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Objectives: \ud The aim of this study was to establish sex differences in remodeling and outcome in aortic stenosis (AS) and their associations with biomarkers of myocardial fibrosis.\ud \ud Background: \ud The remodeling response and timing of symptoms is highly variable in AS, and sex plays an important role.\ud \ud Methods: \ud A total of 174 patients (133 men, mean age 66.2 ± 13.3 years) with asymptomatic moderate to severe AS underwent comprehensive stress cardiac magnetic resonance imaging, transthoracic echocardiography, and biomarker analysis (matrix metalloproteinase [MMP]-2, -3, -7, -8, and -9; tissue inhibitor matrix metalloproteinases-1 and -4; syndecan-1 and -4; and N-terminal pro–B-type natriuretic peptide), and were followed up at 6-month intervals. A primary endpoint was a composite of typical AS symptoms necessitating referral for aortic valve replacement, cardiovascular death, or major adverse cardiovascular events.\ud \ud Results: \ud For a similar severity of AS, male patients demonstrated higher indexed left ventricular (LV) volumes and mass, more concentric remodeling (higher LV mass/volume), a trend to more late gadolinium enhancement (present in 51.1% men vs. 34.1% women; p = 0.057), and higher extracellular volume index than female patients (13.27 [interquartile range (IQR): 11.5 to 17.0] vs. 11.53 [IQR: 10.5 to 13.5] ml/m2, p = 0.017), with worse systolic and diastolic function and higher MMP-3 and syndecan-4 levels, whereas female patients had higher septal E/e′. Male sex was independently associated with indexed LV mass (β = 13.32 [IQR: 9.59 to 17.05]; p < 0.001). During median follow-up of 374 (IQR: 351 to 498) days, a primary outcome, driven by spontaneous symptom onset, occurred in 21.8% of male and 43.9% of female patients (relative risk: 0.50 [95% confidence interval: 0.31 to 0.80]; p = 0.004). Measures of AS severity were associated with the primary outcome in both sexes, whereas N-terminal pro–B-type natriuretic peptide, MMP-3, and mass/volume were only associated in men.\ud \ud Conclusions: \ud In AS, women tolerate pressure overload with less concentric remodeling and myocardial fibrosis but are more likely to develop symptoms. This may be related to higher wall stress and filling pressures in women.

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.

Background: Complete revascularisation in patients with multivessel disease who are treated with primary percutaneous coronary intervention (PPCI) may improve outcomes compared with an infarct-related artery (IRA)-only strategy. However, non-IRA percutaneous coronary intervention (PCI) may result in additional myocardial infarction (MI).Objectives: To determine whether or not in-hospital complete revascularisation was associated with increased total infarct size (IS) in patients participating in the Complete versus Lesion-only PPCI trial (CvLPRIT). Secondary objectives were to assess whether or not myocardial salvage index, myocardial ischaemia and final IS at follow-up were different with a complete revascularisation versus an IRA-only strategy.Design: Multicentre, prospective, randomised, controlled and open-label trial with blinded end-point analysis.Setting: Seven PPCI centres in England, UK.Participants: ST-segment elevation MI (STEMI) patients with multivessel disease (angiographic stenosis > 70% in one view or > 50% in orthogonal views) presenting within 12 hours of symptom onset and treated with the PPCI. Coronary artery bypass surgery, cardiogenic shock and contraindications to cardiovascular magnetic resonance (CMR; substudy only) imaging were exclusions.Interventions: Patients were randomised to either complete in-hospital revascularisation or an IRA-only strategy.Main outcome measures: The primary outcome was IS as measured by CMR undertaken at 48–72 hours post PPCI. Secondary outcome measures included microvascular obstruction, myocardial salvage index, left ventricular volumes and ejection fraction and final IS on the acute and follow-up CMR carried out at 9 months post STEMI.Results: Patients were recruited from May 2011 until May 2013 and followed up for 12 months. Of 296 patients randomised in the main CvLPRIT, 205 consented to participate in the CMR substudy and 203 had analysable images for the primary end point. Patients in the IRA-only group (n = 105) were well matched to those in the complete revascularisation group (n = 98) for all baseline characteristics {mean age 64.1 years [standard deviation (SD) 10.8 years] vs. 63.1 years (SD 11.3 years); male sex 89% vs. 79%, respectively}. Total IS was not significantly different in the IRA-only and complete revascularisation groups {median 13.5% [interquartile range (IQR) 6.2–21.9%] of left ventricular (LV) mass vs. median 12.6% (IQR 7.2–22.6%) LV mass, respectively; 95% confidence interval –4.09% to 31.17%; p = 0.57}. Myocardial salvage index was also not significantly different in the IRA-only and complete revascularisation groups [median 58.5% (IQR 32.8–74.9%) vs. median 60.5% (IQR 40.6–81.9%), respectively; p = 0.14]. The prevalence of non-IRA MI on acute CMR was higher in the complete revascularisation group than in the IRA-only group (22/98 vs. 11/105, respectively; p = 0.02). There was no difference in total IS, ischaemic burden or LV volumes between treatment groups at follow-up CMR.Limitations: The CMR substudy population may not be a true representation of the overall study population. The optimal timing of CMR to measure IS post PPCI is uncertain. Myocardial salvage was assessable in only 70% of patients.Conclusions: Multivessel PCI, compared with an IRA-only revascularisation, in the setting of STEMI led to a small increase in CMR imaging-detected non-IRA MI, but total IS was not increased.Future work: Larger studies are required to (1) confirm that death and MI are reduced by a complete revascularisation strategy; (2) assess whether or not functional assessment of non-IRA lesions results in similar outcomes to a pragmatic angiographic-based revascularisation strategy; and (3) assess the timing of in-hospital versus staged outpatient complete revascularisation.Trial registration: Current Controlled Trials ISRCTN70913605.Funding: This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership. The main CvLPRIT was funded by the British Heart Foundation (SP/10/001) with support from the NIHR Comprehensive Local Research Networks.

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).

BackgroundThe 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.ObjectivesCvLPRIT (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.MethodsAfter 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.ResultsPatient 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.ConclusionsIn 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)