Prior Coronary Artery Disease Research Articles

Left ventricular ejection fraction, myocardial blood flow and hemodynamic variables in adenosine and regadenoson vasodilator 82-Rubidium PET

AimsIn most Rubidium-(Rb)-positron emission tomography (PET) studies, dipyridamole was used as vasodilator. The aim was to evaluate vasodilator PET left ventricular ejection fraction (LVEF), myocardial blood flow (MBF), hemodynamics, and the influence of adenosine and regadenoson on these variables. Methods and resultsConsecutive patients (N = 2299) with prior coronary artery disease (CAD) or no prior CAD undergoing adenosine/regadenoson 82Rb-PET were studied and compared according to CAD status and normal/abnormal PET (summed stress score 0-3 vs. ≥4). Rest and stress LVEF differed significantly depending on CAD status and scan results. In patients with no prior CAD, rest/stress LVEF were 68% and 72%, in patients with prior CAD 60% and 63%. LVEF during stress increased 5 ± 6% in normal compared to 1 ± 8% in abnormal PET (P<0.001). Global rest myocardial blood flow(rMBF), stress MBF(sMBF) and myocardial flow reserve (sMBF/rMBF) were significantly higher in no prior CAD patients compared to prior CAD patients(1.3 ± 0.5, 3.3 ± 0.9, 2.6 ± 0.8 and 1.2 ± 0.4, 2.6 ± 0.8, 2.4 ± 0.8 ml/g/min, respectively, P<0.001) and in normal versus abnormal scans, irrespective of CAD status(no prior CAD: 1.4 ± 0.5, 3.5 ± 0.8, 2.8 ± 0.8 and 1.2 ± 0.8, 2.5 ± 0.8, 2.2 ± 0.7; prior CAD: 1.3 ± 0.4, 3.1 ± 0.8, 2.7 ± 0.8 and 1.1 ± 0.4, 2.3 ± 0.7, 2.2 ± 0.7 ml/g/min, respectively, P<0.001). LVEF and hemodynamic values were similar for adenosine and regadenoson stress. Stress LVEF ≥70% excluded relevant ischemia (≥10%) with a negative predictive value (NPV) of 94% (CI 92-95%). ConclusionsRest/stress LVEF, LVEF reserve and MBF values are lower in abnormal compared to normal scans. Adenosine and regadenoson seem to have similar effect on stress LVEF, MBF and hemodynamics. A stress LVEF ≥70% has a high NPV to exclude relevant ischemia.

Invasive coronary angiography as a tool in cardiac evaluation for liver transplant candidates

BackgroundCardiovascular assessment is central to evaluation of liver transplant (LT) candidates. However, there is a lack of consensus on the diagnostic algorithm for screening for coronary artery disease (CAD), and the place for invasive coronary angiography (ICA) remains undefined. MethodsWe retrospectively analysed 1201 adults who underwent elective LT assessment over a 5-year period. For patients who underwent LT, survival data to 5 years post-LT was collected. ResultsICA was performed in 259 (21.6%): 134 no CAD, 58 mild, 33 moderate, and 34 severe. Detection of CAD was associated with age (OR 1.08, P < 0.01), current smoking (OR 4.92, P < 0.01) and prior CAD (OR 8.93, P < 0.001). Poor performance on cardiopulmonary exercise test (CPET) was associated with age (OR 1.02, P < .05) and diabetes mellitus (OR 1.54, P < 0.05). 122 (10.2%) patients were declined due to severity of cardiovascular disease.169/779 (21.7%) patients listed for LT had undergone ICA, and CAD was present in 73/169 (43.2%). The non-risk-adjusted all-cause post-LT 5-year survival was 82.6%, with no difference in survival in those with and without CAD on ICA. In patients with CAD, diabetes was associated with reduced survival (OR 3.78, P < 0.05). ConclusionsMulti-modality cardiac evaluation is useful in high-risk patients undergoing LT assessment. ICA can be used with non-invasive assessments and risk factors to delineate candidacy. In selected patients with CAD, LT has been undertaken with comparable post-LT survival.

MO982: Determinants of Coronary Artery Calcium Score in Stable Kidney Transplant Recipients 12 Months After Transplantation

