Independent Predictors Of MACE Research Articles

Prognostic value of regional myocardial flow reserve derived from 13N-ammonia positron emission tomography in patients with suspected coronary artery disease

PurposeTo assess the prognostic value of regional quantitative myocardial flow measures as assessed by 13N-ammonia positron emission tomography (PET) myocardial perfusion imaging (MPI) in patients with suspected coronary artery disease (CAD).MethodsWe retrospectively included 150 consecutive patients with suspected CAD who underwent clinically indicated 13 N-ammonia PET-MPI and who did not undergo revascularization within 90 days of PET-MPI. The presence or absence of a decreased global myocardial flow reserve (i.e., MFR < 2) as well as decreased regional MFR (i.e., ≥ 2 adjacent segments with MFR < 2) was recorded, and patients were classified as having preserved global and regional MFR (MFR group 1), preserved global but decreased regional MFR (MFR group 2), or decreased global and regional MFR (MFR group 3). We obtained follow-up regarding major adverse cardiac events (MACE, i.e., a combined endpoint including all-cause death, non-fatal myocardial infarction, and late revascularization) and all-cause death.ResultsOver a median follow-up of 50 months (IQR 38–103), 30 events occurred in 29 patients. Kaplan–Meier analysis showed significantly reduced event-free and overall survival in MFR groups 2 and 3 compared to MFR group 1 (log-rank: p = 0.015 and p = 0.013). In a multivariable Cox regression analysis, decreased regional MFR was an independent predictor for MACE (adjusted HR 3.44, 95% CI 1.17–10.11, p = 0.024) and all-cause death (adjusted HR 4.72, 95% CI 1.07–20.7, p = 0.04).ConclusionsA decreased regional MFR as assessed by 13 N-ammonia PET-MPI confers prognostic value by identifying patients at increased risk for future adverse cardiac outcomes and all-cause death.

Prognostic impact of coronary microvascular dysfunction in patients with myocardial infarction with non-obstructive coronary arteries

BackgroundMyocardial infarction with non-obstructive coronary arteries (MINOCA) has been and remained a puzzling heterogeneous entity. The index of microcirculatory resistance (IMR) is a quantitative and specific index for the assessment of microvascular function. However, the role of IMR in MINOCA has not yet been studied. This study aimed to evaluate the prognostic value of coronary microvascular function, as assessed by coronary angiography‑derived index of microvascular resistance (caIMR) in MINOCA patients. MethodThis study included 109 MINOCA patients. Microvascular function was assessed by caIMR and was analyzed in 280 coronary arteries. The primary endpoint of the study was MACE, defined as cardiovascular death, nonfatal MI, heart failure, stroke and angina rehospitalization. The best cut-off of caIMR was derived from ROC analysis based on MACE prediction. ResultsThe patients were classified into high caIMR (caIMR>43U) and low caIMR (caIMR≤43U) based on a caIMR cut-off value of 43U. High caIMR was observed in 55 (50.5%) patients. A total of 27 MACE occurred during the 2 years of follow-up. MACE rate was significantly higher in patients with high caIMR than in patients with low caIMR (36.4% vs 13.0%, P=0.005). The Kaplan–Meier curves showed a significantly increased risk of MACE in patients with high caIMR (log-rank P=0.001). Cox multivariate analysis showed that caIMR>43 was a highly independent predictor of MACE (HR, 3.08; 95% CI, 1.13 - 8.35; P=0.027). ConclusionscaIMR is a strong predictor of clinical outcome among MINOCA patients. The evaluation of IMR can provide an objective risk stratification method for patients with MINOCA.

372-P: Type 2 Diabetes and Risk of Major Cardiovascular Events in Peripheral Artery Disease vs. Coronary Artery Disease Patients

The prevalence of type 2 diabetes (T2DM) is higher in peripheral artery disease (PAD) than in coronary artery disease (CAD) patients, and PAD overall confers higher cardiovascular risk than CAD. How the incidence of major cardiovascular events compares between PAD and CAD patients when analyses are stratified by the presence of type 2 diabetes (T2DM) is unclear and is addressed in the present study. We prospectively recorded major cardiovascular events and death over 10.0±4.7 years in 923 patients with stable CAD, of whom 26.7% had T2DM and in 292 patients with PAD, of whom 42.1% had T2DM. Four groups were analyzed: CAD patients without diabetes (CAD/T2DM-; n=677), CAD patients with T2DM (CAD/T2DM+; n=246), PAD patients without diabetes (PAD/T2DM-; n=169) and PAD patients with T2DM (PAD/T2DM+; n=123). When compared to the incidence of MACE in CAD+/T2DM- patients (25.1%), it was significantly higher in CAD+/T2DM+ patients (35.4%; p&amp;lt;0.001), in PAD+/T2DM- patients (30.2%; p=0.022) and in PAD+/T2DM+ patients (47.2%; p&amp;lt;0.001). Patients with both PAD and T2DM in turn were at a higher risk than CAD+/T2DM+ or PAD+/T2DM- patients (p=0.001 and p&amp;lt;0.001, respectively). The incidence of MACE did not differ significantly between PAD+/T2DM- and CAD+/T2DM+ patients (p=0.413). Compared to patients with CAD, Cox regression analyses after multivariate adjustment showed an adjusted hazard ratio of 1.46 [1.14-1.87], p=0.002 for the presence of PAD. Conversely, T2DM increased the risk of MACE after multivariate adjustment in CAD and PAD patients (adjusted HR 1.58 [1.27-1.98], p&amp;lt;0.001). In conclusion, our data show that T2DM and the presence of PAD are mutually independent predictors of MACE. Patients with both PAD and T2DM are at an exceedingly high risk of MACE. Disclosure C. H. Saely: None. H. Drexel: None. A. Vonbank: None. B. Larcher: None. A. Mader: None. M. Maechler: None. L. Sprenger: None. B. Mutschlechner: None. A. Leiherer: None. A. Muendlein: None.

