Nonischemic Segments Research Articles

Downregulation of RIP3 ameliorates the left ventricular mechanics and function after myocardial infarction via modulating NF-κB/NLRP3 pathway.

Adverse cardiac mechanical remodeling is critical for the progression of heart failure following myocardial infarction (MI). We previously demonstrated the involvement of RIP3-mediated necroptosis in the loss of functional cardiomyocytes and cardiac dysfunction post-MI. Herein, we investigated the role of RIP3 in NOD-like receptor protein 3 (NLRP3)-mediated inflammation and evaluated the effects of RIP3 knockdown on myocardial mechanics and functional changes after MI. Our findings revealed that mice with MI for 4 weeks exhibited impaired left ventricular (LV) myocardial mechanics, as evidenced by a significant decrease in strain and strain rate in each segment of the LV wall during both systole and diastole. However, RIP3 knockdown ameliorated cardiac dysfunction by improving LV myocardial mechanics not only in the anterior wall but also in other remote nonischemic segments of the LV wall. Mechanistically, knockdown of RIP3 effectively inhibited the activation of the nuclear factor kappa-B (NF-κB)/NLRP3 pathway, reduced the levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18) in the heart tissues, and mitigated adverse cardiac remodeling following MI. These results suggest that downregulation of RIP3 holds promise for preventing myocardial inflammation and cardiac mechanical remodeling following MI by regulating the NF-κB/NLRP3 pathway.

Role of myocardial strain imaging in diagnosing inducible myocardial ischemia with treadmill contrast-enhanced stress echocardiography

IntroductionThe aim of this study is to analyze the diagnostic value of global longitudinal strain (GLS) in detecting inducible myocardial ischemia in patients with chest pain undergoing treadmill contrast-enhanced stress echocardiography (SE).MethodsWe retrospectively enrolled all patients who underwent invasive coronary angiography after treadmill contrast-enhanced SE. Rest and peak-stress myocardial GLS, segmental LS, and LS of 4-chamber (CH), 2-CH, and 3-CH views were reported. Luminal stenosis of more than 70% or fractional flow reserve (FFR) of < 0.8 was considered significant.ResultsIn total 33 patients were included in the final analysis, among whom sixteen patients (48.4%) had significant coronary artery stenosis. Averaged GLS, 3-CH, and 4-CH LS were significantly lower in patients with critical coronary artery stenosis compared to those without significant stenosis (-17.1 ± 7.1 vs. -24.2 ± 7.2, p = 0.041), (-18.2 ± 8.9 vs. -24.6 ± 8.2, p = 0.045) and (-14.8 ± 6.2 vs. -22.8 ± 7.8, p = 0.009), respectively. Receiver operating characteristic (ROC) analysis of ischemic and non-ischemic segments demonstrated that a cut-off value of -20% of stress LS had 71% sensitivity and 60% specificity for ruling out inducible myocardial ischemia (Area under the curve was AUC = 0.72, P < 0.0001).ConclusionMyocardial LS measured with treadmill contrast-enhanced stress echocardiography demonstrates potential value in identifying patients with inducible myocardial ischemia.

Myocardial tissue microstructure with and without stress-induced ischemia assessed by T1 mapping in patients with stable coronary artery disease

BackgroundStress-induced myocardial ischemia seems not to be associated with cardiovascular events. However, its effects on myocardial tissue characteristics remain under debate. Thus, we sought to assess whether documented stress-induced ischemia is associated with changes in myocardial microstructure evaluated by magnetic resonance native T1 map and extracellular volume fraction (ECV). MethodsThis is a single-center, analysis of the previously published MASS V Trial. Multivessel patients with a formal indication for myocardial revascularization and with documented stress-induced ischemia were included in this study. Native T1 and ECV values evaluated by cardiac magnetic resonance imaging of ischemic and nonischemic myocardial segments at rest and after stress were compared. Myocardial ischemia was detected by either nuclear scintigraphy or stress magnetic cardiac resonance protocol. ResultsBetween May 2012 and March 2014, 326 prospective patients were eligible for isolated CABG or PCI and 219 were included in the MASS V trial. All patients underwent resting cardiac magnetic resonance imaging. Of a total of 840 myocardial segments, 654 were nonischemic segments and 186 were ischemic segments. Native T1 and ECV values of ischemic segments were not significantly different from nonischemic segments, both at rest and after stress induction. In addition, native T1 and ECV values of myocardial segments supplied by vessels with obstructive lesions were similar to those supplied by nonobstructive ones. Conclusion and relevanceIn this study, cardiac magnetic resonance identified similar T1 mapping values between ischemic and nonischemic myocardial segments. This finding suggests integrity and stability of myocardial tissue in the presence of stress-induced ischemia.

