History Of Coronary Artery Disease Research Articles

Pulse wave velocity has an additive prognostic value to SCORE2 in apparently healthy subjects at 6 years of follow up

Abstract Backround/Aim: Arterial stiffness is involved in the clinical course of atherogenesis. The purpose of this study was to investigate whether altered arterial wall properties of confers predictively and additively to estimation of cardiovascular risk. Methods Pulse wave velocity carotid-femoral (PWVc-f), the gold standard method to assess arterial stiffness, was measured non-invasively by Complior device. Increased PWV(c-f), especially above 10 m/s, indicates increased arterial stiffness. We measured baseline PWV(c-f) in 747 apparently healthy subjects (51.99±13.41 years old, 43.8% males), without established cardiovascular disease and calculated SCORE2 in each subject according to ESC guidelines.We prospectively monitored the occurrence of major cardiovascular events (MACEs-death, myocardial infarction, stroke) during a 6-year follow-up period using electronic records and clinic visits. Results Fifty-seven MACEs were documented during follow-up. In univariate analysis, subjects with increased PWV were found to exert greater risk for MACEs (hazard ratio (HR):1.12, 95%CI: 1.09-1.15, p<0.001). PWV remained a significant predictor for MACEs in a model including sex, age, hyperlipidemia, diabetes, hypertension, current smoking, family history of coronary artery disease and treatment with ACEi/ARBs or lipid lowering agents after using backward elimination (HR:1.13; 95% CI: 1.08-1.18, p<0.001). PWV was an independent and additive predictor of outcome when added in a model including solely SCORE2 (HR:1.10; 95% CI: 1.07-1.14,p<0.001; Chi-square change:20.08, p<0.001; C-statistic increase from 0.592 to 0.685) and also in a model encompassing risk factors not included in SCORE2, namely diabetes (HR:1.07; 95% CI: 1.04-1.11,p<0.001; Chi-square change: 43.12, p<0.001; C-statistic increase from 0.613 to 0.698). The HR of PWV for the prediction of MACE remained similar in subjects younger or older than the age of 50 years (p>0.05). Conclusion Arterial stiffness is an independent and additive predictor to conventional risk factors and SCORE2 for adverse outcome at 6 years follow-up.

Influence of Lp(a) and systemic inflammation on all-cause mortality in a primary prevention population: data from our clinic database

Abstract Background Epidemiological, pathophysiological, and genetic studies have established Lp(a) as a causal risk factor for development of cardiovascular (CVD) and valvular heart disease. However, there is controversy about how inflammation can modulate Lp(a) risk and major adverse cardiovascular events. We aim to investigate the influence of elevated Lp(a) and systemic inflammation on all-cause mortality in a primary prevention setting. Method We analyzed data obtained from the Preventive Cardiology Information System (PreCis), a database of clinical and laboratory information on 8,136 primary prevention patients seen at our clinic preventive cardiology clinic between 1st Jan 1999-12th Dec 2018. Primary prevention was defined as having no history of coronary artery disease (CAD), coronary and peripheral arterial revascularization, nor atherosclerosis. Lp(a) ≥50 mg/dL was considered as clinically elevated. The association between Lp(a) and the demographic and clinical variables of interest was examined using the student’s t-test or Chi-squared test. All-cause mortality was assessed using Kaplan-Meier estimates, and adjusted Cox proportional hazards models. All statistical analyses were conducted using SAS version 9.4. Result In the overall primary prevention population (n=8,136), the median age was 54 years, with 56.9% women and 84.8% being Caucasian. In this cohort, 21% had hypertension, and 5.5% had diabetes. The median Lp(a) was 21 mg/dL (interquartile interval 7-57 mg/dL). Lp(a) was ≥50 mg/dL in 29% of the population. Of those with elevated Lp(a) (n=2,368), 1,751 (73.9%) patients had hsCRP drawn. In this group, 782 patients (44.7%) had hsCRP <2 mg/L and 969 (55.3%) had hsCRP ≥2 mg/L. The all-cause mortality rate in individuals with elevated Lp(a) and hsCRP ≥2mg/L was 9.2% compared to 4.2% in those with elevated Lp(a) and hsCRP <2mg/L. In a multivariable Cox proportional hazard regression model adjusted for age and gender, in patients with elevated Lp(a), hsCRP ≥2 mg/L was significantly associated with all-cause mortality (HR 2.35, 95% CI (1.57-3.53), p>0.001) (Figure 1). Conclusion In a primary prevention population without established atherosclerosis, elevated Lp(a), increased systemic inflammation was associated with increased all-cause mortality. This finding supports the need for risk classification and targeted primary prevention management of higher risk patients with elevated Lp(a).

Prognostic impact of cardiovascular polypharmacy on octogenarians with heart failure with preserved ejection fraction

