Significant Coronary Heart Disease Research Articles

Coronary artery disease as a risk factor for metabolic dysfunction-associated steatotic liver disease and liver fibrosis

Introduction and ObjectivesPatients with metabolic dysfunction-associated steatotic liver disease (MASLD) are at an increased cardiovascular risk. On the contrary, non-alcoholic fatty liver disease (NAFLD) is highly prevalent in patients with coronary heart disease (CHD). However, it is not known whether patients with significant CHD show a higher frequency of liver fibrosis. This study aimed to determine the frequency of MASLD and liver fibrosis in patients with CHD and to assess whether coronary stenosis is significantly associated with MASLD and fibrosis. Patients and MethodsThis observational and analytical study included adult patients without any known liver disease who underwent coronary angiography for suspected coronary artery disease (Jul 2021–Jul 2022). The presence of significant CHD (> 50% stenosis of at least one coronary artery) was determined. Liver elastography (FibroScan®) was performed up to 6 months after the coronary angiographic study to determine liver fibrosis, a measurement of liver stiffness (> 6.5 Kpa). Fisher's test, Mann–Whitney U test, and logistic regression models were used (p<0.05). ResultsThe study included 113 patients (76% men, average age: 63 years [standard deviation: 9.9]), of which 72% presented with significant CHD. The prevalence rate of MASLD was 52%. Liver fibrosis was present in 12% of the patients and all patients in the significant CHD group (p=0.007). An increase in the number of vessels with significant CHD increased the probability of liver fibrosis (odds ratio, 1.79; 95% confidence interval, 1.06–3.04; p=0.029). ConclusionsMASLD is highly prevalent in patients with significant CHD but without known liver damage. These data suggest that MASLD and liver fibrosis should be investigated in patients with CHD. The presence of confounding variables, especially the presence of type 2 diabetes mellitus, should be evaluated in further studies.

Incidence of coronary heart disease among remote workers: a nationwide web-based cohort study

Coronary heart disease (CHD) risk is influenced by socioeconomic status-related parameters, particularly occupation. We investigated occupational gaps in CHD risk and how the introduction of remote work moderated the observed occupational differences in CHD risk during the coronavirus disease 2019 pandemic in Japan. Data from a web-based, nationwide cohort study, comprising 17,640 workers (aged 20–65 years) with baseline data from December 2020, were analyzed. Participants were grouped by occupation as upper-level nonmanual workers (managers/professionals) and others (reference group). The primary outcome was CHD (angina pectoris/myocardial infarction) onset retrospectively confirmed at the 1-year follow-up survey. Upper-level nonmanual workers exhibited a higher CHD incidence than others (2.3% vs. 1.7%). This association was pronounced in the younger (20–49 years) population, with a significant CHD risk (adjusted risk ratio = 1.88). Upper-level nonmanual workers exhibited nearly 15% higher remote work prevalence, with a significant remote work-related CHD risk (adjusted risk ratio = 1.92). The mediating effects of remote work explained an overall disparity of 32% among the younger population. Occupational gaps in CHD incidence in Japan differ from those in Western countries, where upper-level nonmanual workers have lower cardiovascular risk. In Japan, remote work can mediate CHD risk in the younger population of upper-level nonmanual workers.

Relationship between Vitamin D Levels and Platelet Function in the Elderly Patients with Coronary Heart Disease

Introduction: Coronary Heart Disease (CHD) is a degenerative disease caused by fat accumulation and chronic inflammation. The elderly have a significant CHD risk due to the prevalence of vitamin D insufficiency and decreased platelet function, influencing the inflammatory response in this population. Therefore, this study aims to assess the relationship between vitamin D levels and platelet function measured by the mean platelet volume (MPV) and P-Selectin serum levels of CHD patients. Method: The cross-sectional design was carried out on stable CHD patients aged 60-75. Meanwhile, vitamin D, MPV, and P-Selectin were taken through venous blood, and an ELISA examination was performed to determine their levels in serum. A correlation test using the Pearson product-moment was also conducted between vitamin D and platelet function. Result: The subjects involved were 45 male and 16 female at 73.8% and 23.2%, respectively. The highest risk factor was dyslipidemia found in 45 (73.8%) and all subjects (100%) received statins. This study showed no correlation between vitamin D levels and MPV levels (p= 0.094) and P-Selectin (p=0.362). Conclusion: Vitamin D levels are not associated with platelet function levels (MPV and P-Selectin) in elderly patients with CHD.

Serum Orotidine: A Novel Biomarker of Increased CVD Risk in Type 2 Diabetes Discovered Through Metabolomics Studies.

