Damian J. Kelly

Randomized Trial of Complete Versus Lesion-Only Revascularization in Patients Undergoing Primary Percutaneous Coronary Intervention for STEMI and Multivessel Disease: The CvLPRIT Trial

Background The optimal management of patients found to have multivessel disease while undergoing primary percutaneous coronary intervention (P-PCI) for ST-segment elevation myocardial infarction is uncertain. Objectives CvLPRIT (Complete versus Lesion-only Primary PCI trial) is a U.K. open-label randomized study comparing complete revascularization at index admission with treatment of the infarct-related artery (IRA) only. Methods After they provided verbal assent and underwent coronary angiography, 296 patients in 7 U.K. centers were randomized through an interactive voice-response program to either in-hospital complete revascularization (n = 150) or IRA-only revascularization (n = 146). Complete revascularization was performed either at the time of P-PCI or before hospital discharge. Randomization was stratified by infarct location (anterior/nonanterior) and symptom onset (≤3 h or >3 h). The primary endpoint was a composite of all-cause death, recurrent myocardial infarction (MI), heart failure, and ischemia-driven revascularization within 12 months. Results Patient groups were well matched for baseline clinical characteristics. The primary endpoint occurred in 10.0% of the complete revascularization group versus 21.2% in the IRA-only revascularization group (hazard ratio: 0.45; 95% confidence interval: 0.24 to 0.84; p = 0.009). A trend toward benefit was seen early after complete revascularization (p = 0.055 at 30 days). Although there was no significant reduction in death or MI, a nonsignificant reduction in all primary endpoint components was seen. There was no reduction in ischemic burden on myocardial perfusion scintigraphy or in the safety endpoints of major bleeding, contrast-induced nephropathy, or stroke between the groups. Conclusions In patients presenting for P-PCI with multivessel disease, index admission complete revascularization significantly lowered the rate of the composite primary endpoint at 12 months compared with treating only the IRA. In such patients, inpatient total revascularization may be considered, but larger clinical trials are required to confirm this result and specifically address whether this strategy is associated with improved survival. (Complete Versus Lesion-only Primary PCI Pilot Study [CvLPRIT]; ISRCTN70913605)

Complete Versus Lesion-Only Primary PCI: The Randomized Cardiovascular MR CvLPRIT Substudy

Background Complete revascularization may improve outcomes compared with an infarct-related artery (IRA)-only strategy in patients being treated with primary percutaneous coronary intervention (PPCI) who have multivessel disease presenting with ST-segment elevation myocardial infarction (STEMI). However, there is concern that non-IRA PCI may cause additional non-IRA myocardial infarction (MI). Objectives This study sought to determine whether in-hospital complete revascularization was associated with increased total infarct size compared with an IRA-only strategy. Methods This multicenter prospective, randomized, open-label, blinded endpoint clinical trial evaluated STEMI patients with multivessel disease having PPCI within 12 h of symptom onset. Patients were randomized to either IRA-only PCI or complete in-hospital revascularization. Contrast-enhanced cardiovascular magnetic resonance (CMR) was performed following PPCI (median day 3) and stress CMR at 9 months. The pre-specified primary endpoint was infarct size on pre-discharge CMR. The study had 80% power to detect a 4% difference in infarct size with 100 patients per group. Results Of the 296 patients in the main trial, 205 participated in the CMR substudy, and 203 patients (98 complete revascularization and 105 IRA-only) completed the pre-discharge CMR. The groups were well-matched. Total infarct size (median, interquartile range) was similar to IRA-only revascularization: 13.5% (6.2% to 21.9%) versus complete revascularization, 12.6% (7.2% to 22.6%) of left ventricular mass, p = 0.57 (95% confidence interval for difference in geometric means 0.82 to 1.41). The complete revascularization group had an increase in non-IRA MI on the pre-discharge CMR (22 of 98 vs. 11 of 105, p = 0.02). There was no difference in total infarct size or ischemic burden between treatment groups at follow-up CMR. Conclusions Multivessel PCI in the setting of STEMI leads to a small increase in CMR-detected non-IRA MI, but total infarct size was not significantly different from an IRA-only revascularization strategy. (Complete Versus Lesion-Only Primary PCI Pilot Study [CvLPRIT]; ISRCTN70913605)

Comparison of exercise testing and CMR measured myocardial perfusion reserve for predicting outcome in asymptomatic aortic stenosis: the PRognostic Importance of MIcrovascular Dysfunction in Aortic Stenosis (PRIMID AS) Study