Abstract BACKGROUND AND AIMS Cardiovascular disease remains the primary cause of death after kidney transplantation. Vascular calcification may at least in part explain excess cardiovascular morbidity and mortality, but little is known about the drivers of vascular calcification after kidney transplantation. Remarkably, some patients with kidney failure develop extensive calcifications, whereas others remain free of calcifications. This study aimed to assess the severity of CAC score and investigate potential determinants of vascular calcification in stable kidney transplant recipients (KTRs) at 12 months after transplantation. The second aim was to compare the characteristics of KTRs without any calcifications versus those with a relatively high CAC score. METHOD Adult KTRs with no prior coronary artery disease and eGFR &amp;gt;30 mL/min/1.73 m2 who visited our center between June 2018 and June 2021 underwent non-contrast computed tomography (CT) of the heart to quantify the coronary artery calcium (CAC)-score, calculated by the Agatston method. CAC-score percentiles were calculated using a CAC nomogram available at https://www.calciumscorecalculator.com. Clinical, laboratory, lifestyle and nutritional data, including bioimpedance analysis (BIA), were collected as part of the TransplantLines Biobank and Cohort Study1. The association between potential determinants and CAC-score percentiles was first studied in univariable multinomial logistic regression analysis and subsequently all variables with P &amp;lt; 0.10 were included in a multivariable multinomial logistic regression analysis to study independent determinants of CAC. We subsequently performed a case control analysis, comparing KTRs without calcifications (no-CAC, n = 36) versus those with relatively high calcium score (CAC ≥75th percentile, n = 36), matched by age, sex and dialysis vintage. RESULTS A total of 203 KTRs (54.0 ± 14.7 year old, 61.1% male) at 12 months after transplantation were included in the main analysis. Participants were categorized into three groups according to CAC-score percentiles {P = 0% (CAC = 0), n = 68; P ≥1%—P ≤ 75% [CAC = 67.5 (6.5–247.0)], n = 52; P &amp;gt; 75%, [CAC = 0], 581 (148.0–1652), n = 83}. Individuals in the highest CAC-score percentile group had lower educational level, heart rate, urinary protein excretion, urinary magnesium excretion, physical functioning score and phase angle assessed by BIA (a marker of both hydration status and body cell mass/integrity), and higher prevalence of diabetes mellitus, dialysis vintage, serum triglycerides, PTH, alkaline phosphatase, calcium, use of statins, use of antihypertensives and use of diuretics. In multivariable-adjusted multinomial logistic regression analysis, donor living status and phase angle were inversely associated with CAC-score &amp;gt;75% (Table 1). In the matched case control analysis, KTR with CAC-score &amp;gt;75% had lower plasma magnesium, albuminuria, and phase angle, and were less likely a recipient from a living donor (Table 2). CONCLUSION This study identifies phase angle, reflecting body cell integrity, as an independent determinant of CAC at 12 months after kidney transplantation. Interestingly, in two subgroups with similar dialysis vintage, KTRs with a CAC score of zero were more likely to have received a kidney from a living donor, and had higher plasma magnesium levels, compared with KTRs with relatively high CAC scores. Futures studies should address whether improving magnesium status could retard calcification progression after kidney transplantation.

Abstract 140: Plasma Interleukin-6 Levels And Cardiovascular Events In The Cirt Trial: Consistent Associations For Incident Coronary, Cerebrovascular, And Peripheral Artery Disease

Introduction: Inflammation is causally related to atherothrombosis. Interleukin-1β (IL-1β) and interleukin-18 (IL-18) require NLRP3 inflammasome for activation and have downstream effects on interleukin-6 (IL-6), a marker previously associated with high risk of coronary artery and cerebrovascular disease (CCVD). However, data pertaining to peripheral artery disease (PAD) are sparse and could offer druggable targets in this disease. Methods: We conducted a prospective cohort study of 4248 patients with type 2 diabetes or metabolic syndrome and prior coronary artery disease who participated in the NIH-funded Cardiovascular Inflammation Reduction Trial (CIRT). Participants were followed for up to 5 years for incident CCVD and symptomatic PAD events. Randomized treatment with low-dose methotrexate (vs. placebo) had no effect on event rates or plasma levels of inflammatory biomarkers. Baseline levels of IL-1β, IL-18, and IL-6 were tested for association with incident vascular events. Kaplan-Meier curves and Cox proportional hazards models (adjusted for traditional risk factors) were estimated. Results: In multivariable adjusted analyses, hazard ratios for the lowest (referent) to highest baseline quartiles of IL-6 were 1.0, 1.5, 1.8, and 2.0 (p-trend &lt;0.001) and 1.0, 1.2, 2.5, and 2.0 (p-trend = 0.04) for incident CCVD (N=349) and PAD (N=87), respectively. Baseline IL-6 levels above vs. below the median (2.50 pg/ml) were associated with a 56% increased risk of CCVD (HR 1.56, 95% CI 1.26-1.93) and a 113% increased risk PAD (HR 2.13, 95% CI 1.36-3.32) (Figure 1). Baseline levels of IL-1β and IL-18 did not associate with incident CCVD or PAD. Conclusion: In this contemporary cohort of secondary prevention patients, elevated IL-6 was associated with both incident CCVD and PAD. These data support exploration of direct IL-6 inhibition for PAD prevention, a strategy currently being pursued to reduce risk of coronary artery and cerebrovascular disease.

Intensification of lipid-lowering therapy in very high-risk patients: potential of combination with PCSK9 inhibitors

Aim. To assess the efficacy and safety of 6-month combined lipid-lowering therapy with a PCSK9 inhibitor in patients with very high cardiovascular risk (CVR).Material and methods. This prospective, open-label, single-center exploratory research study with active treatment included 5 outpatients with very high CVR. So, 80% of patients had prior coronary artery disease, 20% peripheral arterial disease, and 60% old myocardial infarction. The key inclusion criterion was the failure to achieve the target low-density lipoprotein cholesterol (LDL-C) &lt;1,4 mmol/l with high-intensity statin monotherapy at the maximal tolerated doses or combination therapy with ezetimibe. On a regular basis, all included patients took atorvastatin 40-80 mg/day or rosuvastatin 20-40 mg/day, or pitavastatin 2-4 mg/day. In addition, 2 patients received a statin in combination with ezetimibe 10 mg/day. Patients were followed up for 6 months as follows: every 2 weeks, with a lipid profile monitoring, subcutaneous injections of alirocumab at a dose of 150 mg/ml were performed. Additionally, clinical and laboratory indicators of the safety of therapy were evaluated.Results. After 6 months, with the combined lipid-lowering therapy with alirocumab, a decrease in median LDL-C from 4,3 (4,11-4,67) to 1,27 (1,06-1,47) (p=0,001) mmol/l, total cholesterol from 6,1 (6-7) to 3,7 (3,5-3,9) (p=0,018) mmol/l, atherogenic index from 3,2 (3-3,26) to 0,8% (0,8-1,5) (p=0,001). There was no significant decrease in median triglycerides and an increase in median high-density lipoprotein cholesterol. Six-month lipid-lowering therapy with a PCSK9 inhibitor had no adverse events and made it possible to achieve a maximum decrease in LDL-C by an average of 75,4% already by 4 months of treatment in actual clinical practice.Conclusion. Six-month combined lipid-lowering therapy with alirocumab 150 mg subcutaneously every 2 weeks in very high-risk patients allows the majority of patients to achieve target LDL-C values.