Evaluation of Myocardial Ischemia with Myocardial Perfusion Scintigraphy and 2D- Speckle Tracking Echocardiography in Non-Obstructive Coronary Artery Patient Group

Introduction: Strain analysis with 2D speckle tracking echocardiography could be used in the diagnosis of severe coronary artery disease. The aim of this study is to evaluate the effectiveness of 2D speckle tracking echocardiography in a group of patients with positive myocardial Perfusion Scintigraphy (MPS) but without severe coronary artery disease (CAD). Methods: Forty (25 female, age: 58.85±9.73) patients with the of angina pectoris and ischemia was found in MPS but non-obstructive CAD (&lt;50% stenosis) was observed in coronary angiography was included. Strain analysis was performed in all patients using 2D speckle tracking echocardiography. Longitudinal strains weremeasured for 17 LV myocardial segments. LV segments were grouped as ischemic and non-ischemic segments according to MPS results and strain parameters of 680 segments were compared. Results: The mean longitudinal strain values of the segments with ischemia were -20.24±6.0%, and the segments without ischemia were found as -20.11±6.46%, and no statistically significant difference was observed (p&gt;0.05). In subgroup analyzes based on gender, hypertension, diabetes mellitus, hyperlipidemia, and hypertriglyceridemia, no difference was observed between ischemic and non-ischemic segments in terms of longitudinal strain. Conclusion: In the patient group without severe coronary artery disease, no difference was observed between the staining parameters in the left ventricle 2D longitudinal strain analysis in terms of MPS positive segments and MPS negative segments. Considering previous studies, by using 2D strain analysis in combination with MPS, we can avoid unnecessary coronary artery angiography in special cases such as kidney failure, suspected MPS positivity.

Coronary flow quantification estimated by dynamic 320-detector CT angiography: validation by 13N ammonia PET myocardial flow reserve.

Resting coronary flow index (rCFI) estimated by 320-detector low-dose dynamic coronary CT angiography (CCTA) is a direct flow quantification using intracoronary attenuation. We propose modified-rCFI from new protocol combining dynamic scan and standard CCTA using dose-modulation, and validate its consistency with quantitative values and ischemia depicted by 13N-ammonia PET (NH3-PET). 46 patients who underwent dynamic CCTA and NH3-PET for coronary artery disease were evaluated using original rCFI in 21 patients and modified-rCFI in 25 patients. Two types of rCFI were calculated for three major coronary arteries. Myocardial blood flow (MBF) at rest and stress, myocardial flow reserve (MFR), and the presence or absence of ischemia for three major territories were depicted by NH3-PET. Coronary territories were categorized as territories with MFR <2.0, ≥2.0, or with and without ischemia. Receiver operating characteristic analysis was performed to determine the optimal cut-off of rCFI to distinguish territories with MFR <2.0 or the presence of ischemia. rCFI and modified-rCFI had significant positive correlations with stress MBF and MFR. The optical cut-offs of rCFI and modified-rCFI of 0.39 and 0.61 could detect territories with MFR <2.0, with AUCs of 0.75 and 0.73, sensitivities of 48 and 34%, and specificities of 97 and 98%. Optimal cut-offs of rCFI and modified-rCFI distinguished ischemic segments from non-ischemic segments, with AUCs of 0.75 and 0.91, sensitivities of 53 and 50%, and specificities of 93 and 95%. Two types of rCFI correlated with quantitative values from NH3-PET, and were consistent with a high specificity in detecting functional ischemia. rCFI can contribute as additional functional test over standard CCTA in clinical work-up.

Repetitive Preload Elevation and Stretch‐Induced Stiffening of Non‐Ischemic Myocardium in a Porcine Model of Multi‐Vessel Coronary Artery Disease

Objective We have recently shown that a transient elevation in left ventricular (LV) preload causes stretch-induced myocyte injury, with repetitive episodes resulting in interstitial fibrosis and reduced diastolic compliance. The present study was designed to test the hypothesis that this phenomenon contributes to stiffening of remote, non-ischemic myocardium that is subjected to repetitive preload elevation secondary to demand-induced ischemia in the setting of chronic multi-vessel coronary artery disease (CAD). Methods Swine (n=12) were instrumented with fixed 1.5 mm constrictors on the proximal left anterior descending (LAD) and left circumflex (LCx) coronary arteries. One month later, continuous ECG and LV pressure monitoring was initiated via implantable telemetry (PhysioTel Digital, DSI) to assess the frequency of preload elevation (LV end-diastolic pressure (EDP) > 30 mmHg) and tachycardia (heart rate > 170 beats/min). Serial physiological studies were performed for 3 months to assess stenosis severity (angiography), coronary flow reserve (fluorescent microspheres at rest and during adenosine vasodilation), and LV function (echocardiography). Circumferential diastolic stiffness was derived from stress-strain relationships obtained via speckle tracking echocardiography and invasive measurements of LV minimum pressure and EDP. Myocardial tissue samples were subsequently collected from the LAD (ischemic) and right coronary artery (RCA; non-ischemic) perfusion territories for post-mortem quantification of collagen content (hydroxyproline assay) and comparison to normal controls (n=8). Results By the end of the 3 month study period, animals exhibited severe LAD (93 ± 2 %) and LCx (91 ± 3 %) stenoses and significant reductions in subendocardial flow reserve (LAD: 1.4 ± 0.2; LCx: 1.3 ± 0.2) relative to the RCA territory (3.8 ± 0.6). Although LV EDP was only mildly elevated at rest (18 ± 2 mmHg), transient preload elevation occurred frequently (63 ± 10 episodes/day) and resulted in a total of 199 ± 45 min/day during which LV EDP exceeded 30 mmHg. Spontaneous tachycardia was also common (26 ± 5 episodes/day) and associated with transient elevations in LV EDP (28 ± 2 mmHg; p<0.05 vs. rest). Although LV ejection fraction was preserved (58 ± 3 %), radial and circumferential strain was depressed in ischemic and non-ischemic segments of the LV compared with controls (Table). Non-ischemic segments also exhibited increased diastolic stiffness, which coincided with a significant ~40% elevation in collagen content (0.31 ± 0.03 mg/g) vs. normal controls (0.22 ± 0.03 mg/g) that was comparable to that observed in the ischemic area of the LV (0.29 ± 0.02 mg/g). Conclusions Transient elevations in preload are common in swine with multi-vessel CAD and associated with interstitial fibrosis and myocardial stiffening in normally-perfused segments of the LV. Repetitive stretch-induced stiffening of remote myocardium may contribute to diastolic dysfunction and could explain the high prevalence of angiographically-significant CAD in patients with heart failure with preserved ejection fraction (HFpEF).

