Epicardial Coronary Arteries Research Articles

Abstract 4127681: Neutrophil-lymphocyte ratio as a marker of cardiovascular outcomes in patients with chronic coronary syndrome

Background: Inflammation is one of the pathophysiological processes involved in the genesis and progression of atherosclerosis and has been increasingly used as a therapeutic target in recent years. The neutrophil-lymphocyte ratio (NLR) is a promptly accessible inflammatory biomarker strongly associated with prognosis in the acute coronary setting. However, there are few data in patients with chronic coronary syndrome (CCS). Objective: Analyze the association between NLR and cardiovascular outcomes in patients with CCS. Methods: Patients with CCS, defined as a previous revascularization procedure (surgical or percutaneous), previous myocardial infarction (MI) or stenosis > 50% in at least one epicardial coronary artery, were included and followed up on an outpatient basis. The NLR was calculated using the baseline blood count. The main outcome was the composite of death, non-fatal myocardial infarction and non-fatal stroke. Results: The study population consisted of 975 patients, with a median age of 65 years and 30% were women. Previous MI was present in 61%, 30% had undergone previous revascularization surgery and 46% had percutaneous coronary intervention. Diabetes was prevalent in 59% and hypertension in 95%. The median NLR was 2.15 (IQR 1.25 - 2.87). Patients with NLR ≥ 2.15, when compared to those with NLR < 2.15, presented more left ventricular (LV) dysfunction (58% vs. 55%; p=0.003) and lower LDL-C serum levels (81 vs. 88 mg/dL; p=0.004). There was no association between NLR and coronary anatomical severity. NLR correlated with age, LDL-C and LV function (p < 0.05 for all). During follow-up, 152 events of the composite primary outcome were registered, with an estimated 3-year incidence of 15.6% in the overall population – higher within patients with NLR ≥ 2.15 when compared to NLR < 2.15 (20% x 14%, p = 0.002), as shown in the figure. In the multivariate analysis, the 3rd quartile of NLR had a 31% higher risk than the 1st quartile (p < 0.05). Conclusion: In this study, the NLR, an easily available inflammatory biomarker, independently correlates with cardiovascular outcomes in a population with CCS.

Abstract 4135951: Single Nuclei RNA Sequencing Reveals Distinct Cellular Composition of Pericoronary Adipose Tissue

Introduction: Adipose tissue is a metabolically active organ with local paracrine interactions on adjacent tissues. Pericoronary adipose tissue (PcAT) is an emerging cardiovascular disease (CVD) risk factor and likely has paracrine effects on coronary vasculature that may promote coronary artery disease (CAD) development. PcAT may be functionally and clinically distinct from epicardial adipose tissue (EAT) given its proximity to the coronary artery adventitia. The cellular composition of PcAT and EAT and whether they have unique inflammatory cell signatures and functional expression at a single cell level has not been explored. Hypothesis: PcAT will have diverse cellular composition with heightened inflammatory cell content compared to EAT. Methods: Visual dissection of paired EAT not adjacent to an epicardial coronary artery and PcAT in direct apposition to an epicardial artery (left anterior descending artery) was performed from a single human heart immediately after explant (prior to heart transplantation). Nuclei were isolated using the Chromium Nuclei Isolation Kit (10x Genomics) with RNAse inhibitor. Cells were counted with a Cellometer K2 and Chromium Next GEM Single Cell libraries were prepared, followed by reverse transcription, PCR and NovaSeq 6000 platform sequencing. Raw sequence reads from single nuclei RNA-seq (snRNA-seq) were processed and after QC filtering, cells were clustered using Seurat. Clusters were annotated using singleR. Results: In PcAT and EAT, >7000 cells were successfully extracted with 73755 and 48750 mean snRNA-seq reads per cell, respectively. snRNA-seq cellular composition analysis delineated a heightened inflammatory milieu and distinct cellular composition of human PcAT vs. EAT. A UMAP (Uniform Manifold Approximation and Projection) plot displays higher inflammatory cell infiltrate with a neutrophil predominance and lesser adipocyte composition in PcAT compared with EAT ( Figure 1) . Conclusions: We have generated snRNA-seq data from human PcAT and shown distinct cellular composition compared to EAT. Given the proximity of PcAT to coronary vasculature, these results are supportive of paracrine inflammatory effects and highlight adipose tissue biology in cardiovascular disease. Understanding this biology may identify novel therapeutic targets for CVD.

Low breast density is associated with epicardial adipose tissue volume and coronary artery disease

Low breast density is associated with epicardial adipose tissue volume and coronary artery disease

Number of inflamed coronary vessels in prediction of cardiac death and MACE among patients undergoing routine CCTA: the Oxford Risk Factors And Non-Invasive Imaging (ORFAN) Study

Abstract Background Coronary inflammation can be assessed by the changes in perivascular adipose tissue on routine coronary CT angiograms (CCTA). Fat attenuation index score (FAI Score) quantifies the degree of inflammation in each epicardial coronary artery, and adjusts for age, sex, scan technical parameters, biological and anatomical factors. Coronary inflammation assessment in a single coronary artery was previously shown to be predictive of cardiac events in the CRISP-CT study. However, the impact of inflammation in multiple coronary arteries on clinical outcome remains unclear. Purpose To evaluate the prognostic value of the number of inflamed coronary arteries with high inflammation in the risk of cardiac death, and major adverse cardiac events (MACE). Methods In a nested cohort within the Oxford Risk Factors And Non-invasive imaging (ORFAN) study, consecutive patients (n=3,393) who underwent routine clinical CCTA were followed up over a median(IQR) 7.7(6.4-9.1) years for cardiac mortality, and MACE (including myocardial infarction, new onset heart failure, cardiac mortality). FAI Score was calculated for each of the 3 epicardial coronary arteries. Results The number of inflamed arteries (FAI Score >75th centile) showed an additive impact on cardiac mortality compared with no inflamed arteries (all vessels FAI Score <25th centile), with hazard ratio 29.8 (95% CI 13.9-63.9, p<0.001) for 3 inflamed arteries, HR 20.4 (95% CI 9.4-44.7, p<0.001) for 2 inflamed arteries, and HR 13.0 (95% CI 5.9-28.8, p<0.001) for 1 inflamed artery. (Panel A) Similarly, patients with multiple inflamed arteries showed progressively higher risk for MACE (HR 7.2, 8.3 and 12.6 for 1-, 2- and 3-inflamed arteries respectively compared to patients with no inflamed artery). (Panel B) Patients with no inflamed arteries showed very low event rates for cardiac mortality and MACE. In patients with no obstructive CAD (n=2,651), similar trends were observed whereby patients with 3-inflamed arteries showed highest risk for cardiac mortality (Panel C) and MACE (Panel D), with intermediate risk for those with 1 or 2 inflamed arteries. Conclusion The number of coronary arteries with high inflammation, measured by FAI Score from routine CCTA, is associated with adverse cardiovascular events and cardiac mortality in an additive dose-response manner.

