Abstract Background Accelerated idioventricular rhythm (AIVR) is known as reperfusion arrhythmia in the setting of acute myocardial infarction (AMI). In healthy individuals, it is usually considered to be benign. Alternating bundle branch block (ABBB) often progresses to complete atrioventricular block requiring permanent pacemaker implantation. We report a case of delayed appearance of AIVR following myocardial infarction (MI) in combination with ABBB as precursor of sudden cardiac arrest due to ventricular fibrillation (VF). Case summary A 62-year-old male with pre-existing left bundle branch block (LBBB) was admitted with an acute non-ST segment elevation MI. He underwent successful percutaneous coronary intervention (PCI) of a subtotal proximal left anterior descending artery (LAD) stenosis. Before and after PCI the electrocardiogram (ECG) demonstrated sinus rhythm with LBBB. The patient was discharged 5 days after PCI, left ventricular function at this time was moderately reduced (ejection fraction of 40%). After another 5 days, the patient was admitted for elective cardiac rehabilitation. At this time, the ECG demonstrated an AIVR with right bundle branch block morphology. Due to ABBB, the patient was scheduled for permanent pacemaker implantation. Before pacemaker implantation could take place, the patient developed a sudden cardiac arrest due to VF and was successfully resuscitated. A follow-up coronary angiography revealed no novel lesions. A cardiac resynchronization therapy defibrillator was implanted for secondary prevention of sudden cardiac death. Discussion Delayed occurrence of AIVR in combination with ABBB following AMI could be a predictor of sudden cardiac death. These patients are probably at high risk for malignant ventricular arrhythmias.

BackgroundSlow pathway modification (SPM) is the therapy of choice for AV-nodal reentry tachycardia (AVNRT). When AVNRT is not inducible, empirical ablation can be considered, however, the outcome in patients with two AV nodal echo beats (AVNEBs) is unknown.MethodsOut of a population of 3003 patients who underwent slow pathway modification at our institution between 1993 and 2013, we retrospectively included 32 patients with a history of symptomatic tachycardia, lack of paroxysmal supraventricular tachycardia (pSVT) inducibility but occurrence of two AVNEBs.ResultspSVT documentation by electrocardiography (ECG) was present in 20 patients. The procedural endpoint was inducibility of less than two AVNEBs. This was reached in 31 (97%) patients. Long-term success was assessed by a telephone questionnaire (follow-up time 63 ± 9 months). A total 94% of the patients benefited from the procedure (59% freedom from symptoms; 34% improvement in symptoms). Among those patients in whom ECG documentation was not present, 100% benefited (58% freedom from symptoms, 42% improvement).ConclusionThis is the first collective analysis of a group of patients presenting with symptoms of pSVT and inducibility of only two AVNEBs. Procedural success and clinical long-term follow-up were in the range of the reported success rates of slow pathway modification of inducible AVNRT, independent of whether ECG documentation was present. Thus, SPM is a safe and effective therapy in patients with two AVNEBs.

Background Permanent AV-block is a recognized and feared complication of slow pathway modulation for AVNRT. We aimed to assess incidence of transient and permanent AV-block as well as consequences of transient AV-block in a large contemporary AVNRT ablation cohort. Methods We searched our single center prospective ablation database for occurrence of transient and permanent AV-block during slow pathway modulation between January 2004 and October 2015. We analyzed patients' and procedural characteristics as well as outcome of patients in whom transient or permanent AV-block occurred. Results Of 9170 patients who underwent a catheter ablation at our institution between January 2004 and October 2015, 2101 patients (64% women, mean age 50±18years) underwent slow pathway modulation. In three patients, permanent AV-block occurred during RF application. Additional two patients had transient AV-block that recovered (after a few minutes and 25min), but recurred within two days of the procedure. All five patients underwent dual chamber pacemaker implantation (0.2%). Transient AV-block related to RF delivery occurred in 44 patients (2%). Transient mechanical AV-block occurred in additional 17 patients (0.8%). In 12 patients, ablation was continued despite transient AV-block. One of these patients developed permanent AV-block. Conclusion Permanent AV-block following slow pathway modulation is a rare event, occurring in 0.2% of patients in a large contemporary single center cohort. Transient AV-block is more frequent (2%).

