scholarly journals Plasma Metabolomic Profiling of Hypertrophic Cardiomyopathy Patients Before and After Surgical Myectomy Suggests Postoperative Improvement in Liver and Kidney Function

Author(s):  
Nicole L. Wolter ◽  
Madison J. LeClair ◽  
Michael T. Chin

Hypertrophic cardiomyopathy (HCM) is a common inherited heart disorder complicated by left ventricle outflow tract (LVOT) obstruction, which can be treated with surgical myectomy. To date, no reliable biomarkers for LVOT obstruction exist. To determine whether metabolomic biomarkers for obstruction can be identified, we conducted metabolomic profiling on plasma samples of 18 HCM patients before and after undergoing surgical myectomy to measure changes in the plasma metabolome in the postoperative state. Plasma was collected approximately 4 weeks before surgery at the preoperative visit and approximately 3 months after the surgery at the postoperative visit. We found that 215 metabolites were altered in the postoperative state (p-value < 0.05). Identified metabolites that were significantly reduced post-myectomy included metabolites of heme, such as bilirubin, and phenylacetylglutamine, a biomarker of urea cycle disorders, which suggests that liver and kidney function are improved in the postoperative state. Markers of arginine metabolism such as homoarginine and dimethylarginine are also decreased in the postoperative state, suggestive of reduction in nitric oxide production, inflammation and heart failure after surgery. 3-hydroxybutyrate (BHBA) was also decreased, suggesting possible increased fatty acid utilization and a return to normal heart function. 12 of these metabolites were notably significant after adjusting for multiple comparisons (q-value < 0.05), including bilirubin, PFOS, PFOA, 3,5-dichloro-2,6-dihydroxybenzoic acid, 2-hydroxylaurate, trigonelline and 6 unidentified compounds, which support improved kidney and liver function and increased lean soft tissue mass. These findings suggest improved organ metabolic function after surgical relief of LVOT obstruction in HCM and further underscore the beneficial systemic effects of surgical myectomy.

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Nicole L. Wolter ◽  
Madison J. LeClair ◽  
Michael T. Chin

Abstract Background Hypertrophic cardiomyopathy (HCM) is a common inherited heart disorder complicated by left ventricle outflow tract (LVOT) obstruction, which can be treated with surgical myectomy. To date, no reliable biomarkers for LVOT obstruction exist. We hypothesized that metabolomic biomarkers for LVOT obstruction may be detectable in plasma from HCM patients. Methods We conducted metabolomic profiling on plasma samples of 18 HCM patients before and after surgical myectomy, using a commercially available metabolomics platform. Results We found that 215 metabolites were altered in the postoperative state (p-value < 0.05). 12 of these metabolites were notably significant after adjusting for multiple comparisons (q-value < 0.05), including bilirubin, PFOS, PFOA, 3,5-dichloro-2,6-dihydroxybenzoic acid, 2-hydroxylaurate, trigonelline and 6 unidentified compounds, which support improved organ metabolic function and increased lean soft tissue mass. Conclusions These findings suggest improved organ metabolic function after surgical relief of LVOT obstruction in HCM and further underscore the beneficial systemic effects of surgical myectomy.


2015 ◽  
Vol 28 (11) ◽  
pp. 1318-1328 ◽  
Author(s):  
Dan G. Halpern ◽  
Daniel G. Swistel ◽  
Jose Ricardo Po ◽  
Rajeev Joshi ◽  
Glenda Winson ◽  
...  

2021 ◽  
Vol 22 (Supplement_2) ◽  
Author(s):  
A Kharabish ◽  
M Eid ◽  
W Elmozy ◽  
A Elguindy ◽  
M Yacoub

