Effects of late, repetitive remote ischaemic conditioning on myocardial strain in patients with acute myocardial infarction.

Late, repetitive or chronic remote ischaemic conditioning (CRIC) is a potential cardioprotective strategy against adverse remodelling following ST-segment elevation myocardial infarction (STEMI). In the randomised Daily Remote Ischaemic Conditioning Following Acute Myocardial Infarction (DREAM) trial, CRIC following primary percutaneous coronary intervention (P-PCI) did not improve global left ventricular (LV) systolic function. A post-hoc analysis was performed to determine whether CRIC improved regional strain. All 73 patients completing the original trial were studied (38 receiving 4 weeks' daily CRIC, 35 controls receiving sham conditioning). Patients underwent cardiovascular magnetic resonance at baseline (5-7 days post-STEMI) and after 4 months, with assessment of LV systolic function, infarct size and strain (longitudinal/circumferential, in infarct-related and remote territories). At both timepoints, there were no significant between-group differences in global indices (LV ejection fraction, infarct size, longitudinal/circumferential strain). However, regional analysis revealed a significant improvement in longitudinal strain in the infarcted segments of the CRIC group (from - 16.2 ± 5.2 at baseline to - 18.7 ± 6.3 at follow up, p = 0.0006) but not in corresponding segments of the control group (from - 15.5 ± 4.0 to - 15.2 ± 4.7, p = 0.81; for change: - 2.5 ± 3.6 versus + 0.3 ± 5.6, respectively, p = 0.027). In remote territories, there was a lower increment in subendocardial circumferential strain in the CRIC group than in controls (- 1.2 ± 4.4 versus - 2.5 ± 4.0, p = 0.038). In summary, CRIC following P-PCI for STEMI is associated with improved longitudinal strain in infarct-related segments, and an attenuated increase in circumferential strain in remote segments. Further work is needed to establish whether these changes may translate into a reduced incidence of adverse remodelling and clinical events. Clinical Trial Registration: http://clinicaltrials.gov/show/NCT01664611 .

Implementation of more sensitive cardiac troponin T assay in a state-wide health service.

AIMS: Explore the impact of deploying high-sensitivity (hs) cardiac troponin T (cTnT) assay across a state-wide health service. METHODS AND RESULTS: Presentations to emergency departments of six tertiary hospitals between January 2008 and August 2019 were included; standard cTnT assay was superseded by hs-cTnT in June 2011 without changing the reference range (≥30 ng/L reported as elevated), despite cTnT level of 30 ng/L being equivalent to ∼44 ng/L with hs-cTnT. Clinical outcomes were captured using state-wide linked health records. Interrupted time series analyses were used adjusted for seasonality and multiple co-morbidities using propensity score matching allowing for correlation within hospitals. In total, 614,847 presentations had ≥1 troponin measurement. Clinical ordering of troponin decreased throughout the study with no increase in elevated measurements amongst those tested with hs-cTnT. Small but statistically significant changes in index myocardial infarction (MI) diagnosis (-0.36%/year, 95%CI [confidence interval]:-0.48, -0.24,p < 0.001) and invasive coronary angiography (0.12%/year,95%CI:0, 0.24,p = 0.02) were seen, with no impact on death/MI at 30 days or 3-year survival in episodes of care (EOCs) with elevated cTnT after hs-cTnT implementation. Length of stay (LOS) was shorter among those with an elevated hs-cTnT (-4.44 h/year, 95%CI:-5.27, -3.60, p < 0.001). Non-elevated cTnT EOCs demonstrated shorter total LOS and improved 3-year survival (adjusted hazard ratio:0.90, 95%CI:0.83, 0.97,p = 0.008) although death/MI at 30 days was unchanged using hs-cTnT. CONCLUSION: Widespread implementation of hs-cTnT without altering clinical thresholds reported to clinicians provided significantly shorter LOS without a clinically significant impact on clinical outcomes. A safer cohort with non-elevated cTnT was identified by hs-cTnT compared to the standard cTnT assay.

Vascular effects of serelaxin in patients with stable coronary artery disease: a randomized placebo-controlled trial.