Background The first‐line therapy for atrioventricular nodal reentry tachycardia (AVNRT) is catheter‐based slow pathway modulation. If AVNRT is not inducible during an electrophysiological study, an empirical slow pathway modulation (ESPM) may be considered in patients with dual atrioventricular nodal physiology and/or a typical electrocardiogram (ECG). Methods We screened 149 symptomatic patients who underwent ESPM in our department between 1993 and 2013. All patients fulfilled the following criteria: (1) either dual atrioventricular nodal (AVN) physiology with up to 2 AVN echo beats or characteristic ECG documentation or both, (2) noninducibility of AVNRT by programmed stimulation, and (3) completion of a telephone questionnaire for long‐term follow‐up. Out of this population we retrospectively investigated 13 patients who were primarily noninducible but in whom an AVNRT occurred during or after radiofrequency (RF) delivery. Results When AVNRT occurred, the procedure lost its empirical character, and RF delivery was continued until the procedural endpoint of noninducibility of AVNRT. This endpoint was reached in all but one patient (92%). After a follow‐up of 73 ± 15 months, this patient was the only one who reported no benefit from the procedure. Conclusions Out of 149 initially noninducible patients, a considerable number (9%) exhibited AVNRT during or after RF delivery. These patients crossed over from empirical to controlled slow pathway modulation resulting in a good clinical outcome. Our observations should encourage electrophysiologists to repeat programmed stimulation even after initial empirical RF delivery to retest for inducibility.

Aims Transseptal punctures (TSP) are routinely performed in cardiac interventions requiring access to the left heart. While pericardial effusion/tamponade are well-recognized complications, few data exist on accidental puncture of the aorta and its management and outcome. We therefore analysed our single centre database for this complication. Methods and results We assessed frequency and outcome of inadvertent aortic puncture during TSP in consecutive patients undergoing ablation procedures between January 2005 and December 2014. During the 10-year period, two inadvertent aortic punctures occurred among 2936 consecutive patients undergoing 4305 TSP (0.07% of patients, 0.05% of TSP) and in one Mustard patient during attempted baffle puncture. The first two patients required left ventricular access for catheter ablation of ventricular tachycardia. In both cases, an 11.5F steerable sheath (inner diameter 8.5F) was accidentally placed in the ascending aorta just above the aortic valve. In the presence of surgical standby, the sheaths were pulled back with a wire left in the aorta. Under careful haemodynamic and echocardiographic observation, this wire was also pulled back 30 min later. None of the patients required a closing device or open heart surgery. None of the patients suffered complications from the accidental aortic puncture and sheath placement. Conclusion Inadvertent aortic puncture and sheath placement are rare complications in patients undergoing TSP for interventional procedures. Leaving a guidewire in place during the observation period may allow introduction of sheaths or other tools in order to control haemodynamic deterioration.

BACKGROUND:There is a lack of procedural and follow-up data on pulmonary vein isolation (PVI) with the second-generation pulmonary vein ablation catheter® (PVAC Gold) in patients with atrial fibrillation (AF). This study provides data on PVI procedures and 1-year follow-up results with PVAC Gold in patients with AF treated in clinical practice.METHODS AND RESULTS:Three hundred and eighty four patients with documented symptomatic paroxysmal (n=198) or persistent (n=186) AF were included in a non-randomized prospectively designed database. Patients were enrolled consecutively at 2 high-volume centers. Procedural as well as 1year follow-up data were systematically analyzed. Average procedure times±standard deviations were 94±23min and 97±23min, respectively, in patients with paroxysmal and persistent AF. Average fluoroscopy times were 14.7±5.4min and 15.2±5.6min and total application times 18.1±5.0min and 18.8±5.2min, respectively, in the 2 patient cohorts. At 12months, 70.7% (70/99) and 61.9% (70/113) of patients with paroxysmal and persistent AF, respectively, were free from AF. Four early complications occurred. In the group with persistent AF, 1 posterior cerebral infarction occurred 2days after the procedure during initiation of anticoagulation. There was no phrenic nerve palsy or esophageal injury associated with the procedures. No thromboembolic events were recorded during follow-up.CONCLUSIONS:In patients with paroxysmal or persistent AF, second generation multi-electrode-phased radiofrequency ablation delivers favorable mid-term PVI success rates with few procedure-related or follow-up complications.