Abstract Backgrounds Drug treatments of heart failure with preserved ejection fraction (HFpEF) have a little clinical benefit, but cardiovascular polypharmacy (CP) trend is observed in elderly HFpEF. We investigated the impact of CP on octogenarian with HFpEF. Methods We examined 783 consecutive octogenarians (≥80 years) enrolled in the PURSUIT-HFpEF registry. We defined medications for hypertension, dyslipidemia, heart failure (HF), coronary artery disease, stroke, peripheral artery disease, and atrial fibrillation as cardiovascular medications (CM). In this study, we defined CP as ≥5 CM. We investigated whether CP was correlated with the composite end point (CE) of all-cause mortality and HF rehospitalization. Results The proportion with CP was 51.9% (n=406). Background characteristics correlated with CP were frailty, history of coronary artery disease, atrial fibrillation and left atrial dimension. Multivariable Cox proportional hazards analysis showed CP was significantly and independently correlated with CE (hazard ratio (HR): 1.31; 95% confidence Interval (CI): 1.01-1.70) in addition to age, clinical frailty scale, history of HF admission and N-terminal pro brain natriuretic peptide (Table). Kaplan-Meier curve analysis showed that, compared with the non-CP group, the CP group had significantly higher risk of CE and HF (HR: 1.27; 95%CI: 1.04-1.56; P=0.02 and HR: 1.46; 95%CI: 1.13-1.88; P<0.01, respectively), but not any-cause death (Figure). In addition, diuretics were correlated with CE (HR: 1.61; 95%CI: 1.17-2.22; P<0.01), but antithrombotic drugs and HFpEF medications were not. Conclusions CP at discharge is a prognostic factor driven by HF rehospitalization in octogenarians with HFpEF. In these patients, diuretics may be correlated with the prognosis.

Characterizing risk factors for the development of cardiovascular events in CAR-T Patients

Abstract Introduction Chimeric antigen receptor (CAR) T-cell therapy, which involves ex-vivo engineering of autologous T-cells against cancer cells, has transformed the management of B and plasma cell malignancies, leading to further efforts in identifying new targets and indications. As the use of CAR T therapy expands, understanding its effects on the cardiovascular (CV) system becomes increasingly relevant. The systemic inflammatory response elicited by CAR T therapy can result in cytokine release syndrome (CRS) with manifestations including sinus tachycardia, hypotension, arrhythmias, and in severe cases, left ventricular dysfunction and cardiogenic shock. Risk factors for CAR T related CV events are not well-described. We evaluated risk factors for a primary composite endpoint of adverse CV events in a real-world cohort of patients with B and plasma cell malignancies receiving standard of care (SOC) CAR T therapy. Methods Medical records from all consecutive patients treated with SOC CAR T cell therapy at a U.S. health system from March 2018 to December 2021 were retrospectively reviewed under an IRB approved protocol. Our outcome was a single composite endpoint of clinically significant CV events including arrhythmia, acute coronary syndrome, stroke, CV death, ejection fraction decrease under 52.5%, heart failure exacerbation, and acute pericardial disease. All events resulted in an inpatient cardiology consult, upgrade to an ICU, or outpatient cardiology appointment. A multivariable Fine-Gray model was used to model CV risk and account for the competing risk of non-CV death. Results 123 patients were evaluated with a median follow-up of 16 months. 32 (26.0%) patients experienced the composite endpoint, with 1 CV death and 18 subsequent non-CV deaths, primarily from progressive disease (PD). Of the 91 patients that did not experience an adverse CV event, 35 (28.5%) died of non-CV causes, most commonly PD. In bivariate analysis, history of Coronary Artery Disease, Atrial Fibrillation (AF), Mantle Cell lymphoma, Tyrosine Kinase Inhibitor (TKI) exposure, Eastern Cooperative Oncology Group (ECOG) score ≥ 1, and CRS grade ≥ 2 were associated with the composite outcome (Table 1). A multivariable Fine-Gray regression model developed with stepwise selection showed a history of AF, ECOG score ≥ 1, Hispanic ethnicity, or CRS grade ≥ 2 were simultaneously associated with the composite outcome (Figure 1). Conclusions Risk factors associated with adverse CV events in CAR T include a history of AF, ECOG score ≥1, CRS grade ≥ 2, and Hispanic ethnicity. These findings are limited by sample size and number of events. These predictors, if validated in larger cohorts, have the potential to identify patients at high risk for CV complications who may benefit from multidisciplinary care pre- and post-CAR T infusion. Enhanced collaboration between oncologists and cardiologists to optimize CV function for this high-risk cohort may lead to improved outcomes.

Stress computed tomography perfusion versus stress cardiac magnetic resonance for the management of suspected or known coronary artery disease: resources and outcomes impact (STRATEGY II Study)

Abstract Background Non-invasive techniques have evolved as "gatekeepers" to invasive coronary angiography (ICA) for symptomatic patients with suspected or known coronary artery disease (CAD). Evaluation of myocardial ischemia with functional tests represents a milestone in CAD detection with proved diagnostic and prognostic power. Coronary computed tomography angiography (CCTA), a non-invasive anatomical assessment, intrinsically lacks physiologic data to categorize the downstream hemodynamic significance of lesions. Stress CT perfusion (stress-CTP) is a recently evolved imaging modality able to assess inducible myocardial perfusion defects. The aim of this study is to compare resources and outcomes Impact of combined CCTA+stress-CTP versus stress cardiovascular magnetic resonance (stress-CMR) in consecutive symptomatic patients with suspected CAD and intermediate to high pre-test likelihood of disease or known CAD or previous history of revascularization. Methods 624 symptomatic patients with intermediate to high risk pre-test likelihood for CAD or previous history of revascularization referred to our hospital for clinically indicated CCTA+stress-CTP or stress-CMR were enrolled. Stress-CTP scans were performed in 223 patients using 256-row whole heart-coverage scanner, static protocol acquisition and vasodilation induced by adenosine. 401 patients with clinically indicated stress-CMR were evaluated in a 1.5-T scanner after vasodilatation induced with dipyridamole. Patient follow-up was performed at 1 year after index test performance. Endpoints were as follow: 1) all cardiac events as a combined endpoint of revascularization, non-fatal MI and death; 2) hard cardiac events as combined endpoint of non-fatal MI and death. Results Stress-CMR group showed lower age, higher prevalence of male gender and higher prevalence of previous revascularization, while CCTA+CTP group showed higher prevalence of family history of CAD and statin use. CCTA was defined positive for obstructive disease in 62% of patients while the addition of CTP on top of CCTA reduced the number of positive patients to 46%. Stress-CMR resulted positive in 23% of subjects. Patients who underwent CCTA+CTP underwent more revascularization (29% versus 7%, p: 0.001) while no differences were found in terms of non-fatal MI and death between the two strategies. According to the predefined endpoints, CCTA+CTP group showed higher rate of all cardiac events (29% vs 8%, p: 0.001) and lower rate of hard cardiac events (0.4% vs 3%, p: 0.033), respectively. Stratifying the baseline characteristics by all cardiac events and hard cardiac events, left ventricle volume and index test strategy predicted all cardiac events while only index test strategy predicted hard cardiac events. Conclusions The use of CCTA+CTP strategy was associated with higher referral to revascularization but with a protective trend in terms of hard cardiac events as compared to the usual strategy with lone functional evaluation.