To identify novel biomarkers of cardiovascular disease (CVD) risk in type 2 diabetes (T2D) via a hypothesis-free global metabolomics study, while taking into account renal function, an important confounder often overlooked in previous metabolomics studies of CVD. We conducted a global serum metabolomics analysis using the Metabolon platform in a discovery set from the Joslin Kidney Study having a nested case-control design comprising 409 individuals with T2D. Logistic regression was applied to evaluate the association between incident CVD events and each of the 671 metabolites detected by the Metabolon platform, before and after adjustment for renal function and other CVD risk factors. Significant metabolites were followed up with absolute quantification assays in a validation set from the Joslin Heart Study including 599 individuals with T2D with and without clinical evidence of significant coronary heart disease (CHD). In the discovery set, serum orotidine and 2-piperidinone were significantly associated with increased odds of incident CVD after adjustment for glomerular filtration rate (GFR) (odds ratio [OR] per SD increment 1.94 [95% CI 1.39-2.72], P = 0.0001, and 1.62 [1.26-2.08], P = 0.0001, respectively). Orotidine was also associated with increased odds of CHD in the validation set (OR 1.39 [1.11-1.75]), while 2-piperidinone did not replicate. Furthermore, orotidine, being inversely associated with GFR, mediated 60% of the effects of declining renal function on CVD risk. Addition of orotidine to established clinical predictors improved (P < 0.05) C statistics and discrimination indices for CVD risk (ΔAUC 0.053, rIDI 0.48, NRI 0.42) compared with the clinical predictors alone. Through a robust metabolomics approach, with independent validation, we have discovered serum orotidine as a novel biomarker of increased odds of CVD in T2D, independent of renal function. Additionally, orotidine may be a biological mediator of the increased CVD risk associated with poor kidney function and may help improve CVD risk prediction in T2D.

514 Usefulness And Clinical Implications Of Plaque Analysis And Pfai For The Evaluation Of Cardiovascular Risk

Introduction: Clinical evidence has emphasized importance of coronary plaques’ characteristics, rather than lumen stenosis’ severity for outcome of cardiovascular events. Coronary Computed Tomographic angiography (CCTA) represents a non-invasive approach to assess plaques. Aim of the study was to compare clinical characteristics and outcomes (death, hospital admissions for percutaneous angioplasty or by-pass procedures) of patients with different plaques composition. Findings were also compared with patients without significant coronary heart disease (CAD).

Survival in Patients With Nonischemic Cardiomyopathy With Preserved vs Reduced Ejection Fraction

BackgroundPrior studies suggest similar long-term mortality rates for patients with heart failure (HF) with preserved ejection fraction (HFpEF) vs reduced ejection fraction. However, although coronary heart disease (CHD) is associated with worse prognosis in HF, clinical outcomes are less well characterized for HF without CHD. We investigated the characteristics and 5-year mortality outcomes among patients with HF without significant CHD, stratified by EF. MethodsPatients with clinical heart failure who underwent coronary angiography at Duke University Medical Center from 1996 through 2009 and had no significant CHD with EF ≤ 40% were compared with patients without significant CHD with EF > 40%. Survival was examined using Kaplan-Meier methods and multivariable Cox proportional hazards modeling. Analyses were repeated using EF ≥ 50%. ResultsOf 3154 patients with HF without significant CHD, 1530 (48.5%) had HFpEF (EF > 40%). These patients were older and more likely to have a Charlson Index ≥ 2 than patients with reduced EF. Patients with HFpEF had a lower risk of death than those with reduced EF (unadjusted hazard ratio [HR] 0.85; 95% confidence interval [CI] 0.74-0.99). From 1996 through 2009, the secular trend of death decreased among patients without CHD and with reduced EF (HR 0.92; 95% CI 0.88-0.97) but not among those with preserved EF (HR 0.99; 95% CI 0.93-1.05; P interaction 0.095). No finding was significant after multivariable risk adjustment. Results were consistent when defining preserved EF as EF ≥ 50%. ConclusionsAmong patients without significant CHD, those with HFpEF had similar risks of 5-year mortality as patients with HF with reduced ejection fraction.

