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American Family Physician Mar 2022Up to 8.6% of infants and 80% of children have a heart murmur during their early years of life. The presence of a murmur can indicate conditions ranging from no...
Up to 8.6% of infants and 80% of children have a heart murmur during their early years of life. The presence of a murmur can indicate conditions ranging from no discernable pathology to acquired or congenital heart disease. In infants with a murmur, physicians should review the obstetric and family histories to detect the possibility of congenital heart pathologies. Evaluation by a pediatric cardiologist is indicated for newborns with a murmur because studies show that neonatal murmurs have higher rates of pathology than in older children, and neonatal murmur characteristics are more difficult to evaluate during examination; referral is preferred over echocardiography. All infants, with or without a murmur, should have pulse oximetry screening to detect underlying critical congenital heart disease. In older children, most murmurs are innocent and can be followed with serial examinations if there are no findings of concern. Findings in older children that warrant referral include diastolic murmurs, loud or harsh-sounding murmurs, holosystolic murmurs, murmurs that radiate to the back or neck, or signs or symptoms of cardiac disease. Referral to a pediatric cardiologist is indicated when a pathologic murmur is suspected. Electrocardiography, chest radiography, and other tests should not be reflexively performed as part of all murmur evaluations because these tests can misclassify a murmur as innocent or pathologic, and they are not cost-effective. Emerging technologies include phonocardiography interpretation of murmurs and artificial intelligence algorithms for differentiating innocent from pathologic murmurs.
Topics: Artificial Intelligence; Child; Echocardiography; Electrocardiography; Heart Defects, Congenital; Heart Murmurs; Humans; Infant; Infant, Newborn
PubMed: 35289571
DOI: No ID Found -
Circulation May 2021Diastolic dysfunction (DD) is associated with the development of heart failure and contributes to the pathogenesis of other cardiac maladies, including atrial...
BACKGROUND
Diastolic dysfunction (DD) is associated with the development of heart failure and contributes to the pathogenesis of other cardiac maladies, including atrial fibrillation. Inhibition of histone deacetylases (HDACs) has been shown to prevent DD by enhancing myofibril relaxation. We addressed the therapeutic potential of HDAC inhibition in a model of established DD with preserved ejection fraction.
METHODS
Four weeks after uninephrectomy and implantation with deoxycorticosterone acetate pellets, when DD was clearly evident, 1 cohort of mice was administered the clinical-stage HDAC inhibitor ITF2357/Givinostat. Echocardiography, blood pressure measurements, and end point invasive hemodynamic analyses were performed. Myofibril mechanics and intact cardiomyocyte relaxation were assessed ex vivo. Cardiac fibrosis was evaluated by picrosirius red staining and second harmonic generation microscopy of left ventricle (LV) sections, RNA sequencing of LV mRNA, mass spectrometry-based evaluation of decellularized LV biopsies, and atomic force microscopy determination of LV stiffness. Mechanistic studies were performed with primary rat and human cardiac fibroblasts.
RESULTS
HDAC inhibition normalized DD without lowering blood pressure in this model of systemic hypertension. In contrast to previous models, myofibril relaxation was unimpaired in uninephrectomy/deoxycorticosterone acetate mice. Furthermore, cardiac fibrosis was not evident in any mouse cohort on the basis of picrosirius red staining or second harmonic generation microscopy. However, mass spectrometry revealed induction in the expression of >100 extracellular matrix proteins in LVs of uninephrectomy/deoxycorticosterone acetate mice, which correlated with profound tissue stiffening based on atomic force microscopy. ITF2357/Givinostat treatment blocked extracellular matrix expansion and LV stiffening. The HDAC inhibitor was subsequently shown to suppress cardiac fibroblast activation, at least in part, by blunting recruitment of the profibrotic chromatin reader protein BRD4 (bromodomain-containing protein 4) to key gene regulatory elements.
