Strategies to attenuate micro-vascular obstruction during P-PCI: the randomized reperfusion facilitated by local adjunctive therapy in ST-elevation myocardial infarction trial.

BACKGROUND: Microvascular obstruction (MVO) following primary percutaneous coronary intervention (PPCI) treatment of ST-segment elevation myocardial infarction (STEMI) contributes to infarct expansion, left ventricular (LV) remodelling, and worse clinical outcomes. The REFLO-STEMI trial tested whether intra-coronary (IC) high-dose adenosine or sodium nitroprusside (SNP) reduce infarct size and/or MVO determined by cardiac magnetic resonance (CMR). METHODS AND RESULTS: REFLO-STEMI, a prospective, open-label, multi-centre trial with blinded endpoints, randomized (1:1:1) 247 STEMI patients with single vessel disease presenting within 6 h of symptom onset to IC adenosine (2-3 mg total) or SNP (500 µg total) immediately following thrombectomy and again following stenting, or to standard PPCI. The primary endpoint was infarct size % LV mass (%LVM) on CMR undertaken 24-96 h after PPCI (n = 197). Clinical follow-up was to 6 months. There was no significant difference in infarct size (%LVM, median, interquartile range, IQR) between adenosine (10.1, 4.7-16.2), SNP (10.0, 4.2-15.8), and control (8.3, 1.9-14.0), P = 0.062 and P = 0.160, respectively, vs. CONTROL: MVO (% LVM, median, IQR) was similar across groups (1.0, 0.0-3.7, P = 0.205 and 0.6, 0.0-2.4, P = 0.244 for adenosine and SNP, respectively, vs. control 0.3, 0.0-2.8). On per-protocol analysis, infarct size (%LV mass, 12.0 vs. 8.3, P = 0.031), major adverse cardiac events (hazard ratio, HR, 5.39 [1.18-24.60], P = 0.04) at 30 days and 6 months (HR 6.53 [1.46-29.2], P = 0.01) were increased and ejection fraction reduced (42.5 ± 7.2% vs. 45.7 ± 8.0%, P = 0.027) in adenosine-treated patients compared with control. CONCLUSIONS: High-dose IC adenosine and SNP during PPCI did not reduce infarct size or MVO measured by CMR. Furthermore, adenosine may adversely affect mid-term clinical outcome. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01747174; https://clinicaltrials.gov/ct2/show/NCT01747174.

Optimization of the precordial leads of the 12-lead electrocardiogram may improve detection of ST-segment elevation myocardial infarction.

BACKGROUND: For the assessment of patients with chest pain, the 12-lead electrocardiogram (ECG) is the initial investigation. Major management decisions are based on the ECG findings, both for attempted coronary artery revascularization and risk stratification. The aim of this study was to determine if the current 6 precordial leads (V(1)-V(6)) are optimally located for the detection of ST-segment elevation in ST-segment elevation myocardial infarction (STEMI). METHODS: We analyzed 528 (38% anterior [200], 44% inferior [233], and 18% lateral [95]) patients with STEMI with both a 12-lead ECG and an 80-lead body surface map (BSM) ECG (Prime ECG, Heartscape Technologies, Bangor, Northern Ireland). Body surface map was recorded within 15 minutes of the 12-lead ECG during the acute event and before revascularization. ST-segment elevation of each lead on the BSM was compared with the corresponding 12-lead precordial leads (V(1)-V(6)) for anterior STEMI. In addition, for lateral STEMI, leads I and aVL of the BSM were also compared; and limb leads II, III, aVF of the BSM were compared with inferior unipolar BSM leads for inferior STEMI. Leads with the greatest mean ST-segment elevation were selected, and significance was determined by analysis of variance of the mean ST segment. RESULTS: For anterior STEMI, leads V(1), V(2), 32, 42, 51, and 57 had the greatest mean ST elevation. These leads are located in the same horizontal plane as that of V(1) and V(2). Lead 32 had a significantly greater mean ST elevation than the corresponding precordial lead V(3) (P = .012); and leads 42, 51, and 57 were also significantly greater than corresponding leads V(4), V(5), V(6), respectively (P < .001). Similar findings were also found for lateral STEMI. For inferior STEMI, the limb leads of the BSM (II, III, and aVF) had the greatest mean ST-segment elevation; and lead III was significantly superior to the inferior unipolar leads (7, 17, 27, 37, 47, 55, and 61) of the BSM (P < .001). CONCLUSION: Leads placed on a horizontal strip, in line with leads V(1) and V(2), provided the optimal placement for the diagnosis of anterior and lateral STEMI and appear superior to leads V(3), V(4), V(5), and V(6). This is of significant clinical interest, not only for ease and replication of lead placement but also may lead to increased recruitment of patients eligible for revascularization with none or borderline ST-segment elevation on the initial 12-lead ECG.