Hyperventilation/Breath-Hold Maneuver to Detect Myocardial Ischemia by Strain-Encoded CMR: Diagnostic Accuracy of a Needle-Free Stress Protocol

ObjectivesThe purpose of this study was to evaluate the diagnostic accuracy of a fast, needle-free test for myocardial ischemia using fast Strain-ENCoded (fSENC) cardiovascular MR (CMR) after a hyperventilation/breath-hold maneuver (HVBH). BackgroundMyocardial stress testing is one of the most frequent diagnostic tests performed. Recent data indicate that CMR first-pass perfusion outperforms other modalities. Its use, however, is limited by the need for both, a vasodilatory stress and the intravenous application of gadolinium. Both are associated with added cost, safety concerns, and patient inconvenience. The combination of 2 novel CMR approaches, fSENC, an ultrafast technique to visualize myocardial strain, and HVBH, a physiological vasodilator, may overcome these limitations. MethodsPatients referred for CMR stress testing underwent an extended protocol to evaluate 3 different tests: 1) adenosine-perfusion; 2) adenosine-strain; and 3) HVBH-strain. Diagnostic accuracy was assessed using quantitative coronary angiography as reference. ResultsA total of 122 patients (age 66 ± 11years; 80% men) suspected of obstructive coronary artery disease were enrolled. All participants completed the protocol without significant adverse events. Adenosine-strain and HVBH-strain provided significantly better diagnostic accuracy than adenosine-perfusion, both on a patient level (adenosine-strain: sensitivity 82%, specificity 83%; HVBH-strain: sensitivity 81%, specificity 86% vs. adenosine-perfusion: sensitivity 67%, specificity 92%; p < 0.05) and territory level (adenosine-strain: sensitivity 67%, specificity 93%; HVBH-strain: sensitivity 63%, specificity 95% vs. adenosine-perfusion: sensitivity 49%, specificity 96%; p < 0.05). However, these differences in diagnostic accuracy disappear by excluding patients with history of coronary artery bypass graft or previous myocardial infarction. The response of longitudinal strain differs significantly between ischemic and nonischemic segments to adenosine (ΔLSischemic = 0.6 ± 5.4%, ΔLSnonischemic = −0.9 ± 2.7%; p < 0.05) and HVBH (ΔLSischemic = 1.3% ± 3.8%, ΔLSnonischemic = −0.3 ± 1.8%; p = 0.002). Test duration of HVBH-strain (t = 64 ± 2 s) was significantly shorter compared with adenosine-strain (t = 184 ± 59 s; p < 0.0001) and adenosine-perfusion (t = adenosine-perfusion: 172 ± 59 s; p < 0.0001). ConclusionsHVBH-strain has a high diagnostic accuracy in detecting significant coronary artery stenosis. It is not only significantly faster than any other method but also neither requires contrast agents nor pharmacological stressors.

Variations in regional strain under different afterload conditions may help to identify ischemic myocardium

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Acute coronary syndromes are a major health problem worldwide. The Speckle Tracking Imaging has been proposed as adjunctive for diagnosis and prognosis purposes in the context of NSTE-ACS. Purpose We sought to determine the regional myocardial strain in ischemic versus non-ischemic segments in subjects with NSTE-ACS, before and during acute pressure overload. Methods Data from 2D-echocardiography were obtained from 21 patients (mean age, 50 ± 10 years) undergoing cinecoronariography for NSTE-ACS indications. A blinded observer performed an offline analysis to obtain the Systolic Positive Peak (P), Systolic Peak Strain (S), Peak Strain (G) and Time to Peak Strain (TTP) of each segment acquired before and during pressure overload-induced by left hand-grip (42± 8 Kg) combined with simultaneous pneumatic constriction of the right arm and both lower limbs. Moreover, LVEF and GLS were also calculated. A second blinded observer labelled the ischemic regions according to AHA-16 Bull’s eye using data from cinecoronariography. Results The handgrip manuever caused mild reductions in the median LVEF (56 %; IQR 48 -58% vs 54%; IQR 51-56%) as well as the median GLS (-17%; IQR-19%-15% vs -16%; IQR -19-15%). For the analysis of regional myocardial function, we obtained 360 segments (29% labelled as ischemic) with optimal tracking quality. Mean regional strain changes during pressure overload were significantly different in ischemic vs non-ischemic segments for Peak S ( 1,07% x -0.5%; p-value &amp;lt;0,01) and Peak G (0.85% x -0.65%; p-value &amp;lt; 0.01)(Table). Notably, however, we found marked increases in the systolic deformation, restricted to the apical ischemic segments during pressure overload (Figure). Conclusions Our data point to a distinct increase in the systolic deformation of the apical segments in contrast to the overall reductions in the GLS and EF in the ischemic left ventricle. Non- Ischemic segments N = 256 Ischemic segments N = 104 Baseline Handgrip Variation (%) Baseline Handgrip Variation (%) p-value* Peak P 0.33(0.57) 0.36(0.7) 0.03(0.7) 0.50(0.7) 0.57(0.8) 0.07(0.8) 0.32 Peak S -17.9(4.4) -16.8(5.3) 1.07(4.1) -16.6 (5.2) -17.2(5.6) -0.5(4.8) 0.0006 Peak G -18.5 (4.2) -17.68 (4.6) 0.85 (3.7) -17.3 (4.5) -18 (4.6) -0.65(4.2) 0.0005 TTP 377(62) 384(66) 6.5(52) 387(65_ 388(62) 1.15(46) 0.17 * t- test comparing the variations baseline-handgrip between the two groups (ischemic versus non-ischemic. Peak P= positive systolic peak; Peak S= systolic peak; Peak G= peak strain; TTP= time to peak Abstract Figure

