coronary intervention (PCI). METHODS: We performed a single-centre, retrospective matched cohort study of patients with RA matched to non-RA patients post PCI. Primary endpoints were time to target lesion revascularisation (TLR) and target vessel revascularisation (TVR) analysed by Cox proportional hazard shared frailty models. RESULTS: A total of 228 lesions (143 patients) were identified in the RA cohort and matched to 677 control lesions (541 patients). TLR occurred in 33% (n=75) of RA lesions versus 25% (n=166) of control lesions (adjusted HR 1.3; 95% CI 0.97 to 1.8). TVR occurred in 39% (n=89) of RA lesions versus 31% (n=213) of control lesions (adjusted HR 1.15; 95% CI 0.82 to 1.6). There was a significant hazard for TLR (adjusted HR 1.48; 95% CI 1.03 to 2.13) and TVR (adjusted HR 1.55; 95% CI 1.12 to 2.14) when excluding lesions with revascularisation events or follow-up less than 1 year. When stratified by treatment with methotrexate or tumour necrosis factor (TNF) α inhibitors or both at discharge, lesions from patients with RA treated with these agents had similar TVR and TLR as control lesions, whereas lesions from patients with RA not treated with these agents had significantly more TLR and TVR (TLR adjusted HR 1.48; 95% CI 1.08 to 2.03; TVR adjusted HR 1.38; 95% CI 1.04 to 1.84). CONCLUSIONS: RA predisposes to repeat revascularisation, specifically in patients followed after the 1-year landmark. In the absence of RA treatments including methotrexate and/or TNFα inhibitors, RA is associated with a 50% increased relative risk of repeat revascularisation following PCI. These findings emphasise the adverse effects of chronic inflammation on the durability of PCI and provide further support for aggressive anti-inflammatory treatment in patients with RA.

Association of Discharge Aspirin Dose With Outcomes After Acute Myocardial Infarction: Insights From the Treatment with ADP Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events after Acute Coronary Syndrome (TRANSLATE-ACS) Study.

BACKGROUND: Aspirin is the most widely used antiplatelet drug postmyocardial infarction, yet its optimal maintenance dose after percutaneous coronary intervention with stenting remains uncertain. METHODS AND RESULTS: We compared outcomes of 10 213 patients with myocardial infarction who underwent percutaneous coronary intervention and were discharged on dual-antiplatelet therapy at 228 US hospitals in the Treatment with ADP Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events after Acute Coronary Syndrome (TRANSLATE-ACS) study from 2010 to 2012. Major adverse cardiovascular events and bleeding within 6 months postdischarge were compared between high-dose (325 mg) and low-dose aspirin (81 mg) by using regression models with inverse probability-weighted propensity adjustment. Overall, 6387 patients (63%) received high-dose aspirin at discharge. Major adverse cardiovascular events risk was not significantly different between groups (high versus low: unadjusted 8.2% versus 9.2%; adjusted hazard ratio, 0.99; 95% confidence interval, 0.85-1.17). High-dose aspirin use was associated with greater risk of any Bleeding Academic Research Consortium-defined bleeding events (unadjusted 24.2% versus 22.7%; adjusted odds ratio, 1.19; 95% confidence interval, 1.06-1.33), driven mostly by minor Bleeding Academic Research Consortium type 1 or 2 bleeding events not requiring hospitalization (unadjusted 21.4% versus 19.5%; adjusted odds ratio, 1.19; 95% confidence interval, 1.05-1.34). Bleeding events requiring hospitalization were similar by aspirin dosing groups (unadjusted 2.8% versus 3.2%, adjusted odds ratio, 1.22; 95% confidence interval, 0.87-1.70). Similar associations were observed in landmark analyses accounting for aspirin dosing change over time, and across subgroup analyses by age, sex, baseline aspirin use, and type of ADP receptor inhibitor (clopidogrel versus prasugrel/ticagrelor). CONCLUSIONS: Among percutaneous coronary intervention-treated patients with myocardial infarction, high-maintenance-dose aspirin was associated with similar rates of major adverse cardiovascular events, but a greater risk of minor bleeding than those discharged on low-dose aspirin.