Objective We had the objective to determine the impact of clinical parameters and anticoagulation status on cerebral microembolic signals (MES) during pulmonary vein isolation (PVI) for atrial fibrillation (AF). Background Thromboembolism and stroke are the most feared complications of PVI. MES can help to evaluate embolic burden. It is unknown whether clinical parameters have an impact on embolic risk during PVI. Methods In this retrospective analysis we investigated the impact of clinical parameters, including the CHADS2- and CHA2DS2-VASc-score, pulmonary vein variants and echocardiographic parameters on MES rates in patients that underwent PVI using three different ablation approaches (radiofrequency ablation (iRF), pulmonary vein ablation catheter (PVAC) with deactivated electrode pair 1 or 5 (PVAC-red) or PVAC without deactivation (PVAC-all). Results 118 AF patients (61±12 years) were included between 2011 and 2013 (Median: 489 MES during PVI). Patients were more likely to have more MES (within 4th quartile) with the PVAC-all approach (60.7% vs. 25.0% (iRF) vs. 14.3% (PVAC-red) respectively (p<0.001). Patients with oral anticoagulation (OAC) pre-ablation were more likely to have lower MES-counts (1st-3rd quartile); (65.6% vs. 35.7%; p = 0.005). Additionally, patients with lower MES counts (1st-3rd quartile) had significantly higher INR values than those in the 4th quartile (1.78 vs. 1.09; p = 0.029). 2 patients developed a potentially thromboembolic event during the procedure. Conclusion Clinical predictors of cerebral emboli and stroke do not correlate with cerebral embolic burden during PVI. Pre-ablation OAC and increased INR values correlate with decreased MES-rates. Therefore, it might be beneficial to perform PVI with pre-ablation anticoagulation even in low risk patients.

BACKGROUND Left atrial tachycardias (LAT) occur in about 5% of patients after irrigated-tip circumferential antral (CA) pulmonary vein isolation (PVI). They may cause debilitating symptoms in the patient and may be very difficult to treat.OBJECTIVE To assess the incidence of LAT after PVI with the multielectrode phased-radiofrequency pulmonary vein ablation catheter (PVAC) compared to circumferential antral PVI with an irrigated-tip catheter.METHODS We analyzed data from our ablation database. A total of 150 patients who underwent their first PVI with the PVAC system and 300 patients who underwent their first PVI with irrigated-tip circumferential antral (CA) radiofrequency ablation were matched by age and sex, as well as by type of atrial fibrillation.RESULTS Of 150 PVAC patients, only 1 patient (0.7%) developed LAT during mean follow-up of 21 +/- 14 months. The mechanism was macroreentry and the patient underwent successful ablation at our institution. Eleven of 300 irrigated-tip CA PVI patients (3.7%) developed LAT during mean follow-up of 22 +/- 14 months and subsequently underwent ablation (P = .05).CONCLUSION LAT occurs more frequently after irrigated-tip CA PVI compared to single-shot-device ablation with PVAC. Apart from being less technically demanding, lower incidence of LAT may influence choice of ablation technology.

In several case reports, proarrhythmic effects of antipsychotic drugs have been reported. The aim of the present study was to investigate if application of risperidone or quetiapine has the potential to provoke polymorphic ventricular tachycardia in a sensitive model of proarrhythmia. In 24 isolated rabbit hearts, risperidone (5 and 10 μM, n = 12) or quetiapine (5 and 10 μM, n = 12) was infused after obtaining baseline data. Eight endocardial and epicardial monophasic action potentials and a simultaneously recorded 12-lead ECG showed a significant QT prolongation after application of risperidone as compared with baseline (5 μM: +29 ms, 10 μM: +35 ms, p < 0.01) accompanied by an increase of action potential duration. Administration of risperidone also significantly increased spatial dispersion of repolarization (5 μM: +16 ms, 4 μM: +19 ms; p < 0.05) as well as temporal dispersion of repolarization. Lowering of potassium concentration in bradycardic AV-blocked hearts provoked early afterdepolarizations (EADs) in 8 of 12 hearts and polymorphic ventricular tachycardia resembling torsade de pointes in 6 of 12 hearts (10 μM, 49 episodes). The results were compared with hearts treated with quetiapine (5 and 10 μM). Quetiapine led to an increase in QT interval (5 μM: +10 ms; 10 μM: +28 ms; p < 0.05) and a similar increase of APD90. However, treatment with quetiapine did not result in significant alterations of spatial and temporal dispersion of repolarization. No ventricular arrhythmias were observed in this group. In the present study, quetiapine demonstrated a safe electrophysiologic profile despite significant QT prolongation. In contrast, risperidone led to a more marked prolongation of myocardial repolarization combined with a more marked increase of dispersion of repolarization.