Medium-term prognostic value of angio-TC in type 2 diabetic patients without known cardiopathy

Abstract Funding Acknowledgements Type of funding sources: None. Introdution The use of coronary angiography by cardiac CT for the active search for coronary disease in asymptomatic diabetic patients is not generally indicated. On the other hand, in the case of high-risk patients with a high calcium score, there are results that do show a potential benefit of expanding the study with CT coronary angiography. Purpose The aim was to determine the medium-term prognostic value of computed tomography non-invasive coronary angiography (CT angiography) to predict major cardiac events in type 2 diabetic patients (p) without previous cardiac symptoms Methods Observational and prospective study in diabetic patients without symptoms suggestive of coronary heart disease (CHD), derived from performing a CT in the previous 5 years, for different reasons, not related to acute coronary syndrome. The presence of CHD was analyzed, as well as the incidence for cardiac events during follow-up. Results 402 diabetic patients, mean evolution time of the disease: 6.8 +/- 2.1 years, mean Hb1Ac 8.1 +/- 0.7%. 60% of patients were male. Regarding other cardiovascular risk factors: 66.3% were hypertensive. 58.8% dyslipidemic. 26.3% obese. 27.5% smokers. 32.5% ex-smokers. 36.3% had a family history of CHD. Most frequent indication for CT: CHD screening, with previous inconclusive tests (26.3%), followed by pre-surgery evaluation (25%). Agatston Score 278.3 ± 235.8, Agatston Score&amp;gt; 400 132 (32.8%), significant CHD 174 (43.2%), Vulnerable plaques 84 (20.9%) The average follow-up was 5 years (+/- 1.3); 90 p (22.3%) suffered cardiac events (63 cardiac deaths, 27 non-fatal myocardial infarction). Best correlation with events was observed with the presence of significant coronary disease (ostruction&amp;gt; 50%) compared to the Agatston score and the presence of vulnerable plaques (adjusted c-index of 0.59 versus univariate c-index of 0.42, respectively) The annual event rate for patients with normal coronary arteries was 1.8%, which translated into a 5-year event-free survival period. The highest annual event rate of 22.3% was detected in patients with obstructive 3-vessel CAD Conclusions Non-invasive CT angiography allows, after quantifying plaque severity in diabetic patients, to reclassify patients at high / very high risk Diabetic patients with normal coronary arteries on CT angiography had a 5-year survival period free of major cardiac events.

Early Detection of Checkpoint Inhibitor-Associated Myocarditis Using 68Ga-FAPI PET/CT.

Objective: Checkpoint inhibitors (ICIs) have gained importance in recent years regarding the treatment of a variety of oncologic diseases. The possibilities of diagnosing cardiac adverse autoimmune effects of ICIs are still limited. We aimed to implement FAPI PET/CT imaging in detecting ICI-associated myocarditis.Methods: In a retrospective study, FAPI PET/CT scans of 26 patients who received ICIs from 01/2017 to 10/2019 were analyzed. We compared tracer enrichment in the heart of patients without any signs of a cardiac disease (n = 23) to three patients with suspected ICI-associated myocarditis. To exclude any significant coronary heart disease, cardiac catherization was performed. All three patients' myocardial biopsies were examined for inflammatory cells.Results: Three patients showed clinical manifestations of an ICI syndrome including myocarditis with elevated levels of hsTnT (175 pg/ml, 1,771 pg/ml, 157 pg/ml). Further cardiological assessments revealed ECG abnormalities, lymphocyte infiltration of the myocardium in the biopsies or wall motion abnormalities in echocardiography. These patients' FAPI PET/CTs showed cardiac enrichment of the marker which was less distinct or absent in patients receiving ICIs without any signs of immunological adverse effects or cardiac impairment (n = 23) [Median SUV myocarditis patients: 1.79 (IQR: 1.65, 1.85), median SUV non-myocarditis patients: 1.15 (IQR: 0.955, 1.52)].Conclusions: Apart from the successful implementation of ICIs in oncological treatments, ICI-associated myocarditis is still a challenging adverse effect. FAPI PET/CT may be used in order to identify affected patients at an early stage. Moreover, when integrated into cancer stage diagnostics, it contributes to cardiac risk stratification besides biomarker, ECG and echocardiography.