Risk model for estimating the 1-year risk of deferred lesion intervention following deferred revascularization after fractional flow reserve assessment.

AIMS: Although lesions deferred revascularization following fractional flow reserve (FFR) assessment have a low risk of adverse cardiac events, variability in risk for deferred lesion intervention (DLI) has not been previously evaluated. The aim of this study was to develop a prediction model to estimate 1-year risk of DLI for coronary lesions where revascularization was not performed following FFR assessment. METHODS AND RESULTS: A prediction model for DLI was developed from a cohort of 721 patients with 882 coronary lesions where revascularization was deferred based on FFR between 10/2002 and 7/2010. Deferred lesion intervention was defined as any revascularization of a lesion previously deferred following FFR. The final DLI model was developed using stepwise Cox regression and validated using bootstrapping techniques. An algorithm was constructed to predict the 1-year risk of DLI. During a mean (±SD) follow-up period of 4.0 ± 2.3 years, 18% of lesions deferred after FFR underwent DLI; the 1-year incidence of DLI was 5.3%, while the predicted risk of DLI varied from 1 to 40%. The final Cox model included the FFR value, age, current or former smoking, history of coronary artery disease (CAD) or prior percutaneous coronary intervention, multi-vessel CAD, and serum creatinine. The c statistic for the DLI prediction model was 0.66 (95% confidence interval, CI: 0.61-0.70). CONCLUSION: Patients deferred revascularization based on FFR have variation in their risk for DLI. A clinical prediction model consisting of five clinical variables and the FFR value can help predict the risk of DLI in the first year following FFR assessment.

The efficacy of ticagrelor is maintained in women with acute coronary syndromes participating in the prospective, randomized, PLATelet inhibition and patient Outcomes (PLATO) trial.

AIMS: The aim of this study was to assess the relationship between sex and clinical outcomes and treatment-related complications in patients with ST-elevation or non-ST-elevation acute coronary syndromes (ACS) randomized to treatment with ticagrelor or clopidogrel in the PLATelet inhibition and patient Outcomes (PLATO) trial. METHODS: The associations between sex subgroup and the primary composite outcomes, secondary outcomes, and major bleeding endpoints as well as interaction of sex subgroup with treatment effects were analysed using Cox proportional-hazards models. RESULTS: Sex was not significantly associated with the probability of the primary composite endpoint [adjusted hazard ratio (HR): 1.02 (0.91-1.16)], or other adverse cardiovascular endpoints. Ticagrelor was similarly more effective than clopidogrel in reducing rates of the primary endpoint in women 11.2 vs. 13.2% [adjusted HR: 0.88 (0.74-1.06)] and men 9.4 vs. 11.1% [adjusted HR: 0.86 (0.76-0.97)] (interaction P-value 0.78), all-cause death in women 5.8 vs. 6.8% [adjusted HR: 0.90 (0.69-1.16)] and men 4.0 vs. 5.7% [adjusted HR: 0.80 (0.67-0.96)] (interaction P-value 0.49), and definite stent thrombosis in women 1.2 vs. 1.4% [adjusted HR: 0.71 (0.36-1.38)] and men 1.4 vs. 2.1% [adjusted HR: 0.63 (0.45-0.89)] (interaction P-value 0.78). The treatments did not differ for PLATO-defined overall major bleeding complications in women [adjusted HR: 1.01 (0.83-1.23)] or men [adjusted HR: 1.10 (0.98-1.24)]. Sex had no significant association with these outcomes (interactions P = 0.43-0.88). CONCLUSION: Female sex is not an independent risk factor for adverse clinical outcomes in moderate-to-high risk ACS patients. Ticagrelor has a similar efficacy and safety profile in men and women.

CHRNA5 variant predicts smoking cessation in patients with acute myocardial infarction.