Assessment of the impedance cardiogram recorded by an automated external defibrillator during clinical cardiac arrest.

OBJECTIVE: To assess the impedance cardiogram recorded by an automated external defibrillator during cardiac arrest to facilitate emergency care by lay persons. Lay persons are poor at emergency pulse checks (sensitivity 84%, specificity 36%); guidelines recommend they should not be performed. The impedance cardiogram (dZ/dt) is used to indicate stroke volume. Can an impedance cardiogram algorithm in a defibrillator determine rapidly circulatory arrest and facilitate prompt initiation of external cardiac massage? DESIGN: Clinical study. SETTING: University hospital. PATIENTS: Phase 1 patients attended for myocardial perfusion imaging. Phase 2 patients were recruited during cardiac arrest. This group included nonarrest controls. INTERVENTIONS: The impedance cardiogram was recorded through defibrillator/electrocardiographic pads oriented in the standard cardiac arrest position. MEASUREMENTS AND MAIN RESULTS: Phase 1: Stroke volumes from gated myocardial perfusion imaging scans were correlated with parameters from the impedance cardiogram system (dZ/dt(max) and the peak amplitude of the Fast Fourier Transform of dZ/dt between 1.5 Hz and 4.5 Hz). Multivariate analysis was performed to fit stroke volumes from gated myocardial perfusion imaging scans with linear and quadratic terms for dZ/dt(max) and the Fast Fourier Transform to identify significant parameters for incorporation into a cardiac arrest diagnostic algorithm. The square of the peak amplitude of the Fast Fourier Transform of dZ/dt was the best predictor of reduction in stroke volumes from gated myocardial perfusion imaging scans (range = 33-85 mL; p = .016). Having established that the two pad impedance cardiogram system could detect differences in stroke volumes from gated myocardial perfusion imaging scans, we assessed its performance in diagnosing cardiac arrest. Phase 2: The impedance cardiogram was recorded in 132 "cardiac arrest" patients (53 training, 79 validation) and 97 controls (47 training, 50 validation): the diagnostic algorithm indicated cardiac arrest with sensitivities and specificities (+/- exact 95% confidence intervals) of 89.1% (85.4-92.1) and 99.6% (99.4-99.7; training) and 81.1% (77.6-84.3) and 97% (96.7-97.4; validation). CONCLUSIONS: The impedance cardiogram algorithm is a significant marker of circulatory collapse. Automated defibrillators with an integrated impedance cardiogram could improve emergency care by lay persons, enabling rapid and appropriate initiation of external cardiac massage.

Changes in the frequency spectrum, the P-P interval, and the bispectral index during ventricular fibrillation are physiologic indicators of ventricular fibrillation duration.