AI-enhanced detection of coronary inflammation predicts 10-year risk for cardiac mortality and MACE in individuals with no or minimal coronary atherosclerosis on routine CCTA

Abstract Background Coronary CT angiogram (CCTA) is one of the first line investigations for patients with chest pain suspected of coronary artery disease (CAD). Current CCTA interpretations mainly focus on luminal obstruction, which is identified in the minority of patients, whereas the majority who have no or minimal atherosclerotic plaques visible on CCTA are often provided with reassurance. However, residual risk from inflammation that drives atherosclerosis and plaque vulnerability are not captured with luminal stenoses alone. Fat attenuation index (FAI) Score quantifies coronary inflammation on routine CCTA, and integrate with clinical risk factors/plaque burden in an artificial intelligence enabled risk algorithm (AI-Risk) that could help to risk stratify this patient group. Purpose To evaluate the prognostic value or FAI Score and AI-Risk in the risk stratification of patients with no or minimal atherosclerosis. Methods In a nested cohort within the Oxford Risk Factors and Non-invasive imaging (ORFAN) study, consecutive patients (n=3,393) who underwent routine clinical CCTA were followed up over a median(IQR) 7.7(6.4-9.1) years for cardiac mortality and major adverse cardiac events (MACE, including myocardial infarction, new onset heart failure, cardiac mortality). CADRADS 2.0 classification 0 or 1 were used to define no or minimal luminal stenoses. FAI Score was calculated for each of the 3 epicardial coronary arteries. Results A total of 1,678 patients had no or minimal atherosclerosis on CCTA [median (IQR) age 53(45-63), 49.8% male]. Cardiac mortality occurred in 3.1% and MACE occurred in 8.8% of the patients during the follow-up period. Patients at the lowest quartile of FAI Score or low/medium AI-Risk classification showed very low event rate during follow up. Patients with the highest quartile of LAD FAI Score showed 9 times higher risk of cardiac mortality (Panel A) and 5 times higher risk of MACE (Panel B) compared to those at lowest quartile. Similar findings were observed for LCX and RCA. Finally, integrating coronary inflammation with clinical risk factors and plaque burden, patients at very high AI-Risk classification showed 5 times higher risk of cardiac mortality (Panel C), and 4 times higher risk of MACE (Panel D) compared to those with low/medium risk classification. Conclusion Coronary artery inflammation measured by FAI Score could stratify the risk of patients with no or minimal coronary atherosclerosis on CCTA, and could help to guide early preventative treatments.

Coexistence of coronary microvascular dysfunction and left ventricular hypertrophy can predict prognosis of patients with nonobstructive coronary arteries

Abstract Background Previous studies have reported that coronary microvascular dysfunction (CMD) and left ventricular hypertrophy (LVH) were associated with adverse cardiovascular events. The aim of this study was to determine the prognostic impact of coexistence of abnormal coronary flow reserve (CFR) and left ventricular mass index (LVMI). Methods and results This study included 297 patients who underwent intracoronary physiological assessment including CFR for suspected myocardial ischemia without significant stenosis in the epicardial coronary artery at our hospital from December 2019 to March 2023. Of 297 patients (female: n=89 [30%], age: 70±11 years), 93 (31%) had CMD (CFR<2.5) and 133 (45%) had LVH (LVMI>95 g/m2 for female and >115 g/m2 for male). We excluded patients with history of heart failure (HF). Patients were classified into 4 groups based on the cut-off values of CFR and LVMI: group 1 (no CMD nor LVH, n=109); group 2 (only LVH, n=95); group 3 (only CMD, n=55) and group 4 (both CMD and LVH, n=38). Patients of group 4 had a larger proportion of female (female 19%, 34%, 24% and 61% in group 1 to 4 respectively). There was no significant difference in left ventricular ejection fraction between patients of each groups. Clinical follow-up was performed for major adverse cardiovascular events (MACE) including cardiovascular death, myocardial infarction and hospitalization for new-onset HF. During a median follow-up of 753 days, the cumulative MACE-free survival rate at 2 year were 99.0%, 98.9%, 95.6% and 90.0% in groups 1 to 4. Group 4 showed significantly higher risk of MACE at 2 year compared with group 1 (hazard ratio [HR] 2.6; 95% confidence interval [CI] 1.3-5.3; p=0.009). Notably, Group 4 showed the highest incidence of hospitalization for new-onset HF than any other groups. Conclusion Patients with both CMD and LVH showed significantly higher risk for MACE and new onset of HF. The combined classification based on CFR and LVMI would identify the high-risk patients for MACE as well as new-onset HF.

