Jamal N Khan

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)

Intertechnique agreement and interstudy reproducibility of strain and diastolic strain rate at 1.5 and 3 Tesla: a comparison of feature-tracking and tagging in patients with aortic stenosis.

To determine the interstudy reproducibility of myocardial strain and peak early‐diastolic strain rate (PEDSR) measurement on cardiovascular magnetic resonance imaging (MRI) assessed with feature tracking (FT) and tagging, in patients with aortic stenosis (AS).

Comparison of cardiovascular magnetic resonance feature tracking and tagging for the assessment of left ventricular systolic strain in acute myocardial infarction

AIMS To assess the feasibility of feature tracking (FT)-measured systolic strain post acute ST-segment elevation myocardial infarction (STEMI) and compare strain values to those obtained with tagging. METHODS Cardiovascular MRI at 1.5T was performed in 24 patients, 2.2 days post STEMI. Global and segmental circumferential (Ecc) and longitudinal (Ell) strain were assessed using FT and tagging, and correlated with total and segmental infarct size, area at risk and myocardial salvage. RESULTS All segments tracked satisfactorily with FT (p<0.001 vs. tagging). Total analysis time per patient was shorter with FT (38.2±3.8 min vs. 63.7±10.3 min, p<0.001 vs. tagging). Global Ecc and Ell were higher with FT than with tagging, apart from FT Ecc using the average of endocardial and epicardial contours (-13.45±4.1 [FT] vs. -13.85±3.9 [tagging], p=0.66). Intraobserver and interobserver agreement for global strain were excellent for FT (ICC 0.906-0.990) but interobserver agreement for tagging was lower (ICC<0.765). Interobserver and intraobserver agreement for segmental strain was good for both techniques (ICC>0.7) apart from tagging Ell, which was poor (ICC=0.15). FT-derived Ecc significantly correlated with total infarct size (r=0.44, p=0.03) and segmental infarct extent (r=0.44, p<0.01), and best distinguished transmurally infarcted segments (AUC 0.77) and infarcted from adjacent and remote segments. FT-derived Ecc correlated strongest with segmental myocardial salvage (rs=-0.406). CONCLUSIONS FT global Ecc and Ell measurement in acute STEMI is feasible and robust. FT-derived strain is quicker to analyse, tracks myocardium better, has better interobserver variability and correlated more strongly with infarct, area at risk (oedema), myocardial salvage and infarct transmurality.

Myocardial T1 and extracellular volume fraction measurement in asymptomatic patients with aortic stenosis: reproducibility and comparison with age-matched controls

AIMS (i) To establish the test-retest reproducibility of myocardial T1 and extracellular volume (ECV) fraction measurement in asymptomatic patients with moderate-severe aortic stenosis (AS), (ii) to compare reproducibility using motion-corrected (MOCO) parametric T1 maps for analysis vs. full MOLLI series of images, and (iii) to compare T1 and ECV between patients and age-matched controls. METHODS AND RESULTS 3 T cardiac MRI was performed twice on 10 patients (median interval 7 days) to assess reproducibility. An additional 40 patients and 22 asymptomatic controls underwent a single MRI. Native T1 and ECV were calculated by outlining the myocardium on T1 maps generated inline, and using an offline T1 fit on the MOCO multiple inversion-time raw image series, in the reproducibility cohort (n = 10). Reproducibility was excellent using the inline T1 maps (CoVs for T1: 1.77%; ECV: 6.52%) and good using the full MOLLI series (CoVs for T1: 8.52%; ECV: 12.98%). On comparing AS and controls, who were well matched for age, gender and co-morbidities, there was no significant difference in the native T1 or ECV (T1 = 1103.32 ± 33.07 vs. 1092.27 ± 34.29; ECV = 0.243 ± 0.019 vs. 0.251 ± 0.026 in patients and controls, P > 0.05), which was maintained even after splitting the patients into moderate and severe AS subgroups. CONCLUSION The test-retest reproducibility of myocardial T1 quantification using MOLLI is excellent in patients with AS and is highest using inline generated T1 maps for analysis. There was no difference in native myocardial T1 or ECV between asymptomatic patients with moderate-severe AS and age-matched controls without valve disease.

