Intracoronary versus intravenous administration of abciximab in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention with thrombus aspiration: the comparison of intracoronary versus intravenous abciximab administration during emergency reperfusion of ST-segment elevation myocardial infarction (CICERO) trial.

BACKGROUND: administration of the glycoprotein IIb/IIIa inhibitor abciximab is an effective adjunctive treatment strategy during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. Although small-scale studies have suggested beneficial effects of intracoronary over intravenous administration of abciximab, this has not been investigated in a medium-scale randomized clinical trial. METHODS AND RESULTS: a total of 534 ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention with thrombus aspiration within 12 hours of symptom onset were randomized to either an intracoronary or an intravenous bolus of abciximab (0.25 mg/kg). Patients were pretreated with aspirin, heparin, and clopidogrel. The primary end point was the incidence of restored myocardial reperfusion, defined as complete ST-segment resolution. Secondary end points included myocardial reperfusion as assessed by myocardial blush grade, enzymatic infarct size, and major adverse cardiac events at 30 days. The incidence of complete ST-segment resolution was similar in the intracoronary and intravenous groups (64% versus 62%; P=0.562). However, the incidence of myocardial blush grade 2/3 was higher in the intracoronary group than in the intravenous group (76% versus 67%; P=0.022). Furthermore, enzymatic infarct size was smaller in the intracoronary than in the intravenous group (P=0.008). The incidence of major adverse cardiac events was similar in both groups (5.5% versus 6.1%; P=0.786). CONCLUSIONS: in ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention with thrombus aspiration, intracoronary administration of abciximab compared with intravenous administration does not improve myocardial reperfusion as assessed by ST-segment resolution. However, intracoronary administration is associated with improved myocardial reperfusion as assessed by myocardial blush grade and a smaller enzymatic infarct size.

Thrombus aspiration during primary percutaneous coronary intervention.

BACKGROUND: Primary percutaneous coronary intervention (PCI) is effective in opening the infarct-related artery in patients with myocardial infarction with ST-segment elevation. However, the embolization of atherothrombotic debris induces microvascular obstruction and diminishes myocardial reperfusion. METHODS: We performed a randomized trial assessing whether manual aspiration was superior to conventional treatment during primary PCI. A total of 1071 patients were randomly assigned to the thrombus-aspiration group or the conventional-PCI group before undergoing coronary angiography. Aspiration was considered to be successful if there was histopathological evidence of atherothrombotic material. We assessed angiographic and electrocardiographic signs of myocardial reperfusion, as well as clinical outcome. The primary end point was a myocardial blush grade of 0 or 1 (defined as absent or minimal myocardial reperfusion, respectively). RESULTS: A myocardial blush grade of 0 or 1 occurred in 17.1% of the patients in the thrombus-aspiration group and in 26.3% of those in the conventional-PCI group (P<0.001). Complete resolution of ST-segment elevation occurred in 56.6% and 44.2% of patients, respectively (P<0.001). The benefit did not show heterogeneity among the baseline levels of the prespecified covariates. At 30 days, the rate of death in patients with a myocardial blush grade of 0 or 1, 2, and 3 was 5.2%, 2.9%, and 1.0%, respectively (P=0.003), and the rate of adverse events was 14.1%, 8.8%, and 4.2%, respectively (P<0.001). Histopathological examination confirmed successful aspiration in 72.9% of patients. CONCLUSIONS: Thrombus aspiration is applicable in a large majority of patients with myocardial infarction with ST-segment elevation, and it results in better reperfusion and clinical outcomes than conventional PCI, irrespective of clinical and angiographic characteristics at baseline. (Current Controlled Trials number, ISRCTN16716833.)

Cardiac death and reinfarction after 1 year in the Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study (TAPAS): a 1-year follow-up study.