The 3-phase time-sensitive model by Weisfeldt and Becker in 2002 has resulted in a redirection of efforts toward developing treatment algorithms specific to each phase of cardiac arrest. In this study, a number of physiologic indicators of ventricular fibrillation (VF) duration were investigated. The bispectral index was recorded at 15-second intervals over 12 minutes and recordings of the atrial electrocardiogram and lead II electrocardiogram were acquired simultaneously using Notocord data acquisition software during sinus rhythm, ventricular tachycardia, and VF, and analyzed using a total of 30 porcine models. A number of frequency markers (fast Fourier transform and density and amplitude of peaks [DA]) were derived. There was a direct relationship between VF duration and bispectral index with a Pearson correlation coefficient (mean) of r = -0.91. The P-P interval recorded in the atria during VF, demonstrated similar findings (r = 0.97) when measured against VF duration. It was interesting to note that P waves were still apparent during VF despite the on-going chaotic activity in the ventricles. The DA was calculated for each episode of prolonged VF and an exponential relationship with VF duration was observed. The dominant frequency during VF, DA, the P-P interval, and the BIS index are all potential physiologic indicators of VF duration.

The impedance cardiogram recorded through two electrocardiogram/defibrillator pads as a determinant of cardiac arrest during experimental studies.

OBJECTIVE: Laypersons are poor at emergency pulse checks (sensitivity 84%, specificity 36%). Guidelines indicate that pulse checks should not be performed. The impedance cardiogram (dZ/dt) is used to assess stroke volume. Can a novel defibrillator-based impedance cardiogram system be used to distinguish between circulatory arrest and other collapse states? DESIGN: Animal study. SETTING: University research laboratory. SUBJECTS: Twenty anesthetized, mechanically ventilated pigs, weight 50-55 kg. INTERVENTIONS: Stroke volume was altered by right ventricular pacing (160, 210, 260, and 305 beats/min). Cardiac arrest states were then induced: ventricular fibrillation (by rapid ventricular pacing) and, after successful defibrillation, pulseless electrical activity and asystole (by high-dose intravenous pentobarbitone). MEASUREMENTS AND MAIN RESULTS: The impedance cardiogram was recorded through electrocardiogram/defibrillator pads in standard cardiac arrest positions. Simultaneously recorded electro- and impedance cardiogram (dZ/dt) along with arterial blood pressure tracings were digitized during each pacing and cardiac arrest protocol. Five-second epochs were analyzed for sinus rhythm (20 before ventricular fibrillation, 20 after successful defibrillation), ventricular fibrillation (40), pulseless electrical activity (20), and asystole (20), in two sets of ten pigs (ten training, ten validation). Standard impedance cardiogram variables were noncontributory in cardiac arrest, so the fast Fourier transform of dZ/dt was assessed. During ventricular pacing, the peak amplitude of fast Fourier transform of dZ/dt (between 1.5 and 4.5 Hz) correlated with stroke volume (r2 = .3, p < .001). In cardiac arrest, a peak amplitude of fast Fourier transform of dZ/dt of < or = 4 dB x ohm x rms indicated no output with high sensitivity (94% training set, 86% validation set) and specificity (98% training set, 90% validation set). CONCLUSIONS: As a powerful clinical marker of circulatory collapse, the fast Fourier transformation of dZ/dt (impedance cardiogram) has the potential to improve emergency care by laypersons using automated defibrillators.

Usefulness of body surface maps to demonstrate ventricular activation patterns during left ventricular pacing and reentrant activation during ventricular tachycardia in men with coronary heart disease and left ventricular dysfunction.

