scholarly journals Distinct Metabolomic Signatures in Preclinical and Obstructive Hypertrophic Cardiomyopathy

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2950
Author(s):  
Maike Schuldt ◽  
Beau van Driel ◽  
Sila Algül ◽  
Rahana Y. Parbhudayal ◽  
Daniela Q. C. M. Barge-Schaapveld ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
High Resolution Mass Spectrometry ◽  
Imaging Techniques ◽  
Disease Stage ◽  
Gradient Boosting ◽  
Incomplete Penetrance ◽  
Healthy Controls ◽  
Gene Variant ◽  
Myocardial Energetics ◽  
Obstructive Hypertrophic Cardiomyopathy

Hypertrophic Cardiomyopathy (HCM) is a common inherited heart disease with poor risk prediction due to incomplete penetrance and a lack of clear genotype–phenotype correlations. Advanced imaging techniques have shown altered myocardial energetics already in preclinical gene variant carriers. To determine whether disturbed myocardial energetics with the potential to serve as biomarkers are also reflected in the serum metabolome, we analyzed the serum metabolome of asymptomatic carriers in comparison to healthy controls and obstructive HCM patients (HOCM). We performed non-quantitative direct-infusion high-resolution mass spectrometry-based untargeted metabolomics on serum from fasted asymptomatic gene variant carriers, symptomatic HOCM patients and healthy controls (n = 31, 14 and 9, respectively). Biomarker panels that discriminated the groups were identified by performing multivariate modeling with gradient-boosting classifiers. For all three group-wise comparisons we identified a panel of 30 serum metabolites that best discriminated the groups. These metabolite panels performed equally well as advanced cardiac imaging modalities in distinguishing the groups. Seven metabolites were found to be predictive in two different comparisons and may play an important role in defining the disease stage. This study reveals unique metabolic signatures in serum of preclinical carriers and HOCM patients that may potentially be used for HCM risk stratification and precision therapeutics.

Link Between Biochemical, Biological and Clinical Assessment Focused on Polycythemia Vera and Stroke

2017 ◽  
Vol 68 (8) ◽  
pp. 1816-1819
Author(s):  
Adriana Sarah Nica ◽  
Roxana Nartea ◽  
Daciana Andrada Costina Stefan ◽  
Roxana Miclaus
Keyword(s):  
Cardiovascular Disease ◽  
Hypertrophic Cardiomyopathy ◽  
Polycythemia Vera ◽  
Clinical Assessment ◽  
Myeloproliferative Neoplasm ◽  
Disease Stage ◽  
Case Presentation ◽  
Obstructive Hypertrophic Cardiomyopathy ◽  
Real Challenge ◽  
Biological Context

This case presentation is of a 58 years old female patient who develops a stroke in 2011 with significant biochemical and biological changes. These manifestations prove to be the result of a hematology disorder, more precise a myeloproliferative neoplasm, Polycythemia Vera. The disease was unidentified and with non-specific symptomology until the occurrence of stroke. The particularity of this case is the presence of severe cardiovascular disease (stage III hypertension. Obstructive hypertrophic cardiomyopathy, chronic ischemic silent disease), with cerebral manifestations (stroke) and associated with mixt hepatitis (alcoholic and deficiency), hypercholesterolemia and hyperuricemia. This biological context represent a real challenge both etiologically and therapeutically (pharmacology and non-pharmacology).

scholarly journals Regional myocardial function at preclinical disease stage of hypertrophic cardiomyopathy in female gene variant carriers

2021 ◽  
Author(s):  
Rahana Y. Parbhudayal ◽  
Celine Seegers ◽  
Pierre Croisille ◽  
Patrick Clarysse ◽  
Albert C. van Rossum ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Circumferential Strain ◽  
Myocardial Function ◽  
Lateral Wall ◽  
Left Ventricular ◽  
Disease Stage ◽  
Gene Variant ◽  
Strain Pattern ◽  
Tissue Tagging ◽  
Cmr Imaging

AbstractWe recently showed more severe diastolic dysfunction at the time of myectomy in female compared to male patients with obstructive hypertrophic cardiomyopathy. Early recognition of aberrant cardiac contracility using cardiovascular magnetic resonance (CMR) imaging may identify women at risk of cardiac dysfunction. To define myocardial function at an early disease stage, we studied regional cardiac function using CMR imaging with tissue tagging in asymptomatic female gene variant carriers. CMR imaging with tissue tagging was done in 13 MYBPC3, 11 MYH7 and 6 TNNT2 gene carriers and 16 age-matched controls. Regional peak circumferential strain was derived from tissue tagging images of the basal and midventricular segments of the septum and lateral wall. Left ventricular wall thickness and global function were comparable between MYBPC3, MYH7, TNNT2 carriers and controls. MYH7 gene variant carriers showed a different strain pattern as compared to the other groups, with higher septal peak circumferential strain at the basal segments compared to the lateral wall, whereas MYBPC3, TNNT2 carriers and controls showed higher strain at the lateral wall compared to the septum. Only subtle gene-specific changes in strain pattern occur in the myocardium preceding development of cardiac hypertrophy. Overall, our study shows that there are no major contractile deficits in asymptomatic females carrying a pathogenic gene variant, which would justify the use of CMR imaging for earlier diagnosis.