Abstract 15809: 68 Gallium Fibroblast Activating Protein Inhibitor Positron Emission Tomography is Able to Diagnose Checkpoint Inhibitor-induced Myocarditis

Introduction: Checkpoint inhibitors (ICIs) have gained importance in recent years regarding the treatment of a variety of oncologic diseases. The possibilities of diagnosing cardiac adverse autoimmune effects of ICIs are still limited. We aimed to implement FAPI PET/CT imaging in detecting ICI-induced myocarditis. Methods: In a retrospective study, FAPI PET/CT scans of 26 patients who received ICIs from 01/2017 to 10/2019 were analyzed. We compared tracer enrichment in the heart of patients without any signs of a cardiac disease (n=23) to three patients with suspected ICI-induced myocarditis. To exclude any significant coronary heart disease, cardiac catherization was performed. Myocardial biopsies were examined, especially in regard to the infiltration of immune cells. Results: Three patients showed clinical manifestations of an ICI syndrome including myocarditis with elevated levels of hsTnT (175 pg/ml, 1771 pg/ml, 157 pg/ml). Further cardiological assessments revealed ECG abnormalities, lymphocyte infiltration of the myocardium in the biopsies or wall motion abnormalities in echocardiography. These patients’ FAPI PET/CTs showed a locally defined cardiac enrichment of the marker which was absent in patients receiving ICIs without any signs of immunological adverse effects and cardiac impairment (n=23) (Median SUV myocarditis patients: 1.79 (IQR: 1.65, 1.85), median SUV non-myocarditis patients: 1.15 (IQR: 0.955, 1.52)). Conclusions: Myocardial biopsy, the current gold standard of the diagnosis of ICI-induced myocarditis, is susceptible to sampling errors and results arrive within a few days. We provide first evidence that FAPI PET/CT is able to diagnose ICI-induced myocarditis and can demonstrate locally enhanced manifestation of ICI-induced myocarditis on time.

Prognostic value of noninvasive combined anatomic/functional assessment by cardiac ct in patients with suspected coronary heart disease

Abstract Background Noninvasive evaluation of patients with stable angina is preferable over invasive testing if it leads to similar patient outcome. The combination of coronary angiography and vasodilator challenge myocardial perfusion imaging by computed tomography allows fast, comprehensive assessment of patients with suspected coronary heart disease. Purpose To compare the long-term prognostic value of combined computed tomography angiography (CTA) and myocardial CT perfusion imaging (CTP) with invasive coronary angiography (ICA) and single photon emission tomography (SPECT) in patients with suspected hemodynamically significant coronary heart disease. Methods At 16 centres, 381 patients were followed for major adverse cardiac events (MACE) for the CORE320 study. All patients underwent coronary CTA, CTP, and SPECT before ICA. Prognostic performance according binary results (normal/abnormal) was assessed by 5-year major cardiovascular events (MACE) free survival and area under the receiver-operating-characteristic curve (AUC). Results Follow up beyond 2-years was available in 323 patients. MACE-free survival rate was greater among patients with normal combined CTA/CTP findings compared to ICA/SPECT: 85 vs. 80% (95% confidence interval [CI] for difference 0.1, 11.3) though event-free survival time was similar (4.54 vs. 4.37 years, 95% CI for difference: 0.03, 0.36). Abnormal results by combined CTA/CTP was associated with 3.83 years event-free survival vs. 3.66 years after abnormal combined ICA/SPECT (95% CI for difference: 0.05, 0.39, CI −1.0, 11.1) (Figure). Predicting MACE by AUC also was similar: 65 vs. 65 (difference 0.1; 95% CI: −4.6, 4.9). When MACE was restricted to death, myocardial infarction, or stroke, AUC for CTA/CTP was 66 vs. 61 by ICA/SPECT (difference 5.1; 95% CI: −7.1, 12.9). Conclusions Combined CTA/CTP yield similar 5-year prognostic performance as joined ICA/SPECT assessment in patients presenting with suspected coronary heart disease and thus may represent a fast, non-invasive alternative to the traditional diagnostic approach. Figure 1. 5-year event-free survival Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): National Institutes of Health

Establishment of a diagnostic model of coronary heart disease for patients with diabetic foot.

This study aims to establish a diagnostic model of coronary heart disease (CHD) for diabetic foot (DF) patients.The clinical data of 489 hospitalized patients with DF were retrospectively analyzed in this case-control study. The patients were divided into the CHD group (DF with CHD, n = 212) and the control group (DF without CHD, n = 277). Univariate analysis was performed to screen for CHD-related risk factors, and multivariate logistic regression analysis was conducted to determine significant CHD risk factors. Scores were assigned according to the ratio of risk factors (OR) to establish a diagnostic model of CHD for patients with DF. The area under the ROC curve was used to test the application value of the diagnostic model.The logistic regression analysis showed that the risk factors for CHD in DF patients were age, duration of diabetes, toe-brachial index, hyperuricemia, and chronic renal insufficiency. The area under the ROC curve of the diagnostic model was 0.798 (0.759–0.837), the diagnostic point of CHD was 6 points, the diagnostic sensitivity was 69.3%, and the specificity was 76.5%.The established model has good diagnostic value and provides the basis for preliminary screening for CHD in patients with DF.

