Presence Of Myocardial Ischemia Research Articles

Time-Warping Analysis of the T-Wave Peak-to-End Interval to Quantify Ventricular Repolarization Dispersion During Ischemia.

The presence of myocardial ischemia can increase ventricular arrhythmic risk due to a raised dispersion of ventricular repolarization. This is reflected on the morphology of the T-wave on the electrocardiogram (ECG), and can be quantified by time-warping based indexes, like dw. However, T-wave morphology can also be affected by ischemia-induced ST segment changes, impacting the accuracy of dw. We hypothesize that ischemia-induced repolarization dispersion can be better quantified by restricting dw to the T-wave peak-to-end (T pe) interval. 101 ECG recordings from patients undergoing a percutaneous coronary intervention (PCI) were analyzed together with their control ECG recordings, acquired before the intervention. A series of dw values was calculated by quantifying the T pe morphological variations between the T-waves from the PCI and a reference derived from the control ECG recordings. We proposed a normalized version of dw, Rd, reflecting relative variations of dw during PCI to control recordings, and compare it with traditional indices behaviour. Values of dw followed a gradually increasing trend as PCI inflation time progressed, reaching a median[range] Rd value of 9.44 [1.01, 80.74] at the occlusion end. During control recordings, dw remained stable, with a low intra-patient standard deviation, range [0.02, 2.09] ms and a median[range] Rd of 1.00 [0.03, 2.93]. Rd at oclussion end was significantly higher than threshold values of 1, 2, 5, and 10 in 94.1%, 85.11%, 64.4% and 48.5% of patients, respectively. The spatial lead-wise analysis of dw showed distinct distributions depending on the occluded artery, suggesting a relation with the ischemia location. The relative variation R with ischemia of index dw (9.4) is greater than for traditional T wave amplitude (7.7), T peak-to-end interval (2.7) and T width (3.0). The index dw, quantifying T pe morphology variations, allows to follow the ischemia induced variations in repolarization in a more robust manner than classical indexes, avoiding ST segment and early T wave distortions not related to repolarization dispersion, and warranting further clinical studies to evaluate its ventricular arrhythmia risk predictive value during ischemia.

A retrospective evaluation of Bayesian-penalized likelihood reconstruction for [15O]H2O myocardial perfusion imaging

BackgroundNew Block-Sequential-Regularized-Expectation-Maximization (BSREM) image reconstruction technique has been introduced for clinical use mainly for oncologic use. Accurate and quantitative image reconstruction is essential in myocardial perfusion imaging with positron emission tomography (PET) as it utilizes absolute quantitation of myocardial blood flow (MBF). The aim of the study was to evaluate BSREM reconstruction for quantitation in patients with suspected coronary artery disease (CAD). Methods and ResultsWe analyzed cardiac [15O]H2O PET studies of 177 patients evaluated for CAD. Differences between BSREM and Ordered-Subset-Expectation-Maximization with Time-Of-Flight (TOF) and Point-Spread-Function (PSF) modeling (OSEM-TOF-PSF) in terms of MBF, perfusable tissue fraction, and vascular volume fraction were measured. Classification of ischemia was assessed between the algorithms. OSEM-TOF-PSF and BSREM provided similar global stress MBF in patients with ischemia (1.84 ± 0.21 g⋅ml−1⋅min−1 vs 1.86 ± 0.21 g⋅ml−1⋅min−1) and no ischemia (3.26 ± 0.34 g⋅ml−1⋅min−1 vs 3.28 ± 0.34 g⋅ml−1⋅min−1). Global resting MBF was also similar (0.97 ± 0.12 g⋅ml−1⋅min−1 and 1.12 ± 0.06 g⋅ml−1⋅min−1). The largest mean relative difference in MBF values was 7%. Presence of myocardial ischemia was classified concordantly in 99% of patients using OSEM-TOF-PSF and BSREM reconstructions ConclusionOSEM-TOF-PSF and BSREM image reconstructions produce similar MBF values and diagnosis of myocardial ischemia in patients undergoing [15O]H2O PET due to suspected obstructive coronary artery disease

TRATAMENTO INVASIVO: BASES PARA A DECISÃO

The spectrum of clinical conditions associated with the presence of myocardial ischemia and related symptoms (angina pectoris or equivalent), regardless of the cau-sative mechanism (obstructive disease, microvascular dysfunction or coronary spasm) is called chronic coronary syndrome (CCS). Although the essence of the treatment of patients with SCC consists of changes in lifestyle and strict control of cardiovascular risk factors, in addition to antianginal therapy in maximally tolerated doses, surgical or percutaneous revascularization procedures are indicated when medical treatment fails to offer adequate symptoms control or in scenarios in which they provide a reduction in the risk of events compared to clinical therapy alone. Thus, patients with left main disease, multivessel disease (especially diabetics or those with high angiographic complexity), patients with HFrEF of ischemic etiology, and those with the last remaining patent vessel or proximal lesion of the anterior descending artery should be candidates for intervention. The choice of the intervention modality should be based on robust scientific evidence as proposed by current guidelines. In general terms, clinical parameters (patient frailty, comorbidities, and analysis of left ventricular function, for example), angiographic para-meters (anatomical complexity), and technical parameters (experience of the local team and availability of specific devices such as IVUS) are analyzed by the Heart Team in the decision-making process.