BACKGROUND: Percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction can be complicated by spontaneous or angioplasty-induced embolisation of atherothrombotic material. Distal blockage induces microvascular obstruction and can result in less than optimum reperfusion of viable myocardium. The Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study (TAPAS) found that thrombus aspiration resulted in improved myocardial reperfusion compared with conventional PCI, but whether this benefit improves clinical outcome is unknown. We aimed to investigate whether the early efficacy of thrombus aspiration seen in TAPAS translated into clinical benefit after 1 year. METHODS: Patients with ST-elevation myocardial infarction enrolled at the University Medical Centre Groningen were randomly assigned in a 1:1 ratio to either thrombus aspiration or conventional treatment, before undergoing initial coronary angiography. Exclusion criteria were rescue PCI after thrombolysis and known existence of a concomitant disease with life expectancy less than 6 months. Of the 1071 patients enrolled between January, 2005, and December, 2006, vital status at or beyond 1 year after randomisation was available for 1060 (99%). The primary endpoint was cardiac death or non-fatal reinfarction after 1 year, and analysis was by intention to treat. The TAPAS trial is registered with Current Controlled Trials number ISRCTN16716833. FINDINGS: Cardiac death at 1 year was 3.6% (19 of 535 patients) in the thrombus aspiration group and 6.7% (36 of 536) in the conventional PCI group (hazard ratio [HR] 1.93; 95% CI 1.11-3.37; p=0.020). 1-year cardiac death or non-fatal reinfarction occurred in 5.6% (30 of 535) of patients in the thrombus aspiration group and 9.9% (53 of 536) of patients in the conventional PCI group (HR 1.81; 95% CI 1.16-2.84; p=0.009). INTERPRETATION: Compared with conventional PCI, thrombus aspiration before stenting of the infarcted artery seems to improve the 1-year clinical outcome after PCI for ST-elevation myocardial infarction.

The feasibility and safety of routine thrombus aspiration in patients with non-ST-elevation myocardial infarction.

OBJECTIVES: To investigate the feasibility and safety of manual thrombus aspiration in patients undergoing percutaneous coronary intervention (PCI) for non-ST-elevation myocardial infarction (NSTEMI). BACKGROUND: Myocardial necrosis in patients with acute coronary syndromes may be a sign of microvascular obstruction, owing to spontaneous or PCI-induced embolization of atherothrombotic material. Manual thrombus aspiration results in improved myocardial reperfusion in patients undergoing PCI for ST-elevation myocardial infarction. Currently, no published data on thrombus aspiration in patients with NSTEMI are available. METHODS: As part of a prospective cohort study, 70 patients undergoing PCI for NSTEMI were treated with thrombus aspiration (Export Aspiration Catheter, Medtronic, Minneapolis, MN). Histopathological analysis was performed on aspirated material. RESULTS: Thrombus aspiration was effective in 58 patients (83%) and resulted in a marked reduction of TIMI-thrombus score 4/5 (40% pre- versus 7% postthrombus aspiration) and increase of the rate of TIMI-flow 3 (36% pre- versus 66% postthrombus aspiration). The incidence of myocardial blush grade 2 and 3 were 39 and 45%, respectively. Distal embolization was visible in three patients (4%) on the final angiogram. CONCLUSION: This study demonstrates that thrombus aspiration in most NSTEMI patients is feasible and safe and is associated with a high rate of retrieval of thrombotic material.

Obesity is associated with impaired long-term success of pulmonary vein isolation: a plea for risk factor management before ablation.

Aims: Obesity is an increasing health problem and is an important risk factor for the development of atrial fibrillation (AF). We investigated the association of body mass index (BMI) on the safety and long-term efficacy of pulmonary vein isolation (PVI) for drug-refractory AF. Methods: 414 consecutive patients who underwent transcatheter PVI for AF between 2003 and 2013 were included. Successful PVI was defined as absence of atrial arrhythmia on Holter monitoring or ECG, without and with antiarrhythmic drugs during follow-up. Obesity was defined as BMI≥30 kg/m². Results: Mean age was 56±10 years, 316 (76%) were male, 311 (75%) had paroxysmal AF and 111 (27%) were obese. After a mean follow-up of 46±32 months (1590 patient-years), freedom from atrial arrhythmia and antiarrhythmic drugs was significantly lower in patients with obesity compared with non-obese patients (30% vs 46%, respectively, P=0.005, log-rank 0.016). With antiarrhythmic drugs, freedom from atrial arrhythmia was 56% vs 68% (P=0.036). No differences in minor and major adverse events were observed between patients with obesity and non-obese patients (major 6% vs 3%, P=0.105, and minor 5% vs 5%, P=0.512). Sensitivity analyses demonstrated that BMI (as continuous variable) was associated with PVI outcome (HR 1.08, 95% CI 1.02 to 1.14, P=0.012). Conclusion: Obesity is associated with reduced efficacy of PVI for drug-refractory AF. No relation between obesity and adverse events was found.