P1628ASSESSING CORONARY HEART DISEASE IN SIMULTANEOUS PANCREAS-KIDNEY TRANSPLANTATION - IS THERE SPACE FOR A RISK SCORE MODEL?

Abstract Background and Aims Type 1 diabetes mellitus (DM1) is associated with an increased risk of coronary heart disease (CHD), which is generally more aggressive and frequently asymptomatic. This risk substantially increases for those with nephropathy. In selected patients, simultaneous pancreas-kidney transplantation (SPKT) is the renal and pancreatic replacement therapy of choice, as it increases longevity and stabilizes diabetic complications. Despite essential, universal screening protocols for silent CHD in this population are still debatable. As so, Gowdak recently developed a simple clinical risk score to determine the pre-test probability of significant CHD in single kidney transplant candidates. Our aim was to identify potential risk factors associated with the presence of significant lesions on pre-SPKT coronary angiography (CA) and test the utility of Gowdak score in SPKT candidates. Method 77 patients submitted to SPKT between 2011 and 2018 were retrospectively included in this study. All subjects underwent CA as screening method for CHD during the eligibility evaluation. Demographic, clinical, laboratory, therapeutic and imaging characteristics were studied. Continuous variables are presented as means or medians; categorical variables as frequencies. Univariate analysis (Qui2 or Fisher test) and multivariate analysis (logistic regression) were performed. Comparison between groups of patients with and without CA injury was performed using SPSS statistics version 23 and a p &amp;lt;0.05 was considered significant. Results In the past 8 years, 99 SPKT were performed; 78% of these patients (N=77) were submitted to preoperative CA; mean age was 36±5.9 years and 64% were male. The mean duration of DM1 was 25 years and 97% had retinopathy, 43% neuropathy, 31% dysautonomia, 19% peripheral arterial disease and 7% cerebrovascular disease. We excluded 1 due to missing data. A minority of SPKT (3%, N=2) was preemptive. The mean time on dialysis was 37 months. Only one patient had angor, wh0 was excluded of Gowdak risk score assessment. Most patients (87%, N=67) were hypertensive; 56% (N=43) were on statin; 48% (N=37) had smoking habits, and 5% (N=4) had a BMI&amp;gt;30 kg/m2. CA identified at least one lesion in 48% (N = 37) of the patients, of which 30% (N=11; 14% of all CA) underwent intervention; none had complaints of angor. Based on Gowdak risk score, mean probability for CHD was 30.8% and 19 patients had a risk &amp;gt;40% - the recommended cut off to pursuit CA as screening method - but only 2 required intervention. In a univariate analysis, we found that the only distinguishing feature between the group of patients with and without CA lesions was smoking (p=0.005). DM1 with 20 or more years of evolution was found to have a significant association with coronary artery disease development (identifiable by any diagnostic test) (p=0.048). In our population of SPKT recipients Gowdak risk score did not predicted those with significant CHD. Conclusion In our study, CA was positive for lesion in almost half of the patients, all of them asymptomatic. Despite the fact that Gowdak probability score failed to identify those with significant CHD before CA (probably because all of our patients were diabetic), in our population for every seven patients submitted to CA, one needed coronary intervention. We highlight that asymptomatic patients with long-term DM and smokers should be carefully evaluated. The task of correctly ascertaining the presence of CAD can be more overwhelming when we take into account that there is a high prevalence of asymptomatic patients with extensive CAD. Facing the importance of an unmissed diagnosis we encourage the use of CA as an initial screening method, even if it is invasive. Further studies should be encouraged to create screening algorithm for SPKT candidates. Finally, medium- and long-term follow-up studies are needed to evaluate the effects of preoperative selection on posttransplant cardiac events and survival rates.

The effects of exercise training on lipid metabolism and coronary heart disease.