Discussion

Presenter: Dr Masaro Nakae Dr William Holman (Birmingham, Ala). In our patients with ischemic cardiomyopathy, sudden death, presumably from arrhythmias, constitutes a substantial source of postsurgical mortality. Thus, the notion that an ICD placed at the time of coronary artery bypass surgery will save lives in appropriately selected patients is intuitively appealing. However, this goal has proven elusive. One reason is the competing risk nature of postsurgical mortality. In other words, there are several potential modes for death after cardiac surgery. They include progressive pump failure and acute myocardial infarction among several others. Accurately identifying the patients who will die of an arrhythmia rather than a death from another cause is difficult, as shown by the CABG Patch Trial in 1997 and other subsequent studies. Moreover, ICDs themselves come with a cost, both in terms of complications and monetary expenditure. This article from Dr Nakae and associates at Osaka University Graduate School of Medicine provides interesting and potentially useful information for surgeons and their collaborators. I thank them for their contribution to our base of knowledge in this area and have the following questions. First, the authors showed a survival benefit for patients with VAs and other risk factors who received an ICD. Within this group, there were 3 subgroups of patients with postoperative VAs. A total of 46 of them had ventricular fibrillation or pulseless, in other words, symptomatic VT, whereas there were 27 patients with asymptomatic sustained VT and 26 patients with nonsustained VT. Was the survival of these 3 groups of patients over time similar or did the benefit for an ICD in the symptomatic patients account for most of the benefit seen in the entire group of patients with postoperative VAs? Second, were there any patients at your hospital who received an ICD at the time of CABG who did not have preoperative VAs? If yes, what were the most common indications for the ICD? Third, the details for managing patients with asymptomatic preoperative VAs are particularly important. For example, does monomorphic self-terminating VT before surgery serve as an indication for an ICD when the surgeon expects to achieve complete revascularization? What risk factors for postsurgical sudden death do the authors view as most crucial and important in their decision [to?] implant an ICD in patients with asymptomatic VT before surgery? Fourth, do the authors ever prescribe a wearable or external defibrillator for patients at risk for arrhythmias and defer reevaluation for an ICD until 3 months after coronary surgery? Dr Masaro Nakae (Osaka, Japan). For the first question, among patients with postoperative VAs, those who had ventricular fibrillation or pulseless VT had the worst prognosis, followed by asymptomatic sustained VT and nonsustained VT. As you mentioned, the benefits for ICD implantation depended on the benefits of the patients with symptomatic VT. Second, were there any patients at my hospital who received an ICD at the of CABG? There were no patients who received a concomitant ICD implantation at CABG in our study. However, during hospitalization, 11 patients who did not have preoperative VAs underwent ICD implantation, and 5 patients developed postoperative asymptomatic VA in [our EP?] and received an implant for secondary prevention. The remaining 6 patients were for primary prevention based on the results of EP study or postoperative [interval?] functional recovery. Third, in our studies, there were no differences in frequency of complete revascularization between the patients who did and did not develop postoperative VAs. On the other hand, our multivariate analysis demonstrated that the degree of preoperative [inaudible], the extent of scar lesion, and redo surgery were the most important determinants of postoperative VAs. Thus, our results implied that VAs could not be directly prevented even if complete revascularization was achieved, in particular, when the patient had some extent of scar lesion. So even if complete revascularization could be achieved, careful follow-up would be needed by doing the detailed stratification by use of predictors, which I just pointed out. Last question, about wearable defibrillator experience. We prescribe a wearable defibrillator for patients when a patient has recurrent nonsustained VT until 3 months after CABG. The presence of myocardial ischemia will be evaluated. If there is known ischemia in myocardium, the patient is indicated for a wearable defibrillator. Unidentified Speaker 1. Was there any relationship between the occurrence of the arrhythmias and the performance of SVR? Dr Nakae. We analyzed the impact of SVR on postoperative VAs. SVR was not significantly considered as a predictor for postoperative VA.

Cardiovascular events in patients with coronary artery disease with and without myocardial ischemia: Long-term follow-up

After the results of the ISCHEMIA Trial, the role of myocardial ischemia in the prognosis of coronary artery disease (CAD) was under debate. We sought to comparatively evaluate the long-term prognosis of patients with multivessel CAD with or without documented myocardial ischemia. This is a single-center, retrospective, observational cohort study that included patients with CAD obtained from the research protocols database of "The Medicine, Angioplasty or Surgery Study," the MASS Study Group. Patients were stratified according to the presence or absence of myocardial ischemia. Cardiovascular events (overall mortality and myocardial infarction) were tracked from the registry entry up to a median follow-up of 8.7 years. Myocardial ischemia was assessed at baseline by a functional test with or without imaging. From 1995 to 2018, 2015 patients with multivessel CAD were included. Of these, 1001 presented with conclusive tests at registry entry, 790 (79%) presenting with ischemia and 211 (21%) without ischemia. The median follow-up was 8.7 years (IQR 4.04 to 10.07). The primary outcome occurred in 228 (28.9%) patients with ischemia and in 64 (30.3%) patients without ischemia (plog-rank=0.60). No significant interaction was observed with the presence of myocardial ischemia and treatment strategies in the occurrence of the combined primary outcome (pinteration=0.14). In this sample, myocardial ischemia was not associated with a worse prognosis compared with no ischemia in patients with multivessel CAD. These results refer to debates about the role of myocardial ischemia in the occurrence of cardiovascular events.