No difference on angiographic features between women and men in patients with acute coronary syndrome: insights from the ADDICT-ICCU study

Abstract Background Previous studies have observed poorer outcomes in women with acute coronary syndrome (ACS). Angiographic features and angioplasty techniques to explain this difference between women and men have rarely been analyzed in recent studies. Purpose To analyze by a core laboratory angiographic finding, coronary artery disease (CAD) complexity and percutaneous intervention outcomes in women and men in patients with ACS. Methods From April 7 to 22, 2021, the Addiction in Intensive Cardiac Care Unit (ADDICT-ICCU) study included prospectively 1575 patients admitted to ICCUs with a systematic urine multidrug test in 39 ICCUs across France. This prespecified study focuses on patients admitted for ACS (n=379) with an independent angiographic core laboratory evaluation. The prevalence, location, and severity of CAD (lesion≥50%), the Syntax score, the residual Syntax score and the characteristics of percutaneous coronary intervention (PCI) were compared between women and men. The primary endpoint was Major Adverse Cardiac Events (MACE) defined by death, resuscitated cardiac arrest, or cardiogenic shock. Results Among the 379 patients with ACS (mean age: 63±13 years), 23% were women (n= 86) and 77% were men (n=286). Cardiovascular risk factors and CAD history were well balanced between women and men except for active smoking with less smokers in women (59% vs 81%, p<0.001). Regarding location of CAD (stenosis ≥50%), there was no significant difference between women and men: left anterior descending artery (56% vs 57%; p=0.90), circumflex (28% vs 39%; p=0.12) and right coronary artery (50% vs 48%; p=0.81). No difference was found for baseline Syntax score (7.98 vs 9.64; p=0.13). Women and men have a similar rate of multivessels disease (44% vs 50%; p=0.46) and 3 vessels disease (16% vs 20%; p=0.57). Concerning PCI, Syntax score of the culprit lesion was significantly lower in women (4.5 vs 5.5, p=0.02). Women and men received a similar number of stents (2.3 vs 2.4; p=0.33). Stent length (28.9 vs. 30.3, p=0.43) or stent diameter (3.1 vs 3.2; p= 0.11) were not significantly different. Final TIMI 3 flow was found in 92.9% of women and 88.1% of men (p=0.23). The rate of procedural complications was low in both groups. At the end of the procedure, the residual Syntax score was similar in women and men (4.4 vs 5.4; p= 0.34). The rate of in-hospital MACE was not different between women and men (4.7% vs 4.4%; p=0.91). Conclusion In this study with an independent angiographic core laboratory analysis of ACS patients, no difference between women and men regarding CAD severity or PCI outcomes was observed. Other reasons should be considered if a difference in prognosis exists between women and men.Angiographic features in Women and menAngiographic analysis by Core Laboratory

Impact of coronary artery disease phenotype on treatment in chronic coronary syndromes: the EURECA registry

Abstract Background The EURECA registry aimed to assess the use of stress ECG and cardiac imaging in the diagnostic process of patients with chronic coronary syndrome (CCS). To which extent the coronary artery disease (CAD) phenotype, defined by the diagnostic process, may influence the management of these patients in clinical practice is not known. Purpose In the present analysis we aimed to evaluate the impact of the CAD phenotype on downstream therapeutic choices in the EURECA population. Methods Among the 5156 patients enrolled in the EURECA registry between May 2019 and March 2020, early treatment choices (within 6 months from enrolment) could be defined in 4874 patients (mean age 63.5 years, 59.7% males). They were categorized as: 1. no treatment change; 2. optimized medical treatment (OMT, i.e. new therapy or increase of previous therapy); 3. revascularization. The CAD phenotypes were defined in 3771 patients as: 1. no CAD; 2. non-obstructive CAD; 3. obstructive CAD without documented ischemia (including patients with no stress test performed); 4. obstructive CAD with documented ischemia. Results In 3049/4874 patients (63%) treatment was unchanged, in 1204 (24%) medical treatment was optimized and in 621 patients (13%) revascularization was performed. At the end of the diagnostic process, the disease phenotype was no CAD in 1409/3771 patients (37%), non-obstructive CAD in 1463 (39%), obstructive CAD without documented ischemia in 374 (10%) and obstructive CAD with documented ischemia in 525 patients (14%). In patients with non-obstructive CAD, medical treatment was optimized more frequently than in those with no CAD (34% vs 19%, P<0.001) but in 65% of these patients treatment was unchanged. In patients with obstructive CAD revascularization frequency was similar in patients without or with documented ischemia (60% vs 61%, P=NS) as well as OMT alone (21% and 18%, P=NS) (Figure 1). Revascularization or OMT alone were associated with enrolment in cardiology departments, older age, male gender, typical symptoms, higher frequency of risk factors, history of previous CAD and positive results of any non-invasive test (Figure 2). At multivariate analysis independent predictors of more intense treatment were enrolment in cardiology department (OR 1.55, 95% CI 1.30-1.83), typical angina (OR 1.96, 95% CI 1.69-2.27), hypertension (OR 1.29, 95% CI 1.11-1.49) and positivity of any non-invasive test. Conclusions In patients with CCS the diagnosis of non-obstructive CAD is associated with a suboptimal medical treatment. On the other hand, the diagnosis of anatomical obstructive CAD drives revascularization procedures, independently of documenting inducible ischemia. The intensity of treatment management depends on the overall estimation of patient risk based more on clinical variables and positivity of any diagnostic test than on specific disease phenotypes.Treatment according to CAD phenotypePredictors of revascularization or OMT