The effect of electrical neurostimulation on collateral perfusion during acute coronary occlusion.

BACKGROUND: Electrical neurostimulation can be used to treat patients with refractory angina, it reduces angina and ischemia. Previous data have suggested that electrical neurostimulation may alleviate myocardial ischaemia through increased collateral perfusion. We investigated the effect of electrical neurostimulation on functional collateral perfusion, assessed by distal coronary pressure measurement during acute coronary occlusion. We sought to study the effect of electrical neurostimulation on collateral perfusion. METHODS: Sixty patients with stable angina and significant coronary artery disease planned for elective percutaneous coronary intervention were split in two groups. In all patients two balloon inflations of 60 seconds were performed, the first for balloon dilatation of the lesion (first episode), the second for stent delivery (second episode). The Pw/Pa ratio (wedge pressure/aortic pressure) was measured during both ischaemic episodes. Group 1 received 5 minutes of active neurostimulation before plus 1 minute during the first episode, group 2 received 5 minutes of active neurostimulation before plus 1 minute during the second episode. RESULTS: In group 1 the Pw/Pa ratio decreased by 10 +/- 22% from 0.20 +/- 0.09 to 0.19 +/- 0.09 (p = 0.004) when electrical neurostimulation was deactivated. In group 2 the Pw/Pa ratio increased by 9 +/- 15% from 0.22 +/- 0.09 to 0.24 +/- 0.10 (p = 0.001) when electrical neurostimulation was activated. CONCLUSION: Electrical neurostimulation induces a significant improvement in the Pw/Pa ratio during acute coronary occlusion.

In vivo coronary lesion differentiation with computed tomography angiography and intravascular ultrasound as compared to optical coherence tomography.

BACKGROUND: In vitro studies have shown the feasibility of coronary lesion grading with computed tomography angiography (CTA), intravascular ultrasound (IVUS) and optical coherence tomography (OCT) as compared to histology, whereas OCT had the highest discriminatory capacity. OBJECTIVE: We investigated the ability of CTA and IVUS to differentiate between early and advanced coronary lesions in vivo, OCT serving as standard of reference. METHODS: Multimodality imaging was prospectively performed in 30 NSTEMI patients. Plaque characteristics were assessed in 1083 cross-sections of 30 culprit lesions, co-registered among modalities. Absence of plaque, fibrous and fibrocalcific plaque on OCT were defined as early plaque, whereas lipid rich-plaque on OCT was defined as advanced plaque. Odds ratios adjusted for clustering were calculated to assess associations between plaque types on CTA and IVUS with early or advanced plaque. RESULTS: Normal findings on CTA as well as on IVUS were associated with early plaque. Non-calcified, calcified plaques and the napkin ring sign on CTA were associated with advanced plaque. On IVUS, fatty and calcified plaques were associated with advanced plaque. CONCLUSIONS: In vivo coronary plaque characteristics on CTA and IVUS are associated with plaque characteristics on OCT. Of note, normal findings on CTA and IVUS relate to early lesions on OCT. Nevertheless, multiple plaque features on CTA and IVUS are related to advanced plaques on OCT, which may make it difficult to use qualitative plaque assessment in clinical practice.

Operator dependence of outcome after primary percutaneous coronary intervention.

AIMS: Primary percutaneous coronary intervention (PCI) is a widely practised therapeutic procedure to treat ST-elevation myocardial infarction (STEMI). However, a significant proportion of patients undergoing primary PCI suffers from adverse events, such as incomplete myocardial reperfusion. It is currently unknown to which degree these adverse events are operator related. METHODS AND RESULTS: We investigated inter-operator variation using objective safety and efficacy endpoints during primary PCI for STEMI. All PCIs were performed by six experienced interventional cardiologists as part of a randomised single centre trial. The primary endpoint of this study was optimal myocardial reperfusion (myocardial blush grade 3 [MBG]). All 1,071 patients enrolled in the Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study (TAPAS) were included in this analysis. In the six operator groups, the rate of the primary endpoint MBG 3 ranged between 29.2% and 55.5%. The variable for operators remained significantly associated with MBG 3 after adjustment for baseline and procedural differences. There were no statistical differences observed with regard to safety endpoints. CONCLUSIONS: This study illustrates the observation that even in a controlled setting significant inter-operator variation may exist in the efficacy of primary PCI. This study supports the routine collection of high-quality datasets to evaluate and improve individual operator competence and skills.