Hyperventilation-breath-hold maneuver to detect ischemia by strain-encoded CMR: a pilot study to evaluate a needle-free stress protocol

Abstract Funding Acknowledgements Type of funding sources: None. Background Safety concerns for gadolinium-containing contrast agents and pharmacological stressors, together with tremendous costs and inconsistent reimbursement modalities are still limiting a widespread application of CMR stress testing despite proven benefits. Like the effect of adenosine, hyperventilation-breath-hold-maneuver (HVBH) has demonstrated to induce myocardial vasodilation and might serve as a stressor to induce coronary steal with consecutive hypokinesia. Purpose To evaluate the diagnostic accuracy of a needle-free, ultrafast stress test to detect myocardial ischemia by strain-encoded CMR (fSENC) after HVBH. Methods Patients referred for CMR stress testing underwent an extended protocol in order to evaluate three different stress forms: (1) Adenosine first-pass perfusion (Ad-FPP), (2) Adenosine-fSENC (Ad-fSENC) and (3) HVBH-fSENC. Diagnostic accuracy was assessed using quantitative coronary angiography as reference. Results One-hundred-twenty-two predominantly male patients (age 66 ± 11years; 80% men) suspected for obstructive CAD were enrolled. Ad-fSENC and HVBH-fSENC provided significantly better diagnostic accuracy than Ad-FPP, both on a patient-level (Ad-fSENC: sensitivity 82%[65-93], specificity 83%[73-90], p &amp;lt; 0.05; HVBH-fSENC: sensitivity 81%[64-93], specificity 86%[77-93], p &amp;lt; 0.05) and territory-level (Ad-fSENC: sensitivity 67%[52-80], specificity 93%[90-96], p &amp;lt; 0.05; HVBH-fSENC: sensitivity 63%[47-76], specificity 95%[91-97], p &amp;lt; 0.05). The stress response of longitudinal strain differs significantly between ischemic and non-ischemic segments to Adenosine (LSischemic = 0.6 ± 5.4%, LSnon-ischemic = 0.9 ± 2.7%, p &amp;lt; 0.05) and HVBH (LSischemic = 1.3 ± 3.8%, LSnon-ischemic=-0.3 ± 1.8%, p = 0.002). Stress test duration of HVBH-fSENC (t = 64 ± 2s) was significantly shortened compared to Ad-fSENC (t = 184 ± 59s, p &amp;lt; 0.0001) or Ad-FPP (t = Ad-FPP: 172 ± 59s, p &amp;lt; 0.0001). Conclusions Stress testing by HVBH-fSENC provides promising diagnostic accuracy to detect myocardial ischemia and is faster than established methods without the necessity to apply contrast agent or pharmacological stressors.

T1 mapping for myocardial tissue evaluation in patients with ischemia and stable coronary artery disease: MASS V-Trial Study Group

Abstract Background T1 mapping is a magnetic resonance imaging (MRI) technique that enables the identification of myocardial structural changes during acute ischemic injury. However, it is not known whether these structural changes are present in patients with chronic effort induced ischemia.Thus, we sought to document the possible T1 mapping changes in chronic coronary artery disease (CAD) patients with documented myocardial ischemia. Methods Multivessel CAD patients from MASS V Trial with indication of myocardial revascularization, were evaluated for the presence of ischemia by myocardial scintigraphy. MRI with T1 mapping was performed in all patients. Based on the results of the scintigraphy, the myocardial segments were identified as ischemic and non-ischemic segments. The corresponding segments of scintigraphy and MRI were compared in relation to native T1 map (NT1), post-contrast T1 (CAT1) and extracellular volume (ECV). Results Of the 720 myocardial segments analyzed, there were 161 ischemic and 559 non-ischemic segments. Comparing ischemic vs non-ischemic segments, respectively, NT1 was 1022.7 (980.0–1052.0) versus 1029.3 (985.0–1066.3), p=0.57, ECV results were 25.4 (24.0–28.1) versus 26.4 (25.3–29.9), p=0.75 and CAT1 results were 492 (461.9–515.4) versus 488 (469.2–521.7), p=0.09. Myocardial segments supplied by obstructive coronary arteries were compared to those supplied by non-obstructive coronary arteries in relation to NT1 and ECV. NT1 values in obstructive and non-obstructive territories were, respectively, 1024.7 (998.5–1043.5) versus 1036.8 (1008.6–1046.9), p=0.30 and ECV results were 26.8 (24.4–29.9) versus 26.8 (24.4–30.0), p=0.90. Conclusion In this study, MRI identified structural similarities between chronic ischemic myocardium compared to the non-ischemic myocardium. This finding supports myocardial tissue stability in the presence of stress induced ischemia. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Zerbini Foundation and also by the FAPESP (2011/ 20876-2)

