Epicardial adipose tissue differentiates in patients with and without coronary microvascular dysfunction.

BACKGROUND/OBJECTIVES: Coronary microvascular dysfunction (CMD) is a common disorder, leading to symptoms similar to obstructive coronary artery disease and bears important prognostic implications. Local inflammation is suggested to promote development of CMD. Epicardial adipose tissue (EAT) is a local visceral fat depot surrounding the heart and the coronary arteries, modifying the inflammatory environment of the heart. We compared EAT in patients with and without CMD. METHODS: We retrospectively included consecutive patients undergoing diagnostic coronary angiography as well as transthoracic echocardiography between March and October 2016. EAT thickness was defined as space between the epicardial wall of the myocardium and the visceral layer of the pericardium and EAT index was calculated as EAT thickness/body surface area. Logistic regression analysis was used to determine the association of EAT index with the presence of CMD. RESULTS: Overall, 399 patients (mean age 60.2 ± 14.0 years, 46% male) were included. EAT thickness was significantly higher in patients with CMD compared to patients without CMD (EAT thickness 4.4 ± 1.8 vs. 4.9 ± 2.4 mm, p = 0,048 for patients without and with CMD, respectively). In univariate regression analysis, EAT index was associated with a 30% higher frequency of CMD (odds ratio [95% confidence interval]: 1.30 [1.001-1.69], p = 0.049). Effect sizes remained stable upon adjustment for body mass index (BMI, 1.30 [1.003-1.70], p = 0.048), but were attenuated when ancillary adjusting for age and gender (1.17 [0.90-1.54, p = 0.25). The effect was more pronounced in patients >65 years of age and independent of BMI and sex (1.85 [1.14-3.00], p = 0.013). CONCLUSION: EAT thickness is independently associated with CMD and can differentiate between patients with and without CMD especially in older age groups. Our results support the hypothesis that modulation of local inflammation by epicardial fat is involved in the development of CMD.

Higher BNP/NT-pro BNP levels stratify prognosis equally well in patients with and without heart failure: a meta-analysis.

AIMS: The initial and dynamic levels of B-type natriuretic peptide (BNP) and N-terminal-prohormone BNP (NT-proBNP) are routinely used in clinical practice to identify patients with acute and chronic heart failure. In addition, BNP/NT-proBNP levels might be useful for risk stratification in patients with and without heart failure. We performed a meta-analysis to investigate, whether the value of BNP/NT-proBNP as predictors of long-term prognosis differentiates in cohorts with and without heart failure. METHODS AND RESULTS: We systematically searched established scientific databases for studies evaluating the prognostic value of BNP or NT-proBNP. Random effect models were constructed. Data from 66 studies with overall 83 846 patients (38 studies with 46 099 patients with heart failure and 28 studies with 37 747 patients without heart failure) were included. In the analysis of the log-transformed BNP/NT-proBNP levels, an increase in natriuretic peptides by one standard deviation was associated with a 1.7-fold higher MACE rate (hazard ratio [95% confidence interval]: 1.74[1.58-1.91], P < 0.0001). The effect sizes were comparable, with a substantial overlap in the confidence intervals, when comparing studies involving patients with and without heart failure (1.75[1.54-2.0], P < 0.0001 vs. 1.74[1.47-2.06], P < 0.0001). Similar results were observed when stratifying by quartiles of BNP/NT-proBNP. In studies using pre-defined cut-off-values for BNP/NT-proBNP, elevated levels were associated with the long-term prognosis, independent of the specific cut-off value used. CONCLUSIONS: BNP/NT-proBNP levels are predictors for adverse long-term outcome in patients with and without known heart failure. Further research is necessary to establish appropriate thresholds, especially in non-heart failure cohorts.

Epicardial fat and incident heart failure with preserved ejection fraction in patients with coronary artery disease.