INTRODUCTION: While smoking is a major modifiable risk factor for secondary prevention of myocardial infarction (MI), active smoking is common among patients hospitalized with acute MI. Recent studies suggest that nicotinic receptor variants, and specifically the high-risk CHRNA5 rs16969968 A allele, are associated with cessation failure among noncardiac patients. This study investigates the association between CHRNA5 rs16969968 and smoking cessation in patients hospitalized with acute MI. METHODS: Using data from the TRIUMPH study, we ascertained smoking status at the time of index hospitalization for acute MI and 1 year after hospitalization. After adjusting for age and sex, we used logistic regression to model the association between smoking cessation and CHRNA5 rs16969968. RESULTS: At index admission, 752 Caucasian subjects were active smokers and 699 were former smokers. Among these ever-smokers, the A allele was associated with significantly decreased abstinence (45.0% abstinence for A allele carriers vs. 51.7% for GG homozygotes; odds ratio [OR] = 0.70, 95% confidence interval [CI] = 0.56-0.88, p = .0027). The A allele was also significantly associated with decreased abstinence at 1 year (69.1% abstinence for A allele carriers vs. 76.0% for GG homozygotes; OR = 0.70, 95% CI = 0.53-0.94, p = .0185). CONCLUSIONS: Among patients who have smoked and who are hospitalized with acute MI, the high-risk CHRNA5 allele was associated with lower likelihood of quitting before hospitalization and significantly less abstinence 1 year after hospitalization with MI. The CHRNA5 rs16969968 genotype may therefore identify patients who would benefit from aggressive, personalized smoking cessation intervention.

Conversations in cardiology: bridging antiplatelet therapy before surgery.

Bridging for antiplatelet therapy remains a subject of debate with data favoring GP blockers but at a risk of bleeding. This Conversation in Cardiology addresses a key and often asked question about use of alternatives to P2Y12 agents in patients requiring surgery within 6 months after drug eluting stent implantation.

Ticagrelor versus clopidogrel in elderly patients with acute coronary syndromes: a substudy from the prospective randomized PLATelet inhibition and patient Outcomes (PLATO) trial.

BACKGROUND: Elderly patients with acute coronary syndrome are at high risk of recurrent ischemic events and death, and for both antithrombotic therapy and catheter-based complications. This prespecified analysis investigates the effect and treatment-related complications of ticagrelor versus clopidogrel in elderly patients (≥75 years of age) with acute coronary syndrome compared with those <75 years of age. METHODS AND RESULTS: The association between age and the primary composite outcome, as well as major bleeding were evaluated in the PLATelet inhibition and patient Outcomes (PLATO) trial using Cox proportional hazards. Similar models were used to evaluate the interaction of age with treatment effects. Hazard ratios were adjusted for baseline characteristics. The clinical benefit of ticagrelor over clopidogrel was not significantly different between patients aged ≥75 years of age (n=2878) and those <75 years of age (n=15 744) with respect to the composite of cardiovascular death, myocardial infarction, or stroke (interaction P=0.56), myocardial infarction (P=0.33), cardiovascular death (P=0.47), definite stent thrombosis (P=0.81), or all-cause mortality (P=0.76). No increase in PLATO-defined overall major bleeding with ticagrelor versus clopidogrel was observed in patients aged ≥75 years (hazard ratio, 1.02; 95% confidence interval, 0.82-1.27) or patients aged <75 years (hazard ratio, 1.04; 95% confidence interval, 0.94-1.15). Dyspnea and ventricular pauses were more common during ticagrelor than clopidogrel treatment, with no evidence of an age-by-treatment interaction. CONCLUSIONS: The significant clinical benefit and overall safety of ticagrelor compared with clopidogrel in acute coronary syndrome patients in the PLATO cohort were not found to depend on age.

Hospital-acquired anemia and in-hospital mortality in patients with acute myocardial infarction.