BACKGROUND:We investigated whether multichannel ECG-recordings are useful to risk-stratify patients with congenital long-QT syndrome (LQTS) for risk of sudden cardiac death under optimized medical treatment. METHODS:In 34 LQTS-patients (11 male; age 31±13 years, QTc 478±51ms; LQT1 n = 8, LQT2 n = 15) we performed a standard 12-channel ECG and a 120-channel body surface potential mapping. The occurrence of clinical events (CE; syncope, torsade de pointes (TdP), sudden cardiac arrest (SCA)) was documented and correlated with different ECG-parameters in all lead positions. RESULTS:Seven patients developed TdP, four survived SCA and 12 experienced syncope. 12/34 had at least one CE. CE was associated with a longer QTc-interval (519±43ms vs. 458±42ms; p = 0.001), a lower T-wave integral (TWI) on the left upper chest (-1.2±74.4mV*ms vs. 63.0±29.7mV*ms; p = 0.001), a lower range of T-wave amplitude (TWA) in the region of chest lead V8 (0.10±0.08mV vs. 0.18±0.07mV; p = 0.008) and a longer T-peak-T-end time (TpTe) in lead V1 (98±23ms vs. 78±26ms; p = 0.04). Receiver-operating-characteristic (ROC) analyses revealed a sensitivity of 96% and a specificity of 75% (area under curve (AUC) 0.89±0.06, p = 0.001) at a cut-off value of 26.8mV*ms for prediction of CE by TWI, a sensitivity of 86% and a specificity of 83% at a cut-off value of 0.11mV (AUC 0.83±0.09, p = 0.002) for prediction of CE by TWA and a sensitivity of 83% and a specificity of 73% at a cut-off value of 87ms (AUC 0.80±0.07, p = 0.005) for prediction of CE by TpTe. CONCLUSIONS:Occurrence of CE in LQTS-patients seems to be associated with a prolonged, low-amplitude T-wave.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, with a projected number of 1 million affected subjects in Germany. Changes in age structure of the Western population allow for the assumption that the number of concerned people is going to be doubled, maybe tripled, by the year 2050. Large epidemiological investigations showed that AF leads to a significant increase in mortality and morbidity. Approximately one-third of all strokes are caused by AF and, due to thromboembolic cause, these strokes are often more severe than those caused by other etiologies. Silent brain infarction is defined as the presence of cerebral infarction in the absence of corresponding clinical symptomatology. Progress in imaging technology simplifies diagnostic procedures of these lesions and leads to a large amount of diagnosed lesions, but there is still no final conclusion about frequency, risk factors, and clinical relevance of these infarctions. The prevalence of silent strokes in patients with AF is higher compared to patients without AF, and several studies reported high incidence rates of silent strokes after AF ablation procedures. While treatment strategies to prevent clinically apparent strokes in patients with AF are well investigated, the role of anticoagulatory treatment for prevention of silent infarctions is unclear. This paper summarizes developments in diagnosis of silent brain infarction and its context to AF.

Assumption of different substrates is the basis for different ablation strategies in patients with paroxysmal and persistent atrial fibrillation (AF). We aimed to investigate pulmonary vein reconnection and influence on progression of initial paroxysmal (pAF) versus persistent atrial fibrillation (perAF).

PURPOSE:The clinical efficacy and toxicity of amiodarone may be determined more effectively by tissue deposition than by levels of the agent in serum. Therefore, corneal densitometry might be useful for therapeutic monitoring. The aim of the study is to evaluate Scheimpflug corneal densitometry in patients with amiodarone keratopathy (AK). DESIGN:Comparative case series. PARTICIPANTS:Sixty-six patients receiving amiodarone therapy and 66 healthy controls were consecutively enrolled in this study. METHODS:Patients were examined using the Oculus Pentacam (Wetzlar, Germany). MAIN OUTCOME MEASURES:Densitometry data from different corneal layers and different annuli were extracted, analyzed, and compared with densitometry values of healthy controls. Duration of treatment, cumulative dose, Orlando stage (slit-lamp biomicroscopy), and serum concentrations of amiodarone and N-desethylamiodarone also were determined, and the correlation to different densitometry data was evaluated. RESULTS:The total corneal light backscatter at total corneal thickness and at total diameter was significantly higher in the amiodarone group compared with the control group (AK group: 28.3±5.2; control group: 24.4±4.2; P < 0.001). Upon dividing the corneal surface into different layers at total thickness, the differences were significant in all layers (P < 0.001). The serum concentrations of the metabolite N-desethylamiodarone correlate with densitometry values, especially in the 0- to 2-mm annulus in the anterior layer (r = 0.419; P = 0.001), whereas the cumulative dose and duration of treatment correlate significantly with the densitometry values in the 0- to 2-mm annulus at total thickness (P = 0.014 and P = 0.022, respectively). CONCLUSIONS:Corneal densitometry is a useful, objective method for quantifying AK and can help in monitoring amiodarone therapy. The serum concentration of the active metabolite N-desethylamiodarone correlates with the extent of keratopathy in the anterior layer, whereas chronic changes in the stroma correlate with the cumulative dose and duration of treatment.