Blood lipoproteins are formed by various amounts of cholesterol (C), triglycerides (TGs), phospholipids, and apolipoproteins (Apos). ApoA1 is the major structural protein of high-density lipoprotein (HDL), accounting for ~70% of HDL protein, and mediates many of the antiatherogenic functions of HDL. Conversely, ApoB is the predominant low-density lipoprotein (LDL) Apo and is an indicator of circulating LDL, associated with higher coronary heart disease (CHD) risk. Thus, the ratio of ApoB to ApoA1 (ApoB/ApoA1) is used as a surrogate marker of the risk of CHD related to lipoproteins. Elevated or abnormal levels of lipids and/or lipoproteins in the blood are a significant CHD risk factor, and several studies support the idea that aerobic exercise decreases CHD risk by partially lowering serum TG and LDL-cholesterol (LDL-C) levels and increasing HDL-C levels. Exercise also exerts an effect on HDL-C maturation and composition and on reverse C transport from peripheral cells to the liver to favor its catabolism and excretion. This process prevents atherosclerosis, and several studies showed that exercise training increases heart lipid metabolism and protects against cardiovascular disease. In these and other ways, it more and more appears that regular exercise, nutrition, and strategies to modulate lipid profile should be viewed as an integrated whole. The purpose of this review is to assess the effects of endurance training on the nontraditional lipid biomarkers, including ApoB, ApoA1, and ApoB/ApoA1, in CHD risk.

Diagnosis and treatment of heart failure with preserved left ventricular ejection fraction.

Nearly six million people in United States have heart failure. Fifty percent of these people have normal left ventricular (LV) systolic heart function but abnormal diastolic function due to increased LV myocardial stiffness. Most commonly, these patients are elderly women with hypertension, ischemic heart disease, atrial fibrillation, obesity, diabetes mellitus, renal disease, or obstructive lung disease. The annual mortality rate of these patients is 8%-12% per year. The diagnosis is based on the history, physical examination, laboratory data, echocardiography, and, when necessary, by cardiac catheterization. Patients with obesity, hypertension, atrial fibrillation, and volume overload require weight reduction, an exercise program, aggressive control of blood pressure and heart rate, and diuretics. Miniature devices inserted into patients for pulmonary artery pressure monitoring provide early warning of increased pulmonary pressure and congestion. If significant coronary heart disease is present, coronary revascularization should be considered.

P1718 Multi-modal imaging characterization of contained aortic subannular rupture after transcatheter aortic valve implantation

Abstract INTRODUCTION Aortic annular rupture is a potentially catastrophic complication after transcatheter aortic valve implantation (TAVI), with an estimated incidence of 1%. Rupture occurs in the anatomical device landing zone, that extends from the aortic root to the distal left ventricular outflow tract (LVOT). It usually occurs in the context of highly calcified aortic valve and LVOT, implantation of balloon-expandable valves, valve oversizing and overdilation to treat paravalvular leakage. CASE REPORT An 80-year old woman with no past relevant medical history was admitted to our Cardiology Department with decompensated heart failure because of symptomatic severe aortic stenosis, moderate aortic regurgitation and mild left ventricular (LV) dysfunction. She was already in waiting list for TAVI procedure, after being refused for conventional aortic valve replacement due to a "porcelain" aorta. Her pre-operative angiography showed no significant coronary heart disease, and the cardiac computed tomography (cardiac-CT) revealed a severely calcified aortic valve (Agatston score = 4940). An Acurate neo L (27mm) valve was implanted after clinical stabilization with no immediate complications. Because of paravalvular regurgitation, sequential post-dilation was performed with 25mm and 26mm balloons. Post-procedural angiography showed no contrast extravasation (Panel A). In the first hours after the procedure, she was hypotensive with non-specific mild chest discomfort. The EKG showed sinus rhythm with left anterior fascicular block. A transthoracic echocardiogram revealed a moderate pericardial effusion, with no signs of tamponade, and a moderate "paravalvular leak "at the level of the non-coronary cusp to a pulsatile cavity, between the aortic root and the left atrium (Panel B and C). The patient evolved with haemodynamic and electrical stability with no recurrence of chest discomfort. A retrospective cardiac-CT was performed that confirmed the presence of a multilobular cavity below the left coronary artery in continuous with the LVOT, compatible with a contained subannular aortic rupture (Panel E and F), at the level of previous gross calcification in the pre-operative cardiac-CT (Panel D). The case was discussed in Heart Team and a conservative strategy was adopted due to clinical stability and inoperable condition. The patient was discharged at day 28, after CT reavaluation,, that demonstrate similar findings. CONCLUSION We report a rare and potentially fatal complication of TAVI with a self-expandable valve. This clinical case illustrates how balloon post-dilation to treat moderate post-procedural paravalvular regurgitation lead to tearing of a highly calcified aortic annulus. A multi-modality imaging approach, with echocardiography and computer tomography, was essential for full anatomical definition of the subannular rupture, clinical decision-making and for follow-up surveillance. Abstract P1718 Figure. Panel A,B,C,D,E,F.

Patatin-like phospholipase domain containing 3 variants differentially impact metabolic traits in individuals at high risk for cardiovascular events.