Diagnostic accuracy of left ventricular diastolic transverse strain imaging by speckle tracking echocardiography for diagnosing chest pain in diabetic patients

Abstract Background Two-dimensional speckle tracking echocardiography (2D-STE) has been reported to be useful for the diagnosis of myocardial ischemia by detecting delayed relaxation (diastolic stunning) after an episode of angina. 2D-longitudinal strain is not specific besides ischemia such as diastolic dysfunction, and diabetes have been associated with abnormal longitudinal fibers. The aim is to evaluate the diagnostic accuracy of Left ventricular (LV) diastolic transverse strain imaging by STE to detect the presence of acute coronary syndrome (ACS) in diabetic patients with acute chest pain. Methods 385 consecutive patients with acute chest pain and without wall motion abnormality, who were admitted to an emergency department (ED) at 1 of 12 clinical sites in Japan, were enrolled and underwent 2D-STE at ED. Left ventricular (LV) transverse strain values at aortic valve closure (A) and one-third of diastole duration (B) were measured. The strain imaging diastolic index (SI-DI) was value was determined as: (A − B)/A × 100% to assess the LV diastolic strain imaging and was used to identify the regional LV delayed relaxation. All patients underwent coronary CT or coronary angiography to establish the diagnosis of ACS. Clinicians were blinded to the 2D-STE results. Results Out of 385 patients, 2D-STE analysis was possible in 365 patients (94%). 76 patients were diabetic (DM+), and 289 patients were non-diabetic (DM-). With assessment of coronary CT or coronary angiography, ACS was diagnosed in 125 patients (34%). 2D-STE was obtained at a mean of 5.3 hours after chest pain episode. Transverse SI-DI of ischemic segments were significantly lower than those of non-ischemic segments (p value &amp;lt;0.001) in both diabetic and non-diabetic patients, and transverse SI-DI of both diabetic and non-diabetic patients demonstrated high area under curve (AUC) for detection of myocardial ischemia (Figure: RCA; right coronary artery, LAD; left anterior descending artery, LCX; left circumferencial artery). In diabetic patients, sensitivity, specificity, and negative predictive value for ACS of transverse SI-DI are 100%, 95%, 100% in RCA (a cut-off value of 36.2), and 86.4%, 95%, 93% in LAD (a cut-off value of 50.2), and 75%, 85%, 94% in LCX (a cut-off value of 52), respectively. Conclusion LV diastolic transverse strain imaging by 2D-STE at ED increase the sensitivity, specificity and accuracy to predict the presence of ACS in diabetic patients with chest pain, as well as non-diabetic patients. (UMIN000013859). Figure 1. Transverse Strain (SI-DI): AUC (95% CI) Funding Acknowledgement Type of funding source: None

Diagnostic performance of quantitative, semi-quantitative, and visual analysis of dynamic CT myocardial perfusion imaging: a validation study with invasive fractional flow reserve.

To investigate the diagnostic performance of absolute myocardial blood flow (MBF), MBFratio, and visual analysis of dynamic CT myocardial perfusion imaging (CT-MPI) for the detection of hemodynamically significant coronary stenosis. Consecutive patients with chest pain and intermediate-to-high pre-test probability of obstructive coronary artery disease were prospectively enrolled. All patients were referred for dynamic CT-MPI and fractional flow reserve (FFR) measurements within 4weeks. Absolute MBF, MBFratio (mean MBF of stenosis-subtended territories versus that of reference territories), and visually identified perfusion defect were tested for the diagnostic performance with reference to FFR. Sixty-two patients with 95 target vessels were included for final analysis. The mean radiation dose for dynamic CT-MPI was 3.0 (2.2-4.0) mSv. The mean lesion-based absolute MBF value was significantly lower in ischemic segments than that in non-ischemic segments (78.0 (65.0-86.0) mL/min/100mL vs. 133.0 (117.5-163.8) mL/min/100mL, p < 0.001). Similarly, the lesion-based MBFratio was also markedly lower in territories with positive FFR results (0.52 (0.44-0.64) vs. 0.93 (0.91-0.97), p < 0.001). According to per-lesion ROC curve analysis, MBF and MBFratio had a similar area under the curve (AUC) for detecting hemodynamically significant lesions (AUC = 0.942 vs. 0.956, p = 0.413), which were larger than that of visual analysis (AUC = 0.802, both p < 0.01). The vessel-based sensitivity, specificity, and diagnostic accuracy were 84.3%, 97.7%, and 90.5% for MBF and 96.1%, 93.2%, and 94.7% for MBFratio. Absolute MBF and MBFratio had similarly excellent diagnostic performance with reference to FFR. In addition, these two parameters outperformed visual analysis for the detection of myocardial ischemia. • The mean MBF and MBFratio were significantly lower in ischemic segments than those in non-ischemic segments. • Absolute MBF and MBFratio had similar AUCs for the detection of hemodynamically significant lesions (AUC = 0.942 vs. 0.956, p = 0.413), which were larger than that of visual analysis (AUC = 0.802, both p < 0.01). • The vessel-based sensitivity, specificity, and diagnostic accuracy were 84.3%, 97.7%, and 90.5% for absolute MBF and 96.1%, 93.2%, and 94.7% for MBFratio.