High-Sensitivity Cardiac Troponin Predicts Major Cardiovascular Events in Diabetic Patients With Critical Limb Ischemia and Foot Lesions.

Background: Diabetic patients with critical limb ischemia (CLI) and foot lesions show a poor prognosis. Optimal risk stratification to guide tailored intervention is still uncertain. The aim of the present study was to assess the prognostic role of high-sensitivity cardiac troponin T (hs-TnT) in such a high-risk population.Methods and Results: Clinical, laboratory, and interventional data, as well as the SPINACH score, were collected. Hs-TnT was measured at hospital admission. All patients were followed up for at least 1 year. The primary endpoint was the cumulative occurrence of major cardiovascular events (MACEs, all-cause death, myocardial infarction, or stroke). The secondary endpoint was all-cause mortality. Overall, 618 patients were included and followed for a median of 981 (557–1,325) days. Diagnosis of coronary artery disease (CAD) was established in 270 (43.7%) patients. Median hs-TnT at admission was 31 (20–59) ng/L, with 525 (85%) patients over the upper reference limit. Hs-TnT values were significantly higher in patients with established CAD (39 vs. 29 ng/L, p < 0.01). Hs-TnT was an independent predictor of MACE (HR 2.440, 95% CI 1.706–3.489, p < 0.001). The best cut-offs were 40 ng/L (AUC 0.711) for patients with established CAD and 25 ng/L (AUC 0.725) for those without. Hs-TnT emerged also as an independent predictor of all-cause mortality. The addition of hs-TnT improved prognostic value of the SPINACH score.Conclusions: Hs-TnT is a powerful biomarker for prognostic stratification of diabetic CLI patients with foot lesions. This is confirmed independently to CAD diagnosis and permits the identification of higher risk patients requiring tailored intervention.

Relationship between CHA2DS2-VASC score on admission to emergency department and in-hospital major adverse cardiovascular events in patients diagnosed with ST-elevation myocardial infarction

Abstract Funding Acknowledgements Type of funding sources: None. Inotroduction . CHA₂DS₂-VASc scoring system, which includes traditional risk factors of coronary artery disease, is actually created to determine the risk of thromboembolism in patients with atrial fibrillation. In this study; the value of CHA₂DS₂-VASc score, which can be calculated easily on admission, was evaluated for predicting in-hospital adverse outcomes in ST elevation miyocardial infarction (STEMI) patients without atrial fibrillation. Method This was a single center cross-sectional study. 1933 STEMI patients enrolled to the study. Primary end points include in-hospital death, cardiopulmonary arrest and cerebrovascular accident and were identified as MACE Results MACE rate was 10% (193 patients), in-hospital mortality rate was 9% (169 patients).In proportional logistic regression analysis, CHA₂DS₂-VASc score was an independent predictor for MACE (OR and CI 95%, 2.31[1.37-3.90]; p value:0.0016). In the regression analysis, the CHA₂DS₂-VASc score was taken as an uncatagorized continuous variable, and the relationship between the CHA₂DS₂-VASc score and MACE was observed to be linear. Additionally heart rate (OR and 95% CI, 1.56 [0.97- 2.50]; p value: 0.0242), killip class on admission (OR and 95% CI, 24.19[10.74-54.46]; p value &amp;lt;0.0001), creatinine level on admission (OR and 95% CI, 1.54 [1.10-2.16]; p value: 0.0024), peak CK-MB level (OR and 95% GA, 1.63 [0.98-2.70]; p value: 0.0001) and presence of no-reflow (OR and 95% CI, 2.45 [1.25-4.80]; p value: 0.0085) were indendified as other independent predictors of MACE. Conclusion CHA₂DS₂-VASc score was observed as an indepented predictor for MACE in STEMI patients. To evaluate the relationship between CHA₂DS₂-VASc score and outcomes, the linear analysis of the CHA₂DS₂-VASc score without categorization in prediction model is used and this is the main difference of our study from others. Table-1 Variables Odss Ratio (OR) and 95% CI p value CHA₂DS₂-VASc ( 0 to 3) 2.31 (1.37-3.90) p = 0,0016 Heart Rate (Beats per minute) ( 68 to 94) 1.56 (0.97-2.50) p =0.0242 Systolic Blood Pressure (mmHg) ( 115 to 156) 0.83 (0.51-1.34) p = 0.3523 Killip Class ( I to IV) 24.19 (10.74-54.46) p &amp;lt; 0.0001 Hemoglobin (g/dL) ( 12 to 15) 0.96 (0.54-1.70) p = 0.4066 Creatinine ( mg/dL) (0.74 to 1.0) 1.54 (1.10-2.16) p = 0.0024 Peak CK-MB (IU/L) (40.8 to 165.1) 1.63 (0.98-2.70) p = 0.0001 No-reflow (yes) 2.45 (1.25-4.80) p = 0.0085 Independent predictors of MACE in STEMI patients according to penalized proportional odds logistic regression analysis Abstract Figure. Partial impact plots of predictors

Cardiac magnetic resonance derived global longitudinal strain outperforms established functional parameters in prognostication after ST-elevation myocardial infarction

