The Impact of Novel X-Ray Systems and X-Ray System Optimization on Patient Radiation Dose Administered During Cardiac Catheterization.

INTRODUCTION: The effect of x-ray system optimization on patient radiation dose has received limited study. METHODS: We analyzed patient radiation dose in 1786 cardiac catheterization procedures (diagnostic coronary angiography and/or percutaneous coronary intervention [PCI]) performed at a single tertiary-care center before and after x-ray system optimization. RESULTS: After optimization, cineangiography dose-area product (DAP) dose was lower in the overall group of patients who underwent diagnostic angiography and/or PCI (1347 µGy•m² [IQR, 645-2345 µGy•m²] vs 1658 µGy•m² [IQR, 640- 2757 µGy•m²]; P=.03), as well as in the diagnostic angiography group (1795 µGy•m² [IQR, 1140-2994 µGy•m²] vs 2356 µGy•m² [IQR, 311-3576 µGy•m²]; P<.01) and PCI group (2152 µGy•m² [IQR, 1338-3477 µGy•m²] vs 2562 µGy•m² [IQR, 1681-3859 µGy•m²]; P=.02). Cineangiography DAP per exposure was also lower in the overall group (143 µGy•m² [IQR, 91-212 µGy•m²] vs 164 µGy•m² [IQR, 106-233 µGy•m²] per exposure; P<.01) and in the diagnostic angiography group (158 µGy•m² [IQR, 102-225 µGy•m²] vs 184 µGy•m² [IQR, 125-271 µGy•m²] per exposure; P<.01). After optimization, cineangiography air kerma (AK) dose (319 mGy [IQR, 197-531 mGy] vs 421 mGy [IQR, 241-600 mGy]; P=.01) and cineangiography AK per exposure (20.7 mGy [IQR, 12.9-29.0 mGy] vs 23.6 mGy [IQR, 14.1-32.9 mGy] per exposure; P=.03) were also lower in the PCI group. There was no significant change in fluoroscopy AK dose after optimization (20.7 mGy [IQR, 12.7-30.1 mGy] vs 20.4 mGy [IQR, 12.8-31.3 mGy] per minute; P=.71) and fluoroscopy DAP dose (156 µGy•m² [IQR, 101-242 µGy•m²] vs 156 µGy•m² [IQR, 102-236 µGy•m²] per minute; P=.91). CONCLUSION: X-ray system optimization was associated with lower cineangiography DAP, but similar fluoroscopy radiation dose.

Randomized Comparison of a CrossBoss First Versus Standard Wire Escalation Strategy for Crossing Coronary Chronic Total Occlusions: The CrossBoss First Trial.

OBJECTIVES: The authors performed a multicenter, randomized-controlled, clinical trial comparing upfront use of the CrossBoss catheter versus antegrade wire escalation for antegrade crossing of coronary chronic total occlusions. BACKGROUND: There is equipoise about the optimal initial strategy for crossing coronary chronic total occlusions. METHODS: The primary endpoints were the time required to cross the chronic total occlusion or abort the procedure and the frequency of procedural major adverse cardiovascular events. The secondary endpoints were technical and procedural success, total procedure time, fluoroscopy time required to cross and total fluoroscopy time, total air kerma radiation dose, total contrast volume, and equipment use. RESULTS: Between 2015 and 2017, 246 patients were randomized to the CrossBoss catheter (n = 122) or wire escalation (n = 124) at 11 U.S. centers. The baseline clinical and angiographic characteristics of the study groups were similar. Technical and procedural success were 87.8% and 84.1%, respectively, and were similar in the 2 groups. Crossing time was similar: 56 min (interquartile range: 33 to 93 min) in the CrossBoss group and 66 min (interquartile range: 36 to 105 min) in the wire escalation group (p = 0.323), as was as the incidence of procedural major adverse cardiovascular events (3.28% vs. 4.03%; p = 1.000). There were no significant differences in the secondary study endpoints. CONCLUSIONS: As compared with wire escalation, upfront use of the CrossBoss catheter for antegrade crossing of coronary chronic total occlusions was associated with similar crossing time, similar success and complication rates, and similar equipment use and cost.

