Joyce Wong

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)

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.

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.

Giant cell myocarditis in the CMR era

Our series of 5 cases of histologically-proven Giant cell myocarditis with concurrent CMR shows a pattern of late gadolinium enhancement which tends to be widespread involving all layers of the myocardium.

A feasibility and safety study of intracoronary hemodilution during primary coronary angioplasty in order to reduce reperfusion injury in myocardial infarction.

We designed a pilot study to evaluate safety and feasibility of an inexpensive and simple approach to intracoronary hemodilution during primary angioplasty (PPCI) to reduce reperfusion injury.

Acute fulminant necrotizing eosinophilic myocarditis: early diagnosis and treatment

Necrotizing eosinophilic myocarditis is a rare but potentially fatal condition that requires prompt recognition and treatment. We describe a case of a young athlete presenting with chest pain and breathlessness, with evidence of rapidly deteriorating cardiac function. The condition was successfully treated with corticosteroids, with no evidence of residual myocardial damage. This is the first reported case to demonstrate the utility of cardiac magnetic resonance imaging for diagnosis and monitoring response to treatment. It also highlights the value of endomyocardial biopsy in establishing a tissue diagnosis in cases of fulminant myocarditis, in order to direct treatment appropriately.

Imaging diagnoses and outcome in patients presenting for primary angioplasty but no obstructive coronary artery disease.

Objective A proportion of patients with suspected ST-elevation myocardial infarction (STEMI) presenting for primary percutaneous coronary intervention (PPCI) do not have obstructive coronary disease and other conditions may be responsible for their symptoms and ECG changes. In this study, we set out to determine the prevalence and aetiology of alternative diagnoses in a large PPCI cohort as determined with multimodality imaging and their outcome. Methods From 2009 to 2012, 5238 patients with suspected STEMI were referred for consideration of PPCI. Patients who underwent angiography but had no culprit artery for revascularisation and no previous history of coronary artery disease were included in the study. Troponin values, imaging findings and all-cause mortality were obtained from hospital and national databases. Results A total of 575 (13.0%) patients with a mean age of 58±15 years (69% men) fulfilled the inclusion criteria. A specific diagnosis based on imaging was made in 237 patients (41.2%) including cardiomyopathies (n=104, 18%), myopericarditis (n=48, 8.4%), myocardial infarction/other coronary abnormality (n=27, 4.9%) and severe valve disease (n=23, 4%). Pulmonary embolism and type A aortic dissection were identified in seven (1.2%) and four (0.7%) cases respectively. A total of 40 (7.0%) patients died over a mean follow-up of 42.6 months. Conclusions A variety of cardiac and non-cardiac conditions are prevalent in patients presenting with suspected STEMI but culprit-free angiogram, some of which may have adverse outcomes. Further imaging of such patients could thus be useful to help in appropriate management and follow-up.

19 The randomised complete vs. lesion only primary PCI trial – cardiovascular MRI substudy (CVLPRIT-CMR)

Background Multivessel disease (MVD) occurs in ~40% of STEMI. Management is controversial. PRAMI and CVLPRIT showed improved clinical outcomes with complete versus infarct-related artery (IRA)-only revascularisation at primary percutaneous coronary intervention (PPCI). However, non-IRA PCI may cause additional infarcts. We aimed to determine whether in-hospital complete revascularisation was associated with increased myocardial injury versus an IRA-only strategy. Methods Multicentre, prospective, randomised, blinded endpoint trial. STEMI patients with MVD and <12 hr symptoms were randomised to IRA-only or complete in-hospital PCI. 1.5T CMR was performed acutely (median 3 days post-PPCI) and with adenosine stress at 9 months. The primary CMR endpoint was acute infarct size on late gadolinium imaging. Myocardial salvage index (MSI) was the proportion of non-infarcted area-at-risk. n = 100 per group gave 80% power to detect ±4% infarct size. The primary clinical outcome was 12 month combined MACE (death, repeat revascularisation, heart failure, MI). Validation studies optimised infarct, area-at-risk and strain quantification. Full-width half-maximum infarct quantification was more accurate, reproducible and correlated strongest with ejection fraction (LVEF) and infarct characteristics. Otsu’s Automated Thresholding most accurately and reproducibly assessed area-at-risk. Compared with tagging, Feature Tracking strain measurement was more robust, quicker, had better interobserver variability and correlated stronger with infarct, area-at-risk and MSI. Results (summarised in Table 1) 203 patients (98 complete revascularisation, 105 IRA-only) completed acute CMR. The groups were well matched. There was no difference in infarct size, MSI, LVEF, circumferential strain or ischaemic burden between groups. Complete revascularisation patients had increased non-IRA MI at acute CMR (Figure 1). 12 month MACE was reduced in complete revascularisation patients (8.2% vs. 17.1%, p = 0.055, hazard ratio 0.43). Conclusions Complete revascularisation in STEMI with MVD leads to a small increase in CMR-detected non-IRA MI, but total infarct size and 12 month MACE are not increased. This provides further reassurance that complete revascularisation can be considered at PPCI. Abstract 19 Table 1 Baseline, angiographic and CMR characteristics Variable IRA-only revascularisation (n = 105) Complete revascularisation (n = 98) p Baseline characteristics Age (y) 64.1 ± 10.8 63.1 ± 11.3 0.53 Male sex (n,%) 83/105 (79.0) 87/98 (88.8) 0.06 Anterior infarct (n,%) 37/105 (37.2) 35/98 (35.7) 0.94 Diabetes Mellitus (n,%) 13/105 (12.4) 15/98 (15.3) 0.55 Angiographic markers TIMI pre PCI grade 0–2 (n,%) 97/105 (92.4) 89/98 (90.8) 0.69 SYNTAX score (total) 18 (14–22) 17.3 (13–23.5) 0.81 Symptom-PCI time (TTR, min) 171 (127–268) 192 (131–302) 0.20 TIMI post PCI grade 3 (n,%) 100/105 (95.2) 89/98 (90.8) 0.21 Acute CMR Time to acute CMR (d) 2.8 (1.8–3.4) 3.0 (2.0–4.3) 0.13 LV ejection fraction (%) 45.1 ± 9.5 45.9 ± 9.9 0.60 Peak LV circumferential strain (Ecc,%) −18.1 ± 6.0 -18.6 ± 6.1 0.86 Total infarct size (% LV mass) 13.5 (6.2–21.9) 12.6 (7.2–22.6) 0.57 Patients with >1 infarct 11/105 (10.5) 22/98 (22.4) 0.02 Patients >1 acute infarct 5/105 (4.8) 17/98 (17.1) 0.004 Myocardial salvage index (%) 60.5 (40.6–81.9) 58.5 (32.8–74.9) 0.14 Follow-up CMR Time to follow-up CMR (CMR2, mth) 9.3 (8.9–9.9) 9.4 (9.0–10) 0.20 LV ejection fraction (%) 50.8 ± 8.7 49.7 ± 9.4 0.42 Peak LV circumferential strain (Ecc,%) −23.6 ± 6.3 −22.5 ± 6.3 0.28 Total infarct size (% LV mass) 7.6 (3.2–15.1) 7.3 (3.0–14.4) 0.41 Patients with >1 infarct (%) 9/80 (11.2) 20/84 (23.8) 0.035 Presence of ischaemia (n,%) in all pats 16/77 (20.8) 17/82 (20.7) 0.99 Global ischaemic burden (%) all pats 4.3 ± 11.3 3.4 ± 8.9 0.81 Abstract 19 Figure 1 Multiple infarcts on late gadolinium imaging in complete revascularisation patients The 2 images on left and 2 images on right are 2 different patients. A = main infarct-related artery territory infarct B = infarct in non-infarct related artery territory