Abstract Funding Acknowledgements Type of funding sources: None. Background Although left ventricular ejection fraction (LVEF) is recommended for left ventricular (LV) systolic function assessment and risk stratification of patients with ST-elevation myocardial infarction (STEMI), its prognostic value is limited. Other measures of LV function such as global longitudinal strain (GLS) and mitral annular plane systolic excursion (MAPSE) might provide additional prognostic information post-STEMI. However, comprehensive investigations comparing these parameters in terms of prediction of hard clinical events following STEMI are lacking so far. Purpose We aimed to investigate the comparative prognostic value of LVEF, MAPSE and GLS by cardiac magnetic resonance (CMR) imaging in acute STEMI patients. Methods This observational study included 407 consecutive acute STEMI patients treated with primary percutaneous coronary intervention (PCI). Comprehensive CMR investigations were performed 3 [interquartile range (IQR): 2-4] days after PCI to determine LVEF, GLS and MAPSE as well as myocardial infarct characteristics. Primary endpoint was the occurrence of MACE defined as composite of death, re-infarction and congestive heart failure. Results During a follow-up of 21 [IQR: 12-50] months, 40 (10%) patients experienced MACE. Patients with MACE showed significantly lower LVEF (49% vs. 53%, p = 0.005) and MAPSE (7.9 mm vs. 9.1 mm, p = 0.001), as well as higher GLS values (-10.2% vs. -12.3 %, p &amp;lt; 0.001). GLS showed the highest prognostic value with an area under the curve (AUC) of 0.71 (95% CI 0.63-0.79; p &amp;lt; 0.001) compared to MAPSE (AUC: 0.67, 95% CI 0.58-0.75; p = 0.001) and LVEF (AUC: 0.64, 95% CI 0.54-0.73; p = 0.005). After multivariable analysis, GLS emerged as independent predictor of MACE (HR: 1.22, 95% CI 1.11-1.35; p &amp;lt; 0.001). Of note, GLS remained associated with MACE (p &amp;lt; 0.001) even after adjustment for infarct size and microvascular obstruction. Conclusion CMR-derived GLS emerged as strong and independent predictor of MACE after acute STEMI with additive prognostic validity to LVEF and parameters of myocardial damage.

Prognostic value of phase analysis on gated single photon emission computed tomography in patients with cardiac sarcoidosis

BackgroundWe aimed to determine the correlation between phase analysis, reflecting the heterogeneity of perfusion defects, and the dyssynchrony of the left ventricle wall motion, and adverse cardiac events in cardiac sarcoidosis (CS) patients. MethodsFifty-seven consecutive patients with diagnosed CS (64 [IQR 55–71] years old, 14 males), who underwent 18F-FDG PET/CT and ECG-gated SPECT, were studied. FDG PET was analysed to measure cardiac metabolic volume (CMV), and total lesion glycolysis (TLG). The SPECT findings, such as LVEF, Summed Rest Score (SRS), bandwidth (BW) were evaluated. ResultsThe median of BW was 56° (IQR 40–95). BW showed a strong inverse correlation with LVEF (r = − 0.60, P < 0.0001), and positive correlation with SRS (r = 0.82, P < 0.0001). However, there were no significant correlations between BW and CMV or TLG. The Kaplan–Meier curves revealed a significantly higher rate of MACE in the high BW group (BW > 56°) than the low BW group (BW ≤ 56°) (15.1%/years vs. 4.4%/years, P = 0.025). In multivariable analysis, BW was a significant independent predictor of MACE (P = 0.015). ConclusionPhase analysis on gated SPECT was a significant and independent predictor of MACE in patients with CS.

Low hemoglobin predicts high-platelet reactivity and major cardiovascular ischemic events at long-term follow-up among ACS patients receiving dual antiplatelet therapy with ticagrelor.

Reduced levels of hemoglobin (Hb) represent an established marker of impaired outcomes and increased cardiovascular risk in patients with coronary artery disease, challenging the management of dual antiplatelet therapy (DAPT). However, while anemia has emerged as an independent predictor of suboptimal platelet inhibition in patients receiving clopidogrel, no study has so far evaluated the impact of Hb levels on high-on treatment platelet reactivity (HRPR) with ticagrelor and their prognostic consequences, that were the aim of the present study. Patients on DAPT with ASA + Ticagrelor (90 mg/twice a day) after percutaneous coronary revascularization for ACS were scheduled for platelet function assessment 30-90 days post-discharge. Aggregation tests were performed by multiple electrode aggregometry. Suboptimal platelet inhibition (HRPR-high residual platelet reactivity was defined if above the lower limit of normality (417 AU*min). The primary study endpoint was defined as the occurrence of major cardiovascular events (a composite of cardiovascular death, recurrent acute coronary syndrome [MI], target vessel revascularization) at longest available follow-up. We included 397 patients that were divided according to tertiles values of Hb (< 12.7, 12-7-14.09, ≥14.1g/dl). Patients with lower Hb were older and displayed a more severe cardiovascular risk profile. Mean levels of platelet reactivity were enhanced in patients with lower Hb after stimulation with TRAP peptide (TRAP test, p=.03) and ADP (p=.02). Elevated platelet reactivity (HRPR) on Ticagrelor was more frequent among patients with reduced Hb (16.4% vs. 12% vs. 5.4%, p=.005, adjusted OR [95%CI]=1.71[0.996;3.01], p=.056). At a mean follow-up of 820.9 ± 553.4 days, 21.4% of the patients experienced the primary composite endpoint, with a higher rate of events in patients with lower Hb (27.6% vs. 22.6% vs. 13.5%, p=.006, adjusted HR [95%CI]=1.51[1.12; 2.03], p=.006), mainly driven by a higher rate of recurrent ACS. After correction for baseline differences lower Hb tertiles but not HRPR emerged as independent predictor of MACE (adjusted HR [95%CI]=0.98[0.50; 1.92], p=.95). In the present study, we demonstrated that among patients on DAPT with ASA and ticagrelor after PCI for ACS, lower Hb levels are independently associated with a higher rate of HRPR and an increased rate of major ischemic events, and especially for recurrent ACS, although with no impact on survival. Neutral prognostic effect of HRPR was observed across Hb tertiles.

