Differential implications of gut-related metabolites on outcomes between heart failure and myocardial infarction.

Gut metabolites, through their role in atherosclerotic plaque formation,1 myocardial fibrosis,2 and myocardial function suppression,3 have been implicated in the pathophysiology of various cardiovascular (CV) diseases.4,5 Clinical studies have shown the association of gut metabolites with adverse outcomes, severity, and risk stratification in several CV diseases [e.g. heart failure (HF)6 and myocardial infarction (MI)7]. Despite most of the past studies having focused mainly on a single metabolite (i.e. trimethylamine N-oxide—TMAO), it has been suggested that additional metabolites of this pathway, involving choline and carnitine (e.g. acetyl-L-carnitine, L-carnitine, betaine, and γ-butyrobetaine), may have an additional role to play.8,9 However, to date, the proper contribution of the different metabolites in the spectrum of the CV diseases still remains unclear; therefore, the aim of the present study is to investigate whether there is a differential contribution of metabolite biomarkers of the choline/carnitine–metabolic pathway in association with the adverse outcomes of MI and HF.</p

Is admission blood glucose concentration a more powerful predictor of mortality after myocardial infarction than diabetes diagnosis? A retrospective cohort study.

Objective: To explore the relative association of admission blood glucose levels and antecedent diabetes on early and long-term survival in a contemporary UK population of patients with ST elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI). Design: Retrospective cohort study based on the Myocardial Ischaemia National Audit Project dataset. Setting: Tertiary care centre. Participants: 4111 (20.3% known diabetes) consecutive patients admitted with acute myocardial infarction (58.3% STEMI) between October 2002 and September 2008. Primary and secondary outcome measures: All-cause mortality at 30 days and 1 year. The relative association of admission blood glucose and of antecedent diabetes with mortality was assessed using multivariate Cox regression analysis. Furthermore, we compared these relationships in patients with STEMI to those with NSTEMI. Results: By 30 days and 1 year, 409 (9.9%) and 677 (16.5%) of patients died. After adjusting for covariates, diabetes did not show independent association with mortality at any time point, in the entire cohort (HR 30 days 0.93 (95% CI 0.63 to 1.38); 1 year 1.00 (0.77 to 1.30)) or in subgroups of STEMI (HR 30 days 1.03 (0.65 to 1.64); 1 year 1.08 (0.77 to 1.51)) and NSTEMI (HR 30 days 0.62 (0.26 to 1.50); 1 year 0.87 (0.56 to 1.36)). In contrast, after adjusting for covariates, admission glucose showed robust and independent association with mortality in the entire cohort (HR: 30 days 1.07 (1.04 to 1.10); 1 year 1.05 (1.03 to 1.08)), and in the subgroup of STEMI (30 days 1.07 (1.03 to 1.10); 1 year 1.07 (1.04 to 1.10)), and NSTEMI (HR 30 days 1.07 (1.00 to 1.14); 1 year 1.02 (0.97 to 1.06)). Conclusions: Admission glucose is strongly associated with mortality in all presentations of acute myocardial infarction (AMI), irrespective of established diabetes diagnosis. The increased risk is maintained up to 1 year. Future studies are required to assess the impact of active management of elevated blood glucose in improving mortality in individuals admitted with AMI

Ethnic differences in associations of outcomes with trimethylamine N-oxide in acute heart failure patients

Aims The aim of this study was to investigate whether ethnicity influences the associations between trimethylamine N-oxide (TMAO) levels and heart failure (HF) outcomes. Methods and results Trimethylamine N-oxide levels were measured in two cohorts with acute HF at two sites. The UK Leicester cohort consisted mainly of Caucasian (n = 842, 77%) and South Asian (n = 129, 12%) patients, whereas patients in the Japanese cohort (n = 116, 11%) were all Japanese. The primary endpoint was the measurement of all-cause mortality and/or HF rehospitalization within 1 year post-admission. Association of TMAO levels with outcome was compared in the entire population and between ethnic groups after adjustment for clinical parameters. TMAO levels were significantly higher in Japanese patients [median (interquartile range): 9.9 μM (5.2–22.8)] than in Caucasian [5.9 μM (3.6–10.8)] and South Asian [4.5 μM (3.1–8.4)] (P < 0.001) patients. There were no differences in the rate of mortality and/or HF rehospitalization between the ethnic groups (P = 0.096). Overall, higher TMAO levels showed associations with mortality and/or rehospitalization after adjustment for confounders ( P = 0.002). Despite no differences between ethnicity and association with mortality/HF after adjustment (P = 0.311), only in Caucasian patients were TMAO levels able to stratify for a mortality/HF event (P < 0.001). Conclusions Differences were observed in the association of mortality and/or rehospitalization based on circulating TMAO levels. Elevated TMAO levels in Caucasian patients showed increased association with adverse outcomes, but not in non-Caucasian patients.</div