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Ventriculoarterial coupling (VAC) is an important surrogate measurement of global cardiovascular efficiency. However, up till recently, this measurement has been rarely used in clinical practice. This could be due to its invasive nature, and the relatively complex methods required for acquisition and interpretation. We here describe a noninvasive method of measuring VA coupling using cardiac magnetic resonance (CMR) in a cohort of hypertrophic cardiomyopathy (HCM). Methods   Cardiac MRI was performed in 61 patients with hypertrophic obstructive cardiomyopathy (HOCM) before and after undergoing extended surgical myectomy. Cardiac MRIs from 15 patients with non-obstructive HCM were also included for comparison. Hypertensive patients were excluded from this study. Vitals signs were recorded during each MRI study. Arterial end-systolic pressure (AESP) was determined non-invasively as previously described (0.9x brachial blood pressure). Left ventricular end-systolic pressure (LVESP) was calculated by adding the echo-derived peak systolic gradient across the left ventricular outflow tract to the arterial end-systolic pressure. Indexed stroke volume (SVI) in the ascending aorta as well as indexed end systolic volume (ESVI) were calculated from CMR. Indexed arterial (Ea) and ventricular (Ev) elastance were calculated as AESP/SVI and LVESP/ESVI. VA coupling was then calculated as Ea/Ev.  Results Compared to the baseline measurements, VAC increased significantly post myectomy (mean VAC pre-myectomy and post-myectomy 0.38 vs. versus 0.62 respectively, p= 0.00001). VAC in non-obstructive HCM patients (mean = 0.64) was statistically similar to that in post-myectomy (p = 0.82) and statistically different from pre-myectomy (p = 0.00016). The mean of LVOTO gradients post- and pre-myectomy were significantly different (p = 0.00001). Significant correlation of the delta-VAC with the delta gradient in the LVOTO was found (r= 0.35, p = 0.005).  Conclusion Non-invasive assessment of VA coupling using CMR is feasible and could be a useful tool in the evaluation of patients with various cardiovascular disorders. Further studies with larger numbers of patients are required to establish the utility of this method in clinical practice.


2021 ◽  
Vol 22 (5) ◽  
pp. 2474
Author(s):  
Amy Larson ◽  
Towia A. Libermann ◽  
Heather Bowditch ◽  
Gaurav Das ◽  
Nikolaos Diakos ◽  
...  

Left Ventricular Outflow Tract (LVOT) obstruction occurs in approximately 70% of Hypertrophic Cardiomyopathy (HCM) patients and currently requires imaging or invasive testing for diagnosis, sometimes in conjunction with provocative physiological or pharmaceutical stimuli. To identify potential biomarkers of LVOT obstruction, we performed proteomics profiling of 1305 plasma proteins in 12 HCM patients with documented LVOT obstruction, referred for surgical myectomy. Plasma was collected at the surgical preoperative visit, approximately one month prior to surgery and then at the post-surgical visit, approximately 3 months later. Proteomic profiles were generated using the aptamer-based SOMAscan assay. Principal Component Analysis using the highest statistically significant proteins separated all preoperative samples from all postoperative samples. Further analysis revealed a set of 25 proteins that distinguished the preoperative and postoperative states with a paired t-test p-value of <0.01. Ingenuity Pathway analysis facilitated the generation of protein interaction networks and the elucidation of key upstream regulators of differentially expressed proteins, such as interferon-γ, TGF-β1, and TNF. Biological pathways affected by surgery included organ inflammation, migration, and motility of leukocytes, fibrosis, vasculogenesis, angiogenesis, acute coronary events, endothelial proliferation, eicosanoid metabolism, calcium flux, apoptosis, and morphology of the cardiovascular system. Our results indicate that surgical relief of dynamic outflow tract obstruction in HCM patients is associated with unique alterations in plasma proteomic profiles that likely reflect improvement in organ inflammation and physiological function.


Author(s):  
Amy Larson ◽  
Towia A. Libermann ◽  
Heather Bowditch ◽  
Gaurav Das ◽  
Nikolaos Diakos ◽  
...  