AIMS:The second-generation multi-electrode-phased radiofrequency pulmonary vein ablation catheter (PVAC GOLD(®)) was redesigned with the intent to improve its safety and efficacy.METHODS AND RESULTS:Using a prospectively designed single-centre database, we retrospectively analysed 128 consecutive patients (102 paroxysmal and 43 female) who underwent their first pulmonary vein isolation with the PVAC GOLD(®). The analysis focused on procedural data as well as in-hospital complications. Baseline characteristics of the patient collective were as follows: mean age 57.9 years, mean CHA2DS2-VASC was 1.73 ± 1.30; structural heart disease was present in seven patients. The PVAC GOLD(®) exhibited procedure durations of 123.1 min ± 27.9, duration of energy delivery was 18.3 min ± 11.4, and fluoroscopy duration was 16.0 min ± 7.7. The redesigned catheter shows major complication [major bleeding, transitory ischaemic attack (TIA), and pericardial tamponade] rates of 2.3% (n = 3). The overall rate of adverse events was 5.4% (n = 7). Bleeding complications were observed in three patients (2.3%), in particular there were two cases (1.6%) of minor bleeding and one case (0.8%) of major bleeding. Two patients suffered pericardial effusion, but there was no need for pericardiocentesis. Besides one TIA, there was no other thrombo-embolic event. Furthermore, one case of post-procedural fever was observed. No deaths, stroke, or haemorrhagic shock occurred. Of the 510 pulmonary veins, 508 could be reached with the PVAC GOLD(®) device using a non-steerable long sheath.CONCLUSION:The PVAC GOLD(®) seems to have an acceptable safety profile. The handling is comparable with the previous generation PVAC(®).

BackgroundThe development of esophageal lesions following atrial fibrillation (AF) ablation has frequently been reported. Mediastinal tissue layers and the posterior wall of the left atrium are in close proximity to the site of ablation. Hence, mucosal lesions might solely represent the tip of the iceberg. We therefore investigated patients undergoing multielectrode phased radiofrequency (RF) ablation (PVAC (R), Medtronic Inc., Minneapolis, MN, USA) for symptomatic AF by radial endosonography (EUS) in conjunction with conventional endoscopy esophago-gastro-duodenoscopy (EGD) to visualize potential mediastinal injuries following pulmonary vein isolation (PVI).Methods and ResultsEighteen patients (six women, mean age 52.8 12.8 years, range 32-72 years) underwent PVI using multielectrode phased RF ablation and EGD and EUS following PVI within 48 hours. Postablation periesophageal lesions were detected by EUS in 10 out of 18 patients (56%). Four out of 10 lesions consisted of mild changes like small pericardial effusions, whereas six out of 10 patients had more severe lesions of the mediastinum, including one patient with changes of the esophageal mucosa. No atrio-esophageal fistula developed during follow-up (FU; mean FU 215 +/- 105 days).ConclusionsMediastinal and esophageal structural changes occurred in a substantial number of patients. These findings highlight the necessity of close FU and the awareness of the potential development of an atrio-esophageal fistula also after multielectrode catheter ablation.

Electrical isolation of pulmonary veins is the cornerstone of catheter ablation for patients with symptomatic atrial fibrillation. However, uncertainty surrounds the choice of energy source in pulmonary vein isolation (PVI). Various alternative techniques such as the Pulmonary Vein Ablation Catheter (PVAC ® , Medtronic Inc., Minneapolis, MN, USA) have been developed to facilitate PVI. This over-the-wire multielectrode catheter is delivering duty-cycled bipolar and unipolar radiofrequency (RF) energy at relatively low power. PVI with this “one-shot” PVACatheter can shorten the procedure duration and lower fluoroscopy time compared to irrigated RF. It enables mapping and ablation with the same array, but fails to show signals during RF energy delivery. The effectiveness of PVAC is comparable to other technologies in randomized studies. The overall complication rate of PVAC PVI is comparable to irrigated RF and possibly slightly higher for cryoballoon PVI. Special attention has to be paid to an effective anticoagulation throughout the ablation procedure, avoidance of embolic events and pulmonary venous stenosis. The novel catheter design of the PVAC Gold ® array may improve safety by reducing embolic events through avoidance of electrode 1-to-10 interaction and by better tissue contact due to the 20° forward tilt. Although clinical data with this new array are lacking so far, the PVAC system has been shown to be a promising tool for PVI. However, prospective studies especially with the novel array are required to determine its true role for catheter ablation of atrial fibrillation in the future.