Coronary inflammation stratifies risk in patients undergoing coronary CT angiography: the Oxford Risk Factors and Non-Invasive Imaging (ORFAN) study

Abstract Background Patients with chest pain symptoms often undergo coronary CT angiography (CCTA) for the diagnosis of obstructive coronary artery disease (CAD) to guide revascularisation. However, acute cardiac events could occur in the absence of obstructive CAD. Further risk stratification of patients could potentially be useful by quantifying coronary inflammation using the Fat Attenuation Index (FAI) Score, and an artificial intelligence (AI)-assisted prognostic model that captures the inflammatory risk by integrating CCTA-derived metrics (including FAI Score and plaque burden) and the patient’s clinical risk factors. Purpose To evaluate the risk of cardiac events among patients without obstructive CAD, and the prognostic value of integrating coronary inflammation in risk stratifying this patient group. Methods From the Oxford Risk Factors and Non-invasive imaging (ORFAN) study, patients undergoing CCTA in 7 UK Hospitals (n=40,091) were followed up for the incidence of cardiac mortality over a median(IQR) of 2.7(1.4-5.3) years. In a nested cohort of 3,393 patients with long-term follow up, we evaluated the long-term prognostic value of FAI Score and the performance of AI-Risk algorithm over a median(IQR) follow up of 7.7(6.4-9.1) years. Reclassification of risk category from AI-Risk was compared with contemporary clinical risk score (QRISK3). Results Patients without obstructive CAD (n=32,533, 81.1%) accounted for 63.7% of all cardiac deaths (n=1,754) during follow up, highlighting the substantial proportion of cardiac events in absolute terms given a large proportion of patients without obstructive CAD. In the nested cohort with long-term follow up, FAI Score in any of the 3 epicardial coronary arteries was significantly associated with cardiac mortality with or without obstructive CAD. In the whole cohort, the highest quartile of FAI Score in LAD showed 20-times higher risk of cardiac death compared with the lowest quartile (Panel A). Integrating coronary inflammation with clinical risk factors and plaque burden, patients with very-high AI-Risk classification showed 6-fold higher risk of cardiac mortality compared to low/medium risk, with good alignment of the incident predicted events from AI-Risk and observed events. (Panel B) The predicted cardiac mortality from AI-Risk also demonstrated good calibration with the observed events in the whole population. (Panel C) Finally, AI-Risk significantly reclassify the risk above clinical risk factor-based prediction (QRISK3) (Panel D). Conclusion Patients with high coronary inflammation measured by FAI Score showed significantly elevated risk for cardiac mortality. The AI-enabled absolute risk prediction algorithm leads to significant reclassification of patients undergoing routine CCTA, and can be used as a precision medicine tool.

Synergic interaction between coronary flow reserve and left atrial diameter as a risk factor for major adverse cardiovascular events in patients with nonobstructive coronary artery disease

Abstract Background Left atrial diameter (LAD) is one of the parameters which indicate left ventricular diastolic disorders (DD) and associated with poor prognosis. Previous studies have reported the relationship between DD and coronary microvascular dysfunction (CMD) but the impact of coexisting DD and CMD on prognosis is unknown. Methods and results This study included 330 patients who underwent intracoronary physiological assessment including CFR for suspected myocardial ischemia without significant stenosis in the epicardial coronary artery from December 2019 to March 2023. Of 330 patients (female: n=96 [29%], age: 70±11 years), 109 (33%) had CMD (CFR<2.5) and 93 (28%) had DD (LAD>40 mm). Patients were classified into 4 groups based on the cut-off values of CFR and LVMI: group 1 (no CMD nor DD n=160); group 2 (only DD, n=61); group 3 (only CMD, n=77) and group 4 (both CMD and DD, n=32). Clinical follow-up was performed for major adverse cardiovascular events (MACE) including cardiovascular death, acute coronary syndrome and hospitalization for heart failure. During a median follow-up of 715 days, the cumulative MACE-free survival rate at 2 year were 97.9%, 100.0%, 95.5% and 75.1% in groups 1 to 4. Group 4 showed significantly higher MACE rate compared with other 3 groups (hazard ratio [HR] 14.3; 95% confidence interval [CI] 3.8-53.9; p<0.001, HR 14.25; 95% CI 1.8-114.4; p=0.01 and HR 4.7; 95% CI 1.4-15.8; p=0.01 respectively). Notably, Bonferroni's multiple comparison showed that Group 4 had the highest incidence of heart failure hospitalization compared with other 3 groups (p=<0.001, p=0.002, p=0.01 respectively). Cox proportional hazards model revealed that CMD and DD had synergic interaction as a risk factor for MACE (HR 9.1; 95% CI 3.4-24.4; p<0.001). Conclusion Patients with both CMD and DD showed significantly higher risk for MACE, especially for heart failure hospitalization. The combined classification based on CFR and LAD would identify the high-risk patients for MACE.MACE-free survival curveheart failure-free survival curve

Impact of systolic coronary flow reversal in patients with aortic stenosis: assessment with transthoracic echocardiography

Abstract Background In patients with aortic stenosis (AS), increased systolic wall stress due to increased afterload reduces systolic coronary flow, often leading to systolic coronary flow reversal (SFR) in epicardial coronary arteries. Purpose We used transthoracic echocardiography (TTE) to evaluate severity of AS, left ventricular function, and coronary flow, and investigated echocardiographic indicators associated with SFR. Methods We prospectively evaluated consecutively presenting patients who visited our valvular heart disease outpatient clinic or were admitted to our hospital for investigation of AS (July 2023 to February 2024). Based on ESC guidelines, severity of AS and the left ventricular function were assessed with TTE. At the same time, TTE was used to measure distal left anterior descending coronary artery flow. SFR was defined as the presence of a reversal coronary flow component in systole. Based on the presence or absence of SFR in coronary flow measurements, patients were classified into SFR+ or SFR− groups. The inclusion criteria were AS of moderate or greater severity, and the exclusion criteria were known coronary stenosis and the inability to assess coronary flow. Results Enrolled 28 patients were classified into SFR+ (7 patients) and SFR − (21 patients) groups. Comparing baseline characteristics between the SFR+ and SFR− groups, although there were no significant differences in left ventricular indicators such as left ventricular mass index, left ventricular ejection fraction, stroke volume index, and E/e’ between the two groups, left ventricular global longitudinal strain was significantly lower in the SFR+ group (12.0±3.1%, 14.9±3.0%, p=0.026) (Table 1). Regarding indexes of AS assessment, aortic valve peak velocity and aortic valve mean pressure gradient values were significantly higher in the SFR+ group than in the SFR − group ([475±68 cm/s, 379±55 cm/s, p<0.001] and [56.2±16.5 mm Hg, 34.8±10.5 mm Hg, p<0.001], respectively) (Table 1). Representative cases show Figure 1. Conclusion The presence of SFR in patients with AS assessed using TTE may be a simple echocardiographic index that may be associated with potential decline in left ventricular function and progression of AS.

