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Pathophysiology of Heart Failure01:17

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Heart failure (HF) is a progressive syndrome involving ventricles that leads to inadequate cardiac output. It can be classified based on location and output or ejection fraction. Ejection fraction (EF) is an essential measurement in the diagnosis and surveillance of HF. Reduced EF corresponds to systolic heart failure (HFrEF). However, HF with preserved ejection fraction (HFpEF) is becoming increasingly prevalent. Also known as diastolic HF, this form of HF is related to aging. The...
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Systolic Heart Failure and Compensatory MechanismsSystolic heart failure (also termed HFrEF, Heart Failure with Reduced Ejection Fraction) is the most prevalent type of heart filure. It results in a decreased volume of blood being pumped from the ventricle. The aortic arch and carotid sinuses have baroreceptors that detect reduced blood pressure, triggering the sympathetic nervous system (SNS) to release epinephrine and norepinephrine. Initially, this response aims to boost heart rate and...
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Heart Failure IV: Classification and Diagnostic Evaluation01:30

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Heart failure can be classified in various ways, with the most common classifications based on physical activity limitations, disease progression, severity, and treatment strategies.The Functional Classification of Heart Failure divides patients into four categories based on physical activity limitation due to symptom burden.Class I: Patients in this class have cardiac disease but no physical activity limitations. Ordinary activities like walking, climbing stairs, or routine tasks do not cause...
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Hypertrophic cardiomyopathy, or HCM, is an autosomal dominant genetic disorder characterized by asymmetric left ventricular hypertrophy without ventricular dilation. It is more common in men and is typically diagnosed in young, athletic adults.EtiologyHCM is primarily genetic and is caused by mutations in genes encoding sarcomeric proteins. Researchers have identified over 1400 mutations across at least 11 different genes. Among these, the most frequently occurring mutations are found in the...
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Cardiac biomarkers are critical in diagnosing, prognosing, and managing cardiovascular diseases. Routine measurement of specific biomarkers such as B-type natriuretic peptide (BNP), C-reactive protein (CRP), and homocysteine (Hcy) is common practice in clinical settings to evaluate heart function and predict cardiovascular events.
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Heart failure refers to a clinical syndrome caused by structural or functional cardiac disorders that prevent the heart from pumping an adequate amount of blood to meet the body's metabolic needs. This condition often arises from myocardial infarction or ischemia, leading to decreased cardiac output, reduced tissue perfusion, impaired gas exchange, fluid volume imbalance, and decreased functional ability.Heart failure can result from disruptions in the mechanisms that regulate cardiac output...
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Differentiating heart failure phenotypes using sex-specific transcriptomic and proteomic biomarker panels.

Mustafa Toma1, George J Mak2, Virginia Chen2,3

  • 1Division of Cardiology, University of British Columbia, Vancouver, Canada.

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|August 4, 2017
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Summary

Researchers developed a male-specific transcriptomic biomarker panel to distinguish heart failure with preserved ejection fraction (HFpEF) from heart failure with reduced ejection fraction (HFrEF). This panel, combined with NT-proBNP, shows promise for improved heart failure diagnosis.

Keywords:
BiomarkersHeart failureHeart failure with preserved ejection fractionHeart failure with reduced ejection fractionProteomicsTranscriptomics

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Area of Science:

  • Biomarker discovery
  • Cardiovascular research
  • Genomics and proteomics

Background:

  • Heart failure with preserved ejection fraction (HFpEF) constitutes a significant portion of heart failure cases.
  • Distinguishing HFpEF from heart failure with reduced ejection fraction (HFrEF) is challenging with current diagnostic methods.
  • Novel biomarkers are needed for accurate HFpEF and HFrEF differentiation.

Purpose of the Study:

  • To develop and validate transcriptomic and proteomic biomarker signatures for differentiating HFpEF from HFrEF.
  • To assess the diagnostic performance of identified biomarker panels compared to established markers like NT-proBNP.

Main Methods:

  • Recruitment of 210 heart failure patients from the Alberta HEART study.
  • Clinical adjudication to classify patients into HFpEF and HFrEF groups.
  • Analysis of transcriptomic and proteomic data in discovery (n=61) and replication (n=70) cohorts.

Main Results:

  • A 22-transcript panel differentiated HFpEF from HFrEF in males (cross-validation AUC=0.74).
  • An ensemble of the transcript panel and NT-proBNP improved differentiation (discovery AUC=0.80, replication AUC=0.90).
  • The combined panel outperformed NT-proBNP alone (replication AUC=0.74) and the transcript panel alone (replication AUC=0.73).

Conclusions:

  • A male-specific transcriptomic biomarker panel effectively differentiates HFpEF from HFrEF.
  • These findings suggest potential for a blood test to aid in heart failure management.
  • Further replication in diverse patient populations is warranted.