Optimal pharmacotherapy is essential to realize the bestoutcomes in patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). In this regard, effectively restoring reperfusion and maintaining the patency of the infarct artery after stenting requires a balance between the haemorrhagic risks and the ischaemic benefits of anticoagulant and antiplatelet agents. Over the last three decades, as the principal device used for primary PCI has evolved from balloon angioplasty to bare metal stents to drug-eluting stents, parallel advances have occurred in antithrombotic and antiplatelet regimens, from unfractionated heparin (UFH) alone, toUFHplus a glycoprotein IIb/IIIa inhibitor (GPI), to bivalirudin with provisional (bailout) GPI use, and from ticlopidine and clopidogrel to prasugrel and ticagrelor (on a background of aspirin). Given the time, complexity, and costs of performing appropriately powered randomized trials, clinical practice has progressed faster than the evidence base required to inform optimal drug and device usage for all possible drug and device permutations. Unfractionated heparin, a heterogeneous mixture of polysaccharides of varying chain lengths, while familiar and inexpensive, has numerous shortcomings, which become most clinically apparent in acute coronary syndromes (ACS). Unfractionated heparin has an indirect mechanism of action (binding to and activation of antithrombin III, the amount of which varies in disease states) and has limited activity against clot-bound thrombin. Non-specific protein and cellular binding of UFH results in variable biological activity and can result in heparin-induced thrombocytopenia and thrombosis. Moreover, UFHbinds to the glycoprotein IIb/IIIa receptor, thereby paradoxically activating platelets. Kastrati and colleagues elegantly demonstrated that, despite pre-treatment with aspirin and clopidogrel, myocardial infarction rates in non-STEMI are substantially reduced after PCI with abciximab. Meta-analysis of eight randomized trials in 3949 patients with STEMI undergoing PCI demonstrated that the addiion of abciximab to UFH reduced the 30 day odds of re-infarction by 37% (P , 0.001) and the 6–12 month odds of mortality by 28% (P 1⁄4 0.01). In the largest such study, CADILLAC, 30 day stent thrombosis was also reduced with abciximab plus UFH vs. UFH alone (P 1⁄4 0.01). These benefits more than offset the increased rates of bleeding and thrombocytopenia that may occur with GPI. As such, aspirin, clopidogrel, and UFH plus GPI became the preferred regimento supportprimary PCI inSTEMI, used in .90%ofpatients in the USA and in the majority of patients in Europe. This regimen remained the standard for more than a decade until challenged by the direct thrombin inhibitor bivalirudin, a rapidly reversible agent (half-life 25 min), which overcomes many of the limitations of UFH. Specifically, bivalirudin does not require antithrombin III for activation, is able to inhibit fibrin-found thrombin, has predictable biological activity and dosing, does not cause thrombocytopenia or activate platelets, and indeed, blocks both collagenand thrombin-induced platelet activation. A series of multicentre randomized PCI trials across the spectrum of coronary artery disease has demonstrated that in comparison to UFH plus GPI, bivalirudin with provisional GPI use results in similar rates of composite ischaemic events,with 40–50% reductions inmajorbleedingand thrombocytopenia. 12 The EuroMax trial confirmed that the bleeding benefits of bivalirudinarepresent inpatients treatedwith radial aswell as femoral access, which is not surprising given that the majority of major bleeding events after PCI in ACS are not access site related. Morevoer, in the largest randomized primary PCI trial to date, anticoagulation with bivalirudin in comparison to UFH plus GPI resulted in reduced cardiac and all-cause mortality at 30 days, benefits which were sustained to 3 years, reflecting both haematological and nonhematological benefits of bivalirudin. As a result, in many countries bivalirudin has supplanted UFH plus GPI as the preferred regimen to support primary PCI in STEMI. How can the results with bivalirudin be improved further? One glaring deficiency of bivalirudin monotherapy in primary PCI during STEMI (which has not been observed in other settings) was first noted in the HORIZONS-AMI trial, and subsequently confirmed in EuroMax; stent thrombosis, occurring within the first 4 h after the