CONCLUSIONS
These findings demonstrate the potential of HDAC inhibition as a therapeutic intervention to reverse existing DD and establish blockade of extracellular matrix remodeling as a second mechanism by which HDAC inhibitors improve ventricular filling. Our data reveal the existence of pathophysiologically relevant covert or hidden cardiac fibrosis that is below the limit of detection of histochemical stains such as picrosirius red, highlighting the need to evaluate fibrosis of the heart using diverse methodologies.
Topics: Animals; Disease Models, Animal; Extracellular Matrix; Female; Heart Murmurs; Histone Deacetylase Inhibitors; Humans; Male; Mice; Ventricular Remodeling
PubMed: 33682427
DOI: 10.1161/CIRCULATIONAHA.120.046462 -
Indian Journal of Critical Care... Dec 2021Pregnancy is a dynamic process, which induces a multitude of anatomic, physiological, biochemical, and psychological changes. Physiological changes during pregnancy...
UNLABELLED
Pregnancy is a dynamic process, which induces a multitude of anatomic, physiological, biochemical, and psychological changes. Physiological changes during pregnancy allow the body to meet the increased metabolic demands of the mother and fetus by maintaining adequate uteroplacental circulation, and ensure fetal growth and development. These changes begin early in the first trimester and are brought on by the increased circulating levels of progesterone and estrogen, which are produced by the ovary in the first 12 weeks of pregnancy and thereafter by the placenta. While some of these cause a change in biochemical values, others may mimic symptoms of medical disease. For instance, cardiac changes such as sinus tachycardia, systolic heart murmurs, and cardiac enlargement could be interpreted as signs of heart disease. It is thus crucial, to differentiate between normal physiological changes and pathological changes, particularly for clinicians involved in the care of pregnant patient.
HOW TO CITE THIS ARTICLE
Gangakhedkar GR, Kulkarni AP. Physiological Changes in Pregnancy. Indian J Crit Care Med 2021; 25(Suppl 3):S189-S192.
PubMed: 35615611
DOI: 10.5005/jp-journals-10071-24039 -
CMAJ : Canadian Medical Association... Sep 2021
Topics: Aged; Anemia, Hemolytic; Heart Murmurs; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Male; Mitral Valve Insufficiency; Prosthesis Failure
PubMed: 34580148
DOI: 10.1503/cmaj.202620-f -
Scandinavian Journal of Primary Health... Dec 2022To investigate interrater and intrarater agreement between physicians and medical students on heart sound classification from audio recordings, and factors predicting...
OBJECTIVE
To investigate interrater and intrarater agreement between physicians and medical students on heart sound classification from audio recordings, and factors predicting agreement with a reference classification.
DESIGN
Intra- and interrater agreement study.
SUBJECTS
Seventeen GPs and eight cardiologists from Norway and the Netherlands, eight medical students from Norway.
MAIN OUTCOME MEASURES
Proportion of agreement and kappa coefficients for intrarater agreement and agreement with a reference classification.
RESULTS
The proportion of intrarater agreement on the presence of any murmur was 83% on average, with a median kappa of 0.64 (range = 0.09-0.86) for all raters, and 0.65, 0.69, and 0.61 for GPs, cardiologist, and medical students, respectively.The proportion of agreement with the reference on any murmur was 81% on average, with a median kappa of 0.67 (range 0.29-0.90) for all raters, and 0.65, 0.69, and 0.51 for GPs, cardiologists, and medical students, respectively.Distinct murmur, more than five years of clinical practice, and cardiology specialty were most strongly associated with the agreement, with ORs of 2.41 (95% CI 1.63-3.58), 2.19 (1.58-3.04), and 2.53 (1.46-4.41), respectively.
CONCLUSION
We observed fair but variable agreement with a reference on heart murmurs, and physician experience and specialty, as well as murmur intensity, were the factors most strongly associated with agreement.Key points:Heart auscultation is the main physical examination of the heart, but we lack knowledge of inter- and intrarater agreement on heart sounds.• Physicians identified heart murmurs from heart sound recordings fairly reliably compared with a reference classification, and with fair intrarater agreement.• Both intrarater agreement and agreement with the reference showed considerable variation between doctors• Murmur intensity, more than five years in clinical practice, and cardiology specialty were most strongly linked to agreement with the reference.