Effects of late, repetitive remote ischaemic conditioning on myocardial strain in patients with acute myocardial infarction

Late, repetitive or chronic remote ischaemic conditioning (CRIC) is a potential cardioprotective strategy against adverse remodelling following ST-segment elevation myocardial infarction (STEMI). In the randomised Daily Remote Ischaemic Conditioning Following Acute Myocardial Infarction (DREAM) trial, CRIC following primary percutaneous coronary intervention (P-PCI) did not improve global left ventricular (LV) systolic function. A post-hoc analysis was performed to determine whether CRIC improved regional strain. All 73 patients completing the original trial were studied (38 receiving 4 weeks’ daily CRIC, 35 controls receiving sham conditioning). Patients underwent cardiovascular magnetic resonance at baseline (5–7 days post-STEMI) and after 4 months, with assessment of LV systolic function, infarct size and strain (longitudinal/circumferential, in infarct-related and remote territories). At both timepoints, there were no significant between-group differences in global indices (LV ejection fraction, infarct size, longitudinal/circumferential strain). However, regional analysis revealed a significant improvement in longitudinal strain in the infarcted segments of the CRIC group (from − 16.2 ± 5.2 at baseline to − 18.7 ± 6.3 at follow up, p = 0.0006) but not in corresponding segments of the control group (from − 15.5 ± 4.0 to − 15.2 ± 4.7, p = 0.81; for change: − 2.5 ± 3.6 versus + 0.3 ± 5.6, respectively, p = 0.027). In remote territories, there was a lower increment in subendocardial circumferential strain in the CRIC group than in controls (− 1.2 ± 4.4 versus − 2.5 ± 4.0, p = 0.038). In summary, CRIC following P-PCI for STEMI is associated with improved longitudinal strain in infarct-related segments, and an attenuated increase in circumferential strain in remote segments. Further work is needed to establish whether these changes may translate into a reduced incidence of adverse remodelling and clinical events. Clinical Trial Registration: http://clinicaltrials.gov/show/NCT01664611

Visualisation of exhaled breath metabolites reveals distinct diagnostic signatures for acute cardiorespiratory breathlessness

Breath analysis can be a useful noninvasive way to detect disease. Here, Ibrahim et al. studied the volatile organic compound (VOC) signatures associated with acute cardiorespiratory diseases in patients presenting breathlessness. Using two-dimensional gas chromatography and mass spectrometry, the authors found clusters of VOCs associated with acute heart failure, asthma, chronic obstructive pulmonary disease, and pneumonia. These breath biomarkers correlated with blood-based biomarkers. An acute disease VOC score based on a 101-biomarker panel was associated with 2-year all-cause mortality. This study demonstrates how breathomics can help diagnose disease and further our understanding of metabolic subgroups

Association of epicardial adipose tissue with early structural and functional cardiac changes in Type 2 diabetes