Glycemic status, non-traditional risk and left ventricular structure and function in the Jackson Heart Study

BackgroundLeft ventricular structure and function abnormalities may be an early marker of cardiomyopathy among African Americans with diabetes (DM) even in the absence of coronary artery disease (CAD), arrhythmia, valvular heart disease and end-stage renal disease (ESRD). This study examined the association of prediabetes (PDM), DM and HbA1c with left ventricular structure and function among Jackson Heart Study (JHS) participants without traditional risk factors.MethodsRetrospective cross-sectional analyses of the association of PDM, DM and HbA1c with, left ventricular ejection fraction (LV EF), fractional shortening (LV FS), stroke volume index (SVI), cardiac index (CI), left ventricular end diastolic volume index (LVEDVI), left ventricular end systolic volume index (LVESVI), relative wall thickness (RWT), myocardial contraction fraction (MCF) and left ventricular mass index (LVMI). The study was conducted in 2234 adult JHS participants without preexisting CAD, arrhythmia, valvular heart disease or ESRD. Statistical analyses included descriptive, univariate and covariate adjusted linear regression analyses. Sensitivity analyses to explore the impact of hypertension on study outcomes were also carried out.ResultsDM compared with no DM was associated with lower, SVI (− 0.96 ml/m2, p = 0.029), LVEDVI (− 1.44 ml/m2p = 0.015), and MCF (− 1.90% p = 0.007) but higher CI (0.14 L/min/m2, p < 0.001), RWT (0.01 cm, p = 0.002) and LVMI (2.29 g/m2, p = 0.009). After further control for DM duration, only CI remaining significantly higher for DM compared with no DM participants (0.12 L/min/m2, p = 0.009). PDM compared with no PDM was associated with lower, SVI (− 0.87 ml/m2, P = 0.024), LVEDVI (− 1.15 ml/m2p = 0.003) and LVESVI (− 0.62 ml/m2p = 0.025). HbA1c ≥ 8.0% compared with HbA1c < 5.7% was associated with lower SVI (− 2.09 ml/m2, p = 0.004), LVEDVI (− 2.11 ml/m2p = 0.032) and MCF (− 2.94% p = 0.011) but higher CI (0.11 L/min/m2, p = 0.043) and RWT (0.01 cm, p = 0.035).ConclusionsGlycemic status is associated with important left ventricular structure and function changes among African Americans without prior CAD, arrhythmia, valvular heart disease and ESRD. Longitudinal studies may further elucidate these relationships.

Major adverse cardiac event rates in moderate-risk patients: Does prior coronary disease matter?

BackgroundDespite negative troponins and nonischemic electrocardiograms (ECGs), patients at moderate risk for acute coronary syndrome (ACS) are frequently admitted. The objective of this study was to describe the major adverse cardiac event (MACE) rate in moderate‐risk patients and how it differs based on history of coronary artery disease (CAD).MethodsA secondary analysis of the HEART Pathway implementation study was conducted. This prospective interrupted time‐series study accrued adults with possible ACS from three sites (November 2013–January 2016). This analysis excluded low‐risk patients determined by emergency providers' HEART Pathway assessments. Non–low‐risk patients were further classified as high risk, based on elevated troponin measures or ischemic ECG findings or as moderate risk, based on HEAR score ≥ 4, negative troponin measures, and a nonischemic ECG. Moderate‐risk patients were then stratified by the presence or absence of prior CAD (MI, revascularization, or ≥70% coronary stenosis). MACE (death, myocardial infarction, or revascularization) at 30 days was determined from health records, insurance claims, and death index data. MACE rates were compared among groups using a chi‐square test and likelihood ratios (LRs) were calculated.ResultsAmong 4,550 patients with HEART Pathway assessments, 24.8% (1,130/4,550) were high risk and 37.7% (1715/4550) were moderate risk. MACE at 30 days occurred in 3.1% (53/1,715; 95% confidence interval [CI] = 2.3% to 4.0%) of moderate‐risk patients. Among moderate‐risk patients, MACE occurred in 7.1% (36/508, 95% CI = 5.1% to 9.8%) of patients with known CAD versus 1.4% (17/1,207, 95% CI = 0.9% to 2.3%) in patients without known prior CAD (p < 0.0001). The negative LR for 30‐day MACE among moderate‐risk patients without prior CAD was 0.08 (95% CI = 0.05 to 0.12).ConclusionMACE rates at 30 days were low among moderate‐risk patients but were significantly higher among those with prior CAD.

Effects of multimorbidity on incident COVID-19 events and its interplay with COVID-19 event status on subsequent incident myocardial infarction (MI).