Prognostic role of neutrophil-to-lymphocyte ratio in patients with ST-elevation myocardial infarction undergoing to pharmaco-invasive strategy

ObjectivesWe sought to determine the relationship between in-hospital mortality and the neutrophil-to-lymphocyte ratio (NLR) in patients with ST-elevation myocardial infarction (STEMI) undergoing with pharmaco-invasive strategy (PIS). BackgroundIncreased levels of white blood cells have been associated with adverse clinical outcomes in patients with (STEMI). NLR has recently emerged as a potent and more specific prognostic marker in predicting short- and long-term mortalityin patients undergoing primary percutaneous coronary intervention. This association has never been reported in patients managed with PIS. MethodsBetween March 2010 and October 2016, 1860 STEMI patients managed with PIS were consecutively included in a dedicated database. The study population was divided into tertiles based on the admission NLR values (lower: <4.0, intermediate: 4.0 to <7.3, and upper: ≥7.3). Co-primary endpoints were in-hospital mortality and MACE (death, non-fatal reinfarction or stent thrombosis). ResultsPatients in the upper NLR tertile had significantly higher in-hospital mortality (9.0% vs. 4.8% versus. 1.8%, p < 0.001) and MACE (11.6% vs. 8.0% versus 2.9%, p < 0.001) than patients with intermediate or low NLR. By multivariable logistic regression analysis, the upper NLR tertile was an independent predictor of MACE (odds radio [OR] 4.19, 95% confidence interval [95% CI] 2.23–7.88, p < 0.001) and in-hospital mortality [OR 3.32, 95% CI 1.19–9.28, p = 0.02]. ConclusionHigh NLR values were independently associated with in-hospital MACE and death in STEMI patients submitted to a PIS. NLR might be a simple and useful risk stratification tool in this high-risk population.

The Role of Ambient Temperature and Plasma Osmolarity on Clinical Outcomes of Acute Myocardial Infarction Patients during Hajj

Background: Performance of Hajj is physically very demanding, especially if performed during the summer season. The aim of this study is to evaluate the importance of ambient temperature and dehydration, indicated by plasma osmolarity on the clinical outcomes of cardiac patients during Hajj season in 2017. Methods: We included all patients referred to tertiary center with acute coronary syndrome during Hajj period of 2017. Plasma osmolarity was calculated using concentrations of sodium, plasma glucose, and blood urea nitrogen at admission. Patients were stratified by groups (G) of admission osmolarity, clinical outcome was compared. The primary endpoints were in-hospital mortality, length of stay, Cardiac complications (heart failure, re-infarction, arrhythmia, shock and thrombus formation), left ventricular function and readmission rate. Result: Total of 300 patients were identified with mean age 56.2 ±12.1, 84% males and 97(32%) were pilgrims. They were exposed to average heat index 61.9 ±10.6° C. Significantly longer admissions were found in the group of higher osmolarity (G2) (≥295 mos/L) as compared to patients with normal osmolarity in G1 [6.7 ±14.9 VS 4.0 ±4.5, P=0.045]. Total in-hospital death rate was 4.3% (13). Using Binary regression analysis; osmolarity Group [p=0.009], Pilrgrim [P=0.005], Heat index [ P=0.005], were independent predictor of inhospital mortality, while Heat index is the only independent predictor for MACE [P=0.001]. Conclusion: Plasma osmolarity and heat index significantly affect cardiac patient’s outcome. These finding underscore the importance of health awareness of protection from dehydration for pilgrims during summer season.

Post-procedural high platelet reactivity with prasugrel loading predicts in-hospital adverse events in ACS patients

Abstract Background/Introduction High platelet reactivity (HPR) is associated with adverse cardiovascular events, primarily intrastent thrombosis, after a percutaneous coronary intervention (PCI). However, the relationship between hyperacute postprocedural HPR with prasugrel loading and clinical outcomes in acute coronary syndrome (ACS) remains unclear. Moreover, factors contributing to HPR in ACS with prasugrel loading are also unknown. Purpose To assess the effects of post-procedural HPR with prasugrel loading on clinical outcomes in ACS during hospitalization, and to define the appropriate cut-off values and identify factors contributing to HPR. Methods A single-center, retrospective observational study that enrolled 154 patients who underwent emergent PCI for ACS with prasugrel loading was performed. The P2Y12 reaction unit (PRU) value was measured immediately after PCI using the VerifyNowR system. The primary end-point was major adverse cardiac events (MACE, defined as the composite of death, myocardial infarction, stroke, heart failure, ventricular arrhythmia needing defibrillation). Results The mean patient age (standard deviation) was 70.7 (±12.5) years, 76.6% were men, and the average time from the prasugrel intake to PRU calculation was 103.2 (±48.5) min. During the mean hospital stay of 15.6 (±8.5) days, 24 in-hospital MACE (15.5%) and 8 deaths (5.2%) occurred. Thrombosis events, including myocardial infarction recurrence, did not occur (only one case of spontaneous coronary artery dissection was considered as myocardial infarction recurrence). PRU was significantly higher in the MACE group than that in Non-MACE group (287±55 and 232±64, respectively, p&amp;lt;0.001). The ROC curve analysis of PRU for discriminating the significant in-hospital MACE showed the cut-off value of 293 (sensitivity: 62.5%, specificity: 83.1% [AUC=0.756, p&amp;lt;0.0001]). A total of 37 patients (24%) were thus categorized as HPR (PRU&amp;gt;293) immediately after the emergent PCI. Kaplan-Meier curve showing MACE events occurred in the HPR group than that in the non-HPR group (40.5% vs 7.6%, p&amp;lt;0.001). Multiple cox analysis demonstrated that HPR was independent predictors of MACE in patients with ACS who underwent PCI (OR 11.01, 95% CI 2.39–20.2, p&amp;lt;0.0001). Multiple logistic regression model showed old age, female sex, low systolic blood pressure, short prasugrel intake to measure time, and large acute gain were independent predictors of HPR. Conclusion PRU was significantly higher in the MACE group, with an appropriate cut-off value of HPR of 293 in this study. HPR was an independent predictor of MACE during hospitalization; however, thrombosis events were not significant. HPR predictors were old age, female sex, low systolic blood pressure, short prasugrel intake to measure time, and large acute gain. This study shows the post-procedural HPR with prasugrel loading in patients with ACS can be a useful predictive marker of adverse events during hospitalization. Funding Acknowledgement Type of funding source: None

