Association of epicardial adipose tissue with different stages of coronary artery disease:A cross-sectional UK Biobank cardiovascular magnetic resonance imaging substudy

Objective: Increased epicardial adipose tissue (EAT) has been identified as a risk factor for the development of coronary artery disease (CAD). However, the exact role of EAT in the development of CAD is unclear. This study aims to compare EAT volumes between healthy controls and individuals with stable CAD and a history of myocardial infarction (MI). Furthermore, associations between clinical and biochemical parameters with EAT volumes are examined.& nbsp;Methods: This retrospective cross-sectional study included 171 participants from the United Kingdom Biobank (56 healthy controls; 60 stable CAD; 55 post MI), whom were balanced for age, sex and body mass index (BMI). EAT volumes were quantified on end-diastolic cardiac magnetic resonance (CMR) imaging short-axis slices along the left and right ventricle and indexed for body surface area (iEAT) and iEAT volumes were compared between groups.& nbsp;Results: iEAT volumes were comparable between control, CAD and MI cases (median [IQR]: 66.1[54.4-77.0] vs. 70.9[55.8-85.5] vs. 67.6[58.6-82.3] mL/m(2), respectively (p > 0.005 for all). Increased HDL-cholesterol was associated with decreased iEAT volume (8 =-14.8, CI =-24.6 to-4.97, p = 0.003) and suggestive associations (P-value = 0.005) were observed between iEAT and triglycerides (beta = 3.26, CI = 0.42 to 6.09, p = 0.02), Apo-lipoprotein A (beta =-16.3, CI =-30.3 to-2.24, p = 0.02) and LDL-cholesterol (beta = 3.99, CI =-7.15 to-0.84, p = 0.01).& nbsp;Conclusions: No significant differences in iEAT volumes were observed between patients with CAD, MI and healthy controls. Our results indicate the importance of correcting for confounding by CVD risk factors, including circulating lipid levels, when studying the relationship between EAT volume and CAD. Further mechanistic studies on causal pathways and the role of EAT composition are warranted

Association of Circulating Ketone Bodies With Functional Outcomes After ST-Segment Elevation Myocardial Infarction

Background: Circulating ketone bodies (KBs) are increased in patients with heart failure (HF), corresponding with increased cardiac KB metabolism and HF severity. However, the role of circulating KBs in ischemia/reperfusion remains unknown. Objectives: This study sought to investigate longitudinal changes of KBs and their associations with functional outcomes in patients presenting with ST-segment elevation myocardial infarction (STEMI). Methods: KBs were measured in 369 participants from a randomized trial on early metformin therapy after STEMI. Nonfasting plasma concentrations of KBs (β-hydroxybutyrate, acetoacetate, and acetone) were measured by nuclear magnetic resonance spectroscopy at presentation, at 24 hours, and after 4 months. Myocardial infarct size and left ventricular ejection fraction (LVEF) were determined by cardiac magnetic resonance imaging at 4 months. Associations of circulating KBs with infarct size and LVEF were determined using multivariable linear regression analyses. Results: Circulating KBs were high at presentation with STEMI (median total KBs: 520 μmol/L; interquartile range [IQR]: 315-997 μmol/L). At 24 hours after reperfusion, KBs were still high compared with levels at 4-month follow-up (206 μmol/L [IQR: 174-246] vs 166 μmol/L [IQR: 143-201], respectively; P < 0.001). Increased KB concentrations at 24 hours were independently associated with larger myocardial infarct size (total KBs, per 100 μmol/L: β = 1.56; 95% confidence interval: 0.29-2.83; P = 0.016) and lower LVEF (β = −1.78; 95% CI: (−3.17 to −0.39; P = 0.012). Conclusions: Circulating KBs are increased in patients presenting with STEMI. Higher KBs at 24 hours are associated with functional outcomes after STEMI, which suggests a potential role for ketone metabolism in response to myocardial ischemia. (Metabolic Modulation With Metformin to Reduce Heart Failure After Acute Myocardial Infarction: Glycometabolic Intervention as Adjunct to Primary Coronary Intervention in ST Elevation Myocardial Infarction (GIPS-III): a Randomized Controlled Trial; NCT01217307