BackgroundWith the spread of COVID‐19 pandemic, there have been reports on its impact on incident myocardial infarction (MI) emanating from studies with small to modest sample sizes. We therefore examined the incidence of MI in a very large population health cohort with COVID‐19 using a methodology which integrates the dynamicity of prior comorbid history. We used two approaches, i.e. main effect modelling and a machine learning (ML) methodology, accounting for the complex dynamic relationships among comorbidity and other variables.MethodsWe studied a very large prospective 18–90‐year US population, including 4,289,481 patients from medical databases in a 12‐month investigation of those with/without newly incident COVID‐19 cases together with a 2‐year comorbid profile in the baseline period. Incident MI outcomes were examined in relationship to diverse multimorbid conditions, COVID‐19 status and demographic variables—with ML accounting for the dynamic nature of changing multimorbidity risk factors.ResultsMultimorbidity, defined as a composite of cardiometabolic/noncardiometabolic comorbid profile, significantly contributed to the onset of confirmed COVID‐19 cases. Furthermore, a main effect model (C‐index value 0.932; 95%CI 0.930–0.934) had medium to large effect sizes with incident MI outcomes in a COVID‐19 cohort for the classic multimorbid conditions in medical history profile which includes prior coronary artery disease (OR 4.61 95%CI 4.49–4.73); hypertension (OR 3.55 95%CI 3.55–3.83); congestive heart failure (2.31 95%CI 2.24–2.37); valvular disease (1.43 95%CI 1.39–1.47); stroke (1.30 95%CI 1.26–1.34); and diabetes (1.26 95%CI 1.23–1.34). COVID‐19 status (1.86 95%CI 1.79–1.93) contributed an independent large size risk effect for incident MI. The ML algorithm demonstrated better discriminatory validity than the main effect model (training: C‐index 0.949, 95%CI 0.948–0.95; validation: C‐index 0.949, 95%CI 0.948–0.95). Calibration of the ML‐based formulation was satisfactory and better than the main effect model. Decision curve analysis demonstrated that the ML clinical utility was better than the ‘treat all’ strategy and the main effect model. The ML logistic regression model was better than the neural network algorithm.ConclusionThe very large investigation conducted herein confirmed the importance of cardiometabolic and noncardiometabolic multimorbidity in increasing vulnerabilities to a higher risk of COVID‐19 infections. Furthermore, the presence of COVID‐19 infections increased incident MI complications both in terms of independent effects and interactions with the multimorbid profile and age.

Endotoxemia and cardiometabolic biomarkers in patients with acute myocardial infarction. Data from the RICO survey

The complex interplay between endotoxemia, inflammation and cardiometabolic diseases including acute myocardial infarction (MI) is poorly understood. From the RICO survey, patients admitted for acute MI were prospectively included (2016 to 2018). Patients with prior coronary artery disease (CAD) or chronic kidney disease were excluded. Blood samples were taken on admission. Endotoxemia was assessed by the LCM-SMS measurement of circulating levels of LPS-derived 3-hydroxymyristate (3HM), a component of the lipid A moiety. Among the 245 patients included, mean age was 62 ± 13 y, most were male (72%), almost half were hypertensive (43%), or current smokers (44%), 38% had hypercholesterolemia, or family history of CAD (31%), median(IQR) BMI was 27(25-29) kg/m 2 and 14% had diabetes. Median LDL-cholesterol was at 132 mg/dL, HDL-cholesterol at 47 mg/dL, total cholesterol at 209 mg/dL and triglycerides (TG) at 116 mg/dL, 3HM levels at 106(83-131) pmol/L. TG levels were the most strongly correlated with LPS levels ( r = 0.201, P = 0.002), beyond HbA 1c ( r = 0.197, P = 0.002), BMI ( r = 0.192, P = 0.003), cholesterol ( r = 0.191, P = 0.003), blood glucose ( r = 0.174, P = 0.006) and age ( r = 0.173, P = 0.007). Inflammatory biomarkers and cytokines (CRP, IL6, IL8, TNFα) did not significantly relate to 3HM levels. When compared with patients without diabetes, patients with diabetes had ≈40% higher levels of 3HM (140 vs. 103 pmol/L, P < 0.001). TG (ß(95%CI) = 0.288(7.757-20.357)) remained an independent determinant of 3HM levels, beyond age (ß(95%CI) = 0.184(0.274-1.374)), and HbA 1c (ß(95%CI) = 0.157(1.764-15.390)). In patients with acute MI, endotoxemia levels related mainly to chronic metabolic disorders including diabetes and hypercholesterolemia. The underlying mechanisms for the LPS-associated TG elevations and its clinical significance at the acute phase of MI remains to be explored.

Prognostic value of myocardial perfusion imaging with D-SPECT camera in patients with ischemia and no obstructive coronary artery disease (INOCA)

BackgroundMyocardial perfusion imaging (MPI) with a novel D-SPECT camera maintains excellent prognostic value compared to conventional SPECT. However, information about the relationship between D-SPECT MPI and the prognosis in patients with ischemia and no obstructive coronary artery disease (INOCA) is limited. The objective of this study was to evaluate the prognostic value of MPI with D-SPECT in INOCA and obstructive coronary artery disease (CAD) patients. MethodsAll consecutive patients with suspected CAD and without prior CAD who underwent D-SPECT MPI and invasive coronary angiography within 3 months were considered. INOCA and obstructive CAD were defined as < 50% and ≥ 50% coronary stenosis, respectively. Patients were followed-up for the occurrence of major adverse cardiac events (MACE: cardiovascular death, nonfatal myocardial infarction, revascularization, stroke, heart failure and angina-related rehospitalization). ResultsAmong 506 patients, 232 (45.8%) were INOCA patients. A total of 33.2% of the INOCA patients had abnormal D-SPECT MPI, whereas 77.7% of the obstructive CAD patients had abnormal D-SPECT MPI. In both groups, patients with abnormal D-SPECT MPI demonstrated higher MACE rates and lower survival free of MACE. In addition, patients with INOCA and abnormal D-SPECT MPI had a poor prognosis similar to that of the obstructive CAD patients. Cox regression analysis showed that the risk-adjusted hazard ratios for abnormal D-SPECT MPI were 2.55 [1.11-5.87] and 2.06 [1.03-4.10] in the INOCA and obstructive CAD patients, respectively. ConclusionsD-SPECT MPI provides excellent prognostic information, with a more severe prognosis in patients with abnormal D-SPECT MPI. INOCA patients with abnormal D-SPECT MPI experience a poor prognosis similar to that of patients with obstructive CAD.