Value and limitations of electromechanical endocardial mapping in the assessment of global and regional left ventricular function and transmural extent of infarction: a comparison with cardiovascular magnetic resonance.

AIMS: To determine the relation between electromechanical endocardial mapping (EEM) and cardiac magnetic resonance (CMR) derived functional and viability parameters in patients with a large myocardial infarction. METHODS AND RESULTS: Forty-two patients with a large ST-elevation myocardial infarction underwent both EEM and CMR four months after primary percutaneous coronary intervention. EEM was performed to assess linear local shortening (LLS), unipolar voltage (UV) and bipolar voltage (BV). CMR cine imaging was performed to determine left ventricular global volumes, ejection fraction and regional function. Late gadolinium enhancement was used to assess size and transmural extent of infarction. Average LLS, UV and BV differed significantly between normal and dysfunctional segments (9.8 vs. 7.3, 11.8 vs. 9.7 and 3.3 vs. 2.8 for LLS, UV and BV respectively; p<0.001 for LLS and UV, p=0.006 for BV). In addition, average LLS, UV and BV, differed significantly between non-, subendocardial and transmural enhanced segments (10.8 vs. 8.8 vs. 5.0, 12.3 vs. 10.5 vs. 9.5 and 3.5 vs. 3.0 vs. 2.3 for LLS, UV and BV, respectively, p<0.001 for all variables). Although regional EEM data showed reasonable correlation with CMR, specific cut-off values for EEM parameters could not be established. CONCLUSIONS: EEM may be helpful in determining both the regional function and the transmural extent of infarction in patients with a large myocardial infarction. However, correlation with CMR parameters was moderate and exact cut-off values for EEM parameters could not be established. Further development of this potentially very useful modality is needed before it can be advocated for exact border-zone endocardial injection.

Is the myocardial blush grade scored by the operator during primary percutaneous coronary intervention of prognostic value in patients with ST-elevation myocardial infarction in routine clinical practice?

BACKGROUND: Multiple trials have documented that myocardial blush grade (MBG) after primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) has prognostic value for long-term clinical outcome. However, to the best of our knowledge, no study has determined the clinical use of MBG in routine clinical practice. We determined the prognostic value of MBG scored by the operator during primary PCI in consecutive patients with STEMI. METHODS AND RESULTS: The prognostic value of MBG scored by the operator in relation to 1-year all cause mortality was evaluated in all patients with STEMI who underwent primary PCI between January 2004 and July 2008 in our hospital. The incidence of MBG 0, 1, 2, and 3 was 12%, 14%, 36%, and 38%, respectively, in 2118 consecutive patients with STEMI. Follow-up of all 2118 patients showed a 1-year all cause mortality rate of 8% (168 of 2118): 24%, 10%, 6%, and 4%, respectively, among patients with MBG 0, 1, 2, and 3 (P<0.001). In the 1763 patients with Thrombolysis in Myocardial Infarction (TIMI) flow grade 3 after PCI, these mortality rates were 17%, 10%, 6%, and 4%, respectively (P<0.001). MBG scored by the operator was a strong independent predictor of 1-year all cause mortality corrected for other well-known predictive variables, including TIMI flow grade. CONCLUSIONS: MBG scored by the operator during primary PCI has prognostic value for 1-year all cause mortality in patients with STEMI in routine clinical practice. Therefore, the MBG should be documented, in addition to the TIMI flow grade, during primary PCI in patients with STEMI in standard PCI reports in routine clinical practice.

Effect of high-dose intracoronary adenosine administration during primary percutaneous coronary intervention in acute myocardial infarction: a randomized controlled trial.

