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A novel pathophysiological model of interest is the association between heart failure (HF) and the gastrointestinal system, the 'gut hypothesis'. The choline and carnitine metabolic by-product, Trimethylamine N-oxide (TMAO) is one of the more prominent molecules associated with the link between HF and the gut. Indeed, TMAO levels are increased in HF populations and higher TMAO levels are associated with poor prognosis, whereas low TMAO levels either at baseline/follow up confer better prognosis. Considering that TMAO levels seem not to be affected by guideline-HF treatment, this model could represent a novel and independent therapeutic target for HF.

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

Background Matrix-assisted laser desorption ionisation (MALDI) mass spectrometry (MS) has been used for more than 30 years. Compared with other analytical techniques, it offers ease of use, high throughput, robustness, cost-effectiveness, rapid analysis and sensitivity. As advantages, current clinical techniques (e.g. immunoassays) are unable to directly measure the biomarker; rather, they measure secondary signals. MALDI-MS has been extensively researched for clinical applications, and it is set for a breakthrough as a routine tool for clinical diagnostics. Content This review reports on the principles of MALDI-MS and discusses current clinical applications and the future clinical prospects for MALDI-MS. Furthermore, the review assesses the limitations currently experienced in clinical assays, the advantages and the impact of MALDI-MS to transform clinical laboratories. Summary MALDI-MS is widely used in clinical microbiology for the screening of microbial isolates; however, there is scope to apply MALDI-MS in the diagnosis, prognosis, therapeutic drug monitoring and biopsy imaging in many diseases. Outlook There is considerable potential for MALDI-MS in clinic as a tool for screening, profiling and imaging because of its high sensitivity and specificity over alternative techniques.

COVID-19 vaccinations have been deployed to mitigate the effects of the COVID-19 pandemic. However, vaccine-associated myocarditis has been reported. Two typical cases in terms of young age and after the second vaccination were admitted to our hospital with symptoms of worsening chest pain, ST elevation on the electrocardiogram (ECG) and creatine kinase elevation. Emergency coronary angiography revealed no coronary arteries, and an endomyocardial biopsy showed no remarkable findings. Their symptoms were resolved within a few days of sufficient rest and non-steroidal anti-inflammatory drug. The ECG of Patient 1 showed typical change; therefore, the diagnosis of myocarditis was easy. However, the ECG of Patient 2 did not show typical change for myocarditis, and there was no abnormality in the wall motion on echocardiography. Cardiac magnetic resonance imaging (MRI), strain analysis by speckle-tracking echocardiography and serial ECG were useful for the diagnosis of myocarditis. This work shows that conducting early examinations with multimodality imaging and sufficient rest are needed to prevent the worsening of vaccine-associated myocarditis. Although the benefits of the vaccines outweigh the risks, we should be aware that myocarditis can occur after COVID-19 mRNA vaccination regardless of race, especially in young males.

Additional supporting information may be found online in the Supporting Information section at the end of the article. Table S1. Added value performance for TMAO or BNP over the BIOSTAT risk model according to geographical groups. Table S2. Association between genetic variants of FMO3 and TMAO levels.