Impact of Abnormal Remote Stress Myocardial Blood Flow by Dynamic CT Perfusion on Clinical Outcomes

The objective of this study was to investigate the incremental prognostic value for adverse events of myocardial blood flow (MBF) derived from stress computed tomography perfusion (CTP) at remote myocardium over cardiac risk factors and ischemia. We prospectively analyzed 242 patients who underwent dynamic CTP and CT angiography. Adverse events were defined as a composite of all-cause mortality, non-fatal myocardial infarction, unstable angina, heart failure requiring hospitalization, peripheral artery disease, and stroke. MBF value was calculated in each myocardial segment and ischemia was defined as mild decrease in MBF in two consecutive segments or moderate decrease in a single segment accompanied with a coronary stenosis ≥50%. The mean MBF of the non-ischemic segments was defined as remote MBF. We divided the patients into two groups by median MBF value of 1.15 ml/min/g. During a median follow-up of 18 months, 18 patients had adverse events. Annual event rate showed a significant difference between patients with low (≤1.15 ml/min/g) and high (>1.15 ml/min/g) MBF (6.1% vs 1.8%, p = 0.02). Univariate analysis showed that low MBF was a significant predictor of events (hazard ratio (HR): 3.4; 95% confidence interval (CI): 1.2 to 12.0; p = 0.02). This relationship maintained significant after adjusted for the presence of ischemia and cardiac risk factors (HR: 3.0; 95%CI: 1.1 to 11.1; p = 0.04). In conclusion, MBF value ≤1.15 ml/min/g derived from dynamic CTP in remote myocardium is significantly related with poor outcome and this relationship was independent of myocardial ischemia and cardiac risk factors.

1037 Differences in reverse remodelling between ischemic and non-ischemic left ventricular segments as assessed by myocardial work after sacubitril-valsartan therapy

Abstract Introduction Myocardial work (MW) is a new transthoracic echocardiographic (TTE) parameter that enhances the information provided through left ventricular (LV) global longitudinal strain (GLS), allowing to investigate LV performance even in cases of changes in afterload. None is known about the effects of Sacubitril-Valsartan (LCZ696) therapy in MW parameters. Purpose Compare the changes in MW parameters between ischemic and non-ischemic segments after LCZ696 therapy. Methods The study was a prospective evaluation of chronic Heart Failure (HF) patients with optimized standard of care therapy and LV ejection fraction ≤40%, in which LCZ696 therapy was started and no other HF treatment was expected to change. A TTE study was performed before and 6 months after LCZ696 therapy, using the GE Vivid E95 ultrasound system. A semiautomated analysis of GLS was performed after two-dimensional images were acquired in the standard apical 4-, 3- and 2 chamber views. MW and related indices were estimated using custom software. Two groups were created according to the 17 segment model TTE study before LCZ696 therapy: G1 (ischemic group): dyskinesia/akinesia/hypokinesia segments in patients with ischemic HF etiology; G2 (non-ischemic group): normokinesia segments in patients with ischemic and all segments in patients with non-ischemic HF etiology; Results Of the 42 patients, 35 (83.3%) completed the six-months follow-up with LCZ696, since 2 patients (4.8%) died and 5 patients (11.9%) discontinued treatment for adverse events. Mean age was 58.6 ± 11.1 years, with ischemic etiology in 15 (42.9%), resulting in a total of 26.5% segments for G1. Baseline global MW index (GWI) had no statistical difference between G1 and G2 (566.1 VS 584.8mmHg%, p = 0.257), but baseline MW efficiency (GWE) were significantly lower in G1 (71.9 VS 78.8%, p &amp;lt; 0.001). The table represents the mean values for MW parameters in G1 and G2 before and 6 months after LCZ696 therapy, with a significantly increase in GWI and GWE values in both groups. Despite no difference in the increase in GWE (p = 0.872), the increase in GWI were higher in G2 than G1 (p &amp;lt; 0.001). Conclusion MW seems to be a new tool providing signs of reverse remodelling and better cardiac performance in ischemic and non-ischemic segments after LCZ696 therapy. Table 1 Time 0 6 months p GWI in ischemic segments (mmHg%) 566.1 ± 364.0 696.5 ± 445.2 &amp;lt;0.001 GWE in ischemic segments (%) 71.9 ± 25.0 78.9 ± 19.1 0.009 GWI in non-ischemic segments (mmHg%) 584.8 ± 434.3 812.3 ± 442.0 &amp;lt;0.001 GWE in non-ischemic segments (%) 78.8 ± 21.2 85.7 ± 15.8 0.004 MW data before and after six months of LCZ696 therapy

1225 Diagnostic accuracy of left ventricular diastolic strain imaging by speckle tracking echocardiography in detecting ischemic etiology of acute chest pain