AIMS: The effects of serelaxin, a recombinant form of human relaxin-2 peptide, on vascular function in the coronary microvascular and systemic macrovascular circulation remain largely unknown. This mechanistic, clinical study assessed the effects of serelaxin on myocardial perfusion, aortic stiffness, and safety in patients with stable coronary artery disease (CAD). METHODS AND RESULTS: In this multicentre, double-blind, parallel-group, placebo-controlled study, 58 patients were randomized 1:1 to 48 h intravenous infusion of serelaxin (30 µg/kg/day) or matching placebo. The primary endpoints were change from baseline to 47 h post-initiation of the infusion in global myocardial perfusion reserve (MPR) assessed using adenosine stress perfusion cardiac magnetic resonance imaging, and applanation tonometry-derived augmentation index (AIx). Secondary endpoints were: change from baseline in AIx and pulse wave velocity, assessed at 47 h, Day 30, and Day 180; aortic distensibility at 47 h; pharmacokinetics and safety. Exploratory endpoints were the effect on cardiorenal biomarkers [N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hsTnT), endothelin-1, and cystatin C]. Of 58 patients, 51 were included in the primary analysis (serelaxin, n = 25; placebo, n = 26). After 2 and 6 h of serelaxin infusion, mean placebo-corrected blood pressure reductions of -9.6 mmHg (P = 0.01) and -13.5 mmHg (P = 0.0003) for systolic blood pressure and -5.2 mmHg (P = 0.02) and -8.4 mmHg (P = 0.001) for diastolic blood pressure occurred. There were no between-group differences from baseline to 47 h in global MPR (-0.24 vs. -0.13, P = 0.44) or AIx (3.49% vs. 0.04%, P = 0.21) with serelaxin compared with placebo. Endothelin-1 and cystatin C levels decreased from baseline in the serelaxin group, and there were no clinically relevant changes observed with serelaxin for NT-proBNP or hsTnT. Similar numbers of serious adverse events were observed in both groups (serelaxin, n = 5; placebo, n = 7) to 180-day follow-up. CONCLUSION: In patients with stable CAD, 48 h intravenous serelaxin reduced blood pressure but did not alter myocardial perfusion.

Inter-study repeatability of circumferential strain and diastolic strain rate by CMR tagging, feature tracking and tissue tracking in ST-segment elevation myocardial infarction.

Strain assessment allows accurate evaluation of myocardial function and mechanics in ST-segment elevation myocardial infarction (STEMI). Strain using cardiovascular magnetic resonance (CMR) has traditionally been assessed with tagging but limitations of this technique have led to more widespread use of alternative methods, which may be more robust. We compared the inter-study repeatability of circumferential global peak-systolic strain (Ecc) and peak-early diastolic strain rate (PEDSR) derived by tagging with values obtained using novel cine-based software: Feature Tracking (FT) (TomTec, Germany) and Tissue Tracking (TT) (Circle cvi42, Canada) in patients following STEMI. Twenty male patients (mean age 56 ± 10 years, mean infarct size 13.7 ± 7.1% of left ventricular mass) were randomised to undergo CMR 1-5 days post-STEMI at 1.5 T or 3.0 T, repeated after ten minutes at the same field strength. Ecc and PEDSR were assessed using tagging, FT and TT. Inter-study repeatability was evaluated using Bland-Altman analyses, coefficients of variation (CoV) and intra-class correlation coefficient (ICC). Ecc (%) was significantly lower with tagging than with FT or TT at 1.5 T (- 9.5 ± 3.3 vs. - 17.5 ± 3.8 vs. -15.5 ± 5.2, respectively, p < 0.001) and 3.0 T (- 13.1 ± 1.8 vs. - 19.4 ± 2.9 vs. - 17.3 ± 2.1, respectively, p = 0.001). This was similar for PEDSR (.s-1): 1.5 T (0.6 ± 0.2 vs. 1.5 ± 0.4 vs. 1.0 ± 0.4, for tagging, FT and TT respectively, p < 0.001) and 3.0 T (0.6 ± 0.2 vs. 1.5 ± 0.3 vs. 0.9 ± 0.3, respectively, p < 0.001). Inter-study repeatability for Ecc at 1.5 T was good for tagging and excellent for FT and TT: CoV 16.7%, 6.38%, and 8.65%, respectively. Repeatability for Ecc at 3.0 T was good for all three techniques: CoV 14.4%, 11.2%, and 13.0%, respectively. However, repeatability of PEDSR was generally lower than that for Ecc at 1.5 T (CoV 15.1%, 13.1%, and 34.0% for tagging, FT and TT, respectively) and 3.0 T (CoV 23.0%, 18.6%, and 26.2%, respectively). Following STEMI, Ecc and PEDSR are higher when measured with FT and TT than with tagging. Inter-study repeatability of Ecc is good for tagging, excellent for FT and TT at 1.5 T, and good for all three methods at 3.0 T. The repeatability of PEDSR is good to moderate at 1.5 T and moderate at 3.0 T. Cine-based methods to assess Ecc following STEMI may be preferable to tagging.