Epicardial electrical events were reconstructed using an inverse model for left ventricular (LV) pacing and during ventricular tachycardia (VT) induced during implantation of a biventricular pacemaker and/or internal defibrillator. The electrocardiographic position of the pacing lead, determined from the region of most negative potential 30 ms after the pacing spike, was compared with the radiographic position. Activation characterized by isochronal maps was correlated with the echocardiographic/myocardial scintigraphic data. Reconstructed epicardial isopotential/isochronal maps during VT were used to determine the presence of reentry. In 7 patients during LV pacing, epicardial isopotential maps located the maximum negative potentials anterolaterally (n = 3), posterolaterally (n = 2), and posteriorly (n = 2). Isochronal maps demonstrated activation patterns including regions of delayed activation that, in 5 patients, correlated with areas of akinesia/hypokinesia or fixed defects on echocardiography/myocardial scintigraphy. The mean difference between the radiographically measured right ventricular to LV pacing lead distance and calculated electrocardiographic right ventricular to LV pacing site distance was 1.7 cm. During VT, induced in 5 patients, single-loop reentry was observed in 3 and figure-of-8 reentry in 2. Exit site and regions of fast/slow conduction and conduction block that correlated with anatomic areas of infarction defined by echocardiography/myocardial scintigraphy were demonstrated. In conclusion, epicardial maps reconstructed from the body surface map can identify LV pacing sites and demonstrate reentry during VT. The body surface map could thus identify optimal pacing sites for LV pacing and targets for VT ablation.

Eptifibatide and low-dose tissue plasminogen activator in acute myocardial infarction: the integrilin and low-dose thrombolysis in acute myocardial infarction (INTRO AMI) trial.

OBJECTIVES: This study was designed to test the hypothesis that eptifibatide and reduced-dose tissue plasminogen activator (t-PA) will enhance infarct artery patency at 60 min in patients with acute myocardial infarction (AMI). BACKGROUND: Combination fibrin and platelet lysis improves epicardial and myocardial reperfusion in AMI. METHODS: Patients were enrolled in a dose finding (Phase A, n = 344) followed by a dose confirmation (Phase B, n = 305) protocol. All patients received aspirin and weight-adjusted heparin and underwent angiography at 60 and 90 min. In Phase A, eptifibatide in a single or double bolus (30 min apart) of 180, 180/90 or 180/180 microg/kg followed by an infusion of 1.33 or 2.0 microg/kg per min was sequentially added to 25 or 50 mg of t-PA. In Phase B, patients were randomized to: 1) double-bolus eptifibatide 180/90 (30 min apart) and 1.33 microg/kg per min infusion with 50 mg t-PA (Group I); 2) 180/90 (10 min apart) and 2.0 g/kg per min with 50 mg t-PA (Group II); or 3) full-dose, weight-adjusted t-PA (Group III). RESULTS: In Phase A, the best rate of Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 was achieved using 180/90/1.33 microg/kg per min eptifibatide with 50 mg t-PA: 65% and 78% at 60 and 90 min, respectively. In Phase B, the incidence of TIMI flow grade 3 at 60 min was 42%, 56% and 40%, for Groups I through III, respectively (p = 0.04, Group II vs. Group III). The median corrected TIMI frame count was 38, 33 and 50, respectively (p = 0.02). TIMI major bleeding was reported in 8%, 11% and 6%, respectively; intracranial hemorrhage occurred in 1%, 3% and 2% of patients (p > 0.5 for both). The incidences of death (4%, 5% and 7%), reinfarction or revascularization at 30 days were similar among the three treatment groups. CONCLUSIONS: In comparison with standard t-PA regimen, double-bolus eptifibatide (10 min apart) with a 48-h infusion and half-dose t-PA (Group II) is associated with improved quality and speed of reperfusion. The safety profile of this therapy is similar to that of other combination regimens.

The role of biphasic shocks for transthoracic cardioversion of atrial fibrillation.

The modern generation of transthoracic defibrillators now employ impedance compensated biphasic waveforms. These new devices are superior to those with monophasic waveforms and practice is currently switching to biphasic defibrillators for the treatment of both ventricular and atrial fibrillation. However, there is no universal guideline for the use of biphasic defibrillators in direct current cardioversion of atrial fibrillation. This article reviews the use of biphasic defibrillation waveforms for transthoracic cardioversion of atrial fibrillation.

Prediction of Recurrent Events by D-Dimer and Inflammatory Markers in Patients with Normal Cardiac Troponin I (PREDICT) Study.

