Sheraz A Nazir

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.

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)

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.

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

BackgroundMicrovascular 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.MethodsThe 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).DiscussionThe 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 registrationTrial registered 20th November 2012: ClinicalTrials.gov Identifier NCT01747174.

Relationship of Myocardial Strain and Markers of Myocardial Injury to Predict Segmental Recovery After Acute ST-Segment–Elevation Myocardial Infarction

Background—Late gadolinium-enhanced cardiovascular magnetic resonance imaging overestimates infarct size and underestimates recovery of dysfunctional segments acutely post ST-segment–elevation myocardial infarction. We assessed whether cardiovascular magnetic resonance imaging–derived segmental myocardial strain and markers of myocardial injury could improve the accuracy of late gadolinium-enhancement in predicting functional recovery after ST-segment–elevation myocardial infarction. Methods and Results—A total of 164 ST-segment–elevation myocardial infarction patients underwent acute (median 3 days) and follow-up (median 9.4 months) cardiovascular magnetic resonance imaging. Wall-motion scoring, feature tracking–derived circumferential strain (Ecc), segmental area of late gadolinium-enhancement (SEE), microvascular obstruction, intramyocardial hemorrhage, and salvage index (MSI) were assessed in 2624 segments. We used logistic regression analysis to identify markers that predict segmental recovery. At acute CMR 32% of segments were dysfunctional, and at follow-up CMR 19% were dysfunctional. Segmental function at acute imaging and odds ratio (OR) for functional recovery decreased with increasing SEE, although 33% of dysfunctional segments with SEE 76% to 100% improved. SEE was a strong predictor of functional improvement and normalization (area under the curve [AUC], 0.840 [95% confidence interval {CI}, 0.814–0.867]; OR, 0.97 [95% CI, 0.97–0.98] per +1% SEE for improvement and AUC, 0.887 [95% CI, 0.865–0.909]; OR, 0.95 [95% CI, 0.94–0.96] per +1% SEE for normalization). Its predictive accuracy for improvement, as assessed by areas under the receiver operator curves, was similar to that of MSI (AUC, 0.840 [95% CI, 0.809–0.872]; OR, 1.03 [95% CI, 1.02–1.03] per +1% MSI for improvement and AUC, 0.862 [0.832–0.891]; OR, 1.04 [95% CI, 1.03–1.04] per +1% SEE for normalization) and Ecc (AUC, 0.834 [95% CI, 0.807–0.862]; OR, 1.05 [95% CI, 1.03–1.07] per +1% MSI for improvement and AUC, 0.844 [95% CI, 0.818–0.871]; OR, 1.07 [95% CI, 1.05–1.10] per +1% SEE for normalization), and for normalization was greater than the other predictors. MSI and Ecc remained as significant after adjustment for SEE but provided no significant increase in predictive accuracy for improvement and normalization compared with SEE alone. MSI had similar predictive accuracy to SEE for functional recovery but was not assessable in 25% of patients. Microvascular obstruction provided no incremental predictive accuracy above SEE. Conclusions—This multicenter study confirms that SEE is a strong predictor of functional improvement post ST-segment–elevation myocardial infarction, but recovery occurs in a substantial proportion of dysfunctional segments with SEE >75%. Feature tracking–derived Ecc and MSI provide minimal incremental benefit to SEE in predicting segmental recovery. Clinical Trial Registration—URL: http://www.isrctn.com. Unique identifier: ISRCTN70913605.

Global myocardial strain assessment by different imaging modalities to predict outcomes after ST-elevation myocardial infarction: A systematic review.