The association between mammographic breast density, epicardial adipose tissue volume and coronary artery disease

Abstract Background Dysfunctional adipose tissue is strongly linked to cardiometabolic disease. Epicardial adipose tissue (EAT) which is measurable on cardiac computed tomography (CT) is well correlated with cardiovascular disease (CVD), however it is not reported clinically. Breast mammography mandates reporting of breast density (BD), which is also a marker of breast adipose tissue quantity with less dense breasts indicating greater adipose tissue volume. Given the widespread use of screening mammography, this presents an opportunity to employ BD as a possible surrogate for CVD risk. Purpose To evaluate the correlation between BD, EAT and coronary artery disease (CAD). Methods Single-centre, retrospective, cross-sectional study, including women who had both clinically indicated coronary computed tomography angiogram (CCTA) and mammography. Epicardial adipose tissue volume (EATv) was quantified using semi-automated software (QFAT 2.0). BD was visually assessed by standard 4-level Breast Imaging-Reporting and Data System (BI-RADS) grade with grade A-B representing low density, and C-D representing high density. CAD was categorised as presence/absence of any coronary artery plaque, and CAD severity was quantified using the Coronary Artery Disease Reporting and Data Systems (CAD-RADS) score, with CAD-RADS 1-2 representing mild disease, CAD-RADS 3 moderate disease and CAD-RADS 4 severe disease. CAD analyses were adjusted for modifiable (hypertension, dyslipidaemia, diabetes, body mass index) and non-modifiable (age, past smoking, family history, breast cancer) risk factors. Logistic regression was performed with results presented as Odds Ratio (OR) and [95% Confidence Intervals]. Results Among 153 patients (mean age 62±10), 103 (67.3%) had low BD (high breast adiposity). Compared with high BD, low BD patients were older, had greater rates of hypertension, had significantly higher mean EAT (106.6 ± 43.0 vs 81.0 ± 31.6ml, p<0.001) (Figure 1), and body mass index (30.5 ± 6.3 vs 26.4 ± 5.4kg/m², p<0.001). Adjusted for age and hypertension, EATv remained independently predictive of low BD (OR:1.02 [1.01-1.03], p=0.006). Low BD made up a higher proportion of mild (76.5%), moderate (73.9%) and severe (80.0%) disease. Low BD was strongly associated with presence of CAD (prevalence 75% vs 48%, OR 3.21 [1.58-6.53], p=0.001) independent of EATv (p=0.25), and independent of modifiable (OR: 2.69 [1.24-5.92], p=0.012) and non-modifiable (OR: 2.42 [1.04-5.85], p=0.047) risk factors (Figure 2). Conclusions Low breast density is associated with higher EATv and independently associated with CAD presence beyond EATv and other risk factors. Consequently, mammographic breast density may act as an early risk identification tool for CAD in women.

Determinants of right ventricular - pulmonary arterial uncoupling in hypertrophic cardiomyopathy

Abstract Background Right ventricular (RV) – pulmonary arterial (PA) coupling, assessed by echocardiography, is a non-invasive surrogate on how the RV is adapted to an increased afterload in the pulmonary circulation. In cases of exhaustion of compensatory RV remodeling, the ratio decreases and there is RV-PA uncoupling. Our objective was to identify what are the determinants of this parameter in patients with hypertrophic cardiomyopathy (HCM). Methods This prospective cohort study enrolled patients with HCM without obstructive epicardial coronary artery disease, that underwent a comprehensive evaluation. Echocardiography was used to assess RV-PA coupling as the ratio of tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP). In addition, coronary flow reserve in the left anterior descending artery (CFR_LAD) was also evaluated: diastolic coronary flow velocity was measured in basal conditions and in hyperemia and CFR was calculated as the ratio of hyperemic and basal peak diastolic flow velocities. This was used as a surrogate marker of coronary microvascular dysfunction. Cardiac magnetic resonance (CMR) was also performed to evaluate RV function (volumes and ejection fraction), and the extent of late gadolinium enhancement (LGE) in the left ventricle (LV). Results We enrolled 62 patients, with a mean age of 55 (15) years, 64% males. In 64% it was an asymmetrical septal hypertrophy phenotype, in 31% an apical hypertrophy, and in 27%, it was an obstructive HCM. Mean TAPSE/PASP was 0.556 (0.23) and median was 0.50. All patients had a normal LV ejection fraction. Univariable linear regression analysis showed that age, maximal wall thickness, E/E’, indexed left atrial volume (LAVi), CFR-LAD, %LGE and % hypoperfusion (by CMR) were correlated with RV-PA uncoupling. The HCM phenotype or the presence of obstruction were not associated with uncoupling. Multivariable stepwise linear regression analysis showed that the independent predictors of RV-PA uncoupling were age (b-estimate: - 0.180, p=0.009), LAVi (b-estimate: -0.645, p=<0.001), CFR-LAD (b-estimate: 0.183, p=0.011) and %LGE (b-estimate: -0.270, p=<0.001). Conclusion In patients with HCM, the presence of coronary microcirculation abnormalities and the extent of LGE in the LV are independent predictors of RV-PA uncoupling.