BACKGROUND: The independent predictive value of d-dimer and inflammatory markers for the risk of recurrent adverse events in patients with acute chest pain but normal levels of cardiac troponin I (cTnI) remains unclear. METHODS: We studied 391 patients admitted to the hospital in 1 year with acute ischemic-type chest pain. Creatine kinase-myocardial band isoenzyme (CK-MB) mass and cTnI levels were measured in initial and 12-hour samples. Soluble intercellular adhesion molecule (sICAM)-1, vascular cell adhesion molecule (sVCAM)-1, sP-selectin, sE-selectin, high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL6), fibrinogen, and d-dimer levels were measured in initial samples. A 1-year incidence of death, myocardial infarction (MI), revascularization, or readmission with chest pain was determined (with death/MI as the primary end point). RESULTS: Patients with normal levels of CK-MB(mass) and cTnI (195/391[50%]) were at a lower risk than patients with elevated levels of CK-MB(mass) or cTnI, but still had an important incidence of events (77/195[39%]). Marker elevation was defined as >75th percentile (upper quartile). Elevated d-dimer levels (>580 ng/mL) was predictive of death/MI (odds ratio, 5.4; 95% CI, 1.5-20.2; P =.005). Elevated sP-selectin levels (>152 ng/mL; odds ratio, 3.2; 95% CI, 0.9-11.6; P =.06) trended to increased death/MI rates, with weaker trends for elevated levels of hsCRP (>7.1 mg/L), IL6 (>10.7 pg/mL), and ST depression. Other markers, other electrocardiogram changes, or classic risk factors were not predictive of death/MI. With a multivariate analysis, d-dimer and sP-selectin were found to be of independent significance for death/MI after adjustment for inflammatory, hemostatic, and electrocardiogram markers and d-dimer after adjustment for classic risk factors. CONCLUSION: Normal cTnI levels after acute chest pain does not confer absence of future risk. Concurrent assessment of d-dimer and inflammatory markers may improve risk stratification.

Efficacy of distinct energy delivery protocols comparing two biphasic defibrillators for cardiac arrest.

Limited data have been published on the use of external defibrillators that deliver impedance compensated biphasic (ICB) waveforms in patients. We compared 2 ICB defibrillators, the Heartstream XL (150-150-150 J protocol) and Heartsine Samaritan (100-150-200 J protocol) in 78 consecutive patients in cardiac arrest. The performance of the 2 devices over the first 2 shocks was statistically equivalent. By the third shock, the Heartsine Samaritan had significantly better performance in removing ventricular fibrillation (p = 0.029). Energy selection for ICB waveforms requires further validation.

Comparison of the 80-lead body surface map to physician and to 12-lead electrocardiogram in detection of acute myocardial infarction.

Diagnosis of non-ST-elevation acute myocardial infarction (AMI) by a 12-lead electrocardiogram has poor sensitivity and specificity and, therefore, relies on biochemical markers of myocardial necrosis, which can only be reliably detected within 14 to 16 hours from symptom onset. The body surface map (BSM) improves AMI detection but is limited by its interpretation by inexperienced medical staff. To facilitate interpretation, an automated BSM algorithm was developed and is evaluated in this study. One hundred three patients with ischemic-type chest pain were recruited for this study from December 2001 to April 2002. A 12-lead electrocardiogram (Marquette Mac 5K) and BSM (PRIME-ECG) were recorded at initial presentation, and cardiac troponin I and/or creatine kinase-MB levels measured at 12 hours after symptom onset. The admitting physician's 12-lead electrocardiographic (ECG) interpretation, 12-lead ECG algorithm (Marquette 12 SL V233) diagnosis, and BSM algorithm diagnosis were documented for each patient. AMI, defined by elevation of troponin I to >1 microg/L and/or creatine kinase-MB to >25U/L, occurred in 53 patients. The admitting physician diagnosed 24 patients with AMI (sensitivity 45%, specificity 94%), the 12-lead ECG algorithm diagnosed 17 patients with AMI (sensitivity 32%, specificity 98%), and the BSM algorithm diagnosed 34 patients with AMI (sensitivity 64%, specificity 94%). The BSM algorithm improved the diagnostic sensitivity by 2.0 (p <0.001) and 1.4 (p = 0.002) compared with the 12-lead ECG algorithm or the admitting physician, respectively. There was no significant difference in specificity. Thus, the BSM algorithm improves detection of AMI compared with the 12-lead ECG algorithm or physician's 12-lead ECG interpretation.