BACKGROUND: We aimed to determine, whether epicardial adipose tissue (EAT) as local source of inflammation, as well as its change over time, associates with the development of heart failure with preserved ejection fraction (HFpEF) in patients with coronary artery disease. METHODS AND RESULTS: We retrospectively included 379patients (aged 65.2 ± 11.7 years, 70.2%male) with coronary artery disease but without heart failure at baseline, undergoing clinical and echocardiographic assessment in 2010-2013 and receiving a second assessment in 2014-2018. EAT thickness was defined as space between the myocardium and the pericardium and indexed (EATi) by body surface area. Change in EATi was calculated as the difference of follow-up and baseline EATi. HFpEF was defined according to presence of dyspnea, elevated natriuretic peptides, and structural and/or functional alterations on echocardiography in accordance with current European Society of Cardiology guidelines. During a median follow-up of 4.3 years, 142patients (37.5%) developed HFpEF. Patients with onset of HFpEF had higher EATi at baseline (2.4 ± 1.3 vs. 1.9 ± 0.9 mm/m2, p = 0.001). In multivariable regression analysis, EATi associated with onset of HFpEF (1.25 [1.01-1.54], p = 0.04). Likewise, an increase in EATi over time was linked HFpEF development, independent of other risk factors and baseline EATi (1.39 [1.04-1.87], p = 0.03). EATi was significantly associated with follow-up b-type natriuretic peptide (BNP) levels (4.31[0.58-8.05], p = 0.024), but not with baseline BNP (2.24[-0.27-4.76], p = 0.08). CONCLUSION: EATi is associated with the development of HFpEF. The finding of changes in EATi altering the risk of HFpEF manifestation support the rationale for further research on epicardial fat modulation as a treatment target for HFpEF.

Epicardial adipose tissue is a robust measure of increased risk of myocardial infarction - a meta-analysis on over 6600 patients and rationale for the EPIC-ACS study.

BACKGROUND: Epicardial adipose tissue (EAT) surrounds the heart and the coronary vessels. EAT produces pro- and anti-inflammatory cytokines. Several studies have already documented the association of EAT and cardiovascular risk factors as well as coronary artery disease manifestations. Currently computed tomography (CT) is considered the gold standard for measurement of 3-dimensional volume of EAT. In addition, echocardiography might be an easy accessible alternative in particular in an emergency setting. METHODS: We performed a metaanalysis of existing studies describing the differences of EAT in patients with and without myocardial infarction. We used established databases and were searching for "epicardial adipose tissue" or "pericardial adipose tissue" and "myocardial infarction", "coronary events", or "acute coronary syndrome". We included over 6600 patients from 7 studies. Random effect models were calculated and all analyses were performed by using the Review Manager 5.3. RESULTS: Patients with myocardial infarction had 37% (confidence interval [0.21-0.54], P value <.001)] higher measures of EAT compared to patients without myocardial infarction. Comparing studies using echocardiography vs CT for assessment of EAT thickness, similar relative differences in EAT with wide overlap of confidence intervals were observed (for echocardiography: 0.4 [0.04-0.76], for CT: 0.36 [0.16-0.57], P value <.001 for both). CONCLUSIONS: Patients with myocardial infarction have more EAT as compared to patients without myocardial infarction independently of the used imaging modality. Further prospective studies are needed to evaluate, how quantification of EAT in clinical routine can improve patients management.

Implications of Alterations in Pre-test Probability in the 2019 Update of ESC Guidelines for Chronic Coronary Syndromes on Diagnostic Accuracy of Pharmacological Stress-Echocardiography: A Retrospective Cohort Study.

BACKGROUND: With the 2019 update of European Society of Cardiology (ESC) guidelines for chronic coronary syndromes, the pre-test probabilities (PTPs) based on age, sex, and symptoms have undergone major revisions. We aimed to determine implications of these alterations on diagnostic accuracy of dobutamine stress echocardiography (DSE). METHODS: We retrospectively included consecutive patients undergoing pharmacological stress-echocardiography for evaluation of suspected obstructive coronary artery disease. DSE was performed as non-invasive imaging test and was indicated by individual treating physician's decision. Sensitivity, specificity, positive and negative predictive value as well as accuracy were assessed for detection of obstructive coronary artery disease, defined as revascularization therapy following DSE. RESULTS: We included 206 patients (mean age 63.2 ± 12.4 years, 59.7% male). 51% of the cohort had a PTP of < 15% according to both scores. 9.2% of patients with PTP < 15% according to the original Diamond and Forrester score had a PTP > 15% according to 2019 ESC guidelines, predominantly due to the accountancy of dyspnea. In contrast, 13.6% of patient had a PTP ≥ 15% according to the original Diamond and Forrester score, while PTP was assessed below this threshold by updated guidelines. The differences in patient selection according to updated guidelines did not alter the diagnostic accuracy of DSE (68% for both). CONCLUSIONS: Changes in assessment of PTP according to updated ESC guidelines from 2019 led to a relevant reclassification of patients with suspected coronary artery disease, ultimately changing the group of patients appropriate for DSE for evaluation of myocardial ischemia. Comparing the diagnostic performance in appropriate PTP groups, however, led to similar results.

Utilization of IVUS improves all-cause mortality in patients undergoing invasive coronary angiography.