Abstract 12457: Atrial Fibrillation is a Cardiovascular Risk Factor for Worse Prognosis in COVID-19

Background: In the presence of comorbid conditions, COVID-19 infections are known to require more advanced treatment, poorer outcomes and have longer-term sequelae. New-onset atrial fibrillation (AF) during COVID-19 infection has been associated with worse cardiovascular outcomes but not mortality. However, it remains unclear whether a prior history (hx) of atrial fibrillation is a cardiovascular risk factor predicting a worse outcome in COVID-19 patients. As such, we examined, using propensity matching accounting for possible confounders, the need for advanced treatment and subsequent major cardiovascular events (MACE) in patients with a prior hx of AF with COVID-19 infection. Methods: From March 2020 to May 2021, patients testing positive for SARS-CoV-2 with a prior AF diagnosis (n=3119) were propensity matched for age, gender, race/ethnicity, prior coronary artery disease (CAD), prior heart failure (HF), prior stroke and hypertension to non-AF SARS-CoV-2 positive patients. Cox hazard regression analysis with multivariable adjustment was used to determine risk of subsequent MACE (all-cause death, myocardial infarction, HF and stroke). Results: Baseline characteristics, treatments, and outcomes stratified by AF status are shown in the Table. While the groups had similar baseline characteristics, AF COVID-19 patients were more likely to require hospitalization, ICU care, and ventilator support. Consistent with our hypothesis, composite MACE event rates were higher in the AF patients (HR=1.60, p&lt;0.0001) secondary to increases in heart failure and all-cause mortality rates. Conclusions: These data support AF as a cardiovascular risk factor predicting worse outcomes in COVID-19 patients. Specifically, AF increases the need for advanced treatments such as hospitalization, ICU care and ventilator support resulting in an increase in subsequent heart failure and all-cause mortality.

Impact of Medication Adherence and Glycemic Control on the Risk of Micro- and Macrovascular Diseases in Patients with Diabetes

PurposeOur purpose in the research was to clarify the impact of medication adherence to oral hypoglycemic agents during a 1-year period and subsequent glycemic control on the risk of micro- and macrovascular diseases. MethodsExamined was a nationwide claims database on 13,256 individuals with diabetic eye disease without requiring prior treatment, 7,862 without prior initiation of dialysis, 15,556 without prior coronary artery disease, 16,243 without prior cerebrovascular disease, and 19,386 without prior heart failure from 2008 to 2016 in Japan. Medication adherence was evaluated by the proportion of days covered. Patients were considered to have poor adherence if the proportion of days covered was <80%. Multivariate Cox regression model identified risks of micro- and macrovascular diseases. ResultsIn each group, mean age was 53 to 54 years, HbA1c was 7.1% to 7.2%, and median follow-up period was 4.6 to 5.1 years, and the percentage of poor adherence was approximately 30%. During the study period, 532 treatment-requiring diabetic eye disease, 75 dialysis, 389 coronary artery disease, 316 cerebrovascular disease, and 144 heart failure events occurred. Multivariate Cox regression model revealed that the hazard ratio (95% confidence interval) of dialysis in the poor adherence group was 2.04 (1.27-3.30) compared with the good adherence group. The hazard ratios in the poor adherence/poor glycemic control group were 3.34 (2.63-4.24) for treatment-requiring diabetic eye disease, 4.23 (2.17-8.26) for dialysis, 1.69 (1.23-2.31) for coronary artery disease, and 2.08 (1.25-3.48) for heart failure compared with the good adherence/good glycemic control group. ConclusionsPoor medication adherence was an independent risk factor for the initiation of dialysis, suggesting that clinicians must pay close attention to these patients.

Abstract 13539: CT-Derived Fractional Flow Reserve in Patients With Non-ST Elevation Myocardial Infarction