ApoJ-Glyc, an early marker of myocardial ischaemia, rapidly maps improved myocardial perfusion in STEMI patients undergoing successful primary PCI

Abstract Background Previous studies using experimental models and clinical retrospective samples have pointed to a potential role of glycosylated apolipoprotein J (ApoJ-Glyc) as a marker for the early detection of myocardial ischaemia. Ischaemia induces intracellular accumulation of non-glycosylated ApoJ that mirrors the reduction in ApoJ-Glyc serum levels in patients presenting with ST-segment elevation myocardial infarction (STEMI). Purpose The EDICA (Early Detection of Myocardial Ischaemia in Suspected Acute Coronary Syndromes by Apo J-Glyc as a Novel Pathologically based Ischaemia Biomarker) clinical trial assessed the performance of ApoJ-Glyc as a biomarker for the early detection of myocardial ischaemia in patients attending the A&E department with chest pain suggestive of acute coronary syndrome. Here, we report the observed changes in ApoJ-Glyc concentration in STEMI patients at baseline and after primary percutaneous coronary intervention (PPCI). Methods The EDICA trial, a multi-centre (10 sites), international, in vitro diagnostic study, assessed 404 patients attending the A&E department with suspected ACS. Of these, 291 patients had a final diagnosis of “non-ischaemic” event and 113 of “ischaemic” event. The main inclusion criterion was chest pain of suspected cardiac origin. Blood samples were obtained for the simultaneous assessment of high sensitivity-troponin and ApoJ-Glyc on admission (time 0) and at 1h and 3h thereafter. Two different glycosylated variants of ApoJ (ApoJ-GlycA2 and ApoJ-GlycA6) were analyzed with a novel ELISA in serum samples. Of the “ischaemic” patients, 33 had STEMI, of whom 85% underwent PPCI. Results As expected, in the presence of myocardial ischaemia, time 0 ApoJ-GlycA2 and ApoJ-GlycA6 serum levels decreased by 34% and 48%, respectively in STEMI patients, compared with non-ischaemic patients, i.e. ApoJ-GlycA2 in STEMI: 66 [52–95] μg/ml vs. non-ischaemic: 100 [72–131] μg/ml; P=0.0002; ApoJ-GlycA6 STEMI: 38 [34–67] vs. non-ischaemic: 73 [56–95] μg/ml; P<0.0001. ApoJ-GlycA6 showed a discriminating ability for the presence of STEMI with a 67% sensitivity and a 83% specificity (AUC=0.747, cut-off of 50μg/ml). In STEMI patients in whom PPCI successfully restored TIMI 3 flow, ApoJ-Glyc levels increased rapidly and significantly compared with time 0 levels (ApoJ-GlycA2: P=0.02 and P=0.003 for 1h and 3h; ApoJ-GlycA6: P=0.02 and P=0.002 for 1h and 3h) and compared to patients in whom PPCI was not performed (Table 1). Conclusions ApoJ-Glyc concentrations are reduced in STEMI patients on admission and increase rapidly after improved perfusion with PPCI, pointing to a potential role of this biomarker in the early detection of reversible ischaemia and the mapping of reversible changes. The mechanisms whereby ApoJ-Glyc levels rapidly and markedly increase after PPCI are speculative at present and deserve further investigation, together with the potential prognostic value of ApoJ-Glyc in this setting. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Commission 2020-EIC-SMEInstrument Phase 2; Spanish Ministry of Science, Innovation and Universities

Microvascular dysfunction is associated with impaired myocardial work in obstructive and nonobstructive hypertrophic cardiomyopathy: a multimodality approach

Abstract Introduction Myocardial work is a dynamic non-invasive method for assessing myocardial deformation. Microvascular dysfunction is a hallmark of hypertrophic cardiomyopathy (HCM). We hypothesized that there is an association between impaired myocardial work, evaluated by echocardiography, and left ventricular (LV) ischemia, detected by cardiac magnetic resonance (CMR). Methods Prospective assessment of HCM patients' (P) myocardial strain parameters with 2D speckle-tracking echocardiography. All P underwent CMR protocol (1.5-T) for the analysis of stress perfusion and late gadolinium enhancement (LGE). Perfusion defects were quantified as burden of ischemia (% of LV mass). Results were stratified according to obstructive (oHCM) and nonobstructive (nHCM) HCM as well as according to the presence of significant replacement fibrosis (LGE of ≥15% or <15% of LV mass). Multivariate regression analyses were used to explore the relation between myocardial work and the burden of ischemia. Results 75 P with HCM (63% male, age 55±15 years), 61% with asymmetric septal LVH, 29% with apical LVH, 8% with concentric LVH and 28% exhibiting LV outflow tract obstruction (mean maximal LVOT gradient of 89±60 mmHg). Perfusion defects were found in 68 P (90.7%), with a mean of 22.5±16.9% of LV mass and 29 P (38.7%) had LGE ≥15% of LV mass. A lower global work index (GWI) significantly correlated with higher burden of myocardial perfusion defects (r=−0.520, β-estimate −0.019, 95% CI −0.028 to −0.010, p<0.001). Likewise, impaired values of global work efficiency (GWE) were linked to higher percentage of hypoperfusion (r=−0.477, β-estimate −0.713, 95% CI −1.250 to −0.176, p<0.001). Moreover, impaired global constructive work (GCW) (r=−0.519, β-estimate −0.021, 95% CI −0.030 to −0.013, p<0.001) and a higher global wasted work (GWW) (r=0.280, p=0.017) were associated with a higher burden of perfusion defects (Figure 1). GWI showed a higher correlation with perfusion defects in oHCM P (r=−0.518, p=0.019) vs. nHCM P (r=−0.492, p<0.001), and the same was also found with GWE (oHCM: r=−0.591, p=0.006 vs. nHCM: r=−0.317, p=0.022) (Figure 2A). Furthermore, GCW showed a slightly higher correlation with hypoperfusion in oHCM P (r=−0.564, p=0.010) vs. nHCM P (r=−0.520, p<0.001). There was no significant difference between oHCM and nHCM P regarding GWW. In P with LGE ≥15%, GWI showed a better correlation with perfusion defects (r=−0.489, p=0.007) vs. P with LGE of <15% (r=−0.369, p=0.007). Moreover, GCW showed a higher correlation with hypoperfusion in P with LGE ≥15% (r=−0.455, p=0.013) comparing with P with LGE <15% LV mass (r=−0.359, p=0.019) (Figure 2B). No difference was found regarding GWE and GWW according to LGE burden. Conclusion In our cohort of P with HCM, impaired GWI, GWE and GCW and a higher GWW were significantly correlated with the presence of myocardial ischemia in CMR. This correlation was greater in P with oHCM and in P with LGE of ≥15% of LV mass. Funding Acknowledgement Type of funding sources: None.