Background Dysregulated epicardial adipose tissue (EAT) may contribute to the development of heart failure in Type 2 diabetes (T2D). This study aimed to evaluate the associations between EAT volume and composition with imaging markers of subclinical cardiac dysfunction in people with T2D and no prevalent cardiovascular disease. Methods Prospective case-control study enrolling participants with and without T2D and no known cardiovascular disease. Two hundred and fifteen people with T2D (median age 63 years, 60 % male) and thirty-nine non-diabetics (median age 59 years, 62 % male) were included. Using computed tomography (CT), total EAT volume and mean CT attenuation, as well as, low attenuation (Hounsfield unit range −190 to −90) EAT volume were quantified by a deep learning method and volumes indexed to body surface area. Associations with cardiac magnetic resonance-derived left ventricular (LV) volumes and strain indices were assessed using linear regression. Results T2D participants had higher LV mass/volume ratio (median 0.89 g/mL [0.82–0.99] vs 0.79 g/mL [0.75–0.89]) and lower global longitudinal strain (GLS; 16.1 ± 2.3 % vs 17.2 ± 2.2 %). Total indexed EAT volume correlated inversely with mean CT attenuation. Low attenuation indexed EAT volume was 2-fold higher (18.8 cm3/m2 vs. 9.4 cm3/m2, p Conclusions Higher EAT volumes seen in T2D are associated with a lower mean CT attenuation. Low attenuation indexed EAT volume is independently, but only weakly, associated with markers of subclinical cardiac dysfunction in T2D.</p

Distinct pathophysiological pathways in women and men with heart failure

Aims: Clinical differences between women and men have been described in heart failure (HF). However, less is known about the underlying pathophysiological mechanisms. In this study, we compared multiple circulating biomarkers to gain better insights into differential HF pathophysiology between women and men. Methods and results: In 537 women and 1485 men with HF, we compared differential expression of a panel of 363 biomarkers. Then, we performed a pathway over-representation analysis to identify differential biological pathways in women and men. Findings were validated in an independent HF cohort (575 women, 1123 men). In both cohorts, women were older and had higher left ventricular ejection fraction (LVEF). In the index and validation cohorts respectively, we found 14/363 and 12/363 biomarkers that were relatively up-regulated in women, while 21/363 and 14/363 were up-regulated in men. In both cohorts, the strongest up-regulated biomarkers in women were leptin and fatty acid binding protein-4, compared to matrix metalloproteinase-3 in men. Similar findings were replicated in a subset of patients from both cohorts matched by age and LVEF. Pathway over-representation analysis revealed increased activity of pathways associated with lipid metabolism in women, and neuro-inflammatory response in men (all p < 0.0001). Conclusion: In two independent cohorts of HF patients, biomarkers associated with lipid metabolic pathways were observed in women, while biomarkers associated with neuro-inflammatory response were more active in men. Differences in inflammatory and metabolic pathways may contribute to sex differences in clinical phenotype observed in HF, and provide useful insights towards development of tailored HF therapies

A high throughput immuno-affinity mass spectrometry method for detection and quantitation of SARS-CoV-2 nucleoprotein in human saliva and its comparison with RT-PCR, RT-LAMP, and lateral flow rapid antigen test

Objectives Many reverse transcription polymerase chain reaction (RT-PCR) methods exist that can detect SARS-CoV-2 RNA in different matrices. RT-PCR is highly sensitive, although viral RNA may be detected long after active infection has taken place. SARS-CoV-2 proteins have shorter detection windows hence their detection might be more meaningful. Given salivary droplets represent a main source of transmission, we explored the detection of viral RNA and protein using four different detection platforms including SISCAPA peptide immunoaffinity liquid chromatography-mass spectrometry (SISCAPA-LC-MS) using polyclonal capture antibodies. Methods The SISCAPA-LC MS method was compared to RT-PCR, RT-loop-mediated isothermal amplification (RT-LAMP), and a lateral flow rapid antigen test (RAT) for the detection of virus material in the drool saliva of 102 patients hospitalised after infection with SARS-CoV-2. Cycle thresholds (Ct) of RT-PCR (E gene) were compared to RT-LAMP time-to-positive (TTP) (NE and Orf1a genes), RAT optical densitometry measurements (test line/control line ratio) and to SISCAPA-LC-MS for measurements of viral protein. Results SISCAPA-LC-MS showed low sensitivity (37.7 %) but high specificity (89.8 %). RAT showed lower sensitivity (24.5 %) and high specificity (100 %). RT-LAMP had high sensitivity (83.0 %) and specificity (100.0 %). At high initial viral RNA loads (<20 Ct), results obtained using SISCAPA-LC-MS correlated with RT-PCR (R2 0.57, p-value 0.002). Conclusions Detection of SARS-CoV-2 nucleoprotein in saliva was less frequent than the detection of viral RNA. The SISCAPA-LC-MS method allowed processing of multiple samples in <150 min and was scalable, enabling high throughput.</p