Total Ischemic Burden Research Articles

Angiogenic Gene Therapy for Refractory Angina: Results of the EXACT Phase 2 Trial.

XC001 is a novel adenoviral-5 vector designed to express multiple isoforms of VEGF (vascular endothelial growth factor) and more safely and potently induce angiogenesis. The EXACT trial (Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment) assessed the safety and preliminary efficacy of XC001 in patients with no option refractory angina. In this single-arm, multicenter, open-label trial, 32 patients with no option refractory angina received a single treatment of XC001 (1×1011 viral particles) via transepicardial delivery. There were no severe adverse events attributed to the study drug. Twenty expected severe adverse events in 13 patients were related to the surgical procedure. Total exercise duration increased from a mean±SD of 359.9±105.55 seconds at baseline to 448.2±168.45 (3 months), 449.2±175.9 (6 months), and 477.6±174.7 (12 months; +88.3 [95% CI, 37.1-139.5], +84.5 [95% CI, 34.1-134.9], and +115.5 [95% CI, 59.1-171.9]). Total myocardial perfusion deficit on positron emission tomography imaging decreased by 10.2% (95% CI, -3.1% to 23.5%), 14.3% (95% CI, 2.8%-25.7%), and 10.2% (95% CI, -0.8% to -21.2%). Angina frequency decreased from a mean±SD 12.2±12.5 episodes to 5.2±7.2 (3 months), 5.1±7.8 (6 months), and 2.7±4.8 (12 months), with an average decrease of 7.7 (95% CI, 4.1-11.3), 6.6 (95% CI, 3.5-9.7), and 8.8 (4.6-13.0) episodes at 3, 6, and 12 months. Angina class improved in 81% of participants at 6 months. XC001 administered via transepicardial delivery is safe and generally well tolerated. Exploratory improvements in total exercise duration, ischemic burden, and subjective measures support a biologic effect sustained to 12 months, warranting further investigation. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04125732.

Abnormal left ventricular subendocardial perfusion and diastolic function in women with obesity and heart failure and preserved ejection fraction

Purpose– Coronary microvascular dysfunction (CMD) is common in patients with heart failure with preserved ejection fraction (HFpEF) and obesity. Stress cardiovascular magnetic resonance (CMR) has been proposed as a non-invasive tool for detection of CMD. The aim of this study was to determine relationship between CMD and diastolic function in patients with HFpEF using a novel CMR technique.Methods– Patients with obesity and HFpEF without epicardial coronary artery disease (CAD) underwent Doppler echocardiography to measure diastolic function, followed by vasodilator stress CMR, using a single bolus, dual sequence, quantitative myocardial perfusion mapping to measure myocardial blood flow (MBF) at rest and at peak hyperemia. With this, myocardial perfusion reserve (MPR), global stress endocardial-to-epicardial (endo:epi) perfusion ratio, and total ischemic burden (IB, defined as myocardial segments with MBF < 1.94 mL/min/g) were calculated. Results are reported as median and interquartile range.Results– Nineteen subjects were enrolled (100% female, 42% Black). Median age was 64 [56–72] years. Global stress MBF was 2.43 ml/min/g [2.16–2.78] and global myocardial perfusion reserve (MPR) was 2.34 [2.07–2.88]. All had an abnormal subendocardial perfusion with an endo:epi of less than 1 (0.87 [0.81–0.90]). Regional myocardial hypoperfusion was detected in 14 (74%) patients with an IB of 6% [0-34.4]. Endo:epi ratio significantly correlated with IB (R=-0.510, p = 0.026) and measures of diastolic function (R = 0.531, p = 0.019 and R=-0.544, p = 0.014 for e’ and E/e’ respectively).Conclusion– Using a novel quantitative stress CMR myocardial perfusion mapping technique, women with obesity and HFpEF were found to have patterns of abnormal subendocardial perfusion which significantly correlated with measures of diastolic dysfunction.