TIME Trial: Effect of Timing of Stem Cell Delivery Following ST-Elevation Myocardial Infarction on the Recovery of Global and Regional Left Ventricular Function: Final 2-Year Analysis.

RATIONALE: The TIME trial (Timing in Myocardial Infarction Evaluation) was the first cell therapy trial sufficiently powered to determine if timing of cell delivery after ST-segment-elevation myocardial infarction affects recovery of left ventricular (LV) function. OBJECTIVE: To report the 2-year clinical and cardiac magnetic resonance imaging results and their modification by microvascular obstruction. METHODS AND RESULTS: TIME was a randomized, double-blind, placebo-controlled trial comparing 150 million bone marrow mononuclear cells versus placebo in 120 patients with anterior ST-segment-elevation myocardial infarctions resulting in LV dysfunction. Primary end points included changes in global (LV ejection fraction) and regional (infarct and border zone) function. Secondary end points included changes in LV volumes, infarct size, and major adverse cardiac events. Here, we analyzed the continued trajectory of these measures out to 2 years and the influence of microvascular obstruction present at baseline on these long-term outcomes. At 2 years (n=85), LV ejection fraction was similar in the bone marrow mononuclear cells (48.7%) and placebo groups (51.6%) with no difference in regional LV function. Infarct size and LV mass decreased ≥30% in each group at 6 months and declined gradually to 2 years. LV volumes increased ≈10% at 6 months and remained stable to 2 years. Microvascular obstruction was present in 48 patients at baseline and was associated with significantly larger infarct size (56.5 versus 36.2 g), greater adverse LV remodeling, and marked reduction in LV ejection fraction recovery (0.2% versus 6.2%). CONCLUSIONS: In one of the longest serial cardiac magnetic resonance imaging analyses of patients with large anterior ST-segment-elevation myocardial infarctions, bone marrow mononuclear cells administration did not improve recovery of LV function over 2 years. Microvascular obstruction was associated with reduced recovery of LV function, greater adverse LV remodeling, and more device implantations. The use of cardiac magnetic resonance imaging leads to greater dropout of patients over time because of device implantation in patients with more severe LV dysfunction resulting in overestimation of clinical stability of the cohort. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00684021.

Effect of the use and timing of bone marrow mononuclear cell delivery on left ventricular function after acute myocardial infarction: the TIME randomized trial.

CONTEXT: While the delivery of cell therapy after ST-segment elevation myocardial infarction (STEMI) has been evaluated in previous clinical trials, the influence of the timing of cell delivery on the effect on left ventricular function has not been analyzed. OBJECTIVES: To determine the effect of intracoronary autologous bone marrow mononuclear cell (BMC) delivery after STEMI on recovery of global and regional left ventricular function and whether timing of BMC delivery (3 days vs 7 days after reperfusion) influences this effect. DESIGN, SETTING, AND PATIENTS: A randomized, 2 × 2 factorial, double-blind, placebo-controlled trial, Timing In Myocardial infarction Evaluation (TIME) enrolled 120 patients with left ventricular dysfunction (left ventricular ejection fraction [LVEF] ≤ 45%) after successful primary percutaneous coronary intervention (PCI) of anterior STEMI between July 17, 2008, and November 15, 2011, as part of the Cardiovascular Cell Therapy Research Network sponsored by the National Heart, Lung, and Blood Institute. INTERVENTIONS: Intracoronary infusion of 150 × 106 BMCs or placebo (randomized 2:1) within 12 hours of aspiration and cell processing administered at day 3 or day 7 (randomized 1:1) after treatment with PCI. MAIN OUTCOME MEASURES: The primary end points were change in global (LVEF) and regional (wall motion) left ventricular function in infarct and border zones at 6 months measured by cardiac magnetic resonance imaging and change in left ventricular function as affected by timing of treatment on day 3 vs day 7. The secondary end points included major adverse cardiovascular events as well as changes in left ventricular volumes and infarct size. RESULTS: The mean (SD) patient age was 56.9 (10.9) years and 87.5% of participants were male. At 6 months, there was no significant increase in LVEF for the BMC group (45.2% [95% CI, 42.8% to 47.6%] to 48.3% [95% CI, 45.3% to 51.3%) vs the placebo group (44.5% [95% CI, 41.0% to 48.0%] to 47.8% [95% CI, 43.4% to 52.2%]) (P = .96). There was no significant treatment effect on regional left ventricular function observed in either infarct or border zones. There were no significant differences in change in global left ventricular function for patients treated at day 3 (−0.9% [95% CI, −6.6% to 4.9%], P = .76) or day 7 (1.1% [95% CI, −4.7% to 6.9%], P = .70). The timing of treatment had no significant effect on regional left ventricular function recovery. Major adverse events were rare among all treatment groups. CONCLUSION: Among patients with STEMI treated with primary PCI, the administration of intracoronary BMCs at either 3 days or 7 days after the event had no significant effect on recovery of global or regional left ventricular function compared with placebo. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00684021.