Automated Acoustic Analysis of Oral Diadochokinesis to Assess Bulbar Motor Involvement in Amyotrophic Lateral Sclerosis

2020 ◽  
Vol 63 (1) ◽  
pp. 59-73 ◽  
Author(s):  
Panying Rong
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Acoustic Analysis ◽  
Speaking Rate ◽  
Disease Stage ◽  
Healthy Controls ◽  
Tongue Movement ◽  
Major Barrier ◽  
Syllable Repetition ◽  
Oral Diadochokinesis ◽  
Lateral Sclerosis

Purpose The purpose of this article was to validate a novel acoustic analysis of oral diadochokinesis (DDK) in assessing bulbar motor involvement in amyotrophic lateral sclerosis (ALS). Method An automated acoustic DDK analysis was developed, which filtered out the voice features and extracted the envelope of the acoustic waveform reflecting the temporal pattern of syllable repetitions during an oral DDK task (i.e., repetitions of /tɑ/ at the maximum rate on 1 breath). Cycle-to-cycle temporal variability (cTV) of envelope fluctuations and syllable repetition rate (sylRate) were derived from the envelope and validated against 2 kinematic measures, which are tongue movement jitter (movJitter) and alternating tongue movement rate (AMR) during the DDK task, in 16 individuals with bulbar ALS and 18 healthy controls. After the validation, cTV, sylRate, movJitter, and AMR, along with an established clinical speech measure, that is, speaking rate (SR), were compared in their ability to (a) differentiate individuals with ALS from healthy controls and (b) detect early-stage bulbar declines in ALS. Results cTV and sylRate were significantly correlated with movJitter and AMR, respectively, across individuals with ALS and healthy controls, confirming the validity of the acoustic DDK analysis in extracting the temporal DDK pattern. Among all the acoustic and kinematic DDK measures, cTV showed the highest diagnostic accuracy (i.e., 0.87) with 80% sensitivity and 94% specificity in differentiating individuals with ALS from healthy controls, which outperformed the SR measure. Moreover, cTV showed a large increase during the early disease stage, which preceded the decline of SR. Conclusions This study provided preliminary validation of a novel automated acoustic DDK analysis in extracting a useful measure, namely, cTV, for early detection of bulbar ALS. This analysis overcame a major barrier in the existing acoustic DDK analysis, which is continuous voicing between syllables that interferes with syllable structures. This approach has potential clinical applications as a novel bulbar assessment.

RF42 LONG TERM RESULTS OF SEPTAL MYECTOMY IN OBSTRUCTIVE HYPERTROPHIC CARDIOMYOPATHY

2018 ◽  
Vol 19 ◽  
pp. e76-00
Author(s):  
G. Saitto ◽  
F. Grimaldi ◽  
A. Varrica ◽  
A. Biondi ◽  
A. Garatti ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Long Term Results ◽  
Septal Myectomy ◽  
Obstructive Hypertrophic Cardiomyopathy

Microglia in Alzheimer’s Disease

2020 ◽  
Vol 17 (1) ◽  
pp. 29-43 ◽  
Author(s):  
Patrick Süß ◽  
Johannes C.M. Schlachetzki
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Current Knowledge ◽  
Imaging Techniques ◽  
Amyloid Β ◽  
Disease Stage ◽  
Disease Modifying Therapy ◽  
Transcriptomic Signature

: Alzheimer’s Disease (AD) is the most frequent neurodegenerative disorder. Although proteinaceous aggregates of extracellular Amyloid-β (Aβ) and intracellular hyperphosphorylated microtubule- associated tau have long been identified as characteristic neuropathological hallmarks of AD, a disease- modifying therapy against these targets has not been successful. An emerging concept is that microglia, the innate immune cells of the brain, are major players in AD pathogenesis. Microglia are longlived tissue-resident professional phagocytes that survey and rapidly respond to changes in their microenvironment. Subpopulations of microglia cluster around Aβ plaques and adopt a transcriptomic signature specifically linked to neurodegeneration. A plethora of molecules and pathways associated with microglia function and dysfunction has been identified as important players in mediating neurodegeneration. However, whether microglia exert either beneficial or detrimental effects in AD pathology may depend on the disease stage. : In this review, we summarize the current knowledge about the stage-dependent role of microglia in AD, including recent insights from genetic and gene expression profiling studies as well as novel imaging techniques focusing on microglia in human AD pathology and AD mouse models.

PCV35 Costs of Septal Reduction Therapy for Obstructive Hypertrophic Cardiomyopathy: A US Claims Analysis

2021 ◽  
Vol 24 ◽  
pp. S73
Author(s):  
M. Butzner ◽  
P. Sarocco ◽  
M. Maron ◽  
E. Rowin ◽  
C.C. Teng ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Claims Analysis ◽  
Obstructive Hypertrophic Cardiomyopathy
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