Cardiac Resynchronization and Circulating Markers of Sarcoplasmic Reticulum Calcium Handling and Sudden Death Risk

Ning Jiang1, Anyu Zhou2, Hafiz Imran2

  • 1Lifespan Cardiovascular Institute, Brown University, Providence, Rhode Island, USA.

Insights

Cardiac resynchronization therapy (CRT) improves heart function by altering circulating biomarkers. CRT reduces nonfunctional sodium channels and enhances SERCA2a expression, potentially lowering sudden death risk.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Biomarkers

Background:

  • Cardiac resynchronization therapy (CRT) is known to improve heart function and reduce arrhythmias.
  • Heart failure is associated with impaired calcium handling and altered sodium channel function.
  • Reduced sarco/endoplasmic reticulum calcium adenosine triphosphatase 2a (SERCA2a) expression is linked to diminished cardiac contractility.

Purpose of the Study:

  • To investigate the effect of CRT on circulating markers of calcium handling.
  • To determine if CRT alters biomarkers associated with sudden cardiac death risk.
  • To explore the relationship between CRT and specific cardiac gene expression in circulation.

Main Methods:

  • Analysis of circulating messenger RNA (mRNA) splicing variants of cardiac sodium channels.
  • Quantification of SERCA2a mRNA expression levels in patients.
  • Comparison of biomarker levels between patients with and without CRT.

Main Results:

  • CRT was associated with a decreased proportion of nonfunctional cardiac sodium channel mRNA variants.
  • Patients receiving CRT showed improved SERCA2a mRNA expression compared to baseline.
  • No significant improvement in these biomarkers was observed in patients without CRT.

Conclusions:

  • CRT may improve cardiac function and reduce arrhythmic risk by favorably altering circulating cardiac biomarkers.
  • Changes in sodium channel variants and SERCA2a expression provide potential mechanistic insights into CRT's benefits.
  • Circulating mRNA markers could serve as indicators of CRT response and therapeutic efficacy.

Related Concept Videos

Blood Studies for Cardiovascular System I: Cardiac Biomarkers01:20

Blood Studies for Cardiovascular System I: Cardiac Biomarkers

Cardiac biomarkers are enzymes, proteins, and hormones released into the blood when cardiac cells are injured. They are powerful tools for triaging.
The essential diagnostic tools for detecting myocardial necrosis and monitoring individuals suspected of having acute coronary syndrome (ACS) include:
Troponins
Troponins, particularly cardiac troponins I and T, are the most precise and sensitive markers of myocardial injury. They are detectable within 4-6 hours of myocardial injury and remain...
438
Cardiomyopathy III: Hypertrophic Cardiomyopathy01:29

Cardiomyopathy III: Hypertrophic Cardiomyopathy

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...
97
Cardiomyopathy II: Dilated Cardiomyopathy01:30

Cardiomyopathy II: Dilated Cardiomyopathy

Dilated cardiomyopathy, or DCM, is a progressive myocardial disorder characterized by ventricular chamber dilation and contractile dysfunction.EtiologyVarious factors can cause DCM, including hypertension and heavy alcohol intake, which contribute to the weakening and enlargement of the heart muscle. Viral infections, such as Coxsackievirus B, adenoviruses, and influenza, can lead to DCM by causing inflammation and damage to heart tissue. Certain chemotherapeutic agents, including daunorubicin,...
84
Blood Studies for Cardiovascular System II: CRP, Hcy, and Cardiac Natriuretic Peptide Markers01:19

Blood Studies for Cardiovascular System II: CRP, Hcy, and Cardiac Natriuretic Peptide Markers

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.
These markers indicate stress or strain on the heart muscle:
Natriuretic Peptides (BNP)
Cardiac myocytes produce these hormones in response to ventricular stretching...
267
Cardiomyopathy IV: Restrictive Cardiomyopathy01:29

Cardiomyopathy IV: Restrictive Cardiomyopathy

Restrictive cardiomyopathy (RCM) is a rare heart muscle disease characterized by impaired ventricular filling due to stiffened ventricular walls, leading to significant diastolic dysfunction.EtiologyRestrictive cardiomyopathy can arise from both inherited and acquired diseases, many of which are systemic. It is categorized into four main types: infiltrative, storage, non-infiltrative, and endomyocardial diseases.Infiltrative diseases, such as amyloidosis, lead to RCM by depositing amyloid...
121
Cardiomyopathy I: Introduction and Classification01:25

Cardiomyopathy I: Introduction and Classification

Cardiomyopathy, or CMP, is a group of diseases affecting the myocardial structure, impairing its ability to pump blood effectively. This condition can lead to arrhythmias, heart failure, or sudden cardiac death.Cardiomyopathies are classified into primary and secondary categories:Primary Cardiomyopathy refers to conditions involving only the heart muscle that are often idiopathic (of unknown cause) or genetic. They primarily affect the myocardium without the involvement of other systemic...
131