Invasive quantitative assessment of coronary microvascular dysfunction in patients with hypertrophic cardiomyopathy

Abstract Background Patients (P) with hypertrophic cardiomyopathy (HCM) commonly suffer from coronary microvascular dysfunction (CMD) - the affection of function/structure of the coronary microvasculature. Invasive assessment of CMD through thermodilution methods allows for the calculation of coronary flow reserve (CFR) and index of microvascular resistance (IMR). These methods, while extensively studied in the context of non-obstructive coronary artery disease and myocardial infarction, have not been thoroughly validated in HCM P. Objectives To invasively assess the presence of CMD in P with HCM and to determine clinical predictors of invasively assessed CMD. Methods In a prospective single-centre study, we opportunistically recruited consecutive adult P with an established diagnosis of HCM with or without LVOTO that had an indication to pursue elective coronarography – such as pre-procedural evaluation for alcoholic septal ablation (ASA) or exclusion of epicardial coronary artery disease. P characteristics and coronary hemodynamic invasive assessment data were extracted. CFR was calculated as the ratio between resting and hyperemia mean transit times (TmnRest;TmnHyper). IMR was calculated as the ratio between distal coronary pressure (Pd) and the inverse of TmnHyper (IMR=Pd/TmnHyper-1). A cutoff of ≤22.0 in IMR, an ≥d 2 in CFR was used. We excluded P with end-stage HCM (LV EF <50% and/or or left ventricular wall thinning), or with epicardial coronary artery disease. Continuous variables were reported as mean ± SD or median and IQR depending on data distribution pattern and categorical data as frequencies and percentages. A linear regression model was used to test predictors of IMR and CFR involvement. Results 25 HCM P with a mean age of 63±10 years were included, 14 (56%) were female. In 20 (80%) of the P the cause for coronary angiography was ASA. All P referred for ASA had LVOTO and were on beta-blocker therapy (Table 1.). Median CFR was 2.5 [1.5-3] and median IMR was 19 [14-22], both within normal range. A total of 13 (44%) P had a reduced CFR and 5 (20%) of P had an increased IMR. 14 P (56%) had an altered CFR or IMR value, with the presence of a functional CMD phenotype in 10 P (40%) (Table 2). Angina was associated with a higher IMR (5.3, 95% CI - 0.05-10, p=0.053) and for each +1 increase in CCS a larger increase in the likelihood of a higher IMR was observed (CCS 1, +7 (95%CI 0.68 – 14); CCS 2, +9 (95%CI 4 – 14); CCS 3, 10 (95%CI 2 – 18)). A similar but non significant trend was observed for higher CCS correlating with lower CFR (Table 3). Conclusion In a prospective cohort of HCM P submited to invasive angiographic evaluation 56% had at least one invasive measure compatible with CMD. Angina, and a higher degree of anginal symptoms correlated positively with the presence of higher IMR and therefore with a higher level of CMD. In the future, we intend to correlate these findings with multimodality imaging/clinical outcomes.Patient characteristics and LR results

Prognostic significance of coexistent coronary artery disease in patients undergoing transcatheter aortic valve implantation for aortic stenosis

Abstract Background The optimal management of coronary artery disease (CAD) in patients undergoing transcatheter aortic valve implantation (TAVI) for aortic stenosis (AS) is uncertain. As TAVI expands into lower risk cohorts with longer life expectancies there is increasing need to determine the prognostic significance of coexistent CAD and identify which lesions may benefit from revascularisation. Purpose To evaluate the prognostic significance of coexistent CAD in patients with AS undergoing TAVI stratified according to myocardial territories at risk. Methods Using a retrospective, single-centre, observational registry, patients undergoing TAVI for severe AS between 2015 and 2020 were included. CAD was angiographically determined using computed tomography or invasive coronary angiography. CAD was stratified into 1) low-risk: <70% stenosis in all major epicardial coronary arteries or <50% in the left main (LM); 2) intermediate-risk: ≥70% stenosis in one or two arteries, except the proximal left anterior descending (LAD) and LM; 3) high-risk: ≥70% stenosis in the proximal LAD, ≥70% stenosis in 3 arteries or LM stenosis ≥50%. Patients with previous CABG were categorised as high-risk if: ≥70% stenosis of 3 coronary grafts or graft supplying a proximally stenosed LAD; and intermediate-risk if: ≥70% stenosis of 1 or 2 non-LAD grafts. Baseline characteristics and procedural outcomes were compared between the 3 cohorts, with the impact of CAD on outcomes evaluated after adjustment for demographics and comorbidities. Results 1805 patients were included; median age 84 (79-88), 51% male sex, median logistic Euroscore 13 (8-21). 1281 (71%), 384 (21%) and 140 (8%) patients were characterised as low-, intermediate- and high-risk coronary anatomy respectively. High risk patients were older than the other groups, however, did not have the highest prevalence of comorbidities (Table 1). Other than pacemaker implantation (9% vs 12% vs 6%, p=0.04), there were no differences in procedural complications or in-hospital mortality between groups (Table 1). At a median follow-up of 3.5 (2.3-4.8) years, 920 patients (51%) died, 292 (16%) had hospitalisation for heart failure (HHF) and 565 patients (31%) had a major adverse coronary event (MACE); defined as either myocardial infarction, HHF or cardiovascular death. Coronary anatomical stratification was associated with MACE (Log rank p<0.001) (Figure 1). After multivariate adjustment, high-risk anatomy was associated with all-cause mortality (hazard ratio (HR): 1.34, 95% confidence interval (CI): 1.06-1.68, p=0.013), HHF (HR: 1.49, 95% CI: 1.01-2.21, p=0.046) and MACE (HR: 1.68, 95% CI: 1.27-2.21, p<0.001). Conclusions Whilst the presence of CAD does not impact TAVI procedural safety, untreated high-risk coronary anatomy is associated with future adverse events and may warrant intensive medical therapy and/or revascularisation.