The prognostic implications of ST-segment and T-wave abnormalities in patients undergoing regadenoson stress SPECT myocardial perfusion imaging

BackgroundThe prognostic implications of ST-segment and T-wave (ST/T) abnormalities in patients undergoing stress SPECT-myocardial perfusion imaging (MPI) are not well defined. Methods and ResultsThis was a single-center, retrospective cohort study of consecutive patients who underwent regadenoson stress SPECT-MPI. Patients with baseline electrocardiogram (ECG) abnormalities that impede ST/T analysis or those with known coronary artery disease were excluded. Patients were categorized as having primary ST abnormalities, secondary ST/T abnormalities due to ventricular hypertrophy or right bundle branch block, T-wave abnormalities, or normal ECG. The primary outcome was major adverse cardiovascular events (MACE) defined as the composite of cardiac death or myocardial infarction. Among 6,059 subjects, 1912 (32%) had baseline ST/T abnormalities. During a mean follow-up of 2.3 ± 1.9 years, the incidence of MACE was significantly higher among patients with secondary ST/T abnormalities compared to those with normal ECG (HR 2.05; 95% confidence interval [CI], 1.04-4.05; P = 0.039). No significant difference in MACE was observed among patients with primary ST abnormalities (HR 1.64; CI 0.87-3.06; P = 0.124) or T-wave abnormalities (HR 1.15; CI 0.62-2.16; P = 0.658) compared with patients who had normal ECG. Among patients with secondary ST/T changes, abnormal MPI was not associated with a significant increase in MACE rates compared to normal MPI (HR 1.18; CI 0.31-4.58; P = 0.808). However, abnormal MPI was associated with higher MACE rates among patients with primary ST abnormalities (HR 4.50; CI 1.44-14.10; P = 0.005) and T-wave abnormalities (HR 3.74; CI 1.20-11.68; P = 0.015). Similarly, myocardial ischemia on regadenoson stress SPECT-MPI was not associated with a significant increase in MACE rates in patients with secondary ST/T abnormalities (HR 1.45; CI 0.38-5.61; P = 0.588), while it was associated with a higher incidence of MACE in patients with primary ST abnormalities (HR 3.012; CI 0.95-9.53; P = 0.049) and T-wave abnormalities (HR 5.06; CI 1.60-15.96; P = 0.002). ConclusionWhile patients with secondary ST/T abnormalities had significantly higher MACE risk, abnormal MPI or presence of myocardial ischemia on regadenoson SPECT-MPI in this group does not add prognostic information. Patients with primary ST abnormalities and T-wave abnormalities do not seem to have a significantly higher MACE risk compared to those with normal ECG; however, abnormal MPI or presence of myocardial ischemia, in these groups, correlates with higher MACE rates.

The Association of Alanine Aminotransferase Levels With Myocardial Perfusion Imaging and Cardiovascular Morbidity.

Studies suggest that non-alcoholic fatty liver disease (NAFLD) is associated with an independent risk of cardiovascular disease (CVD). We utilized a large cohort of patients undergoing myocardial perfusion imaging (MPI) with single photon emission computed tomography (SPECT) to determine the association between alanine aminotransferase (ALT) as a surrogate marker for presumed NAFLD, and the presence of myocardial ischemia and mortality. We retrospectively assessed SPECT-MPI results and medical records of individuals evaluated between 1997 and 2008. We excluded patients with known non-NAFLD liver diseases, ALT values <17 or >340 U/L and absent liver tests. Elevated ALT cases were classified as presumed NAFLD. The primary endpoint was abnormal SPECT-MPI. Secondary endpoints included cardiac death, acute myocardial infarction and all-cause mortality. Of 26,034 patients who underwent SPECT-MPI, 11,324 met inclusion criteria. 1635 (14.4%) patients had elevated ALT. SPECT-MPI results did not differ significantly between subjects with elevated ALT and controls. Elevated ALT was associated with increased risk for the composite endpoint of cardiac death or acute myocardial infarction at 5-year follow-up (hazard ratio [HR] 1.3, 95% confidence interval [CI] 1.01-1.67) and in all-cause mortality (HR 1.27, CI 1.02-1.58) but only in patients with normal SPECT-MPI. The long-term mortality of patients with abnormal SPECT-MPI is not modulated by ALT, likely reflecting an already high risk and established CVD. However, patients with normal SPECT-MPI are at increased risk for a future cardiac event if they have an elevated ALT level, suggesting an important role for NAFLD in earlier stages of CVD.