Chest pain of unknown coronary origin: can exercise ECG testing contribute to long-term risk prediction on top of vasodilator stress cardiac magnetic resonance?

Abstract Background The prognostic value of both exercise ECG testing (ExECG) and vasodilator stress cardiac magnetic resonance (VS-CMR) is well-known in patients with chest pain of unknown coronary origin. However, it is unknown whether performing both techniques can improve the risk stratification of these patients. Purpose We aim to confirm the additive prognostic value of ExECG and VS-CMR in a real-world cohort of patients with chest pain of unknown coronary origin. Methods We retrospectively included 288 patients in which ExECG and VS-CMR had been subsequently performed within one year. Clinical, ExECG and VS-CMR variables were registered. We performed univariate and multivariate analysis to check for the association of variables with the risk of MACE, defined as a combined endpoint of acute coronary syndrome (ACS), admission for heart failure (aHF) or all-cause death. Results During a mean follow-up of 4.2±2.15 years, we registered 27 MACE (15 ACS, 8 aHF and 8 all-cause deaths). The history of hypertension, previous coronary artery disease and/or coronary artery bypass grafting, lower maximal heart rate during ExECG (maxHR) and more extensive ischemic burden (segments with perfusion defects -PD- on stress first-pass perfusion) and myocardial necrosis (number of segments with necrosis at late gadolinium enhancement imaging) associated with the MACE endpoint. However, the only independent predictors of MACE were maxHR during ExECG (HR 0.98 [0.96–0.99], p=0.01) and more extensive segments with PD in the VS-CMR (HR 1.2 [1.07–1.34], p=0.002). We identified the best cut-off using the Youden index derived from receiver operating characteristics (ROC) analysis to predict MACE - it was ≤130bpm for maxHR during ExECG and ≥2 segments with PD on VS-CMR. These cathegories allowed us to stratify the annualized rate of MACE, which was very low (0.97%/year) in patients with normal maxHR and no PD on VS-CMR, intermediate in patients with only abnormal maxHR (1.98%/year) or PD on VS-CMR (3.24%/year) and high in patients with both abnormal maxHR and segments with PD (6.26%/year). Adding maxHR to the multivariable model including stress-induced PD by VS-CMR significantly improved the predictive power of MACE as derived from the continuous reclassification improvement index (0.47 [0.10–0.81], p&amp;lt;0.05). Conclusions ExECG and VS-CMR can have an additive prognostic value to predict the long-term risk of MACE in patients with chest pain of unknown coronary origin. Patients with maxHR during ExECG ≤130bpm and ≥2 segments with PD on VS-CMR are at the highest risk of MACE. Figure 1. MACE risk stratification. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This study was funded by “Instituto de Salud Carlos III” and “Fondos Europeos de Desarrollo Regional FEDER” (PIE15/00013, PI17/01836, and CIBERCV16/11/00486 grants) and by Generalitat Valenciana (GV/2018/116).

Prognostic value of coronary flow capacity assessed by coronary sinus flow obtained by phase contrast cine-magnetic resonance imaging in patients with acute coronary syndrome

Abstract Background The concept of coronary flow capacity (CFC) originated from positron emission tomography has been reported to provide prognostic information. Phase contrast cine-magnetic resonance imaging (PC-CMR) of the coronary sinus (CS) is a promising approach for quantifying global coronary sinus flow (CSF) and global coronary flow reserve (g-CFR) without the need for ionizing radiation, radioactive tracers, or intravascular catheterization. Purpose We evaluated the prognostic value of postprocedural CFC by quantifying CSF using PC-CMR in patients with acute coronary syndrome (ACS) treated with primary or urgent percutaneous coronary intervention (PCI). Methods This study prospectively but nonconsecutively enrolled 569 ACS patients who underwent uncomplicated primary (for ST-segment elevation myocardial infarction (STEMI)) or urgent PCI within 48 hours of symptom onset (for non-ST elevation acute coronary syndrome (NSTE-ACS)). Breath-hold PC-CMR images of CS were acquired to assess absolute CSF at rest and during maximum hyperemia within 30 days after culprit lesion PCI and revascularization of functionally significant non-culprit lesions. The entire cohort was stratified by the CFC according to the thresholds of hyperemic CSF and g-CFR. Impaired CFC was defined as a severely-reduced CFC in the present study. The association of CFC and baseline clinical characteristics with major adverse cardiac events (all-cause death, nonfatal myocardial infarction, hospitalization for congestive heart failure or stroke) was investigated. Results In the final analysis of 502 patients (Male 417 (83.1%), mean age was 67 [58, 73]) and 310 patients (82.3%) with STEMI and 192 patients (38.2%) with NSTE-ACS were studied. In a total cohort, rest and maximal hyperemic CSF and corrected G-CFR were 0.93 [0.68, 1.24] ml/min/g, 2.08 [1.44, 2.77] ml/min/g, and 2.21 [1.58, 3.05], respectively. During a median follow-up of 28 months, MACE occurred in 53 patients (all-cause death: 19, nonfatal myocardial infarction: 16, late revascularization: 59, hospitalization for congestive heart failure: 9, stroke: 9). Cox proportional hazards analysis showed that corrected G-CFR and impaired CFC were both independent predictors of MACE. (hazard ratio (HR), 0.61, 95% confidence interval (CI): 0.45–0.82, p=0.001; HR, 3.51, 95% CI: 1.79–6.86, p≤0.001, respectively). Cardiac event-free survival was significantly worse in patients with impaired CFC (log-rank χ2=22.9, P&amp;lt;0.001). Net reclassification index (NRI) and integrated discrimination improvement (IDI) were both significantly improved when impaired CFC was added to the clinical risk model for predicting MACE. Conclusions In ACS patients successfully revascularized with primary or urgent PCI, CFC categorization stratified by noninvasive PC-CMR provided significant prognostic information independent of infarction size, conventional risk factors and g-CFR. Funding Acknowledgement Type of funding source: None