Comparison of vessel-Fractional Flow Reserve (vFFR) and Quantitative Flow Ratio (QFR) using instantaneous wave-Free Ratio (iFR) or Resting Full-cycle Ratio (RFR) as reference

Abstract Background Angiography-based functional assessment remains the state of the art to assess the hemodynamic relevance of intermediate coronary stenoses. In addition to fractional flow reserve (FFR), adenosin free indices like instantaneous wave-free ratio (iFR) or resting full-cycle ratio (RFR) are widely used for the invasive evaluation. Although these methods are widely accepted, they are underused in clinical routine due to costs, their invasive nature, longer procedural times, and lack of availability. Vessel-fractional flow reserve (vFFR) and quantitative flow ratio (QFR) are new software-based methods for the evaluation of coronary-physiology. The aim of this study is to compare vFFR and QFR with the established invasive methods iFR or RFR. Methods We prospectively analyzed 95 Patients in our QFR-Registry vFFR- and QFR-computation was performed three-times by two certified, blinded, and independent experts using the QAngio XA 3D 3.2- and CAAS-software, respectively. Results: 101 main epicardial coronary arteries (52 LAD; 19 LCx; 30 RCA) were analyzed using vFFR, QFR and iFR or RFR. vFFR showed a good correlation with adenosine-free indices in all 3 measurements (AUC 0.883 with r=0.672, p<0.001; AUC 0.841 with r=0.618 p<0.001; AUC 0.840 with r=0.592, p<0.001 respectively). The diagnostic accuracy between the three vFFR-measurements and iFR/RFR was 83%; 81% and 79% respectively. QFR-computations showed a similar correlation with iFR/RFR (AUC 0.899 with r=0.720, p<0.001; AUC 0.919 with r=0.649, p<0.001; AUC 0.930 with r=0.703, p<0.001 respectively) with a diagnostic accuracy 88%, 89% and 88% respectively. The intra- and inter-observer reliability for vFFR (intra: mean difference 0.002±0.0568; inter: 0.024±0.054) and QFR (intra: mean difference 0.018±0.071; inter: 0.016±0.075) analyzed in a Bland-Altman Blot showed a good correlation between virtual assessments and invasive measurements with iFR/RFR. Conclusion The data show a good diagnostic agreement between vFFR and QFR and adenosine free invasive assessments. vFFR and QFR appear reasonable alternative approaches for the evaluation of intermediate stenoses. These data provide the rational to prospectively test for a clinical noninferiority of the non-invasive flow measurements.Diagnostic performance of vFFR/cQFR

Perfusion metabolism mismatch predicts short-term complications in Takotsubo syndrome

Abstract Background Takotsubo syndrome (TTS) is a transient cardiac condition triggered by sudden emotional or physical stress characterized by LV dysfunction in the absence of obstructive epicardial coronary artery disease. 123I-BMIPP, an iodinated fatty acid analogue, can identify impaired myocardial metabolic activity. With the use of dual SPECT protocol, reduced uptake of 123I-BMIPP compared to perfusion which is called perfusion-metabolic mismatch is observed in apical regions in TTS. The mismatch may indicate jeopardized but viable myocardium, reflecting transient ischemic damage or metabolically stunned myocardium. However, the association between the perfusion metabolism mismatch in TTS and its complications remains underexplored. Purpose Our study aimed to analyze the degree of perfusion metabolism mismatch at the acute phase in TTS and investigate its association with short-term complications. Methods This retrospective study conducted between 2012 and 2024 at a single center included 82 patients diagnosed with TTS. Patients underwent dual SPECT imaging using 99mTc or 201 Tl and 123I-BMIPP within two weeks of admission. We applied quantitative analysis using QGS/QPS software from Cedars-Sinai. Total perfusion deficit ("TPD") was calculated based on sex-matched normal limits providing the extent of perfusion abnormality. Meanwhile, perfusion-metabolism mismatch scores ("worsen") were determined by comparing the total BMIPP counts to the total counts of perfusion. We then assessed the correlation of these imaging findings with biomarkers, regional wall motion abnormalities, and the occurrence of short-term complications. Short-term complications included heart failure, left ventricular outflow (LVOT) obstruction, mitral regurgitation, cardiac arrhythmia, cardiogenic shock, left ventricle (LV) rupture, and cardiac death during the hospitalization period. Results All study patients exhibited wall motion abnormalities seen in apical segments. The count of myocardial segments with regional wall motion abnormality was correlated with both TPD (r=0.34, p=0.002) and perfusion metabolic mismatch score (r=0.40, p<0.001). TPD had a moderate correlation coefficient with max CK-MB (r=0.44, p<0.001) and troponin T (r=0.40, p<0.001) levels. However, perfusion metabolic mismatch did not display correlations with max CK-MB (r=0.05, p=0.65), and Troponin T (r=0.12, p=0.28) levels. Among 82 patients, 37 patients experienced any short-term complications. Importantly, patients with short-term complications had elevated perfusion mismatch scores compared to those without short-term complications (14.0 [6.0-22.5] vs. 5.0 [3.0-10.0], p<0.001). However, no significant difference was observed in TPD between the two groups (9.0 [4.5-20.0] vs. 7.0 [3.0-12.0], p=0.130). Conclusions Our research highlights a significant association between perfusion-metabolism mismatch and an increased risk for short-term complications in patients with Takotsubo syndrome.

Physiological disease pattern as assessed by PPGI in vessels with FFR and iFR discordance