MANTA vascular closure device bleeding and vascular complications in association with cardiovascular risk factors: a large single centre experience

Abstract Background Percutaneous cardiovascular interventions such as transcatheter aortic valve replacement (TAVR), balloon aortic valvuloplasty (BAV), and mechanical circulatory support (MCS) involve large-bore arterial cannulation. Clinically significant bleeding and vascular complications are frequently encountered as a consequence of arterial cannulation. Collagen-based vascular closure devices (VCD) such as MANTA VCD are increasingly utilized to achieve arterial vascular access closure. This study aims to explore the association between cardiovascular risk factors and bleeding and vascular complications in procedures utilizing MANTA VCD. Methods A large single-centre retrospective study was performed of patients who underwent TAVR, BAV, and MCS in which arterial access closure was achieved with MANTA VCD. All cases from June 2019 to September 2020 were included. The primary efficacy outcome was defined as immediate haemostasis. The secondary safety outcome was defined as Valve Academic Research Consortium-3 (VARC-3) criteria bleeding and vascular complications. Baseline patient characteristics were obtained to evaluate the association between cardiovascular risk factors and outcomes. Results One hundred and seventy-four cases involved vascular access site closure using MANTA VCD. Immediate haemostasis of the access site was achieved in 92.5% of cases (n=161) whereas 7.5% of cases had failed immediate haemostasis (n=13). VARC-3 criteria bleeding and vascular complications occurred in 12.1% of cases (n=21). Cardiovascular risk factors including coronary artery disease and smoking history were associated with an increased risk for bleeding and vascular complications. Rate of bleeding and vascular complications among patients with coronary artery disease (CAD) (n=71) was 18.3% whereas the rate among patients without CAD (n=103) was 7.8%; this association was statistically significant with an odds ratio of 2.66 (95% CI 1.04 – 6.81, p < 0.05). Rate of bleeding and vascular complications among patients with a smoking history (n=67) was 19.4% whereas the rate among patients without a smoking history (n=107) was 7.5%; this association was statistically significant with an odds ratio of 2.98 (95% CI 1.16 – 7.63, p < 0.05). There was no statistically significant difference in the rate of bleeding and vascular complications for other cardiovascular risk factors such as, hypertension, peripheral vascular disease, atrial fibrillation, obesity, diabetes, chronic kidney disease, or chronic obstructive pulmonary disease. Conclusions MANTA VCD is a safe and effective tool for arterial access closure in procedures such as TAVR, BAV, and MCS. CAD and smoking are associated with a higher risk for VARC-3 criteria bleeding and vascular complications. Further multicentre studies are necessary to explore the association of cardiovascular risk factors with vascular access site closure complications and improve outcomes.

Phenotyping coronary plaque by computed tomography in premature coronary artery disease

Abstract Background Premature coronary artery disease (CAD) is an aggressive chronic disease with multiple recurrences mostly related to the progression or complication of new coronary lesions. Purpose To compare coronary plaque characteristics of individuals with premature CAD with those of incidental plaques found in matched individuals free of overt cardiovascular disease, using coronary computed tomography angiography (CCTA). Methods 106 individuals with premature CAD were matched by age, sex, smoking status, family history of CAD, and dyslipidemia with 106 controls free of overt cardiovascular disease. CCTA were standardly analyzed for CAD-RADS score, plaque composition (calcified, partially or non-calcified), and the following four high-risk plaque (HRP) features : spotty calcification, positive remodeling, napkin-ring sign, and low-attenuation plaque. Results At least one coronary plaque was found in 85% of individuals with premature CAD vs. 62% of matched controls. The prevalence of non-calcified plaques was higher among individuals with premature CAD (65.1% vs. 30.2%, p<0,001), as well as spotty calcification (42.5% vs. 17.9%, p<0.001), positive remodeling (41.5% vs. 9.4%, p<0.001), low-attenuation plaques (24.5% vs. 3.8%, p<0.001) and napkin-ring sign (1.9% vs. 0.0%) (Figure 1). Individuals with premature CAD exhibited an average of 2.2 (±2.7) HRP features per person, while the control group displayed 0.4 (±0.8) HRP per person (p<0.001). Within a median follow-up of 24 [16,34] months, 24 ischemic recurrent events occurred in 24 individuals, all in the in premature CAD group. Individuals with premature CAD and recurrent ischemic event had more high-risk plaque features (4.3±3.9) than those without ischemic recurrence (1.5±1.9). They displayed more frequently non-calcified plaques (91.7% vs. 57.3%) with positive remodeling (75.0% vs. 31.7%) and low-attenuation plaques (45.8% vs. 18.3%) as compared to those without ischemic recurrence (Figure 2). Conclusions Coronary atherosclerosis in individuals with premature CAD is characterized by a high and predominant burden of non-calcified plaque and unusual high prevalence of high-risk plaque features, contributing to disease progression with multiple recurrences in this setting.HRP features in study populationHRP according to ischemic recurrence