Early detection of obstructive coronary artery disease in the asymptomatic high-risk population:objectives and study design of the EARLY-SYNERGY trial

Background: Coronary artery disease (CAD) burden for society is expected to steeply increase over the next decade. Improved feasibility and efficiency of preventive strategies is necessary to flatten the curve. Acute myocardial infarction (AMI) is the main determinant of CAD-related mortality and morbidity, and predominantly occurs in individuals with more advanced stages of CAD causing subclinical myocardial ischemia (obstructive CAD; OCAD). Unfortunately, OCAD can remain subclinical until its destructive presentation with AMI or sudden death. Current primary preventive strategies are not designed to differentiate between non-OCAD and OCAD and the opportunity is missed to treat individuals with OCAD more aggressively. Methods: EARLY-SYNERGY is a multicenter, randomized-controlled clinical trial in individuals with coronary artery calcium (CAC) presence to study (1.) the yield of cardiac magnetic resonance stress myocardial perfusion imaging (CMR-MPI) for early OCAD diagnosis and (2) whether early OCAD diagnosis improves outcomes. Individuals with CAC score ≥300 objectified in 2 population-based trials (ROBINSCA; ImaLife) are recruited for study participation. Eligible candidates are randomized 1:1 to cardiac magnetic resonance stress myocardial perfusion imaging (CMR-MPI) or no additional functional imaging. In the CMR-MPI arm, feedback on imaging results is provided to primary care provider and participant in case of guideline-based actionable findings. Participants are followed-up for clinical events, healthcare utilization and quality of life. Conclusions: EARLY-SYNERGY is the first randomized-controlled clinical trial designed to test the hypothesis that subclinical OCAD is widely present in the general at-risk population and that early differentiation of OCAD from non-OCAD followed by guideline-recommended treatment improves outcomes

Aspiration–sclerotherapy Results in Effective Control of Liver Volume in Patients with Liver Cysts

Purpose To study the extent to which aspiration–sclerotherapy reduces liver volume and whether this therapy results in relief of symptoms. Results Four patients, group I, with isolated large liver cysts, and 11 patients, group II, with polycystic livers, underwent aspiration–sclerotherapy. Average volume of aspirated cyst fluid was 1,044 ml (range 225–2,000 ml) in group I and 1,326 ml (range 40–4,200 ml) in group II. Mean liver volume before the procedure was 2,157 ml (range 1,706–2,841 ml) in group I and 4,086 ml (range 1,553–7,085 ml) in group II. This decreased after the procedure to 1,757 ml (range 1,479–2,187 ml) in group I. In group II there was a statistically significant decrease to 3,347 ml (range 1,249–6,930 ml, P = 0.008). Volume reduction was 17.1% (range −34.7% to −4.1%) and 19.2% (range −53.9% to +2.4%) in groups I and II, respectively. Clinical severity of all symptoms decreased, except for involuntary weight loss and pain in group II. Conclusion Aspiration–sclerotherapy is an effective means of achieving liver volume reduction and relief of symptoms