Abstract Background Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) disagree on the hemodynamic significance of a coronary lesion in≈20% of cases. It is unclear whether the physiological pattern of disease is an influencing factor for this. This study assessed whether the physiological pattern of coronary artery disease (CAD) as assessed by angiography derived pullback pressure gradient index (PPGI) influences discordance between FFR and iFR measurement. Methods and results This study is a centralized off-line analysis by an independent academic core laboratory (CORRIB Core lab) of a prospective cohort of 444 vessels with both pressure wire-instantaneous wave free ratio (PW-iFR) and pressure wire-fractional flow reserve (PW-FFR) measurements. The study population consisted of a patients presenting with chronic coronary syndrome and having at least one epicardial coronary artery lesion with a 40% to 90% diameter stenosis by visual assessment on invasive coronary angiography. Three-hundred and ninety vessels (355 patients; mean age, 68±10 years; 70% men) with combined FFR, iFR, QFR and angiography derived PPGI were included. QFR was calculated using the QAngio XA 3D 2.1 software package (Medis Medical Imaging System BV, Leiden, The Netherlands). PPGI was calculated using the QFR 2.1.38.2 Research Edition software package. Cut points for hemodynamic significance were FFR ≤0.80 and iFR ≤0.89, respectively. Vessels were classified into FFR+/iFR+ (n=103; 26.4%), FFR-/iFR+ (n=27; 6.9%), FFR+/iFR- (n=38; 9.7%), and FFR-/iFR- (n=222; 57%) groups.. Median FFR, iFR, and QFR were 0.84 (0.77-0.90), 0.92 (0.88-0.97), and 0.83 (0.73-0.90) respectively. FFR disagreed with iFR in 16.7% (65 of 390). The Median PPGI was 0.75 (0.67-0.85). Vessels with PPGI ≥0.75 was considered to have predominantly focal disease pattern and vessels with PPGI <0.75 was considered to have predominantly diffuse disease pattern. The physiological pattern of disease was classified according to the angiography derived pullback pressure gradient index (PPGI) as predominantly physiologically focal (n=209; 53.6%) or predominantly physiologically diffuse (n=181; 46.4%). The median PPGI was significantly lower in FFR-/iFR+ vessels as compared to FFR+/iFR- vessels [0.65(0.60-0.69) vs 0.82(0.75-0.85), p<0.001). The physiological pattern of disease was the influencing factor relating to FFR/iFR discordance: predominantly physiologically focal was significantly associated with FFR+/iFR- (76.3% [29 of 38]), and predominantly physiologically diffuse was significantly associated with FFR-/iFR+ (96.3% [26 of 27]; P<0.001 for pattern of disease between FFR+/iFR- and FFR-/iFR+ groups). Conclusions The physiological pattern of coronary artery disease was an important influencing factor for FFR/iFR discordance.

Primary inflammatory disease in heart failure with preserved ejection fraction

Abstract Background Inflammation plays a fundamental role in the pathogenesis of heart failure (HF) with preserved ejection fraction (HFpEF). In most patients, inflammation develops secondary to cardiometabolic comorbidities, but in some, HFpEF develops in the setting of underlying systemic inflammatory diseases represented by rheumatoid arthritis. Purpose This study aimed to investigate the prevalence, pathophysiology, and outcome of patients with HFpEF and primary inflammatory diseases. Methods Consecutive patients undergoing hemodynamic exercise testing with concurrent expiratory gas analysis to evaluate dyspnea of unknown cause were identified. HFpEF was defined as left ventricular ejection fraction ≥50% and pulmonary capillary wedge pressure ≥15 mmHg (rest) or ≥25 mmHg (exercise). Patients with HFpEF were divided into groups with and without primary inflammatory diseases. Patients without inflammatory disease were divided into tertiles according to the value of C-reactive protein (CRP). Results Of 982 consecutively evaluated patients with HFpEF diagnosed (577 female, mean age 68 years), 79 (8%) had primary inflammatory disease. In multivariable logistic regression, female sex (OR 1.88; 95% CI 1.01-3.52), higher resting heart rate (OR 1.18; 95% CI 1.08-1.30), lower hemoglobin level (OR 0.84; 95% CI 0.70-0.99), absence of history of atrial fibrillation (OR 0.45; 95% CI 0.24-0.86) and absence of epicardial coronary artery disease (OR 0.45; 95% CI 0.22-0.93) were independently associated with inflammatory disease. Hemodynamics at rest and exercise did not differ between the groups, but peripheral oxygen extraction was lower in those with inflammatory disease, reflected by lower arterial-venous oxygen content difference (Ca-vO2) at rest (4.2±0.7 mL/dL vs 4.6±1.0 mL/dL, P<.001) and during exercise (9.3±2.2 mL/dL vs 10.4±2.2 mL/dL, P<.001) (Figure 1A), suggesting a greater peripheral deficit, and ventilatory efficiency (VE/VCO2 slope) was also more impaired (38.0±7.9 vs 36.2±7.3, P=.035). The HFpEF patients without inflammatory disease falling in the highest tertile of CRP) displayed lower Ca-vO2 during exercise, more closely resembling peripheral deficits observed in those with inflammatory disease (Figure 1B). During a median follow-up of 3.0 years, the composite outcome of all-cause deaths and HF hospitalization occurred in 127 patients (14%). Patients with HFpEF and inflammatory disease showed a higher incidence of composite outcome than those without (log-rank P=.030; Figure 2). Patients with inflammatory disease had higher risk of composite outcome compared to those without in adjusted analyses (HR 1.93; 95% CI 1.15-3.23), which was primarily attributable to higher risk of HF hospitalization (HR 2.85; 95% CI 1.08-7.52). Conclusion Patients with HFpEF and primary inflammatory disease have similar hemodynamic derangements but greater peripheral deficits in oxygen transport and higher risk for adverse outcome compared to those without.

Prognostic implications of microvascular resistance reserve in symptomatic patients with intermediate coronary stenosis