126 Predictors of Final Left Ventricular Ejection Fraction <35% and Medium-Term Clinical Outcomes in Patients with Multivessel Disease at Stemi

Background Multivessel disease (MVD) is seen in ˜40% of ST-elevation Myocardial Infarctions (STEMI). Revascularisation strategy and chronic total occlusions affect clinical outcomes in MVD. However, there are no published multivariate data on additional predictors of clinical outcomes in patients with MVD undergoing PPCI. We aimed to provide a comprehensive multimodal, multivariate assessment of independent predictors (clinical, bioanthropometric, angiographic and cardiovascular magnetic resonance [CMR]) of medium-term severe left ventricular systolic dysfunction (LVSD) and clinical outcomes in patients with MVD at PPCI. Methods STEMI patients presenting <12 hr with MVD were prospectively enrolled. Multiparametric contrast-enhanced CMR was undertaken within 48 h of PPCI (‘Acute CMR’) and at 9 months (‘Follow-up CMR’) at 1.5T. LV volumetrics, strain, area-at-risk (AAR) and infarct characteristics were assessed on CMR using SSFP, Feature-Tracking, T2-weighted and late gadolinium imaging. Angiographic predictors included SYNTAX score, Rentrop grade and number of lesions >75% on Quantitative Coronary Angiography (QCA). The primary clinical outcome of 12-month combined MACE comprised all-cause mortality, recurrent MI, heart failure hospitalisation and ischaemia-driven revascularisation. Multivariate logistic regression and log-rank test (Cox regression) assessed independent predictors of severe LVSD (LVEF <35%) at 9-months, and 12-month combined MACE respectively. Results (a) Severe LVSD (LVEF <35%) at 9-months Univariate predictors of final LVEF <35% were anterior STEMI, diabetes, peak CK, time to revascularisation and SYNTAX score. Acute CMR predictors included wall-motion score (WMS), LV volumes, LVEF, infarct size (IS), AAR, extent of microvascular obstruction (MVO), myocardial salvage (MSI), and global strain. At stepwise multivariate regression, WMS was the only independent predictor of final LVEF <35%. ROC AUC was 0.965 and the optimal cut-off for predicting LVEF <35% was WMS ≥28 (Table 1). Abstract 126 Table 1 Multivariate predictors of final LVEF <35% at 9-months (b) Combined MACE at 12-months Univariate predictors of combined MACE at 12-months included age, peak CK, Rentrop grade, SYNTAX score, number of affected vessels and lesions >75% stenosis on QCA. Acute CMR predictors included WMS, LVEF, LV volumes, IS, AAR, MVO, MSI and global strain. At stepwise multivariate regression, IS at acute CMR was the strongest independent predictor, followed by number of lesions >75% severity on QCA, and revascularisation strategy. AUC for IS was 0.729 and the optimal cut-off for predicting MACE was IS≥16.8% LVM (Table 2). Abstract 126 Table 2 Multivariate predictors of combined first MACE at 12-months Conclusions In this novel, comprehensive study assessing multiparametric independent predictors of clinical outcomes for MVD at PPCI in STEMI, WMS at acute CMR was the only independent predictor of final LVEF <35%. Acute IS was the strongest independent predictor of 12-month combined MACE, followed by number of lesions >75% on QCA, and revascularisation strategy. Acute CMR surrogate markers are powerful predictors of medium-term clinical outcomes following PPCI for MVD.