Abstract Funding Acknowledgements none OnBehalf A TRAC-SI Multicenter Trial Background Two-dimensional speckle tracking echocardiography (2D-STE) has been reported to be useful for the diagnosis of myocardial ischemia by detecting delay in regional myocardial expansion (diastolic stunning) up to many hours after an episode of angina. The aim is to evaluate the diagnostic accuracy of Left ventricular (LV) diastolic longitudinal, circumferential, transverse and radial strain imaging by STE to detect the presence of acute coronary syndrome (ACS) in patients with acute chest pain. Methods 388 consecutive patients with acute chest pain and without wall motion abnormality, who were admitted to an emergency department (ED) at 1 of 12 clinical sites in Japan, were enrolled and underwent 2D-STE at ED. Left ventricular (LV) longitudinal, circumferential, transverse and radial strain values at aortic valve closure (A) and one-third of diastole duration (B) were measured. The strain imaging diastolic index (SI-DI) was value was determined as: (A-B)/A × 100% to assess the LV diastolic strain imaging and was used to identify the regional LV delayed relaxation. All patients underwent coronary CT or coronary angiography to establish the diagnosis of ACS. Clinicians were blinded to the 2D-STE results. Results Out of 388 patients, 2D-STE analysis was possible in 358 patients (92%). With assessment of coronary CT or coronary angiography, ACS was diagnosed in 118 patients (33%). 2D-STE was obtained at a mean of 5.3 hours after chest pain episode. SI-DI of longitudinal, circumferential, transverse and radial strain of ischemic segments were significantly lower than those of non-ischemic segments (p value &amp;lt; 0.001), and transverse and radial SI-DI demonstrated high diagnostic accuracy, compared with longitudinal SI-DI (Figure 1). Sensitivity, specificity, and negative predictive value for ACS of transverse SI-DI are 87%, 88%, % and 95%, respectively, using a cut-off value of 63.3. Conclusion LV diastolic strain imaging by 2D-STE at ED increase the sensitivity, specificity and accuracy to predict the presence of ACS in patients with chest pain. Compared with longitudinal diastolic strain imaging, transverse diastolic strain imaging is more sensitive marker to detect the myocardial ischemic episode (UMIN000013859). Abstract 1225 Figure 1

Quantitative low-dose rest and stress CT myocardial perfusion imaging with a whole-heart coverage scanner improves functional assessment of coronary artery disease

ObjectiveWe evaluated the diagnostic accuracy of myocardial blood flow (MBF) and perfusion reserve (MPR) measured from low-dose dynamic contrast-enhanced (DCE) imaging with a whole-heart coverage CT scanner for detecting functionally significant coronary artery disease (CAD). MethodsTwenty one patients with suspected or known CAD had rest and dipyridamole stress MBF measurements with CT and SPECT myocardial perfusion imaging (MPI), and lumen narrowing assessment with coronary angiography (catheter and/or CT based) within 6 weeks. SPECT MBF measurements and coronary angiography were used together as reference to determine the functional significance of coronary artery stenosis. In each CT MPI study, DCE images of the whole heart were acquired with breath-hold using a low-dose acquisition protocol to generate MBF maps. Binomial logistic regression analysis was used to determine the diagnostic accuracy of CT-measured MBF and MPR (ratio of stress to rest MBF) for assessing functionally significant coronary stenosis. ResultsMean stress MBF and MPR in ischemic segments were lower than those in non-ischemic segments (1.37 ± 0.34 vs. 2.14 ± 0.64 ml/min/g; 1.56 ± 0.41 vs. 2.53 ± 0.70; p < 0.05 for all). The receiver operating characteristic curve analysis revealed that MPR (AUC 0.916, 95%CI: 0.885–0.947) had a superior power than stress MBF (AUC 0.869, 95%CI: 0.830–0.909) for differentiating non-ischemic and ischemic myocardial segments (p = 0.045). On a per-vessel and per-segment analysis, concomitant use of MPR and stress MBF thresholds further improved the diagnostic accuracy compared to MPR or stress MBF alone for detecting obstructive coronary lesions (per-vessel: 93.4% vs. 83.6% and 88.5%, respectively; per-segment: 90.0% vs. 83.7% and 83.1%, respectively). The estimated effective dose of a rest and stress CT MPI study was 3.04 and 3.19 mSv respectively. ConclusionQuantitative rest and stress myocardial perfusion measurement with a large-coverage CT scanner improves the diagnostic accuracy for detecting functionally significant coronary stenosis.

Intermodel disagreement of myocardial blood flow estimation from dynamic CT perfusion imaging

PurposeTo assess the intermodel agreement of different tracer kinetic models to determine myocardial blood flow (MBF) and their diagnostic accuracy in coronary artery disease (CAD) at dynamic CT myocardial perfusion imaging (CTMPI). MethodsThree porcine hearts perfused in Langendorff mode and 15 patients with suspected CAD and perfusion single photon emission CT (SPECT) were included. Dynamic CTMPI was performed in shuttle-mode (70 kVp, 350mAs/rot) on 3rd generation dual-source CT. In porcine hearts and patients, myocardial segments (AHA-16-segment model) were drawn. Tissue attenuation curves were constructed per segment and arterial input functions were derived from the aorta. True MBF was calculated with input flow and weight of the porcine hearts. In patients, ischemic segments were based on SPECT results. MBF quantification was performed using the VPCT-software, Upslope, Extended Toft (ET), Two-compartment (TC) and Fermi models. ResultsIn porcine hearts, true MBF was 1.88 (interquartile range [IQR]:1.80-2.80)mL/g/min. Diagnostic accuracy was similar for all models: 0.96, 0.99, 0.92, 0.93 and 0.96 for VPCT software, Upslope method, Fermi, ET and TC model. The VPCT software and Upslope method resulted in lower MBF (median 1.44 [1.29–1.58] and 1.39 [1.25–1.59]mL/g/min) compared to the Fermi, ET, and TC model (median values of 1.76 mL/g/min [1.36–2.44], 2.55 mL/g/min [2.20–2.92], and 1.98 mL/g/min [1.60–2.60], respectively [p < 0.001]). In patients, all models showed a significant difference in MBF between the 34 ischemic and 206 non-ischemic segments (p-value<0.001). ConclusionAbsolute MBF values are significantly different between the models and a uniform threshold could not be determined; however, diagnostic accuracy for detecting ischemia is similar.