Abstract Background Microvascular resistance reserve (MRR) is a novel index reflecting coronary microcirculatory function, irrespective of epicardial coronary artery stenosis. There is limited evidence regarding whether MRR can be an independent prognostic tool in patients with stable ischemic heart disease (IHD). Objective To evaluate clinical outcomes according to MRR in patients with stable IHD accompanied with or without significant epicardial coronary artery stenosis. Methods The current study included 547 consecutive patients undergoing systematic echocardiographic and invasive physiologic assessment for suspected stable IHD. Significant epicardial coronary artery stenosis was defined as fractional flow reserve (FFR)≤0.80. Coronary microvascular dysfunction (CMD) was defined as MRR≤3.0. Primary outcome was major adverse cardiovascular event (MACE), a composite of cardiovascular death, myocardial infarction, repeat revascularization, and admission for heart failure. Results Among the total patients, 172 patients (31.4%) had FFR≤0.80 and 200 patients (36.6%) had CMD defined by MRR≤3.0. MRR showed no significant correlation with FFR (R=-0.031, P=0.469), however, it was significantly correlated with index of microcirculatory resistance (R=-0.353, P<0.001), NT-proBNP (R=-0.296, P<0.001), left ventricular filling pressure (E/e’) (R=-0.224, P<0.001), and diastolic dysfunction grade (P<0.001). During median follow-up of 3.3 years (interquartile range from 2.0 to 4.5 years), MRR was significantly associated with MACE risk (HR 1.23 per-1 decrease, 95% CI 1.12-1.36, P<0.001). CMD defined by MRR≤3.0 was associated with an increased MACE risk in both FFR>0.80 (41.0% vs. 26.0%; HRadj 1.59, 95% CI 1.07-2.35, P=0.021) and FFR≤0.80 (34.7% vs. 14.8%; HRadj 2.32, 95% CI 1.12-4.82, P=0.024) groups. Conclusion Decreased MRR was associated with the presence of cardiac diastolic dysfunction as well as with increased left ventricular filling pressure. The presence of CMD defined by MRR was independently associated with the risk of a composite of cardiovascular death, myocardial infarction, repeat revascularization, and admission for heart failure in patients with stable IHD, irrespective of significant epicardial coronary artery stenosis.

A DIFFERENT VIEW OF MINOCA; A RARE CASE OF CORONARY CAMERAL FISTULA

Abstract Coronary cameral fistula (CCF) is defined as an abnormal connection between the coronary artery and the heart chambers. Although rare, most are asymptomatic, usually arising from the right coronary artery and terminating in the right ventricle or right atrium. Often detected incidentally, CCFs may present with symptoms of heart failure or rarely with anginal symptoms. Introduction A coronary cameral fistula is defined as an abnormal connection between the coronary artery and the heart chambers. CCFs are found in less than 1% of the population.[1] The most common coronary artery fistula is that arising from the right coronary artery and spilling into the right ventricle.[2] In particular, CCFs arising from all three epicardial coronary arteries are rare but can be clinically significant. These cases may present with acute coronary syndrome causing steal syndrome. Since there is usually no underlying obstructive lesion, these cases may be diagnosed as myocardial infarction without obstructive coronary arteries (MINOCA)[3] Case; A 51 years old male patient was admitted to the emergency room with a complaint of stabbing chest pain for the last one week. In his anamnesis, he described that the chest pain increased with exertion and radiated to the back. It was learned that he had no known disease and coronary history, was a 20 pack/year smoker, had no family history and was not taking any medication regularly. Vital signs in the emergency room revealed a blood pressure of 120/80 mmHg, pulse rate of 85 per minute and normal saturation. Electrocardiography (ECG) showed sinus rhythm V 1-6 with T negativity 85/min. (Figure 1) Echocardiography revealed no wall motion defect and no major valve pathology. Laboratory findings showed renal function tests within normal range, C-reactive protein within normal range, hemoglobulin level 17.6 gr/dl, HS Troponin-T level 12.9 ng/l (upper limit 14 ng/l). At 3 hours, the control HS Troponin-T level was 69.2 ng/l and the patient was hospitalized in the coronary intensive care unit with a prediagnosis of acute coronary syndrome. Coronary angiography was performed during follow-up. Angiography showed dilatation in the main coronary artery (LMCA), ectasia in the left anterior descending artery (LAD) and circumflex artery (CX), and diffuse tortuosity in the coronaries. CCF formed by the LAD, CX and right coronary artery (RCA) together and spilled into the left ventricle. Opaque filling was observed in the left ventricle. (Figure 2) Although the patient had a low body mass index, dilatation of the coronary arteries was thought to be the effect of steal syndrome caused by multiple fistulas. The patient was admitted to the coronary intensive care unit with medical follow-up. The patient's medical treatment was adjusted as acetylsalicylic acid (ASA) 100 mg pill 1*1, metaprolol 50 mg pill 1*1 and rosuvastatin 20 mg pill 1*1 due to an LDL cholesterol level of 149 mg/dl. In the patient who currently had no signs of heart failure, medical treatment was decided primarily in terms of CCF. The patient was discharged with the recommendation of outpatient follow-up. Discussion and Conclusion; CCFs are rare coronary anomalies.[1] When we look at the etiology, the most common cause of CCFs is abnormal embryogenesis.[4] While the diagnosis can be made at any age, the diagnosis is usually made in early childhood when a heart murmur occurs in an asymptomatic child or in a child with symptoms of heart failure. However, cases of CCF diagnosed at an advanced age with anginal complaints and signs of acute heart failure are seen in the literature. [5]Treatment depends on the anatomical features of the fistula and, of course, the patient's symptoms. While small fistulas may close spontaneously with age, large fistulas may require closure.It may cause anginal symptoms by causing heart failure symptoms and steal syndrome. [6]When we look at the literature, we can see that patients with CCF also present with acute coronary syndrome. [2, 4, 5,] As in the case reported by Alsancak Y et al., CCFs originating from all three coronary arteries cause steal syndrome and are often diagnosed with a prediagnosis of acute coronary syndrome.[7] The absence of an occlusive lesion after angiography in these patients with high troponin levels suggests atherosclerosis at the microvascular level and the diagnosis of MINOCA. [3]Angiography performed with suspicion of stenosis in the coronary arteries and finding a CHF instead of a stenosis may be considered lucky in these patients. The size of the fistula and the possibility that it may lead to heart failure in the follow-up will be the other side of the unlucky coin.

Transient ST-segment elevation myocardial infarction without flow-limiting obstructions in the epicardial coronary arteries on angiography: coronary artery vasospasm, myocardial infarction with non-obstructive coronary arteries or spontaneous coronary artery dissection?

Transient ST-segment elevation myocardial infarction without flow-limiting obstructions in the epicardial coronary arteries on angiography: coronary artery vasospasm, myocardial infarction with non-obstructive coronary arteries or spontaneous coronary artery dissection?