Pericoronary fat radiomic profile (FRP) predicts long-term cardiac risk in individuals with calcium score below 100 on coronary computed tomography angiography

Abstract Background Coronary computed tomography angiography (CCTA) provides useful information regarding cardiovascular risk assessment. Key aspects of coronary biology induce changes in perivascular adipose tissue composition, detectable by the pericoronary Fat Radiomic Profile (FRP) index. Purpose We assessed the ability of FRP to further stratify cardiac risk in patients with Coronary Artery Calcium (CAC) scoring below 100 following routine CCTA. Methods The study population consisted of 1,575 participants from the CCTA arm of the SCOT-HEART trial (NCT01149590) with images available and eligible for analysis. Pericoronary FRP mapping was performed in perivascular adipose tissue segmentations around the proximal sites of the right and left coronary arteries, as previously validated. The prognostic potential of FRP was initially tested in a sub-cohort, consisting of patients with Coronary Artery Calcium (CAC) score lower than 100. Further analysis was performed after sub-grouping based on the absence of high risk plaque (HRP) features and obstructive coronary artery disease (CAD). The association with future incidence of major adverse cardiac events (MACE: cardiac mortality or non-fatal myocardial infarction) or a composite endpoint of MACE ± late revascularization (MACE-ReVasc) was assessed using adjusted Cox regression models [adjusted for age, sex, systolic blood pressure (SBP), diabetes mellitus (DM), body mass index (BMI), smoking, CAD (≥50% stenosis), total cholesterol, high-density lipoprotein (HDL), and HRP features]. Results Two-thirds (66%) of the study population were at low-risk according to the CAC score (CAC&amp;lt;100). Over a mean follow-up of 4.87±1.06 years, 12 MACE and 47 MACE-ReVasc were recorded. In this sub-cohort, high FRP was associated with a 14.4-fold (95% CI: 3.80–54.78, p&amp;lt;0.001) higher adjusted risk of MACE and a 2.8-fold (95% CI: 1.49–5.36, p=0.001) higher adjusted risk of MACE-ReVasc. Adding high FRP to a baseline model consisting of traditional risk factors (age, sex, systolic blood pressure, diabetes mellitus, BMI, smoking, CAD (≥50% stenosis), total cholesterol, HDL, HRP) significantly enhanced (deltaAUC at 5 years:0.15, p=0.03) the model's performance (A) and reclassified individuals (NRI=0.59, p=0.02). Interestingly, following further filtering of the population by the absence of HRP features and obstructive CAD, high FRP remained an independent predictor of MACE (B). Conclusion The Fat Radiomic Profile biormarker significantly improves risk prediction for adverse clinical events beyond the current state-of-the-art in individuals with low CAC scores. Non-invasive profiling of pericoronary adipose tissue using CCTA-derived FRP captures irreversible changes in perivascular adipose tissue composition associated with chronic vascular inflammation and atherosclerotic disease, and can improve risk stratification and clinical decision making in low-risk populations. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): British Heart Foundation, National Institute of Health Research, Oxford Biomedical Research Centre

Short and medium chain acylcarnitines as markers of outcome in diabetic and non-diabetic subjects with acute coronary syndromes

Abstract Background Dietary carnitine that is not absorbed can serve as a precursor for gut microbiota-dependent generation of trimethylamine N-oxide (TMAO), a pro-atherogenic and pro-thrombosis promoting metabolite. Gut microbiome-derived metabolites of dietary carnitine, including TMAO and g-butyrobetaine, may accelerate atherosclerosis, increase platelet reactivity and in vivo thrombosis. Carnitine metabolism also produces numerous molecular species of short, medium and long chain acylcarnitines, which play important roles in energy metabolism and intracellular fatty acid transport. Purpose We sought to evaluate the differences between diabetics and non-diabetics presenting with ACS with respect to acylcarnitines, and to explore their relationship with incident cardiovascular outcomes. Methods Using a large, prospectively recruited cohort of patients presenting to the cardiac cath lab with suspected acute coronary syndromes, we measured levels of plasma acylcarnitines, carnitine and its gut microbial-derived metabolites to assess their relationship with independently adjudicated major adverse cardiac events (MACE = myocardial infarction, stroke or TIA, need for revascularization or all-cause mortality) amongst diabetics and non-diabetics. Results We analysed 1683 patients who presented with ACS, were treated according to current guidelines and had undergone acylcarnitine analysis. There were 294 diabetics and 1389 non-diabetics. Diabetics had significantly higher plasma levels of all acyl carnitine metabolites than non-diabetics (P&amp;lt;0.001), but not of carnitine itself. Baseline plasma levels of all gut microbiome derived carnitine metabolites (TMAO, g-butyrobetaine and crotonobetaine) were also significantly higher in those who subsequently experienced a MACE. All carnitine metabolites, apart from octenoylcarnitine, were significantly associated with MACE on univariate analysis, while acetylcarnitine and crotonobetaine were independently associated with MACE after multivariate adjustment. Conclusion Serum short- and medium- chain acylcarnitine levels are significantly higher in diabetic patients presenting with ACS and predict MACE. After multivariate adjustment, acetylcarnitine and crotonobetaine remained an independent predictor of MACE. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Zurich Heart House - Foundation for Cardiovascular Research