Computed Tomography-derived Characterization of Pericoronary, Epicardial, and Paracardial Adipose Tissue and Its Association With Myocardial Ischemia as Assessed by Computed Fractional Flow Reserve.

Increased pericoronary adipose tissue (PCAT) attenuation derived from coronary computed tomography (CT) angiography (CTA) relates to coronary inflammation and cardiac mortality. We aimed to investigate the association between CT-derived characterization of different cardiac fat compartments and myocardial ischemia as assessed by computed fractional flow reserve (FFRCT). In all, 133 patients (median 64 y, 74% male) with coronary artery disease (CAD) underwent CTA including FFRCT measurement followed by invasive FFR assessment (FFRINVASIVE). CT attenuation and volume of PCAT were quantified around the proximal right coronary artery (RCA), left anterior descending artery (LAD), and left circumflex artery (LCX). Epicardial adipose tissue (EAT) and paracardial adipose tissue (PAT; all intrathoracic adipose tissue outside the pericardium) were quantified in noncontrast cardiac CT datasets. Median FFRCT was 0.86 [0.79, 0.91] and median FFRINVASIVE was 0.87 [0.81, 0.93]. Subjects with the presence of myocardial ischemia (n=26) defined by an FFRCT-threshold of ≤0.75 showed significantly higher RCA PCAT attenuation than individuals without myocardial ischemia (n=107) (-75.1±10.8 vs. -81.1±10.6 HU, P=0.011). In multivariable analysis adjusted for age, body mass index, sex and risk factors, increased RCA PCAT attenuation remained a significant predictor of myocardial ischemia. Between individuals with myocardial ischemia compared with individuals without myocardial ischemia, there was no significant difference in the volume and CT attenuation of EAT and PAT or in the PCAT volume of RCA, LAD, and LCX. Increased RCA PCAT attenuation is associated with the presence of myocardial ischemia as assessed by FFR, while PCAT volume, EAT, and PAT are not.

Myocardial ischemia and previous infarction contribute to left ventricular dyssynchrony in patients with coronary artery disease

AimsThe aim of this study was to characterize determinants of left ventricular mechanical dyssynchrony (LVMD) in patients with coronary artery disease (CAD). MethodsMedical records and results of myocardial perfusion SPECT/CT studies were evaluated in 326 patients with previously diagnosed CAD. LVMD was assessed with the phase analysis of ECG-gated myocardial SPECT. Dyssynchrony was described with phase histogram bandwidth (PHBW), standard deviation (PHSD) or entropy (PHE) values above limit of the highest normal. ResultsPrevalence of LVMD was 29% in CAD patients. Size of the infarction scar and ischemia extent correlated significantly with PHBW, PHSD and PHE (P < 0.001 for all). Independent predictors of LVMD were myocardial infarction scar (P = 0.004), ischemia extent (P = 0.003), and QRS duration (P = 0.003). Previous percutaneous coronary intervention and coronary artery bypass grafting did not independently predict dyssynchrony. ConclusionsAlmost one-third of CAD patients had significant LVMD. Dyssynchrony was associated with earlier myocardial infarction and presence of myocardial ischemia. Previous percutaneous coronary intervention and coronary artery bypass grafting did not independently predict dyssynchrony.

Abstract 11478: Epicardial Adipose Tissue Volume - Relationship with Coronary Artery Plaque Vulnerability and Myocardial Ischemia in Non-Obstructive Coronary Artery Disease

Introduction: Myocardial ischemia is common among patients with chest pain and non-obstructive coronary artery disease (CAD). Epicardial adipose tissue (EAT) accumulation has been associated with inflammation, atherosclerosis and microvascular dysfunction. Accordingly, we hypothesised that EAT volume is associated with coronary plaque vulnerability and myocardial ischemia in patients with non-obstructive CAD. Methods: We included 125 patients with chest pain and non-obstructive CAD by coronary computed tomography angiography (CCTA). EAT volume was quantified on non-contrast cardiac computed tomography images by a semiautomatic analysis software. CCTA images were analysed with respect to plaque volume and composition. Plaque vulnerability was assessed as total coronary non-calcified plaque volume and positive remodelling index &gt;1.10. Myocardial ischemia was detected by contrast dobutamine stress echocardiography. Patients were grouped in tertiles of EAT volume and high EAT volume was defined as volumes in the highest tertile (≥125 ml). Results: In the total study population (median age 63(58, 69) years and 58% women), the median EAT volume was 104 (77, 141) ml. High EAT volume was more common in men and associated with higher BMI, hypertension and positive remodelling (all p&lt;0.05). There was no difference in age, prevalence of diabetes, total non-calcified plaque volume or presence of myocardial ischemia between groups (all p≥0.34). This was confirmed in univariable logistic regression analyses (Table). After adjusting for covariables in a multivariable model, the association between positive remodelling and high EAT volume was attenuated (Table). Conclusion: High EAT volume was associated with positive remodelling, but not with total non-calcified plaque volume or myocardial ischemia, and the association was attenuated after multivariable adjustments.