Susceptibility to chronic mucus hypersecretion, a genome wide association study

Background: Chronic mucus hypersecretion (CMH) is associated with an increased frequency of respiratory infections, excess lung function decline, and increased hospitalisation and mortality rates in the general population. It is associated with smoking, but it is unknown why only a minority of smokers develops CMH. A plausible explanation for this phenomenon is a predisposing genetic constitution. Therefore, we performed a genome wide association (GWA) study of CMH in Caucasian populations. Methods: GWA analysis was performed in the NELSON-study using the Illumina 610 array, followed by replication and meta-analysis in 11 additional cohorts. In total 2,704 subjects with, and 7,624 subjects without CMH were included, all current or former heavy smokers (≥20 pack-years). Additional studies were performed to test the functional relevance of the most significant single nucleotide polymorphism (SNP). Results: A strong association with CMH, consistent across all cohorts, was observed with rs6577641 (p = 4.25x10-6, OR = 1.17), located in intron 9 of the special AT-rich sequence-binding protein 1 locus (SATB1) on chromosome 3. The risk allele (G) was associated with higher mRNA expression of SATB1 (4.3x10 -9) in lung tissue. Presence of CMH was associated with increased SATB1 mRNA expression in bronchial biopsies from COPD patients. SATB1 expression was induced during differentiation of primary human bronchial epithelial cells in culture. Conclusions: Our findings, that SNP rs6577641 is associated with CMH in multiple cohorts and is a cis-eQTL for SATB1, together with our additional observation that SATB1 expression increases during epithelial differentiation provide suggestive evidence that SATB1 is a gene that affects CMH

Susceptibility to chronic mucus hypersecretion, a genome wide association study

Background: Chronic mucus hypersecretion (CMH) is associated with an increased frequency of respiratory infections, excess lung function decline, and increased hospitalisation and mortality rates in the general population. It is associated with smoking, but it is unknown why only a minority of smokers develops CMH. A plausible explanation for this phenomenon is a predisposing genetic constitution. Therefore, we performed a genome wide association (GWA) study of CMH in Caucasian populations.Methods: GWA analysis was performed in the NELSON-study using the Illumina 610 array, followed by replication and metaanalysis in 11 additional cohorts. In total 2,704 subjects with, and 7,624 subjects without CMH were included, all current or former heavy smokers (&gt;= 20 pack-years). Additional studies were performed to test the functional relevance of the most significant single nucleotide polymorphism (SNP).Results: A strong association with CMH, consistent across all cohorts, was observed with rs6577641 (p = 4.25610(-6), OR = 1.17), located in intron 9 of the special AT-rich sequence-binding protein 1 locus (SATB1) on chromosome 3. The risk allele (G) was associated with higher mRNA expression of SATB1 (4.3610 29) in lung tissue. Presence of CMH was associated with increased SATB1 mRNA expression in bronchial biopsies from COPD patients. SATB1 expression was induced during differentiation of primary human bronchial epithelial cells in culture.Conclusions: Our findings, that SNP rs6577641 is associated with CMH in multiple cohorts and is a cis-eQTL for SATB1, together with our additional observation that SATB1 expression increases during epithelial differentiation provide suggestive evidence that SATB1 is a gene that affects CMH.</p

Selecting heart failure patients for metabolic interventions

Introduction: Heart failure (HF) has become the cardiovascular epidemic of the century and now imposes an immense burden on health care systems. While our understanding of the pathophysiology of HF has increased dramatically, the translation of knowledge into clinical practice has been disappointing. Metabolic dysfunction in HF has been studied for eight decades, but these efforts have not resulted in effective therapies. This paucity in clinical translation probably results from the variable contribution of metabolic dysfunction to the underlying heart disease. A major unmet need in cardiac drug development is therefore the ability to identify a homogeneous subset of patients in whom HF is driven by a specific mechanism that can be targeted.Areas covered: The available literature was evaluated to describe maladaptive metabolic perturbations that occur in failing hearts and may cause metabolic inflexibility, oxidative stress and cardiac energy depletion. Furthermore, the potential utility of various biomarkers and molecular imaging techniques to detect and quantify specific metabolic dysfunctions in HF were compared. Finally, the authors propose ways to utilize these techniques to select patients for specific metabolic interventions.Expert commentary: Metabolic dysfunction is among the most promising therapeutic targets in HF. Meticulous patient-selection with molecular imaging techniques and specific biomarkers appears indispensable for the effective translation of decades of scientific knowledge into clinical therapeutics