Effects of salvianolate on microcirculatory disturbance in patients with stable coronary heart disease: study protocol for a randomized controlled trial

BackgroundObstruction of coronary microcirculation can lead to myocardial ischemia and poor prognosis. Salvianolate exerts cardiovascular protection at cellular levels. However, no studies have confirmed the effect of salvianolate on stable coronary heart disease (CHD) with high fractional flow reserve (FFR) and myocardial microcirculatory disturbances.Methods/designThis study will enroll 78 patients who have stable coronary disease with 50 to 70% stenosis in major coronary arteries and whose FFR > 0.80 and index of microcirculatory resistance (IMR) > 25. Patients will be randomly divided into the salvianolate group or the placebo group. After above evaluations, salvianolate 200 mg will be intravenously dripped immediately for the next 30 min and subsequent 7 days in the salvianolate group, and matching 0.9% normal saline will be arranged in the placebo group. IMR will be reevaluated in immediate phase after first 30 min of salvianolate or placebo treatment. The primary end point will be the IMR change in this phase, and the secondary end points will be the total ischemic burden assessed by the Seattle angina scale, quality of life scale, Holter electrocardiography, and 6-min walk test after 7 days before discharge.DiscussionThis study will firstly clarify the improvement effect of salvianolate on coronary microcirculation and provide an effective treatment method for stable CHD patients with high FFR and myocardial microcirculatory disturbance.Trial registrationChinese Clinical Trial Registry ChiCTR1800018772. Registered on 9 October 2018 and updated on 2 March 2020

Serum Bilirubin Level Predicts Frontal QRS-T Angle Change in Patients with Acute Coronary Syndrome

Abstract Introduction: The predictive role of serum bilirubin levels on the alteration of total ischemic burden expressed via frontal QRS-T angle change has never been studied in patients with acute coronary syndrome (ACS). In this study, we aimed to investigate the relationship between serum bilirubin levels and frontal QRS-T angle change after percutaneous coronary intervention (PCI) in ACS patients. Methods: Frontal QRS-T angle change was accepted as positive or negative according to whether the value of the baseline frontal QRS-T angle minus the post PCI frontal QRS-T angle is positive or negative. A total of 314 consecutive patients with ACS who underwent PCI were divided into two groups based on their negative frontal QRS-T angle change (n = 152 patients) and positive frontal QRS-T angle change (n = 162 patients). Results: Multivariate logistic regression analysis showed that the C-reactive protein (CRP) to albumin ratio (CAR) (Odds ratio [OR]: 0.519, 95% CI: 0.373–0.724, p &lt;0.001), total bilirubin (OR: 3.687, 95% CI: 1.151–8.095, p = 0.03), and low-density lipoprotein (LDL) (OR: 0.985, 95% CI: 0.970–1.000, p = 0.04) were independent predictors of positive QRS-T angle change. In receiver operating characteristics curve analysis, a cut-off value of 0.59 total bilirubin had a 69% sensitivity and a 65% specificity (area under curve: 0.739, p &lt;0.001) for the prediction of positive QRS-T angle change. Conclusion: In ACS patients, serum total bilirubin has been found to be a useful decision-making tool to predict positive frontal QRS-T angle change as a sign of reduced total ischemic burden, to assess early invasive strategy independently from other study parameters.

Acupuncture for chronic stable angina pectoris based on the theory of Meridian-Viscera Association: study protocol for a multicenter randomized controlled trial

BackgroundAcupuncture has long been used to treat chronic stable angina pectoris (CSAP), but the acupuncture prescription for CSAP varies. This trial will compare the therapeutic effects between the acupoints on the Heart Meridian and the acupoints on the Lung Meridian for treating CSAP, so as to provide a better prescription for acupuncture treatment of CSAP.MethodsThis is a multicenter randomized controlled trial. A total of 148 CSAP patients will be randomly allocated into two groups through central randomization in a 1:1 ratio. This trial will include a 2-week screening period, a 4-week treatment period, and a 4-week follow-up period. The primary outcome is the frequency of angina attacks from baseline to 4 weeks after inclusion. Secondary outcomes include the frequency of angina attacks from baseline to 4 weeks after acupuncture treatment, the pain intensity of angina, total ischemia burden, heart rate variability, QT dispersion, the score of Seattle Angina Questionnaire, and the score of Short-Form of McGill Pain Questionnaire. These outcome measures will be evaluated at baseline, at the end of acupuncture treatment, and at the end of follow-up.DiscussionWe hypothesize that the effectiveness of puncturing at acupoints on the Heart Meridian will not be the same as those on the Lung Meridian. The results will provide further evidence of Meridian-Viscera Association theory and references for acupoints selection in the clinical practice.Trial registrationChinese Clinical Trial Registry ChiCTR1900025804. Registered on September 9, 2019

REDUCE-IT: total ischemic events reduced across the full range of baseline LDL cholesterol and other key subgroups