Biostial iatrogenic coronary artery stenosis: a rare complication of aortic valve surgery successfully treated with percutaneous coronary stenting.

A 66-year-old woman presented 4 months after conventional surgical aortic valve replacement with an acute coronary syndrome resulting from rare iatrogenic biostial left main and right coronary artery stenoses, which were successfully treated with percutaneous coronary stenting, optimized by intracoronary imaging.

Accelerated patent hemostasis using a procoagulant disk; a protocol designed to minimize the risk of radial artery occlusion following cardiac catheterization.

PURPOSE: Radial artery occlusion flowing cardiac catheterisation has been linked to flow reduction and prolonged compression. We investigate whether these factors can be optimised following transradial cardiac catheterisation by using an accelerated band removal protocol facilitated by a haemostasis promoting pad, in combination with a patent haemostasis technique. METHODS: In this single centre prospective study, 389 consecutive patients undergoing TRA for coronary angiography or angioplasty were randomised to two haemostasis protocols: use of a Helix™ compression device alone (HC) or in combination with a haemostatic pad (StatSeal® disc) and an accelerated haemostasis protocol (AC). A patent haemostasis technique was employed in both study arms. The primary efficacy endpoint was the time to haemostasis and the secondary safety outcome was access site related complications: re-bleeding, haematoma and radial artery patency assessed within 24 h using reverse Barbeau's Test (BT). RESULTS: Between May and Nov 2017, 191 patients were randomised to receive HC and 198 patients to AC. Compression time was significantly higher with HC as compared to AC (165.8 ±â€¯63.1 versus 79.7 ±â€¯41.2 min, p < 0.001). There were no significant differences in re-bleeding and RAO between groups (3.7% versus 5.6%, p = 0.37 and 6.3% versus 4.1%, p = 0.33) respectively. Incidence of haematoma was higher in AC group (4.7% versus 12.1%, p = 0.009). CONCLUSION: A reduction in radial artery compression time can be achieved by using Statseal in association with an accelerated haemostasis protocol without increasing the risk of access site bleeding and RAO. The combination of reduced compression time combined with maintained radial flow via patent haemostasis has the potential to reduce the risk of radial occlusion after transradial catheterisation.

Daily remote ischaemic conditioning following acute myocardial infarction: a randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning (rIC) is a cardioprotective tool which has shown promise in preclinical and clinical trials in the context of acute ischaemia. Repeated rIC post myocardial infarction may provide additional benefits which have not previously been tested clinically. METHODS: The trial assessed the role of daily rIC in enhancing left ventricular ejection fraction (LVEF) recovery in patients with impaired LVEF (<45%) after ST segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (P-PCI). Patients were recruited from four UK hospitals and randomised to receive either 4 weeks of daily rIC or sham conditioning using the autoRIC Device (CellAegis) starting on day 3 post P-PCI. The primary endpoint was the improvement in LVEF over 4 months assessed by cardiac MRI (CMR). Seventy-three patients (38 cases, 35 controls) completed the study. RESULTS: The treatment and control groups were well matched at baseline including for mean LVEF (42.8% vs 44.3% respectively, p=0.952). There was no difference in the improvement in LVEF over 4 months between the treatment and control groups (4.8%±7.8% vs 4.6%±5.9% respectively, p=0.924). No differences were seen in the secondary outcome measures including changes in infarct size and left ventricular end-diastolic and systolic volumes, major adverse cardiac and cerebral event, mean Kansas City Cardiomyopathy Questionnaire score and change in N-terminal pro-brain natriuretic peptide levels. CONCLUSIONS: Daily rIC starting on day 3 and continued for 4 weeks following successful P-PCI for STEMI did not improve LVEF as assessed by CMR after 4 months when compared with a matched control group. TRIAL REGISTRATION NUMBER: NCT0166461.