AIM To conduct a systematic review relating myocardial strain assessed by different imaging modalities for prognostication following ST-elevation myocardial infarction (STEMI). METHODS An online literature search was performed in PubMed and OVID(®) electronic databases to identify any studies that assessed global myocardial strain parameters using speckle-tracking echocardiography (STE) and/or cardiac magnetic resonance imaging (CMR) techniques [either myocardial tagging or feature tracking (FT) software] in an acute STEMI cohort (days 0-14 post-event) to predict prognosis [either development of major adverse cardiac events (MACE)] or adverse left ventricular (LV) remodelling at follow-up (≥ 6 mo for MACE, ≥ 3 mo for remodelling). Search was restricted to studies within the last 20 years. All studies that matched the pre-defined search criteria were reviewed and their results interpreted. Due to considerable heterogeneity between studies, meta-analysis was not performed. RESULTS A total of seven studies (n = 7) were identified that matched the search criteria. All studies used STE to evaluate strain parameters - five (n = 5) assessed global longitudinal strain (GLS) (n = 5), one assessed GLS rate (GLS-R) (n = 1) and one assessed both (n = 1). Three studies showed that GLS independently predicted the development of adverse LV remodelling by multivariate analysis - odds ratio between 1.19 (CI: 1.04-1.37, P < 0.05) and 10 (CI: 6.7-14, P < 0.001) depending on the study. Four studies showed that GLS predicted the development of MACE - hazard ratio (HR) between 1.1 (CI: 1-1.1, P = 0.006) and 2.34 (1.10-4.97, P < 0.05). One paper found that GLS-R could significantly predict MACE - HR 18 (10-35, P < 0.001) - whilst another showed it did not. GLS < -10.85% had sensitivity/specificity of 89.7%/91% respectively for predicting the development of remodelling whilst GLS < -13% could predict the development of MACE with sensitivity/specificity of 100%/89% respectively. No suitable studies were identified that assessed global strain by CMR tagging or FT techniques. CONCLUSION GLS measured acutely post-STEMI by STE is a predictor of poor prognosis. Further research is needed to show that this is true for CMR-based techniques.

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.

Inter-study reproducibility of circumferential strain and strain rates at 1.5T and 3T: a comparison of tagging and feature tracking

Background Feature Tracking (FT) is a relatively new technique for measuring strain on cardiac magnetic resonance imaging (CMR), that has been shown to have reasonable interstudy reproducibility (Coefficient of variation (CoV) ~20%) in healthy volunteers. The inter-study reproducibility of FT has not yet been reported in any patient groups, nor compared to that of MRI tagging. We sought to determine the inter-study reproducibility of circumferential strain and strain rates using FT and tagging at 1.5T and 3T scanners, in patients with moderate-severe Aortic Stenosis (AS). Methods CMR was performed twice in 8 patients with severe AS on a 1.5T scanner and 10 patients with moderate-severe AS at 3T. Three short-axis tagged images were acquired, in addition to the standard SSFP short-axis cine stack. InTag (Creatis, Lyon, France) in OsiriX (Geneva, Switzerland) was used to calculate the Circumferential Peak Systolic Strain (PSS), Peak Systolic Strain Rate (PSSR) and Peak Early Diastolic Strain Rate (PEDSR). Diogenes CMR FT (TomTec Imaging Systems, Munich, Germany) was used to calculate the same parameters on nearest SSFP cine images. Results Overall, FT gave higher strain and strain rate values when compared to tagging. On paired sample t-tests, there was no significant difference in the strain and strain rate values between scan one and scan two, using both tagging and FT, at both 1.5T and 3T. The inter-study reproducibility of both techniques was higher at 1.5T compared to 3T. (Table 1, Figure 1) Comparing tagging vs FT, PSS was more reproducible with FT at both 1.5T and 3T, while PSSR was more reproducible with tagging. PEDSR demonstrated similar inter-study reproducibility using both techniques, but was much more reproducible at 1.5T than 3T. (CoV’s for circumferential PSS, PSSR and PEDSR at 1.5T- FT: 8.6, 11.8 and 13.1%, tagging: 12.2, 9.4 and 17.5%; CoV’s at 3T-FT: 9.4, 23 and 25.6%, tagging: 17.9, 19.3 and 32.5%). Conclusions Both tagging and FT have good reproducibility at 1.5T and modest reproducibility at 3T scanners. This may partly be due to greater artefacts at 3T. Overall, FT appears to have higher reproducibility than tagging for circumferential PSS, while PSSR is more reproducible with tagging. If the main parameter of interest is PEDSR, scanning at 1.5T and using FT is more preferable. Given that FT does not require additional image acquisitions and involves shorter post-processing time, this technique is likely to become the preferred method for strain and strain rate quantification with CMR.