Abstract Background REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial), a study of 8,179 randomized statin-treated patients with elevated triglycerides (TG) and increased cardiovascular (CV) risk followed for a median of 4.9 years, demonstrated robust results. Icosapent ethyl (IPE), a pure and stable prescription form of eicosapentaenoic acid, 4g/day reduced both time-to-first and total primary endpoint ischemic events (CV death, nonfatal myocardial infarction [MI], nonfatal stroke, coronary revascularization, or hospitalization for unstable angina) by 25% (HR 0.75; 95% CI 0.68–0.83; p&amp;lt;0.0001) and 30% (rate ratio 0.70; 95% CI 0.62–0.78; p&amp;lt;0.0001), respectively. Similar substantial reductions in first and total key secondary endpoint ischemic events (composite of CV death, nonfatal MI, or nonfatal stroke) were also observed. Demographic and baseline disease characteristics were generally balanced across treatment groups. Time-to-first event analyses showed robust and generally consistent benefit across subgroups. Previous total event analyses by baseline TG demonstrated large, consistent, statistically significant reductions across tertiles, suggesting the CV benefit of IPE is tied primarily to non-TG factors. Purpose Further explore the extent to which IPE reduced total primary and key secondary events across prespecified baseline demographic, disease, treatment, and lipid/lipoprotein/inflammatory biomarker subgroups. Methods Total events across subgroups were assessed with the prespecified negative binomial regression method. Main outcomes were total (first and subsequent) primary and key secondary composite endpoint events. Results Median baseline LDL-C levels in ascending tertiles were 58, 76, and 96 mg/dL; there were large, significant relative reductions in total primary endpoint events with IPE across tertiles (35%, 28%, and 27%, respectively; interaction p=0.62), with parallel substantial absolute risk reductions. Similar, significant relative reductions of 33%, 28%, and 24% in total key secondary endpoint events were observed, along with substantial absolute risk reductions. Total events analyses of prespecified subgroups also demonstrated robust and generally consistent findings for the primary and key secondary composite endpoints. Conclusion REDUCE-IT demonstrated substantial reductions in first and total primary and key secondary endpoint ischemic events, with robust and generally consistent results across baseline TG and LDL-C levels, as well as other prespecified baseline biomarker, demographic, disease, and treatment subgroups. These analyses provide useful insights for clinicians considering the range of patients who may benefit from IPE therapy and suggest that mechanisms beyond the lipid/lipoprotein/inflammatory pathways tested, including mechanisms beyond the LDL receptor pathways, may contribute to the observed substantial reductions in total ischemic burden with IPE therapy. Funding Acknowledgement Type of funding source: Other. Main funding source(s): The study was funded by Amarin Pharma, Inc.

The degree of retinopathy correlates with the presence of silent myocardial ischemia in diabetic patients

Abstract Background Silent myocardial is a major component of the total ischemic burden for patients with ischemic heart disease. The disease is more prevalent in diabetic patients than their peers, and early detection of the high-risk group would play an integral role in the prevention of sudden cardiovascular accidents that are common in these patients. Methods A prospective cohort study including asymptomatic 53 diabetic patients with diabetic retinopathy who suffer no ischemic cardiac symptoms was conducted. The presence and degree of diabetic retinopathy were evidenced using fundus examination and optical coherence tomography. All the enrolled patients underwent stress-resting 99mTc SestaMIBI myocardial perfusion scintigraphy to detect the ischemic burden. The relation between diabetic retinopathy and silent myocardial ischemia was stratified using statistical analysis. Results A total of 13 diabetic patients (24.5%) have silent myocardial ischemia in the form of regional myocardial perfusion abnormalities. The strongest predictors of abnormal tests were the presence of moderate to severe retinopathy, comorbid hypertension and diabetic duration for more than 10 years. Conclusion Silent myocardial ischemia affects one in four asymptomatic diabetic patients suffering from diabetic retinopathy. The presence of comorbid risk factors such as high-grade retinopathy, hypertension and/or long diabetic duration surge the incidence and considered additional predictors of the disease. Funding Acknowledgement Type of funding source: None

The Degree of Retinopathy Correlates with the Presence of Silent Myocardial Ischemia in Diabetic Patients