Comparison of global myocardial strain assessed by cardiovascular magnetic resonance tagging and feature tracking to infarct size at predicting remodelling following STEMI.

BACKGROUND: To determine if global strain parameters measured by cardiovascular magnetic resonance (CMR) acutely following ST-segment Elevation Myocardial Infarction (STEMI) predict adverse left ventricular (LV) remodelling independent of infarct size (IS). METHODS: Sixty-five patients with acute STEMI (mean age 60 ± 11 years) underwent CMR at 1-3 days post-reperfusion (baseline) and at 4 months. Global peak systolic circumferential strain (GCS), measured by tagging and Feature Tracking (FT), and global peak systolic longitudinal strain (GLS), measured by FT, were calculated at baseline, along with IS. On follow up scans, volumetric analysis was performed to determine the development of adverse remodelling - a composite score based on development of either end-diastolic volume index [EDVI] ≥20% or end-systolic volume index [ESVI] ≥15% at follow-up compared to baseline. RESULTS: The magnitude of GCS was higher when measured using FT (-21.1 ± 6.3%) than with tagging (-12.1 ± 4.3; p < 0.001 for difference). There was good correlation of strain with baseline LVEF (r 0.64-to 0.71) and IS (ρ -0.62 to-0.72). Baseline strain parameters were unable to predict development of adverse LV remodelling. Only baseline IS predicted adverse remodelling - Odds Ratio 1.05 (95% CI 1.01-1.10, p = 0.03), area under the ROC curve 0.70 (95% CI 0.52-0.87, p = 0.04). CONCLUSION: Baseline global strain by CMR does not predict the development of adverse LV remodelling following STEMI.

Infarct size following complete revascularization in patients presenting with STEMI: a comparison of immediate and staged in-hospital non-infarct related artery PCI subgroups in the CvLPRIT study.

BACKGROUND: The CvLPRIT study showed a trend for improved clinical outcomes in the complete revascularisation (CR) group in those treated with an immediate, as opposed to staged in-hospital approach in patients with multivessel coronary disease undergoing primary percutaneous intervention (PPCI). We aimed to assess infarct size and left ventricular function in patients undergoing immediate compared with staged CR for multivessel disease at PPCI. METHODS: The Cardiovascular Magnetic Resonance (CMR) substudy of CvLPRIT was a multicentre, prospective, randomized, open label, blinded endpoint trial in PPCI patients with multivessel disease. These data refer to a post-hoc analysis in 93 patients randomized to the CR arm (63 immediate, 30 staged) who completed a pre-discharge CMR scan (median 2 and 4 days respectively) after PPCI. The decision to stage non-IRA revascularization was at the discretion of the treating interventional cardiologist. RESULTS: Patients treated with a staged approach had more visible thrombus (26/30 vs. 31/62, p = 0.001), higher SYNTAX score in the IRA (9.5, 8-16 vs. 8.0, 5.5-11, p = 0.04) and a greater incidence of no-reflow (23.3 % vs. 1.6 % p < 0.001) than those treated with immediate CR. After adjustment for confounders, staged patients had larger infarct size (19.7 % [11.7-37.6] vs. 11.6 % [6.8-18.2] of LV Mass, p = 0.012) and lower ejection fraction (42.2 ± 10 % vs. 47.4 ± 9 %, p = 0.019) compared with immediate CR. CONCLUSIONS: Of patients randomized to CR in the CMR substudy of CvLPRIT, those in whom the operator chose to stage revascularization had larger infarct size and lower ejection fraction, which persisted after adjusting for important covariates than those who underwent immediate CR. Prospective randomized trials are needed to assess whether immediate CR results in better clinical outcomes than staged CR. TRIAL REGISTRATION: ISRCTN70913605 , Registered 24th February 2011.