Topics: Humans; Heart Murmurs; Heart Auscultation; Heart Sounds; Students, Medical; Cardiology; Reproducibility of Results
PubMed: 36598178
DOI: 10.1080/02813432.2022.2159204 -
Tidsskrift For Den Norske Laegeforening... Feb 2024Ventricular septal rupture (VSR) following acute myocardial infarction is rare in the modern revascularisation era. Nevertheless, clinical awareness is paramount, as...
BACKGROUND
Ventricular septal rupture (VSR) following acute myocardial infarction is rare in the modern revascularisation era. Nevertheless, clinical awareness is paramount, as presentation may vary.
CASE PRESENTATION
A middle-aged male with no history of cardiovascular disease developed progressive heart failure symptoms while travelling abroad. Initial workup revealed a prominent systolic murmur, but findings were inconsistent with acute coronary syndrome. Transthoracic echocardiogram showed a small hypokinetic area in the basal septum, preserved left ventricular function and no significant valvulopathy. Despite the absence of chest pain, an invasive angiography revealed occlusion of a septal branch emerging from the left anterior descending artery, otherwise patent coronary arteries. Despite administration of diuretics, the patient remained symptomatic and presented two months later to his primary care provider with a persisting systolic murmur. He was subsequently referred to the outpatient cardiology clinic where echocardiography revealed a large VSR involving the basal anteroseptum of the left ventricle with a significant left-to-right shunt. After accurate radiological and haemodynamic assessment of the defect, he successfully underwent elective surgical repair.
INTERPRETATION
Although traditionally associated with large transmural myocardial infarctions, VSR may arise also from minor, subclinical events. A new-onset murmur is a valuable hint for the alert clinician.
Topics: Humans; Male; Middle Aged; Systolic Murmurs; Myocardial Infarction; Ventricular Septal Rupture; Echocardiography; Dyspnea
PubMed: 38349103
DOI: 10.4045/tidsskr.23.0373 -
PLOS Digital Health Sep 2023Cardiac auscultation is an accessible diagnostic screening tool that can help to identify patients with heart murmurs, who may need follow-up diagnostic screening and... (Review)
Review
Cardiac auscultation is an accessible diagnostic screening tool that can help to identify patients with heart murmurs, who may need follow-up diagnostic screening and treatment for abnormal cardiac function. However, experts are needed to interpret the heart sounds, limiting the accessibility of cardiac auscultation in resource-constrained environments. Therefore, the George B. Moody PhysioNet Challenge 2022 invited teams to develop algorithmic approaches for detecting heart murmurs and abnormal cardiac function from phonocardiogram (PCG) recordings of heart sounds. For the Challenge, we sourced 5272 PCG recordings from 1452 primarily pediatric patients in rural Brazil, and we invited teams to implement diagnostic screening algorithms for detecting heart murmurs and abnormal cardiac function from the recordings. We required the participants to submit the complete training and inference code for their algorithms, improving the transparency, reproducibility, and utility of their work. We also devised an evaluation metric that considered the costs of screening, diagnosis, misdiagnosis, and treatment, allowing us to investigate the benefits of algorithmic diagnostic screening and facilitate the development of more clinically relevant algorithms. We received 779 algorithms from 87 teams during the Challenge, resulting in 53 working codebases for detecting heart murmurs and abnormal cardiac function from PCG recordings. These algorithms represent a diversity of approaches from both academia and industry, including methods that use more traditional machine learning techniques with engineered clinical and statistical features as well as methods that rely primarily on deep learning models to discover informative features. The use of heart sound recordings for identifying heart murmurs and abnormal cardiac function allowed us to explore the potential of algorithmic approaches for providing more accessible diagnostic screening in resource-constrained environments. The submission of working, open-source algorithms and the use of novel evaluation metrics supported the reproducibility, generalizability, and clinical relevance of the research from the Challenge.