Background: Silent myocardial ischemia is a major component of the total ischemic burden for patients with ischemic heart disease. The disease is more prevalent in diabetic patients than their peers, and early detection of the high-risk group would play an integral role in the prevention of sudden cardiovascular accidents that are common in these patients. Methods: A prospective cohort study including asymptomatic 53 diabetic patients with diabetic retinopathy who suffer no ischemic cardiac symptoms was conducted. The presence and degree of diabetic retinopathy were evidenced using fundus examination and optical coherence tomography. All the enrolled patients underwent stress-resting 99mTc SestaMIBI myocardial perfusion scintigraphy to detect the ischemic burden. The relation between diabetic retinopathy and silent myocardial ischemia was stratified using statistical analysis. Results: A total of 13 diabetic patients (24.5%) have silent myocardial ischemia in the form of regional myocardial perfusion abnormalities. The strongest predictors of abnormal tests were the presence of moderate to severe retinopathy, comorbid hypertension and diabetic duration for more than 10 years. Conclusion: Silent myocardial ischemia affects one in four asymptomatic diabetic patients suffering from diabetic retinopathy. The presence of comorbid risk factors such as high-grade retinopathy, hypertension and/or long diabetic duration surge the incidence and considered additional predictors of the disease.

Breathing lung transplantation with the Organ Care System (OCS) Lung: lessons learned and future implications.

Ex vivo lung perfusion (EVLP) represents a potentially important advancement in the preservation of donor lungs prior to transplantation. Portable EVLP or "Breathing Lung Transplantation" with the Organ Care System (OCS) Lung combines the fundamental components of EVLP with portability, thus reducing the total ischemic burden. The Food and Drug Administration (FDA) approved OCS for perfusion of standard donor lungs prior to transplant in 2018. The current review discusses the available literature on the clinical outcomes of OCS Lung as well as translational data.

107 The long term prognostic value of dipyridamole stress myocardial contrast echocardiography in comparison with single photon emission tomography in patients with known or suspected coronary artery disease

BackgroundSingle photon emission computed tomography (SPECT) is a well-established method to evaluate patients with coronary artery disease (CAD). Myocardial contrast echocardiography (MCE) is an imaging technique that allows assessment of...

24 The physiological impact of coronary chronic total occlusion (cto) percutaneous coronary intervention (pci) on donor vessel coronary pressure-derived measurements and the influence of collateral circulation

BackgroundThere is strong evidence of FFR guided treatment in multi-vessel disease. Multi-vessel disease is present in up to 66% of patients with CTO in a large registry analysis. The presence...

Oral nicorandil reduces ischemic attacks in patients with stable angina: A prospective, multicenter, open-label, randomized, controlled study

ObjectiveTo evaluate the efficacy and safety of oral nicorandil in coronary heart disease (CHD) patients with stable angina. MethodEligible patients were randomized 1:1 to the nicorandil or control group. Current standard antianginal treatment was continued in both groups, while the patients in the nicorandil group received an additional 12-week treatment of nicorandil (5mg thrice daily). Primary endpoint was the number of myocardial ischemia measured by 24h Holter after 12-week treatment. Secondary endpoints included various 24h Holter indicators, angina occurrence, 6-min walking test (6MWT), ECG QT dispersion (QTd), safety and compliance. Clinical trial registration: NCT01396395. ResultsA total of 402 adult patients with stable angina were enrolled. Two hundred patients were randomized to standard therapy plus nicorandil and 202 patients to standard therapy only. The baseline characteristics of the two groups were comparable. The number of myocardial ischemia attacks after treatment was significantly lower in the nicorandil group (LSMEANS 0.896) than the control group (LSMEANS 1.782), with an adjusted ratio of 0.503 (95% CI: 0.301, 0.840; P=0.0086). No significant differences in total myocardial ischemic burden, maximum ST-depression, longest duration of ST-depression, 6MWT, or heart rate variability were noted between the two groups. Twenty three (11.7%) of nicorandil group and 13 (6.3%) patients of control group reported at least one treatment emergent adverse event, respectively. ConclusionNicorandil significantly reduced the number of ischemic attacks when added to standard antianginal treatment in CHD patients with stable angina. It was well tolerated with no new safety signal identified.

Microvascular ischemia in hypertrophic cardiomyopathy: new insights from high-resolution combined quantification of perfusion and late gadolinium enhancement.