Computed tomography plaque analysis identifies residual inflammation in recent acute myocardial infarction patients

Abstract Introduction Residual inflammatory risk (RIR) following acute myocardial infarction (AMI) patients is associated with recurrent major adverse cardiovascular events. Atherosclerotic plaque quantification using computed tomographic coronary angiography (CTCA) can specifically identify inflamed plaque characteristics. We compared plaque burden and tissue composition in AMI patients with those of stable coronary artery disease (CAD) patients to identify imaging markers of RIR. Purpose We aimed to identify signs of residual inflammation in recent AMI patients via CTCA atheroma quantification. We hypothesised that recent AMI patients have plaque characteristics suggestive of inflammation. Methods 108 patients recruited from multiple sites with AMI <1 month were propensity-matched via CAD risk factors (age, gender, diabetes, hypertension, hyperlipidaemia, smoking and family history of CAD) with stable CAD patients in a 1:1 ratio. Propensity matched recent AMI and stable CAD patient cohorts had similar profiles: age (60±9.7 vs 57±10.0 years), gender (91.7% vs 92.6% male), diabetes (13.9% vs 15.7%), hypertension (44.4% vs 50.9%) and hyperlipidaemia (50.9% vs 63.9%, p>0.05 for all). Total plaque burden (total lesion volume/total vessel volume) and plaque composition (fibrous fatty [fibrofatty, FF, 31 – 130 HU], necrotic core [NC, -30 – 30 HU], fibrous [131 – 350 HU] and calcium [> 350 HU]) were extracted from CTCA scans and aggregated per patient. Culprit lesions of recent AMI patients were excluded from the analysis due to the fact that coronary stents would affect plaque characterisation. Multivariate linear regression, corrected for CAD risk factors, was used to compare these parameters between the two cohorts. Results Recent AMI patients and stable CAD patients had similar total plaque burden (β=0.001±0.013, p=0.950, Figure 1a). Patients with recent AMI had higher non-calcified plaque volume ratio (β=0.071±0.026, p<0.05, Figure 1b) due to higher FF (β=0.094±0.019, Figure 1d) and NC (β=0.025 ± 0.005, Figure 1e) plaque volume (p<0.05 for all), but less fibrous plaque volume (β = -0.048±0.019, p<0.05, Figure 1c). Conclusions Recent AMI patients had a greater non-calcified plaque burden than stable CAD patients due to larger FF and NC plaque burden. Since FF and NC components indicate ongoing inflammation in the plaque, while fibrous content indicates resolved inflammation; increased NC and FF burden suggest increased coronary plaque inflammation in non-culprit lesions of recent AMI patients, supporting the presence of residual inflammation in recent AMI patients.Figure 1

Premature coronary artery disease in all-comers undergoing first PCI

Abstract Background The prevalence of coronary artery disease (CAD) increases with age, yet some individuals develop obstructive CAD at younger age. Purpose The present analysis aimed to assess differences in baseline risk profile and 3-year adverse event risk between patients undergoing percutaneous coronary intervention (PCI) for premature or non-premature CAD. Methods We pooled patient-level data of four randomized PCI trials in all-comers (TWENTE (clinicaltrials.gov: NCT01066650); DUTCH PEERS (NCT01331707); BIO-RESORT (NCT01674803); and BIONYX (NCT02508714)), who had no previous coronary revascularization (by PCI or coronary artery bypass surgery) or myocardial infarction (MI). Premature CAD was defined as CAD in men <50 years and in women <55 years, while non-premature CAD was classified as CAD in older patients. Main clinical endpoint was major adverse cardiac events (MACE), a composite of all-cause mortality, any MI, emergent coronary bypass surgery, or clinically indicated target lesion revascularization. Results Of all 6,171 PCI patients with first revascularizations, one out of seven (n=887, 14.4%) had premature CAD. These patients had lower rates of diabetes (10.6% vs. 16.6%, p<0.001), hypertension (32.7% vs. 50.7%, p<0.001), hypercholesterolemia (35.9% vs. 40.3%, p=0.012), and peripheral arterial disease (2.0% vs. 6.6%, p<0.001). Yet, they were more often overweight (76.2% vs. 69.8%, p<0.001), smoker (60.7% vs. 26.4%, p<0.001), and had more often a family history of CAD (59.8% vs. 44.5%, p<0.001). Patients with premature CAD suffered more often from acute ST-segment elevation MI and underwent less often treatment of calcified or bifurcated lesions (Table 1). At 3-year follow-up, the main endpoint MACE did not differ significantly between patients with premature and non-premature CAD (6.6% vs. 9.4%; adj.HR:0.86, 95%-CI:0.65-1.16, p=0.33; Figure 1). All-cause mortality was lower in patients with premature CAD (0.8% vs. 4.4%; adj.HR:0.23, 95%-CI:0.10-0.52, p<0.001). Yet, in patients with premature CAD the rate of repeated target vessel revascularization was higher than in patients with non-premature CAD (6.1% vs. 4.3%; adj.HR: 1.63, 95%-CI:1.18-2.26, p=0.003). In addition, their definite stent thrombosis risk was higher (1.0% vs. 0.5%; adj.HR:3.20, 95%-CI:1.39-7.38; p=0.006) than in patients with non-premature CAD. Conclusions One out of seven patients who were treated with PCI had premature CAD, and these patients had less complex risk profiles. Patients with premature CAD had higher risks for repeated revascularization and stent thrombosis, but the 3-year all-cause mortality risk was lower. In patients with premature CAD, long-term outcome after PCI might be improved by addressing modifiable risk factors such as smoking and overweight.Figure 1:Kaplan-Meier cumulative event