Computed tomography-derived characterisation of pericoronary,epicardial and paracardial adipose tissue and its association with myocardial ischemia as assessed by computed and invasive fractional flow

Abstract Introduction Increased pericoronary adipose tissue (PCAT) computed tomography (CT) attenuation derived from coronary CT angiography (CTA) around the right coronary artery (RCA) reflects coronary inflammation and relates to cardiac mortality. Purpose We aimed to investigate the yet unclear association between CT-derived characterisation of different cardiac adipose tissue compartments and the presence of myocardial ischemia as assessed by fractional flow reserve (FFR). Methods 133 stable individuals (64 years, 74% male) with coronary artery disease (CAD) underwent CTA including computed FFR (FFR-CT) measurement followed by invasive angiography with FFR (invasive FFR) assessment. The CT attenuation (HU) and volume (mm3) of PCAT were quantified around the RCA (10 to 50 mm from RCA ostium), the proximal 40 mm of the left anterior descending artery (LAD) and the circumflex artery (LCX) with the help of semi-automated software. The per patient PCAT CT attenuation was calculated as followed: (PCAT CT attenuation of RCA+LAD+LCX)/3. Quantification of epicardial adipose tissue (EAT) and paracardial adipose tissue (PAT; all intrathoracic adipose tissue outside the pericardium) were performed in non-contrast cardiac CT data sets using a fully automated deep-learning based algorithm. Results Median FFR-CT was 0.86 [0.79, 0.91] and median invasive FFR was 0.87 [0.81, 0.93]. Patients with presence of myocardial ischemia (n=26) defined by a FFR-CT threshold of ≤0.75 showed a significant higher PCAT CT attenuation of RCA (−75.1 HU vs. −81.1 HU, p=0.011) and per patient (−74.5 HU vs. −77.7 HU, p=0.045) than individuals without myocardial ischemia (n=107). In multivariable analysis adjusted for age, BMI, gender and traditional risk factors, both RCA and per patient PCAT CT attenuation were significant predictors of myocardial ischemia as assessed by FFRCT ≤0.75. Between individuals with myocardial ischemia compared to individuals without myocardial ischemia there was no significant difference neither in the volume and CT attenuation of EAT and PAT nor in the PCAT volume of RCA, LAD, LCX and per patient PCAT volume. Conclusions Our observations suggest that PCAT CT attenuation instead of PCAT volume, EAT and PAT measures might be associated with the presence of myocardial ischemia as assessed by FFR. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): German Heart Foundation e.V.

Small Endogeneous Peptide Mitigates Myocardial Remodeling in a Mouse Model of Cardioselective Galectin-3 Overexpression.

Myocardial Gal3 (galectin-3) expression is associated with cardiac inflammation and fibrosis. Increased Gal3 portends susceptibility to heart failure and death. There are no data reporting the causative role of Gal3 to mediate cardiac fibro-inflammatory response and heart failure. We developed a cardioselective Gal3 gain-of-function mouse (Gal3+/+) using α-myosin heavy chain promotor. We confirmed Gal3-transgene expression with real-time polymerase chain reaction and quantified cardiac/circulating Gal3 with Western blot and immunoassays. We used echocardiogram and cardiac magnetic resonance imaging to measure cardiac volumes, function, and myocardial velocities. Ex vivo, we studied myocardial inflammation/fibrosis and downstream TGF (transforming growth factor) β1-mRNA expression. We examined the effects of acute myocardial ischemia in presence of excess Gal3 by inducing acute myocardial infarction in mice. Two subsets of mice including mice treated with N-acetyl-seryl-aspartyl-lysyl-proline (a Gal3-inhibitor) and mice with genetic Gal3 loss-of-function (Gal3-/-) were studied for comparative analysis of Gal3 function. Gal3+/+ mice had increased cardiac/circulating Gal3. Gal3+/+ mice showed excess pericardial fat pad, dilated ventricles and cardiac dysfunction, which was partly normalized by N-acetyl-seryl-aspartyl-lysyl-proline. Cardiac magnetic resonance imaging showed reduced myocardial contractile velocities in Gal3+/+. The majority of Gal3+/+ mice did not survive acute myocardial infarction, and the survivors had profound cardiac dysfunction. Myocardial histology of Gal3+/+ mice showed macrophage/mast-cell infiltration, fibrosis and higher TGFβ1-mRNA expression, which were mitigated by both Gal3 gene deletion and N-acetyl-seryl-aspartyl-lysyl-proline administration. Our study shows that cardioselective Gal3 overexpression leads to multiple cardiac phenotypic defects including ventricular dilation and cardiac dysfunction. Pharmacological Gal3 inhibition conferred protective effects with reduction of inflammation and fibrosis. Our study highlights the importance of translational studies to counteract Gal3 function and prevent cardiac dysfunction.

Lesion Geometry as Assessed by Optical Coherence Tomography Is Related to Myocardial Ischemia as Determined by Cardiac Magnetic Resonance Imaging.

Introduction: Although the relationship between the geometry of coronary stenosis and the presence of myocardial ischemia is well known, the association between stenosis geometry and severity and/or extent of ischemia is still unexplored. Thus, we investigated this relationship using optical coherence tomography (OCT) to assess stenosis parameters and cardiac magnetic resonance imaging (CMR) to determine both extent and severity of ischemia. Methods: We analyzed 55 lesions from 51 patients with stable angina. Pre-interventionally, all patients underwent OCT-analysis of stenosis morphology as well as CMR to determine both the extent and severity of myocardial ischemia. Results: Percent area stenosis (%AS) was significantly associated with ischemic burden (r = 0.416, p = 0.003). Similar results could be obtained for other stenosis parameters as well as for several other parameters assessing the extent of ischemia. Furthermore, OCT-derived stenosis parameters were associated with the product of ischemic burden and severity of ischemia (%AS: r = 0.435, p = 0.002; similar results for other parameters). A Poiseuille’s-law-modelled combination of stenosis length and minimal lumen diameter yielded a good diagnostic efficiency (AUC 0.787) in predicting an ischemic burden >10%. Conclusions: Our data highlight the key role of the geometry of coronary lesions in determining myocardial ischemia.