Novel uses for recombinant erythropoietin therapy in unlicensed indications.

Clinical uses for recombinant human erythropoietin (rHuEPO) therapy continue to expand. Initial use was in anaemia associated with end-stage renal disease, but more recently there have been many reports of the benefits of erythropoietin in other clinical situations such as cancer-related anaemia. Recombinant erythropoietin reduces the need for blood transfusion and hence exposure to donor blood products as well as improving quality of life. We report four patients who were transfusion dependent, none of whom had licensed indications for the use of recombinant erythropoietin. Two patients had microangiopathic haemolytic anaemia secondary to mechanical valve haemolysis and were unsuitable for any further cardiac intervention. One patient had anaemia of chronic disease and anti-Vel red cell antibodies, making compatible blood transfusions difficult to obtain. The fourth patient had primary thrombocythaemia and developed transfusion-dependent anaemia secondary to myelosuppressive agents. All four patients had a relative deficiency in endogenous erythropoietin levels ranging between 7 and 41 IU/l. After commencing recombinant erythropoietin therapy, all had a response in haemoglobin of at least 1 g/dl with an overall improvement in their quality of life. We conclude that rHuEPO is a very convenient and useful form of treatment in transfusion-dependent anaemia and in some cases beyond the licensed indications.

A multicenter study of the tolerability of tirofiban versus placebo in patients undergoing planned intracoronary stent placement.

BACKGROUND: The use of intravenous glycoprotein IIb/IIIa-receptor antagonists has been shown to improve outcomes in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). Tirofiban has shown benefit in a wide range of patients presenting with acute coronary syndromes. Although this agent has been used in patients undergoing percutaneous coronary intervention, a literature search identified no prospective data comparing tirofiban with placebo in patients undergoing planned intracoronary stent placement. OBJECTIVE: This study examined the tolerability of tirofiban in patients undergoing percutaneous intervention with planned intracoronary stent placement. METHODS: This was a multinational, multicenter, prospective, randomized, double-blind, placebo-controlled trial in patients scheduled to undergo PTCA with planned intracoronary stent placement. Patients were randomized in a 3:2 ratio to receive tirofiban as an intravenous bolus (10 microg/kg over 3 minutes) and maintenance infusion (0.10 microg/kg per minute for 36 hours) or a bolus and infusion of placebo. All patients received periprocedural aspirin and heparin and an optional postprocedural thienopyridine (ticlopidine or clopidogrel). Laboratory and safety monitoring were performed throughout the 36 hours after the procedure and at hour 40 or hospital discharge. The primary end point was the proportion of patients with bleeding, defined according to Thrombolysis in Myocardial Infarction (TIMI) trial criteria. The number of patients with cardiac events (death, myo- cardial infarction, urgent revascularization) during the first 30 days after stent placement was also assessed. RESULTS: Eight hundred ninety-four patients (536 tirofiban, 358 placebo) were enrolled, all of whom received aspirin and heparin periprocedurally and optional ticlopidine or clopidogrel after the procedure. No significant between-group differences were observed in the incidence of TIMI major bleeding (0.2% tirofiban, 0.6% placebo) or any TIMI bleeding (3.2% and 1.7%, respectively). The incidence of TIMI minor bleeding was higher with tirofiban than with placebo (2.8% vs 0.6%). The 30-day incidence of the composite end point of any cardiac event was 3.9% in both groups. CONCLUSIONS: On a background of concomitant aspirin, heparin, and a thienopyridine, tirofiban was generally well tolerated in patients undergoing PTCA with planned intracoronary stent placement. Further investigation is needed to ascertain the optimal dosing of tirofiban and heparin to achieve reductions in ischemic complications of intracoronary stenting with an acceptable incidence of bleeding complications.