Single nucleotide polymorphism (SNP) rs738409 C>G in the patatin‐like phospholipase domain containing 3 (PNPLA3) gene results in an amino acid exchange from isoleucin to methionine at position I148M of PNPLA3. The expression of this loss‐of‐function mutation leads to impaired hepatocellular triglyceride hydrolysis and is associated with the development of liver steatosis, fibrosis, and hepatocellular carcinoma. In contrast to these well‐established associations, the relationship of the PNPLA3 rs738409 variant with other metabolic traits is incompletely understood. We therefore assessed the association of the PNPLA3 rs738409 genotype with relevant metabolic traits in a prospective study of patients at high risk for cardiovascular events, i.e., patients undergoing coronary angiography. In a total of 270 patients, known associations of the PNPLA3 rs738409 GG genotype with nonalcoholic steatohepatitis and liver fibrosis were confirmed. In addition, we found an association of the PNPLA3 rs738409 G allele with the presence of diabetes (22% versus 28% versus 58% for CC versus CG versus GG genotype, respectively; P = 0.02). In contrast to its association with nonalcoholic fatty liver disease, liver fibrosis, and diabetes, the minor G allele of PNPLA3 rs738409 was inversely associated with total serum cholesterol and low‐density lipoprotein serum levels (P = 0.003 and P = 0.02, respectively). Finally, there was a trend toward an inverse association between the presence of the PNPLA3 rs738409 G allele and significant coronary heart disease. Comparable trends were observed for the transmembrane 6 superfamily member 2 (TM6SF2) 167 K variant, but the sample size was too small to evaluate this rarer variant. Conclusion: The PNPLA3 rs738409 G allele is associated with liver disease but also with a relatively benign cardiovascular risk profile. (Hepatology Communications 2018;2:798‐806)

Prediction of Molecular Mechanisms for LianXia NingXin Formula: A Network Pharmacology Study.

Objectives: Network pharmacological methods were used to investigate the underlying molecular mechanisms of LianXia NingXin (LXNX) formula, a Chinese prescription, to treat coronary heart disease (CHD) and disease phenotypes (CHD related diseases and symptoms).Methods: The different seed gene lists associated with the herbs of LXNX formula, the CHD co-morbid diseases and symptoms which were relieved by the LXNX formula (co-morbid diseases and symptoms) were curated manually from biomedical databases and published biomedical literatures. Module enrichment analysis was used to identify CHD-related disease modules in the protein–protein interaction (PPI) network which were also associated to the targets of LXNX formula (LXNX formula’s CHD modules). The molecular characteristics of LXNX formula’s CHD modules were investigated via functional enrichment analysis in terms of gene ontology and pathways. We performed shortest path analysis to explore the interactions between the drug targets of LXNX formula and CHD related disease phenotypes (e.g., co-morbid diseases and symptoms).Results: We identified two significant CHD related disease modules (i.e., M146 and M203), which were targeted by the herbs of LXNX formula. Pathway and GO term functional analysis results indicated that G-protein coupled receptor signaling pathways (GPCR) of M146 and cellular protein metabolic process of M203 are important functional pathways for the respective module. This is further confirmed by the shortest path analysis between the drug targets of LXNX formula and the aforementioned disease modules. In addition, corticotropin releasing hormone (CRH) and natriuretic peptide precursor A (NPPA) are the only two LXNX formula target proteins with the low shortest path length (on average shorter than 3) to their respective CHD module and co-morbid disease and symptom gene groups.Conclusion: G-protein coupled receptor signaling pathway and cellular protein metabolic process are the key LXNX formula’s pathways to treat CHD disease phenotypes, in which CRH and NPPA are the two key drug targets of LXNX formula. Further evidences from Chinese herb pharmacological databases indicate that Pinellia ternata (Banxia) has relatively strong adjustive functions on the two key targets.

Diagnostic Test Squatting Stress Echocardiography and Coronary Angiography in Diagnosing Coronary Heart Disease

Background: In patients with significant coronary heart disease (CHD), increased preload and afterload during a squat can cause wall motion abnormalities (WMA) which can be detected on echocardiography. This study was conducted to determine the diagnostic value of stress echocardiography squatting as a non-invasive examination of a relatively simple, inexpensive, and safe in the detection of coronary artery stenosis in stable CHD and unstable angina patients.Methods: This study was a cross-sectional design. The subjects were all patients with stable CHD and unstable angina whom were treated in Instalasi Pusat Jantung Rumah Sakit Dr. M. Djamil Padang from May to July 2016. Subjects underwent squatting stress echocardiography procedures followed by coronary angiography. Diagnostic test was used to determine the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of squatting stress echocardiography.Results: The sensitivity, specificity, and accuracy of squatting echocardiography for diagnosis of CAD were 90.3%, 88.9% and 89.7%, respectively.Conclusion: Squatting stress echocardiography can be proposed as a non-invasive examination which is relatively simple, inexpensive and safe to detect coronary artery stenosis on patients with stable CHD and unstable CHD.