Effect of intracoronary delivery of autologous bone marrow mononuclear cells 2 to 3 weeks following acute myocardial infarction on left ventricular function: the LateTIME randomized trial.

CONTEXT: Clinical trial results suggest that intracoronary delivery of autologous bone marrow mononuclear cells (BMCs) may improve left ventricular (LV) function when administered within the first week following myocardial infarction (MI). However, because a substantial number of patients may not present for early cell delivery, the efficacy of autologous BMC delivery 2 to 3 weeks post-MI warrants investigation. OBJECTIVE: To determine if intracoronary delivery of autologous BMCs improves global and regional LV function when delivered 2 to 3 weeks following first MI. DESIGN, SETTING, AND PATIENTS: A randomized, double-blind, placebo-controlled trial (LateTIME) of the National Heart, Lung, and Blood Institute-sponsored Cardiovascular Cell Therapy Research Network of 87 patients with significant LV dysfunction (LV ejection fraction [LVEF] ≤45%) following successful primary percutaneous coronary intervention (PCI) between July 8, 2008, and February 28, 2011. INTERVENTIONS: Intracoronary infusion of 150 × 10(6) autologous BMCs (total nucleated cells) or placebo (BMC:placebo, 2:1) was performed within 12 hours of bone marrow aspiration after local automated cell processing. MAIN OUTCOME MEASURES: Changes in global (LVEF) and regional (wall motion) LV function in the infarct and border zone between baseline and 6 months, measured by cardiac magnetic resonance imaging. Secondary end points included changes in LV volumes and infarct size. RESULTS: A total of 87 patients were randomized (mean [SD] age, 57 [11] years; 83% men). Harvesting, processing, and intracoronary delivery of BMCs in this setting was feasible. Change between baseline and 6 months in the BMC group vs placebo for mean LVEF (48.7% to 49.2% vs 45.3% to 48.8%; between-group mean difference, -3.00; 95% CI, -7.05 to 0.95), wall motion in the infarct zone (6.2 to 6.5 mm vs 4.9 to 5.9 mm; between-group mean difference, -0.70; 95% CI, -2.78 to 1.34), and wall motion in the border zone (16.0 to 16.6 mm vs 16.1 to 19.3 mm; between-group mean difference, -2.60; 95% CI, -6.03 to 0.77) were not statistically significant. No significant change in LV volumes and infarct volumes was observed; both groups decreased by a similar amount at 6 months vs baseline. CONCLUSION: Among patients with MI and LV dysfunction following reperfusion with PCI, intracoronary infusion of autologous BMCs vs intracoronary placebo infusion, 2 to 3 weeks after PCI, did not improve global or regional function at 6 months. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00684060.

Cell therapy and satellite centers: the Cardiovascular Cell Therapy Research Network experience.