Low CT temporal sampling rates result in a substantial underestimation of myocardial blood flow measurements

The purpose of this study was to evaluate the effect of temporal sampling rate in dynamic CT myocardial perfusion imaging (CTMPI) on myocardial blood flow (MBF). Dynamic perfusion CT underestimates myocardial blood flow compared to PET and SPECT values. For accurate quantitative analysis of myocardial perfusion with dynamic perfusion CT a stable calibrated HU measurement of MBF is essential. Three porcine hearts were perfused using an ex-vivo Langendorff model. Hemodynamic parameters were monitored. Dynamic CTMPI was performed using third generation dual source CT at 70 kVp and 230–350 mAs/rot in electrocardiography(ECG)-triggered shuttle-mode (sampling rate, 1 acquisition every 2–3 s; z-range, 10.2 cm), ECG-triggered non-shuttle mode (fixed table position) with stationary tube rotation (1 acquisition every 0.5–1 s, 5.8 cm), and non-ECG-triggered continuous mode (1 acquisition every 0.06 s, 5.8 cm). Stenosis was created in the circumflex artery, inducing different fractional flow reserve values. Volume perfusion CT Myocardium software was used to analyze ECG-triggered scans. For the non-ECG triggered scans MASS research version was used combined with an in-house Matlab script. MBF (mL/g/min) was calculated for non-ischemic segments. True MBF was calculated using input flow and heart weight. Significant differences in MBF between shuttle, non-shuttle and continuous mode were found, with median MBF of 0.87 [interquartile range 0.72–1.00], 1.20 (1.07–1.30) and 1.65 (1.40–1.88), respectively. The median MBF in shuttle mode was 56% lower than the true MBF. In non-shuttle and continuous mode, the underestimation was 41% and 18%. Limited temporal sampling rate in standard dynamic CTMPI techniques contributes to substantial underestimation of true MBF.

Tmax is a sensitive indicator of myocardial ischaemia under adenosine stress as determined by static PET imaging: a study in a porcine model

To evaluate Tmax, defined as the time of residual function R(t) reaching its maximum, as an indicator of myocardial ischaemia and compare its efficacy with other computed tomography perfusion (CTP) parameters. Eight Bama miniature pigs with 50-90% left anterior descending artery stenosis underwent adenosine stress myocardial CTP and 13NNH3 position-emission tomography (PET) perfusion imaging. Tmax, myocardial blood flow (MBF), myocardial blood volume (MBV), mean transit time (MTT), and time to peak (TTP) were calculated from CTP images. PET images were evaluated as ischaemia or non-ischaemia. Using PET as a reference standard, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated. Multiple comparisons of the receiver operating characteristic (ROC) curves between Tmax and other parameters were performed. The diagnostic performance of the combination of each two parameters was calculated and compared with Tmax. RESULTS: Tmax was significantly higher in ischaemic segments compared with non-ischaemic segments. Multiple comparisons of the ROCs indicated that Tmax was better than MBF or TTP but not statistically different from MBV. Tmax was superior to the combination of (MBF+MBV) but not to (MBF+TTP) or (MBV+TTP). Tmax in dynamic stress CTP provides good diagnostic accuracy for detecting myocardial ischaemia, especially in sensitivity and NPV, compared with PET method. Tmax has better performance than MBF or TTP or combination of (MBF+MBV) in diagnosing myocardial ischaemia.

High levels of soluble CD59 in CSF compared to plasma suggests intrathecal source of soluble CD59

To determine the optimal timing of arterial first pass computed tomography (CT) myocardial perfusion imaging (CTMPI) based on dynamic CTMPI acquisitions.Twenty-five patients (59 ± 8.4 years, 14 male)underwent adenosine-stress dynamic CTMPI on second-generation dual-source CT in shuttle mode (30 s at 100 kV and 300 mAs). Stress perfusion magnetic resonance imaging (MRI) was used as reference standard for differentiation of non-ischemic and ischemic segments. The left ventricle (LV) wall was manually segmented according to the AHA 16-segment model. Hounsfield units (HU) in myocardial segments and ascending (AA) and descending aorta (AD) were monitored over time. Time difference between peak AA and peak AD and peak myocardial enhancement was calculated, as well as the, time delay from fixed HU thresholds of 150 and 250 HU in the AA and AD to a minimal difference of 15 HU between normal and ischemic segments. Furthermore, the duration of the 15 HU difference between ischemic and non-ischemic segments was calculated.Myocardial ischemia was observed by MRI in 10 patients (56.3 ± 9.0 years; 8 male). The delay between the maximum HU in the AA and AD and maximal HU in the non-ischemic segments was 2.8 s [2.2–4.3] and 0.0 s [0.0–2.8], respectively. Differentiation between ischemic and non-ischemic myocardial segments in CT was best during a time window of 8.6 ± 3.8 s. Time delays for AA triggering were 4.5 s [2.2–5.6] and 2.2 s [0–2.8] for the 150 HU and 250 HU thresholds, respectively. While for AD triggering, time delays were 2.4 s [0.0–4.8] and 0.0 s [−2.2–2.6] for the 150 HU and 250 HU thresholds, respectively.In CTMPI, the differentiation between normal and ischemic myocardium is best accomplished during a time interval of 8.6 ± 3.8 s. This time window can be utilized by a test bolus or bolus tracking in the AA or AD using the time delays identified here.