BACKGROUND: Hospital-acquired anemia (HAA) is common during acute myocardial infarction (AMI) and associated with higher long-term mortality. The relationship between HAA and adverse in-hospital outcomes may be particularly relevant to hospitals' efforts to implement prevention programs, but the association between HAA and in-hospital mortality is unclear. METHODS: We studied 17,676 patients with AMI with normal admission hemoglobin level who did not undergo bypass surgery. Hospital-acquired anemia was defined as development of new anemia during hospitalization (based on nadir hemoglobin) using age-, gender-, and race-specific criteria. In-hospital mortality of patients with mild (hemoglobin level less than HAA threshold but >11 g/dL), moderate (hemoglobin level 9-11 g/dL), and severe HAA (hemoglobin level, < 9 g/dL) was compared with those without HAA using hierarchical logistic regression, adjusting for site and potential confounders. RESULTS: Hospital-acquired anemia developed in 10,166 patients (57.5%); 6,615 (37.4%) had mild; 2,740 (15.5%), moderate; and 811 (4.6%), severe HAA. In-hospital mortality was higher in patients with HAA and increased with HAA severity (no HAA 266 [3.5%], mild HAA 260 [3.9%], moderate HAA 222 [8.1%], and severe HAA 148 [18.3%], P < .001). The adjusted odds of in-hospital death were greater in patients with moderate (odds ratio 1.38, 95% CI 1.10-1.73) and severe HAA (3.39, 95% CI 2.59-4.44) versus no HAA. CONCLUSIONS: Moderate and severe HAAs are independently associated with higher in-hospital mortality during AMI. Studies are needed to determine whether HAA is preventable and if preventing HAA improves outcomes.

Baseline coronary angiographic findings in the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial (BARI 2D).

This report describes the baseline angiographic findings in the Bypass Angioplasty Revascularization Investigation (BARI) 2 Diabetes (BARI 2D) trial, a randomized study that was initiated after the original BARI trial (BARI 1). Unlike BARI 1, which compared coronary artery bypass graft surgery with coronary angioplasty (percutaneous coronary intervention) in patients with and without diabetes, BARI 2D is investigating early versus deferred revascularization as needed in selected patients with type 2 diabetes mellitus and significant stable coronary artery disease (CAD). This analysis included 1,773 patients without previous procedures. The intended mode of revascularization, percutaneous coronary intervention or coronary artery bypass graft surgery, was specified before randomization. Angiographic findings in those randomized to revascularization versus medical treatment were similar. Overall, the mean number of lesions >or=20% diameter stenosis was 4.6 +/- 2.3, and the myocardial jeopardy index was 46 +/- 24%. Patients selected for the coronary artery bypass graft stratum had a higher mean number of lesions >or=20% diameter stenosis (5.7 vs 4.0, p <0.0001) and a higher myocardial jeopardy index (61% vs 38%, p <0.0001) than those selected for the percutaneous coronary intervention stratum. Female gender, black race, and higher body mass index were associated with less extensive CAD, whereas a history of hypertension, age at entry, low-density lipoprotein cholesterol, and ankle-brachial index

Coronary circulation responses to binodenoson, a selective adenosine A2A receptor agonist.

The purpose of this study was to define binodenoson dosing regimens that produce coronary hyperemia comparable to those of adenosine and that are tolerated well by patients. An open-label, randomized, parallel-group, multicenter study enrolled adult patients who had completed diagnostic cardiac catheterization. Coronary blood flow velocity (CBFV) was measured with a Doppler flow wire, and CBFV reserve was determined before binodenoson administration. Patients (n = 133) received a 3-minute infusion of 0.3, 0.5, or 1 microg/kg/min or a bolus intravenous injection of 1.5 or 3 microg/kg. Coronary hyperemic responses were evident within seconds of administering binodenoson, and the magnitudes and durations of coronary hyperemic responses were dose related. The 1.5- and 3-microg/kg doses, by infusion or bolus, produced maximal coronary hyperemia equivalent to CBFV reserve. All doses transiently decrease blood pressure and increased heart rate and rate-pressure product. In conclusion, the 1.5-microg/kg binodenoson bolus dose produced nearly maximal coronary hyperemia by 4.5 +/- 3.7 minutes that was sustained for 7.4 +/- 6.86 minutes, was accompanied by modest changes in blood pressure, heart rate, and rate-pressure product, and produced no adverse changes on electrocardiogram, including no second- or third-degree atrioventricular block.