Feasibility and Prognostic Value of Vasodilator Stress Perfusion CMR in Patients With Atrial Fibrillation

ObjectivesThe aim of this study was to assess the feasibility and prognostic value of vasodilator stress perfusion cardiovascular magnetic resonance (CMR) in patients with atrial fibrillation (AF). BackgroundBecause most studies have excluded arrhythmic patients, the prognostic value of stress perfusion CMR in patients with AF is unknown. MethodsBetween 2008 and 2018, consecutive patients with suspected or stable chronic coronary artery disease and AF referred for vasodilator stress perfusion CMR were included and followed for the occurrence of major adverse cardiovascular event(s) (MACE), defined as cardiovascular death or nonfatal myocardial infarction. The diagnosis of AF was defined by 12-lead electrocardiography before and after CMR. Univariate and multivariate Cox regressions were performed to determine the prognostic value of inducible ischemia or late gadolinium enhancement (LGE) by CMR. ResultsOf 639 patients (mean age 72 ± 9 years, 77% men), 602 (94%) completed the CMR protocol, and 538 (89%) completed follow-up (median 5.1 years); 80 had MACE. Using Kaplan-Meier analysis, the presence of ischemia (hazard ratio [HR]: 7.56; 95% confidence interval [CI]: 4.86 to 11.80) or LGE (HR: 2.41; 95% CI: 1.55 to 3.74) was associated with the occurrence of MACE (p < 0.001 for both). In a multivariate Cox regression including clinical and CMR indexes, the presence of ischemia (HR: 5.98; 95% CI: 3.68 to 9.73) or LGE (HR: 2.61; 95% CI: 1.89 to 3.60) was an independent predictor of MACE (p < 0.001 for both). ConclusionsIn patients with AF, stress perfusion CMR is feasible and has good discriminative prognostic value to predict the occurrence of MACE.

Incidence and predictors of outcomes after a first definite coronary stent thrombosis.

Stent thrombosis (ST) is a rare but potentially fatal complication of coronary artery stenting. Little is known about the optimal treatment strategy at the time of an ST event. We aimed to identify the incidence and predictors of adverse cardiac events after treatment of a definite ST. A total of 695 patients with definite ST were included between 1996 and 2017 in two academic medical centres. The primary endpoint was MACE, the composite of cardiac death, myocardial infarction (MI) and target vessel revascularisation (TVR). Mean age was 62.8±12.1 years and 76.3% were male. ST occurred at a median of 22 days (IQR 3-551 days); 50.8% were early and 49.2% were late/very late ST. At 60-month follow-up, the MACE rate was 43.7%, cardiac death 19.5%, MI 17.9%, TVR 24.8%, and repeat definite ST was 12.1% (10.5% in target vessel). Independent predictors of MACE were cardiogenic shock (HR 2.54, 95% CI: 1.75-3.70; p<0.001), ST in the LAD (HR 1.76, 95% CI: 1.32-2.35; p<0.001), prior CVA/TIA (HR 1.68, 95% CI: 1.08-2.62; p=0.020), peripheral vascular disease (HR 1.55, 95% CI: 1.00-2.39; p=0.046), multivessel disease (HR 1.53, 95% CI: 1.12-2.08; p=0.007), and final TIMI flow 2-3 (HR 0.54, 95% CI: 0.34-0.85; p=0.009). No specific treatment of ST influenced MACE; however, new-generation P2Y12 inhibitors reduced the risk of MI (HR 0.56, 95% CI: 0.32-0.99; p=0.049). The incidence of adverse events remains high after a first episode of ST. New-generation P2Y12 inhibitors reduce the risk of MI. Additional stenting, GP IIb/IIIa inhibitors and thrombectomy did not improve outcomes following ST.

Effect of Sex Difference of Coronary Microvascular Dysfunction on Long-Term Outcomes in Deferred Lesions

ObjectivesThis study investigated the sex difference of long-term cardiovascular outcomes on coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) in patients with deferred coronary artery lesions. BackgroundCoronary microvascular dysfunction is associated with poorer long-term outcomes. It can be assessed by CFR and the IMR. MethodsThe study prospectively enrolled 434 patients (133 women and 301 men) and analyzed CFR, IMR, fractional flow reserve, and quantitative coronary angiography. Clinical outcomes were assessed by major adverse cardiovascular event(s) (MACE) of cardiac death, myocardial infarction, and revascularization during 5 years of follow-up. The study protocol was approved by the Institutional Review Board or Ethics Committee at each participating center, and all patients provided written informed consent. The study protocol was in accordance with the Declaration of Helsinki. ResultsWomen had milder epicardial disease compared with men (fractional flow reserve: 0.91 [interquartile range (IQR): 0.87 to 0.96] vs. 0.90 [IQR: 0.86 to 0.95]; p = 0.037). IMR was similar between the sexes, but CFR was lower in women (2.69 [IQR: 2.08 to 3.90] vs. 3.20 [IQR: 2.20 to 4.31]; p = 0.006) due to a shorter resting mean transit time, whereas hyperemic mean transit times were similar. At 5-year follow-up, MACE was significantly lower in women compared with men (1.1% vs. 5.5%; p = 0.017). Sex, diabetes mellitus, and CFR were independent predictors for MACE for all patients. The risk of MACE was significantly higher in men with low versus high CFR (hazard ratio: 4.58; 95% confidence interval: 1.85 to 11.30; p = 0.011) which was not seen in women. ConclusionsThere was no sex difference in microvascular function by IMR. CFR was lower in women due to a higher resting coronary flow; however, long-term clinical outcomes in deferred lesions were better in women compared with men. (Clinical, Physiological and Prognostic Implication of Microvascular Status; NCT02186093).