Aims To assess cardiovascular magnetic resonance (CMR) measured myocardial perfusion reserve (MPR) and exercise testing in asymptomatic patients with moderate-severe AS. Methods and results Multi-centre, prospective, observational study, with blinded analysis of CMR data. Patients underwent adenosine stress CMR, symptom-limited exercise testing (ETT) and echocardiography and were followed up for 12–30 months. The primary outcome was a composite of: typical AS symptoms necessitating referral for AVR, cardiovascular death and major adverse cardiovascular events. 174 patients were recruited: mean age 66.2 ± 13.34 years, 76% male, peak velocity 3.86 ± 0.56 m/s and aortic valve area index 0.57 ± 0.14 cm2/m2. A primary outcome occurred in 47 (27%) patients over a median follow-up of 374 (IQR 351–498) days. The mean MPR in those with and without a primary outcome was 2.06 ± 0.65 and 2.34 ± 0.70 (P = 0.022), while the incidence of a symptom-limited ETT was 45.7% and 27.0% (P = 0.020), respectively. MPR showed moderate association with outcome area under curve (AUC) = 0.61 (0.52–0.71, P = 0.020), as did exercise testing (AUC = 0.59 (0.51–0.68, P = 0.027), with no significant difference between the two. Conclusions MPR was associated with symptom-onset in initially asymptomatic patients with AS, but with moderate accuracy and was not superior to symptom-limited exercise testing. ClinicalTrials.gov (NCT01658345).

Infarct Size Following Treatment With Second‐ Versus Third‐Generation P2Y12 Antagonists in Patients With Multivessel Coronary Disease at ST‐Segment Elevation Myocardial Infarction in the CvLPRIT Study

Background Third‐generation P2Y12 antagonists (prasugrel and ticagrelor) are recommended in guidelines on ST‐segment elevation myocardial infarction. Mechanisms translating their more potent antiplatelet activity into improved clinical outcomes versus the second‐generation P2Y12 antagonist clopidogrel are unclear. The aim of this post hoc analysis of the Complete Versus Lesion‐Only PRImary PCI Trial‐CMR (CvLPRIT‐CMR) substudy was to assess whether prasugrel and ticagrelor were associated with reduced infarct size compared with clopidogrel in patients undergoing primary percutaneous coronary intervention. Methods and Results CvLPRIT‐CMR was a multicenter, prospective, randomized, open‐label, blinded end point trial in 203 ST‐segment elevation myocardial infarction patients with multivessel disease undergoing primary percutaneous coronary intervention with either infarct‐related artery–only or complete revascularization. P2Y12 inhibitors were administered according to local guidelines. The primary end point of infarct size on cardiovascular magnetic resonance was not significantly different between the randomized groups. P2Y12 antagonist administration was not randomized. Patients receiving clopidogrel (n=70) compared with those treated with either prasugrel or ticagrelor (n=133) were older (67.8±12 versus 61.5±10 years, P<0.001), more frequently had hypertension (49% versus 29%, P=0.007), and tended to have longer symptom‐to‐revascularization time (234 versus 177 minutes, P=0.05). Infarct size (median 16.1% [quartiles 1–3, 10.5–27.7%] versus 12.1% [quartiles 1–3, 4.8–20.7%] of left ventricular mass, P=0.013) and microvascular obstruction incidence (65.7% versus 48.9%, P=0.022) were significantly greater in patients receiving clopidogrel. Infarct size remained significantly different after adjustment for important covariates using both generalized linear models (P=0.048) and propensity score matching (P=0.025). Conclusions In this analysis of CvLPRIT‐CMR, third‐generation P2Y12 antagonists were associated with smaller infarct size and lower microvascular obstruction incidence versus the second‐generation P2Y12 antagonist clopidogrel for ST‐segment elevation myocardial infarction. Clinical Trial Registration URL: http://www.isrctn.com/ISRCTN70913605.