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.

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.

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

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.

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

BACKGROUND: There 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). METHODS: Ten 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). RESULTS: FWHM 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. CONCLUSIONS: FWHM 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.

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.

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.

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.

PURPOSE: 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). MATERIALS AND METHODS: Cardiac MRI was performed twice (1-14 days apart) in 18 patients (8 at 1.5 Tesla [T], 10 at 3T) with moderate-severe AS. Circumferential peak systolic strain (PSS) and PEDSR were measured in all patients. Longitudinal PSS and PEDSR were assessed using FT in all patients, and tagging in the 3T sub-group. RESULTS: PSS was higher with FT than tagging (21.0 ± 1.9% versus 17.0 ± 3.4% at 1.5T, 21.4 ± 4.0% versus 17.7 ± 3.0% at 3T, P < 0.05), as was PEDSR (1.3 ± 0.3 s(-1) versus 1.0 ± 0.3 s(-1) , P = 0.10 at 1.5T and 1.3 ± 0.4 s(-1) versus 0.8 ± 0.3 s(-1) , P < 0.05 at 3T). The reproducibility of PSS was excellent with FT (coefficient of variation [CoV] 9-10%) and good with tagging at 1.5T (13-19%). Reproducibility of circumferential PEDSR was best at 1.5T when only basal/mid slices were included (CoV 12%), but moderate to poor at 3T (29-35%). Reproducibility of longitudinal strain was good with FT (10-16%) but moderate for PEDSR (∼30%). CONCLUSION: In patients with AS, FT consistently produces higher values compared with tagging. The interstudy reproducibility of PSS is excellent with FT and good with tagging. The reproducibility of circumferential PEDSR at 1.5T is good when only basal and mid slices are used.

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.

BACKGROUND: Microvascular 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. METHODS: The 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). DISCUSSION: The 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 REGISTRATION: Trial registered 20th November 2012: ClinicalTrials.gov Identifier NCT01747174.

Prevalence and extent of infarct and microvascular obstruction following different reperfusion therapies in ST-elevation myocardial infarction.

BACKGROUND: Microvascular obstruction (MVO) describes suboptimal tissue perfusion despite restoration of infarct-related artery flow. There are scarce data on Infarct Size (IS) and MVO in relation to the mode and timing of reperfusion. We sought to characterise the prevalence and extent of microvascular injury and IS using Cardiovascular magnetic resonance (CMR), in relation to the mode of reperfusion following acute ST-Elevation Myocardial Infarction (STEMI). METHODS: CMR infarct characteristics were measured in 94 STEMI patients (age 61.0 ± 13.1 years) at 1.5 T. Seventy-three received reperfusion therapy: primary percutaneous coronary-intervention (PPCI, n = 47); thrombolysis (n = 12); rescue PCI (R-PCI, n = 8), late PCI (n = 6). Twenty-one patients presented late (>12 hours) and did not receive reperfusion therapy. RESULTS: IS was smaller in PPCI (19.8 ± 13.2% of LV mass) and thrombolysis (15.2 ± 10.1%) groups compared to patients in the late PCI (40.0 ± 15.6%) and R-PCI (34.2 ± 18.9%) groups, p <0.001. The prevalence of MVO was similar across all groups and was seen at least as frequently in the non-reperfused group (15/21, [76%] v 33/59, [56%], p = 0.21) and to a similar magnitude (1.3 (0.0-2.8) v 0.4 [0.0-2.9]% LV mass, p = 0.36) compared to patients receiving early reperfusion therapy. In the 73 reperfused patients, time to reperfusion, ischaemia area at risk and TIMI grade post-PCI were the strongest independent predictors of IS and MVO. CONCLUSIONS: In patients with acute STEMI, CMR-measured MVO is not exclusive to reperfusion therapy and is primarily related to ischaemic time. This finding has important implications for clinical trials that use CMR to assess the efficacy of therapies to reduce reperfusion injury in STEMI.