Due to the changing population in patients with myocardial infarction, recruiting patients in clinical trials continues to challenge clinical investigators. The Cardiovascular Cell Therapy Research Network (CCTRN) chose to expand the reach and power of its recruitment effort by incorporating both referral and treatment satellite centers. Eight treatment satellites were successfully identified and they screened patients over a two year period. The result of this effort was an increase in recruitment, with these treatment satellites contributing 30% of the patients to two of the three Network studies. The hurdles that these satellite treatment centers faced and how they surmounted them provide instruction to clinical research groups eager to expand to satellite systems and to health care practitioners who are interested in taking part in multicenter clinical trials.

A clinical risk score for the prediction of very late stent thrombosis in drug eluting stent patients.

AIMS: Very late stent thrombosis (VLST; >1 year) is an infrequent but potentially serious complication, whose risk factors have not been fully elucidated. This investigation sought to develop a clinically useful risk stratification score for VLST following drug eluting stent (DES) placement. METHODS AND RESULTS: A Cox proportional hazards multivariate model of VLST was developed based on follow-up into a second year of patients enrolled in the ARRIVE registries, utilising readily available baseline clinical and angiographic characteristics. ST predictors between one and two years were identified among 7,459 consecutively enrolled patients who received a TAXUS® Express2™ (Boston Scientific, Natick, MA, USA) DES. Six significant predictors were found: presence of renal disease, prior myocardial infarction, multiple stenting, bifurcation lesions, prior CABG, and smoking at baseline. Each predictor was assigned a score, then summed for a maximum possible score of 10. Stratification into low and high risk groups revealed that VLST developed in 0.5% of 6,759 patients with scores<5, and 2.6% of 700 patients with scores≥5. CONCLUSIONS: We defined a VLST risk score for patients during the second year post DES-placement that provides a useful tool for risk stratification.

Integration of pre-hospital electrocardiograms and ST-elevation myocardial infarction receiving center (SRC) networks: impact on Door-to-Balloon times across 10 independent regions.

OBJECTIVES: The aim of this study was to evaluate the rate of timely reperfusion for ST-elevation myocardial infarction (STEMI) with primary percutaneous coronary intervention (PPCI) in regional STEMI Receiving Center (SRC) networks. BACKGROUND: The American College of Cardiology Door-to-Balloon (D2B) Alliance target is a >75% rate of D2B

A clinical risk score for prediction of stent thrombosis.

The aim was to develop a clinically useful patient risk score predictive for stent thrombosis (ST). Using readily available baseline clinical and angiographic characteristics, a Cox proportional hazards multivariate model was used to identify significant (p <0.10) predictors of ST through 1 year in 2,487 patients receiving a TAXUS Express (Boston Scientific Corp., Natick, Massachusetts) drug-eluting stent (DES) in the ARRIVE 1 registry. Hazard ratios of significant predictors were rounded to an integer value ranging from 2 to 5. These values were summed for a maximum possible score of 24. The model was validated using 1-year data from a similar DES data set (ARRIVE 2, n = 4,820 patients). The 8 significant predictors found were thienopyridine therapy discontinuation before 6 months, insulin-requiring diabetes, smoker at baseline, left main stent placement, multiple stent placement, lesion length >28 mm, moderate to severe lesion calcification, and reference vessel diameter <3 mm. Model discrimination was high, indicated by an area under the receiver-operator characteristic curve of 0.819. Stratification of patients into low-, medium-, and high-risk groups showed that ST developed in 0.8% of patients with a score <6, 3.6% of patients with a score of 7 to 13, and 12.6% of patients with a score >or=14. In conclusion, using 8 readily available clinical and angiographic characteristics, we defined an ST risk score for patients receiving a DES during the first year. Analysis of patients from ARRIVE 1 and 2 showed that most (73%) were in the lowest risk category, with 25% in the moderate risk category. Less than 2% were at highest risk of developing ST.

Electrocardiographic findings in cardiogenic shock, risk prediction, and the effects of emergency revascularization: results from the SHOCK trial.