Left Ventricular Outflow Tract (LVOT) obstruction occurs in approximately 70% of Hypertrophic Cardiomyopathy (HCM) patients and currently requires imaging or invasive testing for diagnosis, sometimes in conjunction with provocative physiological or pharmaceutical stimuli. To identify potential biomarkers of LVOT obstruction, we performed proteomics profiling of 1305 plasma proteins in 12 HCM patients with documented LVOT obstruction referred for surgical myectomy. Plasma was collected at the surgical preoperative visit approximately one month prior to surgery and then at the post surgical visit approximately 3 months later. Proteomic profiles were generated using the aptamer-based SOMAscan assay. Principal Component Analysis using the highest statistically significant proteins separated all preoperative samples from all postoperative samples. Further analysis revealed a set of 25 proteins that distinguished the preoperative and postoperative states with a paired t-test p value of &lt;0.01. Ingenuity Pathway analysis facilitated the generation of protein interaction networks and the elucidation of key upstream regulators of the differentially expressed proteins such as interferon-, TGF-1 and TNF. Biological pathways affected by the surgery included organ inflammation, migration and motility of leukocytes, fibrosis, vasculogenesis, angiogenesis, acute coronary events, endothelial proliferation, eicosanoid metabolism, calcium flux, apoptosis and morphology of the cardiovascular system. Our results indicate that surgical relief of dynamic outflow tract obstruction in HCM patients is associated with unique alterations in plasma proteomic profiles that likely reflect improvement in organ inflammation and physiological function.


2020 ◽  
Vol 2 (2) ◽  
pp. 66-71
Author(s):  
Parti ◽  
Sumiati Malik ◽  
Nurhayati

Most causes of infant death are problems that occur in newborn/neonatal (0-28 days old), Low Birth Weight Babies (LBW) is one of the factors which has a contribution to infant mortality, especially in the neonatal period. Infant Mortality Rate (IMR) is a benchmark in determining the degree of public health, both at the National and Provincial levels. This study aimed to determine the effect of the Kangaroo Mother Care Method (KMC) on the prevention of hypothermia in low birth weight infants at Morowali District Hospital in 2019. The type of research used was a quasi-experiment. The population is all low birth weight babies born from May to July 2019. The sample in this study was all newborns with low birth weight born from May to July 2019, totaling 30 babies. There is a difference (influence) on the baby's body temperature before and after KMC with a p-value=0,000. The kangaroo mother care can continue to be affiliated considering its benefits for both infants and mothers, as well as increasing the ability of health workers in conducting KMC so that they can provide in-house training for mothers to be carried out at home.


Author(s):  
Juliana Widyastuti Wahyuningsih Juliana Widyastuti Wahyuningsih

ABSTRAK Tidur merupakan kebutuhan yang harus terpenuhi terutama pada fase perkembangan karena selama tidur akan terjadi perkembangan otak maupun tubuh, sehingga gangguan tidur merupakan masalah yang akan menimbulkan dampak buruk terhadap pertumbuhan dan perkembangan bayi. Kualitas tidur bayi yang baik dapat diciptakan dengan memberikan pemijatan bayi secara rutin. Penelitian ini bertujuan untuk membuktikan bahwa pemijatan dapat mempengaruhi kualitas tidur bayi umur 0-3 bulan. Penelitian ini menggunakan desain penelitian Quasy Eksperimental dengan metode One Group Pretest-Postest. Sampel 22 bayi yang dipilih dengan tehnik Total Sampling yang di observasi sebelum dan sesudah diberikan pemijatan. Variabel yang diukur dalam penelitian ini adalah kualitas tidur bayi 0-3 bulan. Hasil penelitian menunjukkan bahwa ada pengaruh pijat bayi terhadap kualitas tidur bayi umur 0-3 bulan (p value  0,008 < α = 0,05).Berdasarkan hasil penelitian ini disarankan agar keluarga dan masyarakat memberikan pemijatan secara rutin dan mandiri untuk meningkatkan kebutuhan tidur bayi yang berkualitas.   ABSTRACT Sleep is a human necessity that must be met, especially in the development phase because during sleep will occur the brain and body developments, so that sleep disturbance is a problem that would cause adverse effects on infants’ growth and development. The good quality of sleep can be created by providing the infants massage routinely. This study aimed to prove that the massage could affect the quality of sleep on the 0-3 months old baby. This study used Quasy-experimental design with One Group Pretest-Posttest. The sample 22 infants selected by total sampling technique observed on before and after the massage. The variables measured in this study are the quality of sleep. The results of study indicate that there is an effect of infant massage to the sleep quality on 0-3 months old babies (p value 0,008 < α = 0,05).Based on the results of this study it recommended for the families and communities to provide infant massage regularly and independently to increase the quality of sleep on the baby.  