Introduction: In patients with non-ST Elevation Myocardial Infarction (NSTEMI), coronary CTA has high diagnostic accuracy to diagnose obstructive coronary artery disease (CAD). The value of CT-derived fractional flow reserve (FFRCT) in NSTEMI patients is unclear. Hypothesis: In acute chest pain (ACP) patients diagnosed with an NSTEMI, FFRCT is feasible, safe and adjudicates the need for immediate revascularization. Methods: In ACP patients with NSTEMI and no prior coronary artery disease, those undergoing coronary CTA with FFRCT were compared to those having CTA alone for the composite major adverse cardiac event (MACE) endpoint of death, nonfatal myocardial infarction, unplanned percutaneous (PCI) or surgical (CABG) revascularization over 2 years. NSTEMI was defined as peak troponin I levels ≥ 0.04 ng/mL. FFRCT ≤ 0.80 was considered positive for hemodynamically significant stenosis. Results: From September 2015 to July 2018, 276 ACP patients with NSTEMI (mean age 59 years, 45% female) underwent CTA of which 35 (13%) had FFRCT (14 negative, 21 positive). Of the total, 126 (45.6%) had normal coronaries and 11 (4.0%) were uninterpretable. FFRCT patients were older (p&lt;0.001) with no difference in diabetes (14.3% vs. 14.1%, p=1.0), hypertension (57.1% vs. 49.4%, p=0.391), hyperlipidemia (34.3% vs. 28.2%, p=0.460) and mean troponin I levels (0.49 ± 0.9 ng/mL vs. 1.10 ± 4.58 ng/mL, p = 0.061). All FFRCT patients had &gt;25% stenosis on CTA (100% vs. 42%, p&lt;0.001). Among patients with comparable stenosis on CTA, FFRCT and CTA had equivalent MACE (5.7% vs. 18.5%, p=0.137), with no difference between FFRCT negative and positive patients (Table 1). Conclusions: In this small study, FFRCT did not add incremental value to CTA in patients with NSTEMI across similar stenosis categories with respect to MACE. Larger prospective studies are needed to examine FFRCT in NSTEMI.

Abstract 10363: Mitochondrial DNA Copy Number is Associated with Severe Coronary Artery Disease and Risk of Subsequent Long-Term Major Adverse Cardiovascular Events

Introduction: Mitochondrial DNA copy number (mtDNA-CN) is associated with cardiovascular disease (CVD) and mortality. Here we examine, in a high-risk CVD population, the association with prevalent coronary artery disease (CAD) and subsequent major adverse events (MACE) at 1-,5- and 10-year follow-up of mtDNA-CN. Methods: Consecutive subjects (n=2267) consenting to a blood sample drawn for the Intermountain INSPIRE biorepository at the time of a coronary angiogram from July 1994 to Sept 2003 were included. The mtDNA-CN was determined by multiplexed real-time polymerase chain reaction coamplifying a stable site of mt D- Loop and a region of a single copy genomic β-2-microglobulin gene(β2M). MtDNA-CN is given as the ratio of Mt to β2M DNA. The presence of severe CAD (&gt;70% stenosis) was analyzed using multivariate logistic regression. The subsequent MACE (including all-cause mortality and non-fatal MI) outcomes were studied using multivariate Cox proportional hazard regression. Results: The average age of subjects was 62.3 ± 13.8, 35% were female, and 50% had prior CAD. Over half (55%) had severe CAD at the angiogram. As the mtDNA-CN increased, severe CAD decreased (58% for 1 st quartile vs. 51% for 4 th quartile). After adjustment for baseline differences, subjects with mtDNA-CN in the 1 st quartile were 1.31 times more likely to have severe CAD than subjects with mtDNA-CN in the 4 th quartile (95% CI: 1.01, 1.71; p=0.04). A total of 902(39.8%) had a subsequent MACE event within 10-years (193[8.5%] in 1-year and 548[24.2%] in 5-years). There was no association between mtDNA-CN and 1-year MACE. However, mtDNA-CN was associated with 5-year (p=0.006) and 10-year (p=0.003) MACE. After adjustment, subjects with mtDNA-CN in the 1 st quartile were at 1.29 increased risk of 10-year MACE than subjects with mtDNA-CN in the 4 th quartile (95% CI: 1.07, 1.56; p=0.008). Conclusions: In a coronary angiographic population, mtDNA-CN was associated with severe CAD and the risk of subsequent long-term MACE. These findings suggest that mtDNA-CN could be used as a clinical biomarker for risk. Moreover, understanding the factors impacting mtDNA-CN may also help in the prevention of secondary CVD outcomes.

Abstract 1122‐000237: Prior Vascular Risk Factors Affecting Presentation Time and Utilization of Acute Ischemic Stroke Therapies

Introduction : Multiple factors have been reported to influence the time between onset of symptoms in acute ischemic stroke and hospital presentation. Although education level is one independent factor in presentation, as we previously reported, health literacy has not been fully assessed regarding specific patient knowledge on stroke or its known risk factors. This study aims to determine whether having a history of vascular risk factors such as prior stroke, coronary artery disease (CAD), or atrial fibrillation (AF) influence presentation time and acute ischemic stroke therapy utilization. Methods : This study included 250 acute ischemic stroke patients presenting to a large academic community hospital from February to December 2018. Educational level was defined within four categories: Grade School, High School, College or Higher, and Unknown. Last seen normal, symptom onset, and arrival times were acquired. Vascular risk factors chosen for this study included prior stroke, CAD, and AF. History of vascular risk factors was verified by medical documentation showing prior diagnosis by physician. Initial NIH Stroke Scale score, stroke location, vessel involved, LDL, hemoglobin A1c, gender, and race were also obtained. Patients were categorized based on their level of education, the presence or absence of vascular risk factors, and utilization of tPA or thrombectomy (MT). The primary outcomes were onset‐to‐arrival time (OTA), in minutes, and utilization rates of acute ischemic stroke therapies (either tPA, MT, or both). Subgroup analysis was conducted to associate education level with each vascular risk factor, comparing OTA and acute ischemic stroke therapy utilization rate. Results : As previously reported, educational level was inversely associated with OTA and positively associated with utilization of at least one acute ischemic stroke therapy. Prior stroke, CAD, and AF showed a substantial OTA decrease for all education groups except for College. Prior stroke decreased OTA in Grade School by 24% (764 vs. 579); High School by 30% (222 vs. 154) and College by 20% (52 vs. 41). CAD decreased OTA in Grade School by 65% (734 vs. 253), High School by 14% (209 vs. 180), and College by 3% (50 vs 49). AF decreased OTA in Grade School by 88% (764 vs. 91) and High School by 56% (216 vs. 95), but increased in College by 35% (47 vs. 64). History of prior stroke decreased utilization of both tPA and MT by 14%; CAD increased tPA use by 8% and MT by 5%; while AF increased tPA use by 9% and MT by 12%. Conclusions : Having at least one prior vascular risk factor (prior stroke, CAD, AF), diagnosed by a physician, was associated with lower OTA in Grade School and High School educated patients. A history of prior stroke was associated with lower acute stroke therapy utilization (tpa and MT), while both CAD and AF were associated with increased acute stroke therapy utilization.

