Clinical mass spectrometry in heart disease

Clinical mass spectrometry in heart diseas

Mass spectrometry in medicine: a technology for the future?

Mass spectrometry in medicine: a technology for the future

B-type natriuretic peptide molecular forms for risk stratification and prediction of outcome after acute myocardial infarction

Background: B-type natriuretic peptide (BNP) is known to be a risk marker following acute myocardial infarction (MI). More recently, truncated molecular forms of the BNP molecule have been identified, with the association of these forms and outcome in acute MI not known. The present study investigated their use as risk stratifying biomarkers of this condition. Methods: BNP molecular forms (BNP 5-32, BNP 4-32 and BNP 3-32) were measured in plasma from 1,078 acute MI patients using immunocapture followed by MALDI-ToF-mass spectrometry. Associations of molecular forms with short-term and long-term adverse outcomes were assessed. Results: BNP molecular forms were independent predictors of mortality/reinfarction, mortality/rehospitalization due to heart failure, and a composite of all events at 6 months, 1 year and 2 years and showed prognostic ability comparable with conventional BNP measurements (P <0.001-0.026 vs. N-terminal [NT]-proBNP P <0.001-0.020, respectively). Reclassification analyses showed BNP molecular forms successfully reclassified patient risk when used in addition to the GRACE clinical risk score (P ≤0.005). BNP 5-32 showed utility as a secondary risk stratification biomarker when used in combination with the GRACE score and NT-proBNP by successful down-classification of high-risk patients. Conclusions: BNP molecular forms were associated with poor prognosis at 6 months, 1 year and at 2 years in patients with acute MI. BNP 5-32 showed successful utility as a secondary marker in combination with NT-proBNP after GRACE scoring. This study suggests a potential role for BNP molecular forms in prognosis and risk stratification after acute MI

In reply: Response to letter to the editor ‘Predictive Value of NT-proBNP in Patients with Acute Myocardial Infarction’; Regarding Article ‘Trimethylamine N-oxide and Risk Stratification after Acute Myocardial Infarction"

In reply: Response to letter to the editor ‘Predictive Value of NT-proBNP in Patients with Acute Myocardial Infarction’; Regarding Article ‘Trimethylamine N-oxide and Risk Stratification after Acute Myocardial Infarction

Assessment of breath volatile organic compounds in acute cardiorespiratory breathlessness: a protocol describing a prospective real-world observational study

Introduction Patients presenting with acute undifferentiated breathlessness are commonly encountered in admissions units across the UK. Existing blood biomarkers have clinical utility in distinguishing patients with single organ pathologies but have poor discriminatory power in multifactorial presentations. Evaluation of volatile organic compounds (VOCs) in exhaled breath offers the potential to develop biomarkers of disease states that underpin acute cardiorespiratory breathlessness, owing to their proximity to the cardiorespiratory system. To date, there has been no systematic evaluation of VOC in acute cardiorespiratory breathlessness. The proposed study will seek to use both offline and online VOC technologies to evaluate the predictive value of VOC in identifying common conditions that present with acute cardiorespiratory breathlessness. Methods and analysis A prospective real-world observational study carried out across three acute admissions units within Leicestershire. Participants with self-reported acute breathlessness, with a confirmed primary diagnosis of either acute heart failure, community-acquired pneumonia and acute exacerbation of asthma or chronic obstructive pulmonary disease will be recruited within 24 hours of admission. Additionally, school-age children admitted with severe asthma will be evaluated. All participants will undergo breath sampling on admission and on recovery following discharge. A range of online technologies including: proton transfer reaction mass spectrometry, gas chromatography ion mobility spectrometry, atmospheric pressure chemical ionisation-mass spectrometry and offline technologies including gas chromatography mass spectroscopy and comprehensive two-dimensional gas chromatography-mass spectrometry will be used for VOC discovery and replication. For offline technologies, a standardised CE-marked breath sampling device (ReCIVA) will be used. All recruited participants will be characterised using existing blood biomarkers including C reactive protein, brain-derived natriuretic peptide, troponin-I and blood eosinophil levels and further evaluated using a range of standardised questionnaires, lung function testing, sputum cell counts and other diagnostic tests pertinent to acute disease. Ethics and dissemination The National Research Ethics Service Committee East Midlands has approved the study protocol (REC number: 16/LO/1747). Integrated Research Approval System (IRAS) 198921. Findings will be presented at academic conferences and published in peer-reviewed scientific journals. Dissemination will be facilitated via a partnership with the East Midlands Academic Health Sciences Network and via interaction with all UK-funded Medical Research Council and Engineering and Physical Sciences Research Council molecular pathology nodes. Trial registration number NCT0367299

Longitudinal association among endothelial function, arterial stiffness and subclinical organ damage in hypertension

Objectives: To examine the longitudinal mutual association between endothelial dysfunction and arterial stiffness, and also to determine which of the two variables was more closely associated with the progression of subclinical organ damage. Methods: The brachial-ankle pulse wave velocity (baPWV), carotid intima-media thickness (CIMT), estimated glomerular filtration rate, microalbuminuria and flow-mediated vasodilatation of the brachial artery (FMD) were measured three times at 1.5-year intervals in 674 Japanese patients receiving antihypertensive treatment. Results: The change of the baPWV during the study period was larger in the subjects with baseline FMD values in the lowest tertile as compared to those with baseline FMD values in the highest tertile. The change of the CIMT was smaller in the subjects with baseline baPWV values in the lowest tertile than in those with baseline baPWV values in the highest tertile. After the adjustment, the FMD value at the baseline was inversely associated with the baPWV at the end of the study period (beta = − 0.07, p = 0.01), although, the reverse association was not significant. The baPWV, but not the FMD value, at the baseline was associated with the CIMT (beta = 0.06, p = 0.04) measured at the end of the study period. Conclusions: In hypertension, endothelial dysfunction was associated with the progression of arterial stiffness, although the reverse association was not confirmed. The increased arterial stiffness rather than endothelial dysfunction may be more closely associated with the progression of atherosclerotic vascular damage, and the endothelial dysfunction-arterial stiffness-atherosclerosis continuum may be important in hypertension

Targeting Transforming Growth Factor-β Signaling in Aortopathies in Marfan Syndrome

Targeting Transforming Growth Factor-β Signaling in Aortopathies in Marfan Syndrom

Clinical mass spectrometry in heart disease

Not required for Editorial

Biomarkers in Cardiovascular Disease: The Dilemma of Racial Differences.

See Article Hackler et al. https://doi.org/10.1161/JAHA.119.01272

In reply: The emerging value of molecular forms of B-type natriuretic peptide in heart failure

We would like to commend Drs Yang and Wang for their forward-thinking perspectives and positive implications of the clinical measurements of molecular forms of B-type natriuretic peptide (BNP) (1). We share the view that these processed forms of BNP can provide beneficial clinical information for cardiovascular disease prognoses and therapeutic monitoring with an emphasis on personalized medicine. We have previously demonstrated the prognostic capabilities of BNP molecular forms in the acute setting through measurement in acute heart failure (HF) patients (2), and support the further investigation of these forms across cardiovascular conditions