BackgroundMicrovascular ischemia is one of the hallmarks of hypertrophic cardiomyopathy (HCM) and has been associated with poor outcome. However, myocardial fibrosis, seen on cardiovascular magnetic resonance (CMR) as late gadolinium enhancement (LGE), can be responsible for rest perfusion defects in up to 30 % of patients with HCM, potentially leading to an overestimation of the ischemic burden. We investigated the effect of left ventricle (LV) scar on the total LV ischemic burden using novel high-resolution perfusion analysis techniques in conjunction with LGE quantification.Methods30 patients with HCM and unobstructed epicardial coronary arteries underwent CMR with Fermi constrained quantitative perfusion analysis on segmental and high-resolution data. The latter were corrected for the presence of fibrosis on a pixel-by-pixel basis.ResultsHigh-resolution quantification proved more sensitive for the detection of microvascular ischemia in comparison to segmental analysis. Areas of LGE were associated with significant reduction of myocardial perfusion reserve (MPR) leading to an overestimation of the total ischemic burden on non-corrected perfusion maps. Using a threshold MPR of 1.5, the presence of LGE caused an overestimation of the ischemic burden of 28 %. The ischemic burden was more severe in patients with fibrosis, also after correction of the perfusion maps, in keeping with more severe disease in this subgroup.ConclusionsLGE is an important confounder in the assessment of the ischemic burden in patients with HCM. High-resolution quantitative analysis with LGE correction enables the independent evaluation of microvascular ischemia and fibrosis and should be used when evaluating patients with HCM.

The randomised Complete versus Lesion-only PRimary percutaneous coronary Intervention Trial: Cardiovascular Magnetic Resonance imaging substudy (CvLPRIT-CMR)

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

Complete Versus Lesion-Only Primary PCI: The Randomized Cardiovascular MR CvLPRIT Substudy

BackgroundComplete 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). ObjectivesThis study sought to determine whether in-hospital complete revascularization was associated with increased total infarct size compared with an IRA-only strategy. MethodsThis 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. ResultsOf 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. ConclusionsMultivessel 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)

Plaque assessment by coronary CT.

Coronary CT angiography (CTA) has emerged as a highly reliable and non-invasive modality for the exclusion of coronary artery disease. Recent technological advancements in coronary CTA imaging allow for robust qualitative and quantitative assessment of atherosclerotic plaques. Furthermore, CTA is a promising modality for functional evaluation of coronary lesions. Individual plaque features, the extent and severity of atherosclerotic plaque burden were proposed to improve cardiovascular risk stratification. It has been suggested that total atherosclerotic plaque burden is a stronger predictor of coronary events than total ischemia burden. The quest to noninvasively detect individual vulnerable plaques still remains. In the current review we sought to summarize state-of-the-art coronary artery plaque assessment by CTA.

Beta blockers or combination of beta blocker with ivabradine better alters the course of heart failure with reduced ejection fraction when the target heart rate is achieved

β-blockers (BB) and ivabradine (I) has been shown to be beneficial in heart failure with reduced EF (HFREF). The main benefit of I derives from heart rate reduction (HRR), whereas BB have broader spectrum of action. We conducted this study to evaluate whether HRR plays a major role in the treatment of HFREF in pts on standard therapy. Methods: 180 pts (55 female) 62±9 years with postinfarction HFREF (EF≤35%) on standard therapy with ACEI/ARB, spironolacton, loop diuretics and in sinus rhythm were randomized to two groups to receive nebivolol (N) titrated up to the achievement of the target HRR (THRR) <70 BPM or I titrated to 10mg BID in order to achieve THRR. THRR were achieved in 43 N tolerated pts, and 56 pts on I and the rest received the combination of N and I on order to reach THRR. All pts on N alone and the same number of pts on I or N+I were selected for the study and comprised 3 groups. EchoCG indexes of LV EDV, ESV and LAV, septal E/Em, mean longitudinal LV strain rate (LSR), Tei index (TI) as IVCT+IVRT/ET, as well as the total ischemic burden (TIB) as a total time of ST segment depressions ≥ 1 mm and ≥1 min duration and HRV as a standard deviation of normal RR intervals (SDNN) were measured by 24-hour ECG monitoring at baseline, 90 and 180 days follow up. Results: After 90 days follow up all parameters were similar between groups but significantly improved at the same degree within each group compared with baseline (p < 0.05). After 180 days follow up LV remodeling was better altered, contractility, SDNN parameters significantly improved at the same degree in N and N+I groups compared with I without differences between N and N+I, TIB did not differ between groups (ESVI: N 59.7±7.4 ml/m2 vs N+I 60.5±7.6 ml/m2 vs I 69.8±7.9* ml/m2, *p<0.05; EDVI: N 95.8±9.4 ml/m2 vs N+I 93.4±9.2 ml/m2 vs I 109.4±9.8* ml/m2, *p<0.05; TI: N 0.76±0.24 vs N+I 0.73±0.22 vs I 0.89±0.28*, *p < 0.05; E/Em: N 11.4±4.1 vs N+I 11.1±4.5 vs I 14.8±5.2*, *p < 0.05; TIB: N 35±13 min vs N+I 34±10 min vs I 33±9 min, p=NS; SDNN: N 103.04±15 ms vs N+I 104.06±16 ms vs I 126±18*ms, *p<0.05; LSR: N 1.59±0.16 vs N+I 1.54±0.14, 1.30±0.12*, *p < 0.05). Both N and I were well tolerated by pts throughout follow up. Conclusion: BB or in case of intolerance their combination with I to further reduce HR are more beneficial than reduction of HR at the same degree solely with I. Additional properties of BB are of importance and neurohormonal modulation with HR reduction better alters the course of HF.