Global Myocardial Work Combined with Treadmill Exercise Stress to Detect Significant Coronary Artery Disease

Myocardial work (MW) derived from the left ventricular pressure-strain loop is a novel and noninvasive method for assessing left ventricular function that accounts for loading conditions. We aimed to explore whether global MW combined with treadmill exercise stress could detect significant coronary artery disease (CAD) in patients with angina pectoris. Eighty-five patients with angina pectoris and no prior CAD history were included. All patients underwent treadmill exercise stress echocardiography and coronary angiography. Global MW was constructed from speckle-tracking echocardiography indexed to the brachial systolic blood pressure. The association between MW parameters and the presence of significant CAD was assessed with logistic regression. The discriminative power of MW parameters to detect CAD was assessed with receiver operative characteristic curve, net reclassification improvement, and integrated discrimination improvement analysis. Twenty-five patients had a positive exercise echocardiogram, while significant coronary artery stenosis (≥70% in one or more major epicardial vessels or ≥50% in the left main coronary artery) was observed in 41 patients. The global wasted work (GWW) and global work efficiency (GWE) were significantly higher or lower, respectively, in patients with significant CAD compared with those of nonsignificant CAD at the peak exercise and during recovery periods (P<.05 for all). Multivariate logistic regression analysis demonstrated that peak GWE and recovery GWW could predict significant CAD. Peak GWE had the highest area under the receiver operating characteristic curve (AUC) among all global MW parameters (AUC=0.836). Furthermore, a model comprising peak GWE and recovery GWW performed better for the identification of significant CAD than peak GWE alone (AUC=0.856). Peak GWE could detect significant CAD. The new model, incorporating peak GWE and recovery GWW, not only identified but also provided additional value for estimating the probability of significant CAD. Global MW parameters combined with exercise stress perform as an accurate noninvasive screening before the invasive diagnostic technique.

Endotoxemia and cardiometabolic biomarkers in patients with acute myocardial infarction. Data from the RICO survey

Abstract Background The complex interplay between endotoxemia, inflammation and cardiometabolic diseases including acute myocardial infarction is poorly understood. Aim Our prospective study aimed to address the determinants of endotoxemia, including blood lipids and metabolic biomarkers, in patients admitted for an acute MI. Methods From the RICO survey, patients admitted to the coronary care unit of our University Hospital for type 1 acute MI were prospectively included between 2016 and 2018. Patients with prior coronary artery disease (CAD) or chronic kidney disease were excluded. Blood samples for biomarkers measurement were taken on admission. Endotoxemia was assessed by the LCMSMS measurement of circulating levels of LPS-derived 3-hydroxymyristate (3HM), a component of the lipid A moiety. Results Among the 245 patients included, mean age was 62±13 y, most were male (72%), almost half were hypertensive (43%), or current smokers (44%), 38% had hypercholesterolemia, or family history of CAD (31%), median (IQR) BMI was 27 (25–29) kg/m2 and 14% had diabetes. Median LDL-cholesterol was at 132 mg/dL, HDL-cholesterol at 47 mg/dL, total cholesterol at 209 mg/dL and triglycerides (TG) at 116 mg/dL. Median (IQR) 3HM levels were at 106 (83–131) pmol/L. Among biomarkers, TG levels were the most strongly correlated with LPS levels (r=0.201, p=0.002), beyond HbA1c (r=0.197, p=0.002), BMI (r=0.192, p=0.003), cholesterol (r=0.191, p=0.003), blood glucose (r=0.174, p=0.006) and age (r=0.173, p=0.007). Inflammatory biomarkers and cytokines (CRP, IL6, IL8, TNF α) did not significantly relate to 3HM levels. When compared with patients without diabetes, patients with diabetes had ≈40% higher levels of 3HM (140 vs 103 pmol/L, p&amp;lt;0.001). By multivariate regression linear analysis, TG (β(95% CI)=0.288 (7.757–20.357), p&amp;lt;0.001) remained an independent determinant of 3HM levels, beyond age (β(95% CI)=0.184 (0.274–1.374), p=0.003), and HbA1c (β(95% CI)=0.157 (1.764–15.390), p=0.014). Conclusions In a former analysis of our prospective study in patients with acute MI, endotoxemia levels related mainly to chronic metabolic disorders including diabetes and hypercholesterolemia. The underlying mechanisms for the LPS-associated TG elevations and its clinical significance at the acute phase of MI remains to be explored. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): CHU Dijon Bourgogne ARS Bourgogne Franche comté

Clinical epidemiology and costs of type 2 diabetic patients with or without prior coronary artery disease or stroke. A longitudinal 5-year claims-data analysis of over 7 million inhabitants