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 839.2-840
Author(s):  
C. Vesel ◽  
A. Morton ◽  
M. Francis-Sedlak ◽  
B. Lamoreaux

Background:NHANES data indicate that approximately 9.2 million Americans have gout,1 with a small subset having uncontrolled disease.2 Pegloticase is a PEGylated recombinant uricase enzyme indicated for treating uncontrolled gout that markedly reduces serum uric acid levels (sUA)3 and resolves tophi in treatment responders.4 Despite pegloticase availability in the US for many years, real world demographics of pegloticase users in the treatment of uncontrolled gout have not been previously reported in a population-based cohort.Objectives:This study utilized a large US claims database to examine demographics and co-morbidities of uncontrolled gout patients treated with pegloticase. Kidney function before and after pegloticase treatment and concomitant therapy with immunomodulators were also examined.Methods:The TriNetX Diamond database includes de-identified data from 4.3 million US patients with gout (as of September 2019), including demographics, medical diagnoses, laboratory values, procedures (e.g. infusions, surgeries), and pharmacy data. Patients who had received ≥1 pegloticase infusion were included in these analyses. The number of infusions was evaluated for a subgroup of patients who were in the database ≥3 months before and ≥2 years after the first pegloticase infusion (i.e. first infusion prior to September 2017) to ensure only complete courses of therapy were captured. In this subpopulation, kidney function before and after pegloticase therapy was examined, along with the presence of immunomodulation prescriptions (methotrexate, mycophenolate mofetil, azathioprine, leflunomide) within 60 days prior to and 14 days after the first pegloticase infusion.Results:1494 patients treated with pegloticase were identified. Patients were 63.1 ± 14.0 years of age (range: 23–91), mostly male (82%), and white (76%). Mean sUA prior to pegloticase was 8.7 ± 2.4 mg/dL (n=50), indicating uncontrolled gout in the identified population. The most commonly reported comorbidities were chronic kidney disease (CKD, 48%), essential hypertension (71%), type 2 diabetes (39%), and cardiovascular disease (38%), similar to pegloticase pivotal Phase 3 trial populations. In patients with pre-therapy kidney function measures (n=134), pre-treatment eGFR averaged 61.2 ± 25.7 ml/min/1.73 m2, with 44% having Stage 3-5 CKD. In patients with complete therapy course capture and pre- and post-therapy eGFR measures (n=48), kidney function remained stable (change in eGFR: -2.9 ± 18.2 ml/min/1.73 m2) and CKD stage remained the same or improved in 81% of patients. In 791 patients with complete treatment course capture, patients had received 8.7 ± 13.8 infusions (median: 3, IQR: 2-10). Of these, 189 (24%) patients received only 1 pegloticase infusion and 173 (22%) received ≥12 infusions. As the data cut-off for this analysis pre-dated emerging data on the use of immunomodulation as co-therapy, only 19 of 791 (2%) patients received immunomodulation co-therapy with pegloticase.Conclusion:This relatively large group of patients with uncontrolled gout treated with pegloticase had similar patient characteristics of those studied in the phase 3 randomized clinical trials. Patients with uncontrolled gout are significantly burdened with systemic co-morbid diseases. The majority of patients had stable or improved kidney function following pegloticase treatment. As these results reflect patients initiating treatment prior to 2018, before co-treatment with immunomodulation was introduced, this cohort only included a small percentage of patients who were co-treated with an immunomodulator. Future studies using more current datasets are needed to evaluate real world outcomes in patients treated with pegloticase/immunomodulator co-therapy and to evaluate the impact of systemic co-morbid diseases.References:[1]Chen-Xu M, et al. Arthritis Rheumatol 2019 71:991-999.[2]Fels E, Sundy JS. Curr Opin Rheumatol 2008;20:198-202.[3]Sundy J, et al. JAMA 2011;306:711-720.[4]Mandell BF, et al. Arthritis Res Ther 2018;20:286.Disclosure of Interests:Claudia Vesel Shareholder of: Horizon Therapeutics plc, Employee of: Horizon Therapeutics plc, Allan Morton Speakers bureau: Sanofi, Amgen, and Horizon, Megan Francis-Sedlak Shareholder of: Horizon Therapeutics plc, Employee of: Horizon Therapeutics plc, Brian LaMoreaux Shareholder of: Horizon Therapeutics plc, Employee of: Horizon Therapeutics plc.


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