Subclinical diastolic dysfunction in young adults with Type 2 diabetes mellitus: a multiparametric contrast-enhanced cardiovascular magnetic resonance pilot study assessing potential mechanisms

AIMS To assess the cardiac, vascular, anthropometric, and biochemical determinants of subclinical diastolic dysfunction in younger adults with Type 2 diabetes mellitus (T2DM) using multiparametric contrast-enhanced cardiovascular magnetic resonance (CMR) imaging. METHODS AND RESULTS Twenty adults <40 years with T2DM [mean age 31.8(6.6) years, T2DM duration 4.7(4.0) years] and 20 age and sex-matched controls [10 obese non-diabetic controls and 10 lean controls (LC)] were studied. Cardiac volumes and function, circumferential strain and peak early diastolic strain rate (PEDSR), myocardial perfusion reserve, aortic stiffness (distensibility, pulse-wave velocity), focal fibrosis on late gadolinium enhancement, and pre- and post-contrast T1 mapping for contrast agent partition coefficient (subset, n = 26) were determined by CMR. In the T2DM cohort, mean aortic distensibility correlated with PEDSR (r = 0.564, P = 0.023) and diabetes duration correlated inversely with PEDSR (r = -0.534, P = 0.015) on univariate analysis. There was a close association between PEDSR and peak systolic strain (r = -0.580, P = 0.007). CONCLUSION In young adults with T2DM, diabetes duration and aortic distensibility were associated with diastolic dysfunction. Interventional studies are required to assess whether cardiac dysfunction can be reversed in this phenotype of patients.

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)

Type 2 diabetes mellitus and obesity in young adults: the extreme phenotype with early cardiovascular dysfunction.

A pilot study to phenotype young adults (< 40 years) with Type 2 diabetes mellitus.

Rationale and design of the PRognostic Importance of MIcrovascular Dysfunction in asymptomatic patients with Aortic Stenosis (PRIMID-AS): a multicentre observational study with blinded investigations.

Introduction Aortic stenosis (AS) is the commonest valve disorder in the developed world requiring surgery. Surgery in patients with severe asymptomatic AS remains controversial. Exercise testing can identify asymptomatic patients at increased risk of death and symptom development, but with limited specificity, especially in older adults. Cardiac MRI (CMR), including myocardial perfusion reserve (MPR) may be a novel imaging biomarker in AS. Aims (1) To improve risk stratification in asymptomatic patients with AS and (2) to determine whether MPR is a better predictor of outcome than exercise testing and brain natriuretic peptide (BNP). Method/design Multicentre, prospective observational study in the UK, comparing MPR with exercise testing and BNP (with blinded CMR analysis) for predicting outcome. Population 170 asymptomatic patients with moderate-to-severe AS, who would be considered for aortic valve replacement (AVR). Primary outcome Composite of: typical symptoms necessitating referral for AVR and major adverse cardiovascular events. Follow-up: 12–30 months (minimum 12 months). Primary hypothesis MPR will be a better predictor of outcome than exercise testing and BNP. Ethics/dissemination The study has full ethical approval and is actively recruiting patients. Data collection will be completed in November 2014 and the study results will be submitted for publication within 6 months of completion. ClinicalTrials.gov identifier NCT01658345.

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

Abstract 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

Comparison of semi-automated methods to quantify infarct size and area at risk by cardiovascular magnetic resonance imaging at 1.5T and 3.0T field strengths.

BackgroundThere is currently no gold standard technique for quantifying infarct size (IS) and ischaemic area-at-risk (AAR [oedema]) on late gadolinium enhancement imaging (LGE) and T2-weighted short tau inversion recovery imaging (T2w-STIR) respectively. This study aimed to compare the accuracy and reproducibility of IS and AAR quantification on LGE and T2w-STIR imaging using Otsu’s Automated Technique (OAT) with currently used methods at 1.5T and 3.0T post acute ST-segment elevation myocardial infarction (STEMI).MethodsTen patients were assessed at 1.5T and 10 at 3.0T. IS was assessed on LGE using 5–8 standard-deviation thresholding (5-8SD), full-width half-maximum (FWHM) quantification and OAT. AAR was assessed on T2w-STIR using 2SD and OAT. Accuracy was assessed by comparison with manual quantification. Interobserver and intraobserver variabilities were assessed using Intraclass Correlation Coefficients and Bland-Altman analysis. IS using each technique was correlated with left ventricular ejection fraction (LVEF).ResultsFWHM and 8SD-derived IS closely correlated with manual assessment at both field strengths (1.5T: 18.3 ± 10.7% LV Mass [LVM] with FWHM, 17.7 ± 14.4% LVM with 8SD, 16.5 ± 10.3% LVM with manual quantification; 3.0T: 10.8 ± 8.2% LVM with FWHM, 11.4 ± 9.0% LVM with 8SD, 11.5 ± 9.0% LVM with manual quantification). 5SD and OAT overestimated IS at both field strengths. OAT, 2SD and manually quantified AAR closely correlated at 1.5T, but OAT overestimated AAR compared with manual assessment at 3.0T. IS and AAR derived by FWHM and OAT respectively had better reproducibility compared with manual and SD-based quantification. FWHM IS correlated strongest with LVEF.ConclusionsFWHM quantification of IS is accurate, reproducible and correlates strongly with LVEF, whereas 5SD and OAT overestimate IS. OAT accurately assesses AAR at 1.5T and with excellent reproducibility. OAT overestimated AAR at 3.0T and thus cannot be recommended as the preferred method for AAR quantification at 3.0T.