Current management of unstable angina: lessons from the TACTICS-TIMI 18 trial.

Patients presenting with unstable angina pectoris or non-Q-wave myocardial infarction (MI), if treated inadequately, are at a high risk of MI and subsequent mortality. The use of intravenous small molecule glycoprotein IIb/IIIa inhibitors along with standard therapeutic management options improves outcome. Since the publication of the Thrombolysis in Myocardial Ischemia IIIB, Veterans Affairs Non-Q-Wave Infarction Strategies In-Hospital (VANQWISH) and Fragmin and Fast Revascularization during InStability in Coronary artery disease II (FRISC II) studies, there is great debate about the advantages of following an early 'invasive' treatment option with coronary angiography and revascularization after initial medical therapy compared with the 'conservative' approach, where angiography is reserved for those who remain symptomatic. The Treat angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy--Thrombolysis in Myocardial Infarction 18 (TACTICS-TIMI 18) study has helped to resolve some of the controversies since it was designed with more current medical (early and routine use of tirofiban) and revascularization (use of stents during percutaneous coronary interventions) options as part of the invasive treatment protocol. This study indicated that an early invasive strategy in risk stratified patients combined with early use of tirofiban with standard medical therapy significantly improves outcome and appears well tolerated.

Body surface potential mapping improves detection of ST segment alteration during percutaneous coronary intervention.

BACKGROUND: The 12-lead electrocardiogram underestimates ST segment alteration in acute coronary syndromes compared with multi-lead body surface mapping. We assessed whether 80-lead mapping would improve detection of ST alteration during percutaneous coronary intervention. METHODS: Simultaneous maps and 12-lead electrocardiograms were recorded pre-procedure, during balloon inflation and post-procedure from patients undergoing elective intervention to native coronary arteries. Recordings were obtained from 39 inflations (19 patients). All arteries were successfully stented. RESULTS: Mean 'lead specific' ST alteration (the difference in ST elevation/depression between pre-procedure and inflation recordings in the lead showing maximal ST alteration) was greater on the map than on electrocardiogram, both for ST elevation (0.16+/-0.02 vs. 0.06+/-0.01 mV; p<0.001) and ST depression (0.11+/-0.017 vs. -0.03+/-0.006 mV; p<0.001). During first inflations (n=19), mean lead specific ST elevation and depression on map were greater than on electrocardiogram (0.20+/-0.034 vs. 0.07+/-0.015 mV; p<0.001 and 0.11+/-0.029 vs. 0.03+/-0.009 mV; p=0.001, respectively). Mapping detected greater summated ST elevation and depression during inflation than electrocardiogram (0.04+/-0.005 vs. 0.021+/-0.003 mV; p<0.001 and 0.026+/-0.004 vs. 0.011+/-0.002 mV; p<0.001, respectively). Qualitative analysis of maps and electrocardiograms showed that 21/39 (53.8%) maps recorded during inflation met criteria for myocardial ischaemia compared with 7/39 (17.9%) electrocardiograms (p<0.001). CONCLUSION: Body surface mapping compared with the 12-lead electrocardiogram improves detection of myocardial ischaemia during intervention.

Considerations in combination therapy: fibrinolytics plus glycoprotein IIb/IIIa receptor inhibitors in acute myocardial infarction.