The natural history and prediction of 10-year plaque progression on serial coronary CT angiography

Abstract Background Several studies have shown that plaque subcomponents such as low-attenuation or non-calcified plaque volume from coronary CT angiography (CCTA) are associated with the occurrence of major adverse cardiovascular events. However, it remains unknown how plaque morphology progresses over the long-term. Furthermore, it is unknown which plaque characteristics put patients at increased risk of plaque progression which would require more intensive image-guided follow-up. This study investigated the natural history and predictors of long-term coronary plaque progression in a serial CCTA cohort of patients with suspected coronary artery disease (CAD). Methods In this follow-up study, 539 patients from an earlier published CCTA cohort (Diemen, 2021) were invited for repeat CCTA imaging per-protocol, regardless of symptoms. A total of 299 patients underwent follow-up CCTA imaging with a median scan interval of 10.2 [8.7-11.2] years. Patients who underwent coronary artery bypass grafting (CABG) between baseline and follow-up imaging were excluded. All scans were analyzed using artificial intelligence-guided quantitative CCTA (AI-QCT). Revascularized vessels were excluded. Quantitative plaque volumes (total, low-density, non-calcified and calcified plaque) depicted by AI-QCT were divided by the total vessel volume to represent percent atheroma volume (PAV). PAV progression was calculated subtracting baseline PAV from follow-up PAV. The association of the plaque components with PAV progression was evaluated in a multivariate linear regression model adjusted for clinical risk characteristics (age, sex, hypertension, hypercholesterolemia, diabetes, BMI, smoking, family history of CAD and statin use). Results In total, 274 patients without CABG were used for the serial analysis, mean age was 57 years, 42% were women. At baseline, median PAV was 2.5% [IQR 0.7-8.1], which increased to 6.1% [IQR 1.2-12.9] at follow-up (Figure). The mean PAV progression was 0.4±0.5% per year. Adjusted for clinical risk characteristics and other plaque volumes, baseline percent non-calcified plaque volume (NCP) was the only plaque volume associated with PAV progression (0.5% PAV progression increase per % increase in baseline non-calcified plaque volume). Conclusion Using an unique long-term serial CCTA cohort undergoing per-protocol repeat imaging with a 10-year scan interval, we found that coronary plaque burden more than doubled. Interestingly, the amount of non-calcified plaque volume at baseline was the only predictor for disease progression.Figure

Abstract 15668: The Incidence and Predictors of Delayed and Late Response to Cardiac Re-Synchronization Therapy

Background: The incidence and predictors of delayed response to cardiac resynchronization therapy (CRT) have not been well established. Our study aimed to investigate the incidence and predictors of delayed and late response in CRT patients. Research Question: What patient-specific characteristics are associated with delayed or late response to CRT? Goal/Aim: To investigate the incidence and predictors of delayed and late response in CRT patients. Methods: We conducted a retrospective analysis of 201 patients who underwent CRT implantation with placement of a CS lead. Patients meeting the enrollment criteria were categorized into three groups: Group A comprised conventional responders with a response observed at the 6-month follow-up, Group B consisted of delayed responders with a response seen between 6 months and 1-year follow-up, and Group C included late responders with a response observed after 1 year of follow-up. CRT response was defined as an absolute increase of ≥ 5% in left ventricular ejection fraction. All echocardiograms were performed at the same institution. Only patients who were defined as responders to CRT were included in the analysis. Results: Among the patients analyzed, 59 patients (67.2 ± 12.3 years, 39 male) achieved a conventional response to CRT, while 40 patients (69.6 ± 9.5 years, 30 male) experienced a delayed response, and 29 patients exhibited a late response (66.1 ± 11.4 years, 18 male). The mean follow-up time was 267 days (± 341 days). The incidence of delayed and late responses was 19.9% and 14.43%, respectively. In univariable logistic regression analysis, a history of coronary artery disease (p = 0.047) was associated with delayed and late CRT responses. Conclusions: Our findings demonstrate a significant proportion of patients experiencing delayed and late responses to CRT. This study suggests the need for reconsidering the waiting time for CRT response, particularly in patients with a history of coronary artery disease. Keywords: cardiac resynchronization therapy, delayed response, heart failure

Abstract 15468: Factor VII Induced Coronary Thrombosis

Case Description: 69-year-old male with a history of factor VII deficiency and coronary artery disease (CAD) with a stent in the distal left anterior descending (LAD) artery, underwent diagnostic laparoscopy for suspected appendiceal carcinoma. He is a non-smoker, has good exercise tolerance and takes aspirin only three times a week, due to epistaxis. Post-surgery, he complained of 10/10 substernal chest pain. Initial troponin (TnI) was 0.11 ng/dL, peaking at >80 ng/dL in 2 hours. EKG was compatible with an anterior wall STEMI. An emergent coronary angiogram showed a patent distal LAD stent and a 99% occlusive lesion in the mid-LAD, which was treated with a drug-eluting stent. With careful clinical judgment and hematology consultation, dual antiplatelet therapy was continued despite a history of coagulopathy. On probing, it was discovered that the patient received two doses of recombinant factor VII (rVII) prior to the surgery to reduce operative bleeding. Discussion: Recombinant factor VII is known to cause serious arterial and venous thromboembolic events. This risk increases to almost 10% in patients who are elderly with concomitant vascular disease. In our patient with prior history of CAD and in the setting of acute surgical stress, exogenous factor VII unbalanced the coagulation system leading to a STEMI. Surgical teams should be aware of the detrimental consequences of administration of rVII in high cardiovascular risk patients and seek alternative hemostatic strategies. Prothrombotic agents should be used with caution and close monitoring for acute coronary syndromes, especially in patients with a high risk of CAD.