Background Trimethylamine N-oxide (TMAO), a gut-related metabolite, is associated with heart failure (HF) outcomes. However, TMAO is the final product of a complex metabolic pathway (ie, choline/carnitine) that has never been entirely investigated in HF. The present study investigates a panel of metabolites involved in the TMAO-choline/carnitine metabolic pathway for their associations with outcome in acute HF patients. Methods In total, 806 plasma samples from acute HF patients were analyzed for TMAO, trimethyllysine, L-carnitine, acetyl-L-carnitine, γ-butyrobetaine, crotonobetaine, trimethylamine, betaine aldehyde, choline, and betaine using a developed liquid chromatography-tandem mass spectrometry method. Associations with outcome of all-cause mortality (death) and a composite of all-cause mortality and/or rehospitalization caused by HF (death/HF) at 30 days and 1 year were investigated. Results TMAO, trimethyllysine, L-carnitine, acetyl-L-carnitine, and γ-butyrobetaine were associated with death and death/HF at 30 days (short term; hazard ratio 1.30-1.49, P≤ .021) and at 1 year (long term; hazard ratio 1.15-1.25, P≤ .026) when adjusted for cardiac risk factors. L-carnitine and acetyl-L-carnitine were superior for short-term outcomes whereas TMAO was the superior metabolite for association with long-term outcomes. Furthermore, acetyl-L-carnitine and L-carnitine were superior for in-hospital mortality and improved risk stratification when combined with current clinical risk scores (ie, Acute Decompensated HEart Failure National REgistry, Organized Program To Initiate Lifesaving Treatment In Hospitalized Patients With Heart Failure, and Get With The Guidelines-Heart Failure; odds ratio (OR) ≥ 1.52, P≤ .020). Conclusions Carnitine-related metabolites show associations with adverse outcomes in acute HF, in particular L-carnitine and acetyl-L-carnitine for short-term outcomes, and TMAO for long-term outcomes. Further studies are warranted to investigate the role and implications of carnitine metabolites including intervention in the pathogenesis of HF.

Background N-terminal pro-brain natriuretic peptide (NT-proBNP) is a well-known predictor of acute heart failure (HF). Congestion volume status estimated by bioelectrical impedance analysis (BIA) is also associated with adverse cardiovascular events in HF patients. However, it is unclear whether these biomarkers reflecting pathophysiological pathways are different between HF with preserved (HFpEF) and reduced ejection fraction (HFrEF). Purpose The aim of this study was to investigate whether the prognostic value of NT-proBNP and extracellular water/free fat mass (ECW%) assessed by BIA is different between HFrEF and HFpEF in acute HF patients. Methods and results One hundred-and-forty-three patients admitted for acute HF between November 2013 and January 2015 were estimated for NT-proBNP levels and ECW% by BIA on admission. A total of 49 HFrEF (LVEF Conclusion Elevated levels of NT-proBNP in acute HF were predictive for mortality and hospitalisation due to HF in HFrEF but may not be for HFpEF patients, and ECW% had a better predictive value than NT-proBNP in HFpEF patients.

Aims: Association of elevated circulating levels of trimethylamine N-oxide (TMAO) with adverse outcomes in patients with heart failure (HF) has been described. However, response of TMAO levels to treatment and medications has not been investigated. Therefore, we investigated whether TMAO levels are responsive to guideline-recommended treatment and medications, and further reflect changes in outcomes. Methods and results: TMAO levels were investigated in the systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF), which addressed response to guideline-recommended pharmacological treatment. TMAO levels in 2234 patients with new-onset or progressively worsening HF showed strong associations with adverse events (mortality and/or rehospitalisation) at 1, 2 and 3 years [hazard ratio (HR) 1.37–1.51, P ≤ 0.019). Analysis of 972 patients with plasma available at both enrolment and follow-up visit showed reductions of B-type natriuretic peptide (BNP) levels with guideline-based treatment (P < 0.001), but not for TMAO levels. Moreover, patients with higher TMAO levels than median before and after treatment showed increased association with adverse outcomes [HR 2.21, 95% confidence interval (CI) 1.43–3.43, P < 0.001] compared to patients with lower than median levels either before or after treatment (HR 1.13, 95% CI 0.63–2.04, P = 0.684 and HR 1.14, 95% CI 0.64–2.03, P = 0.662, respectively). Conclusion: TMAO levels were associated with adverse outcomes (mortality and/or rehospitalisation) in BIOSTAT-CHF, and did not respond to guideline-based pharmacological treatment in contrast to BNP levels which did as expected. Lower TMAO levels were associated with favourable outcome regardless of treatment.

