Sayan Sen

Why Does Primary Angioplasty Not Work in Registries? Quantifying the Susceptibility of Real-World Comparative Effectiveness Data to Allocation Bias

Background—Meta-analysis of registries (comparative effectiveness research) shows that primary angioplasty and fibrinolysis have equivalent real-world survival. Yet, randomized, controlled trials consistently find primary angioplasty superior. Can unequal allocation of higher-risk patients in registries have masked primary angioplasty benefit? Methods and Results—First, we constructed a model to demonstrate the potential effect of allocation bias. We then analyzed published registries (55022 patients) for allocation of higher-risk patients (Killip class ≥1) to determine whether the choice of reperfusion therapy was affected by the risk level of the patient. Meta-regression was used to examine the relationship between differences in allocation of high-risk patient to primary angioplasty or fibrinolysis and mortality. Initial modeling suggested that registry outcomes are sensitive to allocation bias of high-risk patients. Across the registries, the therapy receiving excess high-risk patients had worse mortality. Unequal distribution of high-risk status accounted for most of the between-registry variance (adjusted R2meta=83.1%). Accounting for differential allocation of higher-risk patients, primary angioplasty gave 22% lower mortality (odds ratio, 0.78; 95% confidence interval, 0.64–0.97; P=0.029). We derive a formula, called the number needed to abolish, highlighting situations in which comparative effectiveness studies are particularly vulnerable to this bias. Conclusions—In ST-segment elevation myocardial infarction, clinicians’ preference for management of a few high-risk patients can shift mortality substantially. Comparative effectiveness research in any disease is vulnerable to this, especially diseases with an immediately identifiable high-risk subgroup that clinicians prefer to allocate to 1 therapy. For this reason, preliminary indications from registry-based comparative effectiveness research should be definitively tested by randomized, controlled trials.

Management of Migration of a SVC Wallstent into the Right Atrium

Computed tomography (CT) demonstrated a large right upper lobe mass and mediastinal lymphadenopathy compressing the SVC (Fig. 1). The tumor was too advanced for radical radiotherapy. SVC stenting was performed via the right common femoral vein. The SVC was easily traversed using a Headhunter catheter (Torcon NB Advantage Hinck; William Cook, Europe) and a 3-mm ‘J’ guidewire (Inwire, 0.035-in.; Merit Medical, Galway, Ireland). A SVC cavogram was performed by injection of contrast via a 4-Fr pigtail catheter in the right brachiocephalic vein. This confirmed 80% stenosis of the SVC due to external compression by the tumor. After predilation with a 16 9 40mm balloon (XXL balloon dilation catheter; Boston Scientific, Galway, Ireland), a 16 9 40-mm Wallstent (Boston Scientific) was advanced and deployed over a 260cm (0.035-in.) Amplatz guidewire (Boston Scientific) via a 10-Fr introducer (Super Sheath XL; Boston Scientific). However, the stent migrated on deployment, so that only a short segment was within the SVC lesion and about 90% within the right atrium (Fig. 2). The Amplatz guidewire was still in a satisfactory position traversing the lumen of the stent. No mechanism of retrieving the stent was thought suitable, and so to stabilize the stent a second, 16 9 60mm Wallstent was deployed superior to and overlapping the first stent. While the degree of overlap initially appeared satisfactory, the second stent subsequently shortened such that there was insufficient overlap. Therefore a third, 16 9 40-mm Wallstent was deployed across the junction of the two indwelling stents to form a brace. A 16 9 40-mm balloon dilation catheter (Boston Scientific) was serially inflated within the overlapping stents to maximize the interlock. An SVC cavogram (Fig. 3), via a pigtail catheter in the right brachiocephalic vein, showed good flow through the stents, with little filling of collateral vessels. Another SVC cavogram, at 8 frames per second, showed no significant movement of the stents. The patient was commenced on warfarin to reduce the chance of thrombus formation. Transthoracic echocardiography performed 24 h postprocedure also confirmed that there was no significant stent motion during the cardiac cycle. The patient obtained good symptomatic relief from her SVCO and underwent palliative radiotherapy. CT performed 1 month later showed no significant change in the position of the stents or thrombus formation. Subsequently she developed recurrent right pleural effusion and died 6 weeks following the procedure from causes unrelated to the SVC stent. M. J. Warren (&) Diagnostic Imaging, Luton and Dunstable NHS Foundation Trust Hospital, Lewsey Road, Luton LU4 ODZ, UK e-mail: martin.warren@ldh.nhs.uk

019 Development and validation of a novel pressure-only intra-coronary index of coronary stenosis severity

Background Assessment of stenosis severity with fractional flow reserve (FFR) requires that coronary resistance is stable and minimised. This is usually achieved by administration of pharmacological agents such as adenosine, which adds to the cost of the procedure and cannot be administered to all patients. In this study we determine (1) if there is a time when resistance is naturally minimised at rest and (2) assess the diagnostic efficiency, compared to FFR, of a new pressure-derived adenosine-free index of stenosis severity over that time. Methods 157 stenoses were assessed. In part 1 (39 stenoses), intracoronary pressure and flow-velocity were measured distal to the stenosis; in part 2 (118 stenoses), intracoronary pressure alone was measured. Measurements were made at baseline and under pharmacological vasodilatation with adenosine. Results Wave intensity analysis identified a wave-free period where intracoronary resistance at rest is similar in variability and magnitude (coefficient of variation: 0.08±0.06 and 284±147 mm Hg.s/m) to those during FFR (coefficient of variation: 0.08±0.06 and 302±315 mm Hg.s/m, p=NS for both). The resting distal to proximal pressure ratio during this period, the instantaneous wave-Free Ratio (iFR), correlated closely with FFR (r=0.9, p<0.001) with excellent diagnostic efficiency (receiver operating characteristic area under curve of 93%, at FFR<0.8), specificity, sensitivity, negative and positive predictive values of 91%, 85%, 85% and 91%, respectively. Conclusion Intra-coronary resistance is naturally constant and minimised during a diastolic wave-free period. The instantaneous wave-Free Ratio calculated over this period produces a drug-free index of stenosis severity comparable to FFR. Adoption of instantaneous wave-Free Ratio would enable the benefits of physiologically guided angioplasty to be applicable to a larger patient population.