The combined use of a fibrinolytic and a platelet glycoprotein (GP) IIb/IIIa receptor inhibitor to target the fibrin and platelet components of occlusive thrombi offers the potential for more rapid and complete reperfusion in patients with acute myocardial infarction (MI), although there have been concerns about the safety of this combination therapy. Data from the recent GUSTO-V and the ASSENT-3 trials support the use of this regimen in that the 30-day death or nonfatal reinfarction rate (7 days) in GUSTO-V and death or in-hospital reinfarction or in-hospital refractory ischemia rate in ASSENT-3 were reduced (p = 0.001 and p = 0.0001, respectively). The need for revascularization in both these trials was also reduced significantly. There was no increased risk of intracranial hemorrhage or stroke with the combination therapy, but an increased rate of nonintracranial severe or major bleeding was observed. At present, patients aged > 75 years should not receive combination therapy. Further studies in subgroup patient populations are warranted.

The REFLO-STEMI trial comparing intracoronary adenosine, sodium nitroprusside and standard therapy for the attenuation of infarct size and microvascular obstruction during primary percutaneous coronary intervention: study protocol for a randomised controlled trial.

BACKGROUND: Microvascular obstruction (MVO) secondary to ischaemic-reperfusion injury is an important but underappreciated determinant of short- and longer-term outcome following percutaneous coronary intervention (PCI) treatment of ST-elevation myocardial infarction (STEMI). Several small studies have demonstrated a reduction in the degree of MVO utilising a variety of vasoactive agents, with adenosine and sodium nitroprusside (SNP) being most evaluated. However, the evidence base remains weak as the trials have had variable endpoints, differing drug doses and delivery. As such, the results regarding benefit are conflicting. METHODS: The REperfusion Facilitated by LOcal adjunctive therapy in STEMI (REFLO-STEMI) trial is a multicentre, prospective, randomised, controlled, open label, study with blinded endpoint analysis: Patients presenting within 6 h of onset of STEMI and undergoing planned primary PCI (P-PCI) with TIMI 0/1 flow in the infarct-related artery (IRA) and no significant bystander coronary artery disease on angiography, are randomised into one of three groups: PCI with adjunctive pharmacotherapy (intracoronary adenosine or SNP) or control (standard PCI). All receive Bivalirudin anticoagulation and thrombus aspiration. The primary outcome is infarct size (IS) (determined as a percentage of total left ventricular mass) measured by cardiac magnetic resonance imaging (CMRI) undertaken at 48 to 72 h post P-PCI. Secondary outcome measures include MVO (hypoenhancement within infarct core) on CMRI, angiographic markers of microvascular perfusion and MACE during 1-month follow-up. The study aims to recruit 240 patients (powered at 80% to detect a 5% absolute reduction in IS). DISCUSSION: The REFLO-STEMI study has been designed to address the weaknesses of previous trials, which have collectively failed to demonstrate whether adjunctive pharmacotherapy with adenosine and/or SNP can reduce measures of myocardial injury (infarct size and MVO) and improve clinical outcome, despite good basic evidence that they have the potential to attenuate this process. The REFLO-STEMI study will be the most scientifically robust trial to date evaluating whether adjunctive therapy (intracoronary adenosine or SNP following thrombus aspiration) reduces CMRI measured IS and MVO in patients undergoing P-PCI within 6 h of onset of STEMI. TRIAL REGISTRATION: Trial registered 20th November 2012: ClinicalTrials.gov Identifier NCT01747174.

Giant true saphenous vein graft aneurysm causing cardiac compression: a rare cause of atrial flutter.

A 67 year old man presented with new-onset atrial flutter. He had a history of coronary artery bypass graft (CABG) surgery on two occasions. Subsequent investigation revealed the presence of a large saphenous vein graft (SVG) aneurysm compressing the right heart. We postulate that the SVG aneurysm was the precipitating cause for the atrial flutter. This case is the first in the literature to document an atrial arrhythmia as the presenting feature of a SVG aneurysm.