OBJECTIVES: To evaluate electrocardiographic (ECG) parameters as predictors of 1-year mortality in patients developing cardiogenic shock after acute myocardial infarction (AMI), and to document associations between these ECG parameters and the survival benefit of emergency revascularization versus initial medical stabilization. BACKGROUND: Emergency revascularization reduces the risk of mortality in patients developing cardiogenic shock after AMI. The prognostic value of ECG parameters in such patients is unclear, and it is uncertain whether emergency revascularization reduces the mortality risk denoted by ECG parameters. METHODS: In a prospective substudy of 198 SHOCK (SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK) trial patients, ECGs recorded within 12 hours of shock were interpreted by personnel blinded to the patients' treatment assignment and outcome. RESULTS: The baseline heart rate was higher in non-survivors than in survivors (106 +/- 20 versus 95 +/- 24 beats/minute, P = .001). There was a significant association between the QRS duration and 1-year mortality in medically stabilized patients (115 +/- 28 ms in non-survivors versus 99 +/- 23 ms in survivors, P = .012), but not in emergently revascularized patients (110 +/- 31 versus 116 +/- 27 ms respectively, P = .343). The interaction between the QRS duration, mortality and treatment assignment was significant (P = .009). Among patients with inferior AMI, a greater sum of ST depression was associated with higher 1-year mortality in medically stabilized patients (P = .029), but not in emergently revascularized patients (P = .613, treatment interaction P = .025). On multivariate analysis, the independent mortality predictors were increasing age, elevated pulmonary capillary wedge pressure, heart rate, sum of ST depression in medically stabilized patients, and interaction (P = .016) between a prolonged QRS duration and treatment assignment. The adjusted hazard ratio for 1-year mortality per 20 ms increase in the QRS duration was 1.19 (95% CI 0.98-1.46) in medically stabilized patients and 0.81 (95% CI 0.63-1.03) in emergently revascularized patients. CONCLUSION: ECG parameters identified patients with cardiogenic shock who were at high risk. Emergency revascularization eliminated the incremental mortality risk associated with cardiogenic shock in patients with a prolonged QRS duration, or inferior AMI accompanied by precordial ST depression. Prospective assessments of the magnitude of the treatment effect based on ECG parameters are required.

Association of the timing of ST-segment resolution with TIMI myocardial perfusion grade in acute myocardial infarction.

BACKGROUND: More complete ST-segment resolution (ST res) in acute myocardial infarction (MI) has been associated with better epicardial and myocardial reperfusion as assessed with the Thrombolysis in Myocardial Infarction (TIMI) flow grade (TFG) and the TIMI myocardial perfusion grade (TMPG), respectively. However, no data exist comparing the speed of ST resolution on continuous electrocardiogram (ECG) monitoring with the TMPG on coronary angiography. We hypothesized that delayed ST res is associated with impaired TMPGs. METHODS: Continuous 12-lead ECG recordings and 60-minute angiographic data were analyzed in 120 patients with acute MI who received tenectaplase monotherapy or combination therapy with low-dose tenectaplase and eptifibatide in the Integrilin and Tenecteplase in Acute Myocardial Infarction (INTEGRITI) trial. RESULTS: More rapid ST res on continuous ECG monitoring was associated with improved TMPGs on coronary angiography performed 60 minutes after study drug administration. For TMPG 3, the median time to ST resolution was 53 minutes. For TMPG 2, 1, and 0, the corresponding times were 64 minutes, 80 minutes, and 106 minutes, respectively (P =.01 for trend). Likewise, more rapid ST res was also associated with faster epicardial flow. For TFG 3, the median time to ST resolution was 46 minutes, compared with 109 minutes for TIMI flow grades 0 to 2 (P =.001). The corresponding times for a corrected TIMI frame count < or =40 versus >40 were 52 minutes and 112 minutes, respectively (P <.001). CONCLUSIONS: Although the static ECG has been associated with epicardial and myocardial blood flow in the past, this study extends these observations to demonstrate that more rapid ST res on continuous ECG monitoring is associated with improved myocardial perfusion after thrombolytic administration.

Combination reperfusion therapy with eptifibatide and reduced-dose tenecteplase for ST-elevation myocardial infarction: results of the integrilin and tenecteplase in acute myocardial infarction (INTEGRITI) Phase II Angiographic Trial.