Triglyceride-glucose index predicts outcome in patients with chronic coronary syndrome independently of other risk factors and myocardial ischaemia.

AimsThe triglyceride-glucose (TyG) index, a surrogate marker of insulin resistance (IR), is a prognostic risk factor in the general population. We aimed to assess whether it is an independent predictor of outcome also in patients with chronic coronary syndrome (CCS).Methods and resultsTyG index was evaluated in 1097 consecutive patients (75% men, median age 72 years) with known (26%) or suspected coronary artery disease (CAD), undergoing stress-rest myocardial perfusion scintigraphy, and coronary angiography and followed up for a median of 4.5 years. Moderate/severe perfusion abnormalities during stress (summed stress score >7) were documented in 60% of patients, obstructive CAD in 74%, and 36% underwent early revascularization. TyG index was 8.9 (median, interquartile interval 8.6–9.2). Cardiac death or myocardial infarction occurred in 103 patients and all-cause death in 65. After correction for clinical risk factors, LV function and common bio-humoral variables, TyG index (HR 2.42, 95% CI 1.57–3.72, P < 0.001), and moderate/severe stress perfusion abnormalities (hazard ratio (HR) 2.17, 95% confidence interval (CI) 1.25–3.77, P < 0.001) independently predicted cardiac events. TyG index (HR 3.64, 95%CI 2.22–5.96, P < 0.001) and high-sensitivity C-reactive protein (HR 1.11, 95% CI 1.04–1.19, P = 0.002) independently predicted all-cause death.ConclusionIn patients with CCS, the TyG index identifies a cardiometabolic profile associated with an additional risk of cardiac events, over the presence of myocardial ischaemia and independently of other clinical, common bio-humoral or imaging risk determinants.

CT-derived characterization of pericoronary, paracardial and epicardial adipose tissue and its association with myocardial ischemia as assessed by adenosine stress CMR perfusion imaging

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): German Heart Foundation e.V. Introduction Increased attenuation of pericoronary adipose tissue (PCAT) around the right coronary artery (RCA) is a new imaging biomarker to detect coronary inflammation derived from routine coronary CT angiography (CTA) and has been shown to be associated with cardiac mortality. Increased volume of epicardial adipose tissue (EAT) has been reported be associated with myocardial ischemia. Purpose We aimed to investigate a potential association between CTA-derived PCAT measures and myocardial ischemia as assessed by adenosine stress CMR perfusion imaging. Methods In this single-centre study 109 stable individuals (mean age of 62 ± 11 years, 77% males) with coronary artery disease underwent CTA followed by adenosine stress CMR perfusion imaging to detect myocardial ischemia. PCAT CT attenuation (HU) and PCAT volume (cm3) was measured around the RCA (10 to 50 mm from RCA ostium), the proximal 40 mm of the left anterior descending artery (LAD) and the circumflex artery (LCX) using semi-automated software. Per patient PCAT CT attenuation was calculated as followed: (PCAT attenuation of RCA + LAD + LCX)/3). Non-contrast CT data sets were used for coronary calcium scoring and the quantification of EAT (located between the myocardial surface and the pericardium) and paracardial adipose tissue (PAT; intrathoracic and outside of the pericardium). Results Between patients with evidence of significant myocardial ischemia as assessed by adenosine stress CMR perfusion imaging (n = 35) and patients without myocardial ischemia (n = 74) there was no significant difference in the CT attenuation of RCA (-85.3 HU vs. -85.7 HU, p = 0.87), LAD (-84.8 HU vs. -85.7 HU, p = 0.66) and LCX (-82.8 HU vs. -83.2 HU, p = 0.79) as well as in the per patient PCAT CT attenuation (-84.2 HU vs. -84.9 HU, p = 0.76). Neither did patients with myocardial ischemia within the RCA territory show increased RCA PCAT CT attenuation (-87.7 HU vs. -85.3 HU, p = 0.40); nor was such a relationship found for the territory of the LAD (-80.6 HU vs. 85.8 HU, p = 0.11) or LCX (-83.1 HU vs. -83.0 HU, p = 0.99). The CT attenuation of EAT (-77.9 vs. -78.7 HU, p = 0.65) and PAT (-89.9 HU vs. -90.0 HU, p = 0.93) did not differ between patients with myocardial ischemia compared to patients without myocardial ischemia. Between patients with myocardial ischemia and patients without myocardial ischemia there was no significant difference in the volumes of EAT (118.1 cm3 vs. 110.6 cm3, p = 0.55), PAT (279.5 cm3 vs. 240.9 cm3, p = 0.20) and the per patient PCAT volume (1021.9 mm3 vs. 1015.5 mm3, p = 0.90). In logistic regression analysis the volume and CT attenuation of the different intrathoracic fat compartments PCAT, EAT and PAT were not independently associated with the presence of myocardial ischemia (n.s.). Conclusions In this single-centre study CTA-derived quantified CT attenuation and volume of PCAT, EAT and PAT were not associated with myocardial ischemia as assessed by adenosine stress CMR perfusion imaging.