Background and aims: Available data suggest that the use of IVUS for guidance of percutaneous coronary interventions (PCIs) improves the prognosis of patients undergoing complex interventions. We aimed to examine how the utilization of intravascular ultrasound (IVUS) affects patient survival irrespective of procedure complexity. Methods: The present analysis is based on the longitudinal ECAD registry of consecutive patients undergoing coronary angiography between 2004 and 2019. The incidence of death due to any cause was evaluated during a mean follow-up of 3.4 years. Cox regression analysis was used to determine the association of IVUS utilization with incident mortality. Results: Overall, data from 30,814 coronary angiography exams (mean age 64.9 ± 12.5 years, 70.3% male) were included, among which 4991 procedures (16.2%) were guided by IVUS. Utilization of IVUS was associated with a 35% reduction in mortality, independent of traditional risk factors (0.64(0.58-0.71), p < 0.0001). The effect of IVUS on mortality was equally present in patients undergoing IVUS-guided coronary interventions (0.75[0.67-0.84], p < 0.0001) as well as purely diagnostic coronary angiography exams (0.62[0.56-0.72], p < 0.0001). In patients without coronary intervention, IVUS utilization led to a higher frequency of aspirin (82.6% vs. 61.9% for IVUS vs. no IVUS, p < 0.0001) and statin therapy (74.9% vs. 62.5%, p < 0.0001). Conclusions: In a large longitudinal registry cohort of patients undergoing invasive coronary angiography, IVUS utilization was associated with lower long-term mortality. The beneficial role of IVUS utilization on survival was equally present for coronary interventions and diagnostic coronary angiograms. Our results support the use of intravascular imaging for decision making in interventional cardiology.

Treatment Patterns of Lipid-Lowering Therapy in Patients with Coronary Artery Disease Aged Above and Below 75 Years: A Retrospective Cross-Sectional Study of 1500 Patients in a Tertiary Care Referral Center in Germany.

INTRODUCTION: Lipid-lowering therapy of elderly patients with coronary artery disease (CAD) inherits a medical challenge, as these patients experience a higher absolute risk reduction but may be more prone to side effects. We aimed to evaluate the treatment patterns in lipid-lowering therapy, comparing CAD patients above versus below 75 years of age. METHODS: We retrospectively included patients with known CAD admitted to the West German Heart and Vascular Center. Low-density lipoprotein cholesterol (LDL-C) levels and intensity of statin therapy (based on dosage and type of statin) were assessed from all available hospital records. RESULTS: We included 1500 patients (mean age 68.4 ± 11.2 years, 75.7% male) from 813 referring treating primary care physicians in 98 cities of Germany in our analysis. A total of 982 patients were < 75 years of age, whereas 518 were ≥ 75 years of age. LDL-C levels did not differ between age groups (≥ 75: 96.0 ± 35.1 mg/dl; < 75: 98.9 ± 35.8 mg/dl, p = 0.13). Simvastatin was most frequently prescribed in both age groups (54.9% vs. 50.7% for age ≥ 75 vs. < 75 years, p = 0.16), followed by atorvastatin (31.6% vs. 33.3%, p = 0.53). Elderly patients received slightly lower statin doses as compared to patients < 75 years of age (28.8 ± 12.8 mg vs. 31.4 ± 13.7 mg, p = 0.0007). Interestingly, patients ≥ 75 years of age achieved LDL-C < 70 mg/dl slightly more frequently than younger patients (24.0% vs. 20.1%, p = 0.09), while only a minority had LDL-C < 55 mg/dl in both age groups. Excluding patients with myocardial infarction at presentation, creatine kinase levels were not relevantly different between age groups (131.9 ± 450.0 U/l vs. 127.5 ± 111.4 U/l, p = 0.78). CONCLUSION: Patients ≥ 75 years of age receive lower doses of statin therapy and reach slightly lower LDL-C levels. However, the majority of elderly patients miss current recommendations regarding LDL-C thresholds.

Liver parameters as part of a non-invasive model for prediction of all-cause mortality after myocardial infarction.