A Meta-Analysis of Randomized Controlled Trials and Prospective Cohort Studies of Eicosapentaenoic and Docosahexaenoic Long-Chain Omega-3 Fatty Acids and Coronary Heart Disease Risk

ObjectiveTo conduct meta-analyses of randomized controlled trials (RCTs) to estimate the effect of eicosapentaenoic and docosahexaenoic acid (EPA+DHA) on coronary heart disease (CHD), and to conduct meta-analyses of prospective cohort studies to estimate the association between EPA+DHA intake and CHD risk. MethodsA systematic literature search of Ovid/Medline, PubMed, Embase, and the Cochrane Library from January 1, 1947, to November 2, 2015, was conducted; 18 RCTs and 16 prospective cohort studies examining EPA+DHA from foods or supplements and CHD, including myocardial infarction, sudden cardiac death, coronary death, and angina, were identified. Random-effects meta-analysis models were used to generate summary relative risk estimates (SRREs) and 95% CIs. Heterogeneity was examined in subgroup and sensitivity analyses and by meta-regression. Dose-response was evaluated in stratified dose or intake analyses. Publication bias assessments were performed. ResultsAmong RCTs, there was a nonstatistically significant reduction in CHD risk with EPA+DHA provision (SRRE=0.94; 95% CI, 0.85-1.05). Subgroup analyses of data from RCTs indicated a statistically significant CHD risk reduction with EPA+DHA provision among higher-risk populations, including participants with elevated triglyceride levels (SRRE=0.84; 95% CI, 0.72-0.98) and elevated low-density lipoprotein cholesterol (SRRE=0.86; 95% CI, 0.76-0.98). Meta-analysis of data from prospective cohort studies resulted in a statistically significant SRRE of 0.82 (95% CI, 0.74-0.92) for higher intakes of EPA+DHA and risk of any CHD event. ConclusionResults indicate that EPA+DHA may be associated with reducing CHD risk, with a greater benefit observed among higher-risk populations in RCTs.

PS 02-11 Upstroke Time Is an Independent Predictor for the Presence of Coronary Artery Disease in Patients with Chronic Kidney Disease

Objective: Pulse wave velocity is a marker for arterial stiffness, and indicative of increased cardiovascular morbidity and mortality in the general population. Upstroke time (UT) of arterial pulse, defined as time from the initial rise to the peak of the wave, is another parameter for arterial stiffness that is obtained during brachial-ankle pulse wave velocity (baPWV) measurement. Studies have shown significant association between baPWV and cardiovascular events or mortality in hemodialysis patients. However, there are few studies examining such relationship in non-hemodialysis chronic kidney disease (CKD) patients. Moreover, clinical utility of UT among these patients remains unknown. The present study aimed to examine the association between UT and the presence of coronary heart disease (CAD) in non-hemodialysis CKD patients. Design and Method: We enrolled 105 patients (35 non-hemodialytic CKD; 70 non-CKD) who measured baPWV and UT and underwent elective coronary angiography for suspected CAD. CKD was defined as estimated glomerular filtration rate below 60 ml/min/1.73m2. Significant coronary artery disease (sCAD) was defined as one or more stenosis over 50%. To examine the contribution of baPWV and UT for the presence of sCAD, multivariate logistic regression analysis with adjustment for potential confounders was performed in each patient group. Results: In non-hemodialysis CKD patients, UT but not baPWV was associated with sCAD (UT: Odds Ratio(OR) 1.62[95% Confidence Interval (95% CI) 1.05–2.50], p = 0.029; baPWV: OR 1.13[95% CI 0.90–1.42], p = 0.280) in univariate logistic regression analysis. In multivariate analysis, UT remained significant after adjusting traditional risk factors and other potential confounders (OR 12.4 [95% CI 1.02–151.3]; p = 0.036). In non-CKD patients, neither UT nor baPWV was associated with sCAD in both univariate and multivariate analysis. Conclusions: In non-hemodialysis CKD patients, UT serves as independent predictive risk for the presence of significant CAD.