Background: The ankle-brachial pressure index (ABI) is widely used as a standard screening method for arterial occlusive lesion above the knee. However, the sensitivity of ABI is low in hemodialysis (HD) patients. Exercise stress (Ex-ABI) may reduce the false negative results. Patients and Methods: After measuring resting ABI and toe-brachial pressure index (TBI), ankle pressure and ABI immediately after walking (Post-AP, Post-ABI) were measured using one-minute treadmill walking in 52 lower limbs of 26 HD patients. The definition of peripheral arterial occlusive disease (PAD) required an ABI value of less than 0.90, TBI value of less than 0.60, and decrease of more than 15% of the Post-ABI value and 20 mmHg of Post-AP in Ex-ABI. Computed tomographic angiography (CTA) was performed in 32 lower limbs of 16 HD patients. PAD is defined as presence of stenosis of more than 75% in the case of lesions from an iliac artery to knee on CTA. Results: The accuracy of Ex-ABI (Sensitivity, 85.7%; Specificity, 77.7%) was higher than those of ABI (Sensitivity, 42.9%; Specificity, 83.3%) or TBI (Sensitivity, 78.6%; Specificity, 61.1%). Conclusion: Ex-ABI with one-minute treadmill walking is the most useful tool for the screening of arterial occlusive lesions above the knee in maintenance HD patients.

The prognostic and diagnostic values of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) in ischemic heart disease have already been investigated in many previous studies. Although NT-pro-BNP is affected by many factors, these previous studies did not strictly exclude them. This study included 110 patients who received coronary arteriography between November 2007 and September 2009. Excluded from the study were those patients who had clinical symptoms of heart failure, asynergy by echocardiography or left ventriculography (LVG), atrial fibrillation, prior myocardial infarction, valvular disease, lung disease, anemia or renal dysfunction. We compared the laboratory data, LVG and early transmitral-to-early diastolic annular velocity ratio (E/E (a)) in echocardiography between the group with coronary stenosis and the group without it. NT-pro-BNP and the low-density lipoprotein/high-density lipoprotein ratio (LDL/HDL) independently associated with the presence of coronary artery stenosis (odds ratio of NT-pro-BNP, each 50 pg/ml 2.367, 95% confidence interval 1.302-4.303, p = 0.005). The area under the curve of the receiver-operating characteristic (ROC) curve of NT-pro-BNP, used to predict coronary artery stenosis, was 0.801 (0.719-0.883, p 0.001). According to the ROC curve, the optimal cut-off level for predicting coronary stenosis was 64.3 pg/ml (sensitivity 82.5%, false-positive 34%). NT-pro-BNP is an attractive supplemental marker to predict the presence of coronary artery stenosis in a population that strictly excluded any affecting factors. In the population without factors affecting NT-pro-BNP, a slight increase suggests the presence of ischemic heart disease. The normal criteria for NT-pro-BNP in the patients undergoing coronary angiography may be much lower than the one currently used.

Background: Anemia is associated with poor outcomes in patients with acute decompensated heart failure (ADHF). Whereas pseudoanemia with hemodilution due to fluid retention is also observed in ADHF patients. Thus, we investigated the association between hematocrit (Hct) and volume-overload with

Background: Obesity is associated with incident heart failure, but it is paradoxically associated with better prognosis during acute heart failure(AHF). Currently, obesity is usually identified by body mass index(BMI). Bioelectrical impedance analysis is a noninvasive modality for evaluating the

Summary Background: Chronic kidney disease (CKD) is associated with poor outcomes after percutaneous coronary intervention (PCI). This study aimed to evaluate the relationship between the degree of renal function at baseline and long-term clinical outcomes in coronary artery disease patients who underwent paclitaxel-eluting stent implantation. Methods: A total of 336 patients with 400 de-novo lesions underwent PCI between May 2007 and March 2009. The patients were divided into 4 groups: control (glomerular filtration rate (GFR) 90 ml/min; n = 132); mild CKD (GFR 60—89 ml/min; n = 112); moderate CKD (GFR