Abstract Aims Contemporary, real-world data on type 2 diabetes mellitus (T2DM) are limited. We analysed prevalence, comorbidities, outcomes and costs of T2DM patients with and without coronary artery disease (CAD) or stroke in &amp;gt;7 million inhabitants. Methods T2DM patients were identified in 2015 (accrual period) from the Ricerca e Salute (ReS) database linking administrative records to demographics. From 2013–2015 information, four cohorts were considered: #1 with CAD and/or stroke; #2 without CAD and/or stroke; #3 with chronic CAD but no myocardial infarction or stroke; #4 with chronic CAD undergoing percutaneous coronary interventions (PCI). Hospitalizations, drugs and other outpatient care were assessed from 2015 to 2017. Results Prevalence of T2DM was 6% (441,085/7,365,954). CAD and/or stroke in the previous 3 years affected 7.5% of T2DM patients (33,153); this cohort was generally older, of male sex, with more comorbidities, prescriptions, and hospital admissions (50% versus 13.4%) compared to cohort #2. Yearly costs were &amp;gt;3-fold for cohort #1 versus #2, main drivers being hospitalizations in the former and drugs in the latter. Unexpectedly, two-year cardiovascular events were significantly higher in cohort #4 compared to any other (Figure). Guideline-recommended therapies were suboptimal in all cohorts. Conclusions The present analysis points to three areas of potential improvement in T2DM management: 1) undertreatment of T2DM patients with recommended drugs; 2) three-fold recurrences and costs in T2DM patients with, compared to those without, prior cardiovascular events; 3) highest risk of events in those with chronic CAD and PCI, warranting specific studies aimed at defining more effective preventive strategies. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): This research was partially supported by an unrestricted grant from Astra Zeneca. Astra Zeneca was not involved in data collection, analysis and interpretation, in writing the report, nor in deciding to submit the article for publication.

Artificial intelligence approach improves ischaemia prediction beyond the known pretest probability scores

Abstract Background Pre-test probability (PTP) assessment is crucial in the assessment of patients with suspected ischaemia/coronary artery disease. Presently there is no established role for artificial intelligence in estimating PTP. Purpose Comparison of a recently developed memetic pattern based algorithm (MPA) with the diagnostic power of established scores in predicting ischaemia on positron emission tomography myocardial perfusion imaging (PET MPI). Methods Consecutive patients undergoing Rubidium PET MPI for routine clinical evaluation of ischaemia were included. The PTP for each patient was estimated by MPA, the Diamond and Forrester scores (DFS), the PTP models from the European Society of Cardiology Guidelines from 2013 (ESC 2013) and 2019 (ESC 2019) and the Framingham scores (FRS). The PET MPI studies were assessed for the presence of ischaemia. Ischaemia was defined as a summed difference score (SDS) ≥2. Results The mean age of the 531 patients was 66±11 years, 34% were female, and 50% had known prior coronary artery disease; 208 patients had evidence of ischaemia. No ischaemia was found in 323 patients. The areas under the curve (AUC) are shown in the figure. The artificial intelligence based MPA provided an AUC of 0.76, PTP (ESC 2013) AUC of 0.67, PTP (ESC 2019) AUC 0.67, DFS AUC 0.56, FRS 0.68. Conclusion The MPA outperforms the established scores for PTP assessment of the ESC, DFS and FRS in prediction of ischaemia on PET MPI. It has the potential to improve the accuracy of the established diagnostic algorithm for CAD and ischaemia. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The study was in part funded by the Swiss Heart Foundation.

Left ventricular outflow morphology as a predictor of arrhythmic disturbances after TAVI

Abstract Introduction Left bundle branch block (LBBB) and permanent pacemaker (PM) are frequent complications after transcatheter aortic valve implantation (TAVI), but few predictors have been reported. Purpose This study sought to determine the relationship between left ventricular outflow tract (LVOT) morphology and the development of conduction disturbances after TAVI. Methods From 1/2020 to 12/2020 consecutive patients who underwent TAVI and an analyzable CT scan in our center were selected. Patients were categorized according to the LVOT morphology into three groups. The delta value between mean aortic root diameter (AA-d) and mean LVOT-d were calculated, and divided into terciles. In patients in the third tercile the AA-d was greater than LVOT-d and was defined as tapered-LVOT (group 1). First and second terciles had tubular or flared-LVOT shape and were defined as group 2. We compared conductance disorders after TAVI with and without tapered-LVOT. Primary endpoint was the combined of new-onset of transient/persistent LBBB, and PM. Factors with p&amp;lt;0.05 on the univariate analysis were entered into the multivariate analysis. Results Among 98 eligible patients thirty-two patients (33%) presented a tapered-LVOT (Group 1) and 66 (67%) had tubular or flared-LVOT morphology (group 2). The mean age was 80.5±5.5 years and 60% were female. Baseline characteristics were similar between groups except for the incidence of dyslipidemia that was higher in group 2. The primary study endpoint was significantly higher in group 1 (78% vs. 59%: p=0.036). After adjusting for confounding factors, this relationship remained statistically significant (OR: 2.81 (CI95%: 1–7.96), p 0.046). Independent predictors of conduction disturbance were: tapered-LVOT, prior coronary artery disease and prior surgical valve replacement. Conclusions After TAVI, patients presenting a tapered-LVOT morphology have a 2.8-fold greater risk to develop LBBB or require permanent PM when compared to another LVOT shapes. Funding Acknowledgement Type of funding sources: None.