Myocardial Perfusion Reserve but not fibrosis predicts outcomes in initially asymptomatic patients with moderate to severe aortic stenosis: the PRognostic Importance of MIcrovascular Dysfunction in AS study- PRIMID AS

Myocardial Perfusion Reserve but not fibrosis predicts outcomes in initially asymptomatic patients with moderate to severe aortic stenosis: the PRognostic Importance of MIcrovascular Dysfunction in AS studyPRIMID AS Anvesha Singh, Michael Jerosch-Herold, John P Greenwood, Colin Berry, Dana K Dawson, Chim C Lang, Damian J Kelly, David Sprigings, Jeffrey P Khoo, Kai Hogrefe, Richard P Steeds, Vijay Anand Dhakshinamurthy, Gerry P McCann

Activation of Hypoxia-Inducible Factor by Di-Methyl Oxalyl Glycine (DMOG) Increases Neovascularization within Ischaemic Myocardium in a Porcine Coronary Artery Occlusion Model

Introduction: Chronic total coronary artery occlusion (CTO) in man remains a significant challenge for percutaneous coronary intervention (PCI) and a common reason for coronary artery bypass surgery, as often the CTO cannot be crossed. This study investigated whether a potential angiogenic treatment, the prolyl-4-hydroxylase inhibitor, di-methyl oxalyl glycine (DMOG), would increase collateral vessel formation and myocardial perfusion without opening the CTO in a porcine model of coronary CTO. Methods: We assessed the effect of DMOG upon tube formation of HUVEC in a matrigel assay in vitro. DMOG was loaded onto a polymer-coated coronary stent. Copper-coated stents were used to produce a coronary CTO in 20 pigs. DMOG-loaded or control stents were implanted in an alternating, blinded manner at day 28, proximal to the CTO. Angiographic and physiological flow data were collected at day 56, when the animals were sacrificed and the collateral vessels counted. Results: DMOG increased tubule formation in vitro by 77% compared with control (p<0.0001). DMOG was successfully loaded onto the polymer coated stent, as evidenced by the same assay. A CTO was present at angiography in all animals 28 days. At 56 days there was a trend towards a greater increase in angiographic collateral vessel area around the CTO in the DMOG group compared with controls +84.5% vs. +16.5%, respectively, p=0.057). Histology revealed a significant increase in the number of collateral vessels around the site of occlusion in the DMOG group vs control (29.9?2.6 vs 18.4?3.1, respectively; p=0.01). There was no difference between the groups in terms of collateral flow index at day 56. Conclusion: DMOG, delivered on a polymer-coated stent, proximal to an occluded porcine coronary artery, increased the number of collateral vessels seen at the site of vessel occlusion but not to a level sufficient to increase measures of functional flow.

Ischemia and Infarction in STEMI Patients With Multivessel Disease : Insights From the CvLPRIT Nuclear Substudy

The CvLPRIT (Complete versus Lesion-only PRimary PCI Trial) trial was undertaken in 7 UK centers (1,2). Patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary stenoses were randomized to primary percutaneous coronary intervention (PPCI) to the infarct-related artery (IRA) only, or complete revascularization. At 12-month follow-up, the rate of the combined primary endpoint (all-cause mortality, recurrent MI, heart failure, ischemia-driven revascularization) was lower after complete revascularization. All surviving patients were asked to undergo myocardial perfusion scintigraphy (MPS) 6 to 8 weeks post-admission. It was expected that this a priori nuclear substudy would provide mechanistic insights into the outcome of the main trial, and help to define the clinical role of MPS in the PPCI era.

Reply : Complete Revascularization in Patients Undergoing Primary Percutaneous Coronary Intervention for STEMI: Is It Really What We Should Be Doing?

We read with interest the letter from Dr. Dastidar and colleagues in which they express their views and compare our report of the randomized CvLPRIT (Complete Versus Lesion-Only Primary PCI Trial) [(1)][1] with their in-house clinical experience. They suggest that the trial was not run according to

Preventing and Treating Radial Spasm

Use of radial artery access for percutaneous coronary intervention (PCI) has increased greatly in recent years although uptake varies widely throughout the world. While an increasing body of evidence supports use of the radial artery as a safe access route for PCI, a ‘radial learning curve’ remains an obstacle to uptake, especially for established femoral operators seeking to increase the proportion of radial procedures. Untreated radial artery spasm is not only painful, but may result in patient harm if alternate arterial access (e.g. the femoral artery) is unavailable. An understanding of simple procedural modifications can be the difference between procedural success and failure.

Coronary Air Embolism

Few coronary complications are as unpredictable as coronary air embolism (CAE). Sequelae range from asymptomatic transient slow-flow to devastating cardiovascular collapse and death. Unlike many PCI complications, CAE is almost always avoidable; as such a sound knowledge of both prevention and management are mandatory for every operator.