Abstract 18121: Gaps in Initiation of Evidence-Based Medical Therapies in Patients With Ischemia With Nonobstructive Coronary Artery Disease

Introduction: Ischemia with nonobstructive coronary artery disease (INOCA) is associated with major adverse cardiovascular events (MACE) due to atherosclerotic plaque progression, rupture of high-risk plaque and microvascular dysfunction. While there is evidence for use of ACE inhibitors/ARBs and statins to reduce MACE in patients with coronary artery disease (CAD), gaps in implementation of maximal medical therapy in patients after diagnosis of INOCA is not well described. We hypothesize that cardioprotective medications may be underutilized in patients with INOCA. Methods: Patients (n=443) with ischemic symptoms associated with ECG changes or troponin rise, no history of CAD and with nonobstructive CAD on noninvasive or invasive coronary assessment between 2010-2021 at Indiana University Health, Indianapolis, were included in this study. Results: In 226 women and 217 men with mean age 58.5 yrs, 315 underwent invasive angiography and 128 coronary CTA. Compared to baseline, initiation rates of cardioprotective agents were low after INOCA diagnosis for statins (37.9%) and aspirin (ASA, 36.1%) (Figure 1A). Among eligible patients, statins and ASA were underutilized in 42% and 44% respectively. There were no statistically significant differences in prescribing patterns of ASA and statin based on gender or race (Figure 1B). Conclusions: There are significant gaps in the prescription of cardioprotective medications including statins, ASA, ACEI/ARB and beta blockers in patients with INOCA at a quaternary care hospital. If this pattern is similar to the rest of the country, the factors associated with underutilization of these medications needs to be explored further.

Abstract 15871: Clinical Characteristics Associated With Response to Exercise and Serious Adverse Events During Home-Based Walking Exercise in People With Lower Extremity Peripheral Artery Disease

Background: Home-based walking exercise improves walking performance in people with lower extremity peripheral artery disease (PAD). However, whether clinical and sociodemographic factors, such as age, sex, race, comorbidities, and income, are associated with response to exercise or rates of serious adverse events (SAEs) during a home-based walking exercise intervention for PAD is unclear. Methods: Data from participants randomized to two clinical trials of home-based walking exercise for PAD were pooled. Both clinical trials used behavioral methods to help participants adhere to walking exercise up to 5 days/week for up to 50 minutes/session for 6-months. Outcomes were change in six-minute walk (6MW) at 6-months and rates of SAEs at 12-months. SAEs were defined as death or hospitalization. Results: 325 unique participants [mean age 69.8 (9.1), 161 (49.5%) female, 182 (56.0%) Black] had available 6MW and SAE data. Home-based walking exercise improved 6MW distance, compared to control, at 6-month follow-up [mean: +46.4 meters (95% CI: +31.5 meters, 61.2 meters)]. The effect of home-based exercise on 6MW was similar across clinical and sociodemographic characteristics. 51 (27.3%) participants reported SAEs in the home-based exercise group and 32 (23.2%) reported SAEs in the control group (p=0.40). Among those randomized to home-based walking exercise, odds of SAE were significantly higher among Black compared to White participants, those with history of coronary artery disease (CAD) and heart failure (HF) compared to those without (Figure). Statistically significant interactions were identified between Black race (P<0.001), coronary artery disease (P=0.006) and lower income zipcodes (P=0.047) and the effect of exercise on rates of SAEs. Conclusion: In people with PAD randomized to home-based exercise, those who were Black, had a history of CAD or HF were significantly more likely to experience SAEs, compared to people without these characteristics.

Abstract 14822: Portopulmonary Hypertension Unveiled: Effects of Transjugular Intrahepatic Portopulmonary Shunt Placement

Introduction: Transjugular intrahepatic portosystemic shunts (TIPS) treat portal hypertension by connecting the portal vein to the hepatic vein in the liver. The resultant shunting of portal venous flow to the systemic circulation helps reduce the portosystemic gradient and is used to treat complications of portal hypertension. Right heart failure and the development of pulmonary hypertension after TIPS are known complications; however, portopulmonary hypertension (POPH) is rare. Description of Case: A 61-year-old male presents to the clinic for six months of exertional dyspnea, weight gain, and lower extremity edema. He has a history of coronary artery disease and nonalcoholic steatohepatitis cirrhosis, with TIPS placement four years prior for esophageal variceal bleeding. An echocardiogram revealed right ventricular (RV) dilatation with moderately reduced function, a flattened left ventricular septum, and an estimated pulmonary artery systolic pressure of 91 mmHg. An echocardiogram and right heart catheterization (RHC) performed before his TIPS showed normal RV function and pulmonary artery pressures (PAP). Decision Making: The patient was promptly started on furosemide and spironolactone, and after adequate diuresis, a repeat RHC was obtained, which showed significantly elevated PAP, and normal left-sided filling pressures and cardiac output. Other causes of pulmonary hypertension were ruled out, and the patient was started on tadalafil monotherapy for severe POPH, with significant improvement in his PAP (Table 1). Conclusion: POPH after TIPS is a rare complication that should be suspected in patients presenting with signs of right-sided volume overload. The mechanism by which TIPS leads to POPH is not entirely understood. The degree of RV dysfunction correlates with mortality, and prompt treatment is warranted.