PubMed: 37695769
DOI: 10.1371/journal.pdig.0000324 -
Clinical and Translational Medicine Nov 2022Altered splicing landscape is an emerging cancer hallmark; however, the dysregulation and implication of the cellular machinery controlling this process (spliceosome...
INTRODUCTION
Altered splicing landscape is an emerging cancer hallmark; however, the dysregulation and implication of the cellular machinery controlling this process (spliceosome components and splicing factors) in hepatocellular carcinoma (HCC) is poorly known. This study aimed to comprehensively characterize the spliceosomal profile and explore its role in HCC.
METHODS
Expression levels of 70 selected spliceosome components and splicing factors and clinical implications were evaluated in two retrospective and six in silico HCC cohorts. Functional, molecular and mechanistic studies were implemented in three cell lines (HepG2, Hep3B and SNU-387) and preclinical Hep3B-induced xenograft tumours.
RESULTS
Spliceosomal dysregulations were consistently found in retrospective and in silico cohorts. EIF4A3, RBM3, ESRP2 and SRPK1 were the most dysregulated spliceosome elements in HCC. EIF4A3 expression was associated with decreased survival and greater recurrence. Plasma EIF4A3 levels were significantly elevated in HCC patients. In vitro EIF4A3-silencing (or pharmacological inhibition) resulted in reduced aggressiveness, and hindered xenograft-tumours growth in vivo, whereas EIF4A3 overexpression increased tumour aggressiveness. EIF4A3-silencing altered the expression and splicing of key HCC-related genes, specially FGFR4. EIF4A3-silencing blocked the cellular response to the natural ligand of FGFR4, FGF19. Functional consequences of EIF4A3-silencing were mediated by FGFR4 splicing as the restoration of non-spliced FGFR4 full-length version blunted these effects, and FGFR4 inhibition did not exert further effects in EIF4A3-silenced cells.
CONCLUSIONS
Splicing machinery is strongly dysregulated in HCC, providing a source of new diagnostic, prognostic and therapeutic options in HCC. EIF4A3 is consistently elevated in HCC patients and associated with tumour aggressiveness and mortality, through the modulation of FGFR4 splicing.
Topics: Humans; Spliceosomes; Carcinoma, Hepatocellular; Retrospective Studies; Liver Neoplasms; Oncogenes; RNA Splicing Factors; Heart Murmurs; Protein Serine-Threonine Kinases; RNA-Binding Proteins; Eukaryotic Initiation Factor-4A; DEAD-box RNA Helicases
PubMed: 36419260
DOI: 10.1002/ctm2.1102 -
Current Problems in Cardiology Feb 2023A heart murmur in adults is a common reason for referral for echocardiography at most general cardiology clinics in Europe. A murmur may indicate either a mild... (Review)
Review
A heart murmur in adults is a common reason for referral for echocardiography at most general cardiology clinics in Europe. A murmur may indicate either a mild age-related valvular calcification or regurgitation, or represent a significant heart valve disease requiring valvular intervention. Generally, the correlation between murmurs by auscultation and severity of heart valve disease by echocardiography is poor. Particularly, the severity and characterization of diastolic murmurs by auscultation may poorly correlate with echocardiographic findings. This narrative review aims to summarize the differential diagnoses of physiological and pathological murmurs, describes the current referral practice of murmur patients for echocardiography, and presents a single-center experience on the correlation of auscultation and echocardiographic findings with a particular focus on aortic and mitral valve diseases. A careful auscultation of the heart prior to the echocardiogram is mandatory and may help to predict the echocardiographic findings and their interpretation in view of the clinical information. The correlation between clinical examination, point of care ultrasound and standard echocardiography is a matter of continued exploration.
Topics: Adult; Humans; Heart Auscultation; Cardiologists; Heart Murmurs; Echocardiography; Heart Valve Diseases
PubMed: 36336114
DOI: 10.1016/j.cpcardiol.2022.101479