OBJECTIVES: The goal of this study was to evaluate combinations of eptifibatide with reduced-dose tenecteplase (TNK) in ST-elevation myocardial infarction (STEMI). BACKGROUND: Glycoprotein IIb/IIIa inhibitors enhance thrombolysis. The role of combination therapy in clinical practice remains to be established. METHODS: Patients (n = 438) with STEMI <6 h were enrolled. In dose-finding, 189 patients were randomized to different combinations of double-bolus eptifibatide and reduced-dose TNK. In dose-confirmation, 249 patients were randomized 1:1 to eptifibatide 180 microg/kg bolus, 2 microg/kg/min infusion, and 180 microg/kg bolus 10 min later (180/2/180) plus half-dose TNK (0.27 mg/kg) or standard-dose (0.53 mg/kg) TNK monotherapy. All patients received aspirin and unfractionated heparin (60 U/kg bolus; infusion 7 U/kg/h [combination], 12 U/kg/h [monotherapy]). The primary end point was Thrombolysis In Myocardial Infarction (TIMI) grade 3 epicardial flow at 60 min. RESULTS: In dose-finding, TIMI grade 3 flow rates were similar across groups (64% to 68%). Arterial patency was highest for eptifibatide 180/2/180 plus half-dose TNK (96%, p = 0.02 vs. eptifibatide 180/2/90 plus half-dose TNK). In dose-confirmation, this combination, compared with TNK monotherapy, tended to achieve more TIMI 3 flow (59% vs. 49%, p = 0.15), arterial patency (85% vs. 77%, p = 0.17), and ST-segment resolution (median 71% vs. 61%, p = 0.08) but was associated with more major hemorrhage (7.6% vs. 2.5%, p = 0.14) and transfusions (13.4% vs. 4.2%, p = 0.02). Intracranial hemorrhage occurred in 1.0%, 0.6%, and 1.7% of patients treated with any combination, eptifibatide 180/2/180 and half-dose TNK, and TNK monotherapy, respectively. CONCLUSIONS: Double-bolus eptifibatide (180/2/180) plus half-dose TNK tended to improve angiographic flow and ST-segment resolution compared with TNK monotherapy but was associated with more transfusions and non-cerebral bleeding. Further study is needed before this combination can be recommended for general use.

The relationship of intracoronary stent placement following thrombolytic therapy to tissue level perfusion.

BACKGROUND: Stenting has been shown to improve lumen diameters and thereby improve epicardial blood flow, but the impact of stent placement on tissue level perfusion has not been well characterized. METHODS: Data were drawn from the LIMIT trial of rhuMAb CD18 (anti WBC antibody) in acute myocardial infarction (AMI). Adjunctive/rescue stenting was performed at the discretion of the investigator. The TIMI Myocardial Perfusion Grade (TMPG) was assessed and digital subtraction angiography (DSA) was used to quantify brightness of the myocardial blush. RESULTS: TIMI 3 flow was 54.2% (64/118) before stent placement, and improved to 87.2% (102/117, p < 0.001) following stent placement. Likewise, Corrected TIMI Frame Counts (CTFCs) improved from medians of 37.6 to 21 (p < 0.001). By DSA, the rate of growth in brightness also tended to be greater after stenting (2.3 +/- 0.4 Gray/sec, n = 54 vs 3.1 +/- 0.3, n = 54, p = 0.07). The incidence of TMPG 0 decreased following stent placement (25.2% (29/118) vs 14.3% (16/118), p = 0.03) and the incidence of a stain in the myocardium (TMPG 1) increased (13.5% (16/118) vs 28.6% (34/118), p = 0.004). CONCLUSION: Adjunctive stenting following thrombolytic administration in AMI improves epicardial TIMI 3 flow and TIMI frame counts as well as dye inflow into the myocardium: TMPG 0 is reduced and myocardial blush measured quantitatively by DSA tends to be brighter. However, more TMPG 1 or dye staining was present on next injection, suggesting dye outflow may be impaired.