The conundrum of protection from AKI by adenosine in rodent clamp ischemia models

Kim et al. show that isoflurane uses a tubule-based transforming growth factor-β/CD73-dependent process that generates adenosine to protect mice from ischemic acute kidney injury (AKI) with effects to prevent the 'no-reflow phenomenon' and decrease inflammation. While direct cytoprotection occurred in culture, extensive research suggests that in vivo adenosine protection from rodent ischemic AKI is mediated by a mutually cooperative mechanism involving blood flow, inflammation, and innate immunity through multiple adenosine receptors with promiscuous actions on diverse cell types.

TCT-224 Long-term Clinical Outcomes of Medical Therapy Versus Coronary Revascularisation in Patients with Intermediate Stenoses Guided by Pressure Wire

Background: Extent and severity of myocardial hypoperfusion correlates with patient outcome in CHD. The nuclear substudy of COURAGE indicates patients with ischaemia 10% total myocardial volume benefit from PCI. Radionuclide perfusion imaging allows complete myocardial coverage throughout the R-R interval with tracer uptake regionally distributed in proportion to blood flow. Cardiac Magnetic Resonance (CMR) perfusion sequences provide myocardial coverage at discrete time periods in the cardiac cycle. Myocardial blood flow varies during the cardiac cycle and may impact upon how accurately different perfusion imaging techniques quantify physiologically significant ischaemia. Methods: Simultaneous pressure wire and coronary catheter pressure recordings were sampled in 22 patients. Instantaneous Fractional Flow Reserve (iFFR) and Rest TransStenotic Pressure Ratios (iRTPR) were interrogated at 5 millisecond (ms) intervals. Analysis of these indices were performed representative of Single Photon Emission Computerised Tomography (SPECT) and CMR myocardial perfusion sequences. Comparison with conventional FFR (cFFR) and conventional RTPR (cRTPR) were assessed. Results: Maximum iFFR differed from minimum iFFR by 0.20 / 0.17 over 234 / 131ms. Similarly maximum iRTPR differed from minimum by 0.16 / 0.13 over 247 / 136ms. Difference between maximum and minimum iFFR and iRTPR correlated with cFFR(r 0.85) and cRTPR(r 0.97) respectively. For SPECT, the ratio of cFFR to cRTPR moderately correlated with cFFR(r 0.58). For CMR, hypothetical phase specific slice averaged iFFR differed from cFFR by 0.08 / 0.09 and iRTPR from cRTPR by 0.05 / 0.08 in the diastolic period. The largest difference between period averaged iFFR & iRTPR values was 0.08 / 0.10 and occurred at lower cFFR & cRTPR values during the diastolic period. Conclusions: iFFR, iRTPR, and the difference and ratio between each varies during the cardiac cycle. This has considerable implication for quantification of physiologically significant total myocardial ischaemic burden by myocardial perfusion imaging, particularly pertinent to CMR. Variation of tracer uptake during the cardiac cycle may aid diagnosis in the setting of balanced ischaemia when adopting SPECT.

141 Cardiac troponin reflects silent myocardial ischaemia in patients with stable coronary artery disease

BackgroundCardiac troponin is an independent predictor of cardiovascular mortality in patients with stable coronary artery disease, yet the factors that determine circulating troponin concentration in these patients are not known....