CT-derived characterization of pericoronary, paracardial and epicardial adipose tissue and its association with myocardial ischemia as assessed by adenosine stress CMR perfusion imaging

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Kaltenbach scholarship of the german heart foundation Background Increased attenuation of pericoronary adipose tissue (PCAT) around the right coronary artery (RCA) is a new imaging biomarker to detect coronary inflammation derived from routine coronary CT angiography (CTA) and has been shown to be associated with cardiac mortality. Increased volume of epicardial adipose tissue (EAT) has been reported be associated with myocardial ischemia. Purpose We aimed to investigate for the first time a potential association between CTA-derived PCAT measures and myocardial ischemia as assessed by adenosine stress CMR perfusion imaging. Methods In this single-centre study 109 stable individuals (mean age of 62 ± 11 years, 77% males) with coronary artery disease underwent CTA followed by adenosine stress CMR perfusion imaging to detect myocardial ischemia. PCAT CT attenuation (HU) and PCAT volume (cm³) was measured around the RCA (10 to 50 mm from RCA ostium), the proximal 40 mm of the left anterior descending artery (LAD) and the circumflex artery (LCX) using semi-automated software. Per patient PCAT CT attenuation was calculated as followed: (PCAT attenuation of RCA + LAD + LCX)/3). Non-contrast CT data sets were used for coronary calcium scoring and the quantification of EAT (located between the myocardial surface and the pericardium) and paracardial adipose tissue (PAT; intrathoracic and outside of the pericardium). Results Between patients with evidence of significant myocardial ischemia as assessed by adenosine stress CMR (n = 35) and patients without myocardial ischemia (n = 74) there was no significant difference in the PCAT CT attenuation of RCA (-85.3 vs. -85.7 HU, p = 0.87), LAD (-84.8 vs. -85.7 HU, p = 0.66) and LCX (-82.8 vs. -83.2 HU, p = 0.79) as well as in the per patient PCAT CT attenuation (-84.2 vs. -84.9 HU, p = 0.76). Neither did patients with myocardial ischemia within the RCA territory show increased RCA PCAT CT attenuation (-87.7 vs. -85.3 HU, p = 0.40); nor was such a relationship found for the territory of the LAD (-80.6 vs. 85.8 HU, p = 0.11) or LCX (-83.1 vs. -83.0 HU, p = 0.99). The CT attenuation of EAT (-77.9 vs. -78.7 HU, p = 0.65) and PAT (-89.9 vs. -90.0 HU, p = 0.93) did not differ significantly between patients with myocardial ischemia compared to patients without myocardial ischemia. Between patients with myocardial ischemia and patients without myocardial ischemia there was no significant difference in the volumes of EAT (118.1 vs. 110.6 cm³, p = 0.55), PAT (279.5 vs. 240.9 cm³, p = 0.20) and the per patient PCAT volume (1021.9 vs. 1015.5 cm³, p = 0.90). In logistic regression analysis the volume and CT attenuation of the different intrathoracic fat compartments PCAT, EAT and PAT were not independently associated with the presence of myocardial ischemia (n.s.). Conclusions In this single-centre study CTA-derived quantified CT attenuation and volume of PCAT, EAT and PAT were not associated with myocardial ischemia as assessed by adenosine stress CMR perfusion imaging.

Computed Tomography-derived Characterisation Of Pericoronary, Epicardial And Paracardial Adipose Tissue And Its Association With Myocardial Ischemia As Assessed By Computed And Invasive Fractional Flow Reserve

Introduction: Increased pericoronary adipose tissue (PCAT) computed tomography (CT) attenuation derived from coronary CT angiography (CTA) around the right coronary artery (RCA) is a promising biomarker to detect coronary inflammation and relates to cardiac mortality. We aimed to investigate the yet unclear association between CT-derived characterisation of different cardiac adipose tissue compartments and the presence of myocardial ischemia as assessed by fractional flow reserve (FFR).

Total coronary atherosclerotic plaque burden is associated with myocardial ischemia in non-obstructive coronary artery disease.

AimWhether the total coronary atherosclerotic plaque burden is independently associated with myocardial ischemia in non-obstructive coronary artery disease (CAD) is not well established. We aimed to test the association of total plaque burden quantified by coronary computed tomography angiography (CCTA) with myocardial ischemia in patients with chronic coronary syndrome and non-obstructive CAD.MethodsWe included 125 patients (age 62 ± 9 years, 58% women) with chronic coronary syndrome and non-obstructive CAD (stenosis < 50%) by CCTA, who were grouped according to presence or absence of myocardial ischemia by myocardial contrast stress echocardiography. Total plaque burden was quantified by CCTA as the total plaque volume in the main coronary arteries, and positive remodelling was defined as remodelling index > 1.10.ResultsPatients with myocardial ischemia (n = 66) had higher total plaque burden (847 ± 245 mm3 vs. 758 ± 251 mm3, p = 0.049) and higher left ventricular (LV) mass index (42.1 ± 9.9 g/m2.7 vs. 37.3 ± 8.0 g/m2.7, p = 0.004), while age, sex, prevalence of hypertension, diabetes, calcium score and positive remodelling did not differ between the groups (all p > 0.05). In multivariable regression analysis, total plaque burden remained associated with presence of myocardial ischemia (OR 1.02, 95% CI 1.00–1.04, p = 0.045) independent of age, sex, hypertension, diabetes, LV mass index, coronary calcium score and positive remodelling.ConclusionTotal coronary artery plaque burden by CCTA was independently associated with myocardial ischemia in patients with non-obstructive CAD. Whether plaque quantification is useful for clinical management of patients with non-obstructive CAD should be tested in prospective studies.ClinicalTrials.gov: Identifier NCT01853527.