BACKGROUND: Coronary microvascular dysfunction is frequently seen in patients with ST-elevation myocardial infarction after primary percutaneous coronary intervention. Previous studies have suggested that the administration of intravenous adenosine resulted in an improvement of myocardial perfusion and a reduction in infarct size. Intracoronary adenosine (bolus of 30 to 60 microg) is a guideline-recommended therapy to improve myocardial reperfusion. The effect of intracoronary adenosine during primary percutaneous coronary intervention has not been investigated in a large randomized trial. METHODS AND RESULTS: Patients presenting with acute ST-elevation myocardial infarction were randomized to 2 bolus injections of intracoronary adenosine (2 x 120 microg in 20 mL NaCl) or placebo (2 x 20 mL NaCl). The first bolus injection was given after thrombus aspiration and the second after stenting of the infarct-related artery. The primary end point was the incidence of residual ST-segment deviation <0.2 mV, 30 to 60 minutes after percutaneous coronary intervention. Secondary end points were ST-segment elevation resolution, myocardial blush grade, Thrombolysis in Myocardial Infarction flow on the angiogram after percutaneous coronary intervention, enzymatic infarct size, and clinical outcome at 30 days. A total of 448 patients were randomized to intracoronary adenosine (N=226) or placebo (N=222). The incidence of residual ST-segment deviation <0.2 mV did not differ between patients randomized to adenosine or placebo (46.2% versus 52.2%, P=NS). In addition, there were no significant differences in secondary outcome measures. CONCLUSIONS: In this randomized placebo controlled trial enrolling 448 patients with ST-elevation myocardial infarction, administration of intracoronary adenosine after thrombus aspiration and after stenting of the infarct-related artery did not result in improved myocardial perfusion.

Differences between early, intermediate, and late angioplasty after coronary artery bypass grafting.

The aim of the present study was to identify patients with recurrent ischemia after coronary artery bypass surgery (CABG) treated by percutaneous coronary intervention (PCI). Graft failure after CABG may be managed conservatively or treated by surgery or PCI. We thought to investigate clinical, angiographic, and procedural characteristics in relation to clinical outcome. This was a retrospective single-center study. Patients who underwent revascularization by PCI with a previous CABG were analyzed. Patients were divided in 3 groups, depending on interval between CABG and index PCI: group 1, interval <72 hours; group 2, interval between 72 hours and 1 year; group 3, interval >1 year. Two hundred twenty-one patients were studied. Clinical characteristics and survival curves were comparable in groups 2 and 3. Postoperative creatine kinase MB and troponin values were significantly higher in group 1 (P = 0.000). From group 1, significantly more patients (10.5%) required emergency CABG after the index PCI than compared with group 2 (2.1%) and group 3 (0%), (P = 0.003). There were more off-pump CABGs in group 1 than in the other 2 groups. Group 1 received less PCIs in native ungrafted vessels compared with the other 2 groups. Mortality in group 1 (18.4%) was higher than in the other 2 groups (7.4 and 4.5%, respectively; P < 0.05). Mortality in group 1 was higher in the acute phase of follow-up. PCI performed less than 72 hours after CABG is feasible but accompanied by a higher mortality and redo CABG. This outcome is probably related to the high-risk patient category.

Incidence and angiographic predictors of collateral function in patients with stable coronary artery disease scheduled for percutaneous coronary intervention.

OBJECTIVES: To investigate the incidence and angiographic predictors of functional collateral perfusion in patients with stable coronary artery disease, scheduled for elective PCI. BACKGROUND: Functional collateral perfusion is defined as a Pw/Pa ratio>or=0.24. Since this can only be measured intracoronary, it is important to investigate baseline clinical and angiographic predictors for functional collateral perfusion. METHODS: Collateral perfusion was measured during balloon inflation, with the use of a pressure-monitoring guide wire. Baseline clinical and angiographic characteristics were analyzed and collateral grading was done according to Rentrop's classification for coronary angiograms. RESULTS: Functional collateral perfusion was found in 40 of the 89 patients (45%). Angiographic signs of collaterals (Rentrop>or=1) were present in 15 of the 89 patients. Of the 40 patients with the functional collateral perfusion 11 patients (28%) had Rentrop>or=1; of the 49 patients without functional collaterals there were 4 patients with Rentrop>or=1 (8%) (P=0.02). There were no significant differences in baseline clinical characteristics or in other angiographic characteristics. CONCLUSIONS: In patients with stable coronary artery disease scheduled for elective PCI, 45% have functional collaterals. Rentrop's angiographic classification can be used to predict the presence or absence of functional collaterals, however with a rather modest positive and negative predictive value.