Abstract 14630: Young Female Presenting With Chest Pain Due to Left Main Aneurysm

Background: Incidence of ACS is increasing in young patients. While atherosclerosis needs to be ruled out, there should be high suspicion for alternate causes. Case: A 36-year-old African American woman with obesity, prediabetes and tobacco use, presented to the ED with chest pain. Initial cardiac investigations unremarkable. CTA chest ruled out pulmonary embolism and aortic dissection. Her pain had resolved and she was discharged home. Within hours, the pain recurred and became progressively worse. She returned to the ED and was found to have an anterior STEMI with a troponin I 0.72 ng/ml. Cardiology was consulted, left heart cath revealed a large left main aneurysm (LMA) with large thrombus burden, with mildly aneurysmal LAD, RCA and LCx, moderate decrease in systolic function and no significant arch or main vessel aneurysms. Case was discussed with cardiothoracic surgery, who recommended medical management. Her symptoms resolved while on anticoagulation. Discussion: Coronary artery aneurysms (CAA) are a rare cause of ACS. The reported incidence of CAA ranges from 0.3% to 5%, most often affecting men. The RCA is the most commonly affected artery followed by the LAD, with the LM being the least common. Risk factors include hypertension, dyslipidemia, smoking, diabetes, and a family history of coronary artery disease. Known etiologies include atherosclerosis, Kawasaki disease, inflammatory, congenital, and degenerative conditions. Transient myocardial ischemia may result from aneurysm-related blood stasis that may predispose to thromboembolic events, coronary spasm, and microvascular dysfunction. Conclusion: Although considered extremely rare, the number of LMA reported has increased in the last decades and may continue to grow with the widespread use of invasive and noninvasive coronary imaging. Considering the rarity of CAA and absence of dedicated studies, both the interventional and the pharmacological management of patients with LMA are challenging.

Abstract 17428: Severity of Diastolic Dysfunction Predicts Risk of Myocardial Infarction

Background: Diastolic dysfunction (DD) is known to be a predictor of mortality. However, the impact of DD on the risk for myocardial infarction (MI) is not well defined. Research Question: We sought to examine whether DD is an independent predictor of risk of MI in patients with a preserved ejection fraction. Methods: This was a retrospective study of consecutive patients who underwent an echocardiogram that showed normal systolic function and had ≥3 months of follow-up. DD was graded using the contemporaneous guidelines at the time of the echocardiogram. Subsequent MI was determined by the presence of an inpatient encounter with a primary diagnosis of MI. Results/Data: 136,455 patients were included (mean age 56 years; 58% women). DD was present in 18.3% of patients (14.1% Grade 1, 3.8% Grade 2, 0.4% Grade 3). Patients with DD were more likely to be older (71 vs 53 years) and have coronary artery disease (27% vs 12%), diabetes (27% vs 14%), hypertension (69% vs 47%) and hyperlipidemia (64% vs 41%), among other comorbidities. Survival free from MI was significantly lower as diastolic dysfunction severity increased (Figure 1). Multivariate Cox proportional hazards modeling demonstrated that DD was an independent predictor of MI (hazard ratios [CI]: Grade 1: 1.51 [1.35-1.69]; Grade 2: 1.92 [1.64-2.25]; Grade 3: 2.82 [1.94-4.09]). Conclusions: Our data demonstrate that the risk of MI is significantly increased in the presence of DD, with higher risk at higher grades of DD. The increased risk associated with grade 3 DD is comparable to that from a prior history of coronary artery disease. These findings suggest that the severity of DD may be a useful tool in risk stratifying patients for risk of MI.

Abstract 15986: Very Rare Case of a Interatrial Thrombus Following Watchman Device Placement

Introduction: Device related thrombus (DRT) is a known complication of left atrial appendage closure (LAAC). We present a case of a thrombus at the interatrial septum following LAAC detected eight months after the procedure. Case: Eighty-six years old woman with a history of coronary artery disease s/p percutaneous coronary intervention with drug eluting stent to right coronary artery in 2016, heart failure with preserved ejection fraction, atrial fibrillation (AF) s/p 27mm Watchman device placement (on aspirin only) due to recurrent episodes of hematuria, hypertension, hyperlipidemia, chronic kidney disease presented to the hospital with complaints of right flank pain. Initial labs were unremarkable except for anemia, hemoglobin of 10g/dl. Computed tomography (CT) abdomen and pelvis showed an incidental finding of new mass like filling defect within the left atrium. Transthoracic echocardiogram (TTE) showed mobile mass 1.7 x 1.6 cm attached to the interatrial septum on the left atrial side.(Figure 1.A) Low dose apixaban was started. Follow up transesophageal echocardiogram (TEE) in four months interval showed the thrombus attached to the interatrial septum had slightly reduced in size to 1.5 x 0.9 cm, but an additional large thrombus measuring 2.5 x 1.3 cm was seen on top of the Watchman device (Figure 1.B) and Apixaban was increased to full dose. Discussion: Incidence of DRT after LAAC is 3.74% with most cases occurring in the first year after LAAC. Exposed and incompletely endothelialized device are foci for DRT. Iatrogenic pericardial effusion, hypercoagulable state, deep implant, renal insufficiency, non-paroxysmal AF are some of the factors increasing the risk of device related thrombus. Most cases of DRT described are attached to the device. In our case, a large interatrial thrombus was identified incidentally which likely formed at the site of septal puncture during device insertion which highlights the importance of follow up echocardiogram at intervals.