INTRODUCTION: Liver parameters are associated with cardiovascular disease risk and severity of stenosis. It is unclear whether liver parameters could predict the long-term outcome of patients after acute myocardial infarction (AMI). We performed an unbiased analysis of the predictive value of serum parameters for long-term prognosis after AMI. MATERIAL AND METHODS: In a retrospective, observational, single-center, cohort study, 569 patients after AMI were enrolled and followed up until 6 years for major adverse cardiovascular events, including cardiac death. Patients were classified into non-survivors (n = 156) and survivors (n = 413). Demographic and laboratory data were analyzed using ensemble feature selection (EFS) and logistic regression. Correlations were performed for serum parameters. RESULTS: Age (73; 64; p < 0.01), alanine aminotransferase (ALT; 93 U/l; 40 U/l; p < 0.01), aspartate aminotransferase (AST; 162 U/l; 66 U/l; p < 0.01), C-reactive protein (CRP; 4.7 U/l; 1.6 U/l; p < 0.01), creatinine (1.6; 1.3; p < 0.01), γ-glutamyltransferase (GGT; 71 U/l; 46 U/l; p < 0.01), urea (29.5; 20.5; p < 0.01), estimated glomerular filtration rate (eGFR; 49.6; 61.4; p < 0.01), troponin (13.3; 7.6; p < 0.01), myoglobin (639; 302; p < 0.01), and cardiovascular risk factors (hypercholesterolemia p < 0.02, family history p < 0.01, and smoking p < 0.01) differed significantly between non-survivors and survivors. Age, AST, CRP, eGFR, myoglobin, sodium, urea, creatinine, and troponin correlated significantly with death (r = -0.29; 0.14; 0.31; -0.27; 0.20; -0.13; 0.33; 0.24; 0.12). A prediction model was built including age, CRP, eGFR, myoglobin, and urea, achieving an AUROC of 77.6% to predict long-term survival after AMI. CONCLUSIONS: Non-invasive parameters, including liver and renal markers, can predict long-term outcome of patients after AMI.

Association of echocardiographic measures of left ventricular diastolic dysfunction and hypertrophy with presence of coronary microvascular dysfunction.

BACKGROUND: Coronary microvascular dysfunction (CMD) is a common disorder, leading to symptoms similar to obstructive coronary artery disease. We aimed to determine whether measures of left ventricular (LV) diastolic function and hypertrophy may predict presence of CMD. METHODS: We retrospectively included patients undergoing diagnostic coronary angiography and transthoracic echocardiography, excluding patients with obstructive coronary artery disease, previous revascularization therapy, moderate or severe mitral valve disease, or atrial fibrillation. The following markers of LV diastolic function and hypertrophy were assessed: E- and A-wave velocity, E-wave deceleration time, E/A- and E/E'-ratio, left atrial area, left LV mass index, LV ejection time (LVET) and mitral valve closure to opening time. Logistic regression analysis was used to determine the association of echocardiographic parameters with presence of CMD. RESULTS: From 378 patients (mean age ± SD 59.7 ± 13.6 years, 45.6% male) included, the majority had CMD (n = 293, 77.5%). Patients with CMD were older (60.5 ± 13.4 years vs. 56.9 ± 14.3 years, p = 0.03), were less frequent male (42.3% vs. 57.0%, p = 0.02), and had higher systolic blood pressure (137.9 ± 25.7 mmHg vs. 124.7 ± 25.6 mmHg, p < 0.0001). LVET was significantly associated with CMD (1.42 [1.02-1.96], p = 0.04), while a non-statistically significant link was observed for A-wave velocity and E/E'-ratio (1.39 [0.96-2.00], p = 0.08 and 1.40 [0.92-2.13], p = 0.1, respectively). For all other echocardiography-derived measures, odds ratio for the association with CMD was <1.3 per each SD increase. CONCLUSIONS: In this cross-sectional single-center cohort study, CMD was a frequent finding in patients undergoing coronary angiography for suspected obstructive coronary artery disease. LVET from transthoracic echocardiography is associated with the presence of CMD.

In Acute Myocardial Infarction Liver Parameters Are Associated With Stenosis Diameter.

Detection of high-risk subjects in acute myocardial infarction (AMI) by noninvasive means would reduce the need for intracardiac catheterization and associated complications. Liver enzymes are associated with cardiovascular disease risk. A potential predictive value for liver serum markers for the severity of stenosis in AMI was analyzed.Patients with AMI undergoing percutaneous coronary intervention (PCI; n = 437) were retrospectively evaluated. Minimal lumen diameter (MLD) and percent stenosis diameter (SD) were determined from quantitative coronary angiography. Patients were classified according to the severity of stenosis (SD ≥ 50%, n = 357; SD < 50%, n = 80). Routine heart and liver parameters were associated with SD using random forests (RF). A prediction model (M10) was developed based on parameter importance analysis in RF.Age, alkaline phosphatase (AP), aspartate aminotransferase (AST), and MLD differed significantly between SD ≥ 50 and SD < 50. Age, AST, alanine aminotransferase (ALT), and troponin correlated significantly with SD, whereas MLD correlated inversely with SD. M10 (age, BMI, AP, AST, ALT, gamma-glutamyltransferase, creatinine, troponin) reached an AUC of 69.7% (CI 63.8-75.5%, P < 0.0001).Routine liver parameters are associated with SD in AMI. A small set of noninvasively determined parameters can identify SD in AMI, and might avoid unnecessary coronary angiography in patients with low risk. The model can be accessed via http://stenosis.heiderlab.de.