Prognostic importance of visit-to-visit blood pressure variability for micro- and macrovascular outcomes in patients with type 2 diabetes: The Rio de Janeiro Type 2 Diabetes Cohort Study

BackgroundThe prognostic importance of an increased visit-to-visit blood pressure variability (BP-VVV) for the future development of micro- and macrovascular complications in type 2 diabetes has been scarcely investigated and is largely unsettled. We aimed to evaluate it in a prospective long-term follow-up study with 632 individuals with type 2 diabetes.MethodsBP-VVV parameters (systolic and diastolic standard deviations [SD] and variation coefficients) were measured during the first 24-months. Multivariate Cox analysis, adjusted for risk factors and mean BP levels, examined the associations between BP-VVV and the occurrence of microvascular (retinopathy, microalbuminuria, renal function deterioration, peripheral neuropathy) and macrovascular complications (total cardiovascular events [CVEs], major adverse CVEs [MACE] and cardiovascular and all-cause mortality). Improvement in risk discrimination was assessed by the C-statistic and integrated discrimination improvement (IDI) index.ResultsOver a median follow-up of 11.3 years, 162 patients had a CVE (132 MACE), and 212 patients died (95 from cardiovascular diseases); 153 newly-developed or worsened diabetic retinopathy, 193 achieved the renal composite outcome (121 newly-developed microalbuminuria and 95 deteriorated renal function), and 171 newly-developed or worsened peripheral neuropathy. Systolic BP-VVV was an independent predictor of MACE (hazard ratio: 1.25, 95% CI 1.03–1.51 for a 1-SD increase in 24-month SD), but not of total CVEs, cardiovascular and all-cause mortality, and of any microvascular outcome. However, no BP-VVV parameter significantly improved cardiovascular risk discrimination (increase in C-statistic 0.001, relative IDI 0.9%).ConclusionsSystolic BP-VVV was an independent predictor of MACE, but it did not improve cardiovascular risk stratification. The goal of anti-hypertensive treatment in patients with type 2 diabetes shall remain in controlling mean BP levels, not on decreasing their visit-to-visit variability.

Major Adverse Cardiac Events after first time elective isolated Coronary Artery

Abstract Background Major adverse cardiovascular events (MACE) are useful endpoints to evaluate cardiovascular outcomes. The aim of this study was to report our results in concordance with the expected improvement of records after using the online Research Electronic Data Capture (RedCap) software. Methods: We included patients who benefited from first time elective isolated coronary bypass grafting (CABG) at Ain-Shams university main hospital, in the period between April 2014 and April 2016; providing a minimum 2 years follow-up . Incidences, risk factors and independent predictors for MACE were calculated including; mortality, the occurrence or re-hospitalization for: heart failure, recurrence of angina or myocardial infarction (MI), cerebrovascular stroke (CVS), need of coronary angiography (CA), repeat percutaneous intervention (PTCA) or CABG. Results: 607 cases met our inclusion criteria and 105 patients (18.7%) developed 184 MACE, including 45 hospital mortalities (7.4%), 13 late mortalities (2.1%) and 126 non-fatal events recorded in 47 patients (7.7%); a majority (40 patients; 6.6%) had suffered from at least 3 non-fatal events. Two-years follow-up was complete for the 562 hospital survivors with a total of 1113 patient-years. The annualized incidence rates of ICU admission, repeated angina or MI, need for CA, PTCA, or CABG, development of CVS, heart failure, and late mortality were: 3.6%, 2.8%, 1.8%, 0.5%, 0.09%, 0.35%, 2% and 1.2% per patient-year; respectively. Independent predictors of hospital mortality were: advanced age at surgery (OR 1.06: 1-1.12; P = 0.049), female sex (OR 3.4: 1.3-8.9; P = 0.01), prolonged durations of: cardiopulmonary bypass CPB (OR 1.02: 1.01- 1.04; P &amp;lt; 0.001), mechanical ventilation (OR 1.07: 1.04- 1.09; P &amp;lt; 0.001) positive inotropic support (OR 1.03: 1.02- 1.05; P &amp;lt; 0.001) and ICU stay (OR 1.09: 1.07- 1.11; P &amp;lt; 0.001). Independent predictors of overall MACE were advanced age at surgery (OR 1.04: 1.01-1.07; P = 0.011), prolonged durations of: aortic cross clamp (OR 1.09: 1.04-1.11; P = 0.003), CPB (OR 1.06: 1.04-1.08; P &amp;lt; 0.001) and mechanical ventilation (OR 1.02: 1.01-1.03; P &amp;lt; 0.001). Conclusion: Our results suggested that more care should be given to females, elderly and to shorten and improve the quality of our operative times. The repetition of non-fatal MACE could be modified by closer observation of the patient, once developing his first event.