GC–MS and LC–MS Map Heart Tissue in Valve Disease

Tricuspid regurgitation (TR) is a heart condition in which the valve between the two chambers on the right side of the heart doesn’t close properly, letting blood leak backward into the upper right chamber, known as the right atrium (RA). The condition is linked to poorer health outcomes, but scientists still know little about how it changes the heart tissue at the molecular level.

To learn more, researchers at Hacettepe University in Turkey studied tissue taken from the right atrium of patients to see how the condition affects the small molecules and fats in the heart. They used gas chromatography–mass spectrometry (GC–MS) to separate and measure chosen sets of small molecules, and liquid chromatography-quadrupole time-of-flight mass spectrometry (LC–qTOF–MS) to provide a broad picture of all the different fats present in a sample. A paper based on their research was published in the journal BMC Cardiovascular Disorders.¹

Why Has Tricuspid Regurgitation Been Overlooked?

Tricuspid regurgitation was long seen as a minor valve problem, but it is now recognized as a serious condition linked to more illness, worsening heart failure, more hospital stays, and a higher risk of death. Even so, it has often been overlooked and undertreated, partly because doctors have traditionally focused on how well the lower right chamber of the heart is pumping rather than on problems in the upper right chamber, the right atrium.^2,3

At the same time, doctors have increasingly recognized a form of the condition that is driven mainly by enlargement of the right atrium and the ring of tissue around the tricuspid valve, often in people who have had irregular heart rhythms in the upper chambers for a long time. This suggests that the right atrium plays an active role in causing the condition rather than simply being affected by it.⁴

Why Did the Researchers Focus on the Right Atrium?

Because there is growing awareness that problems in the right atrium affect how patients with tricuspid regurgitation fare, and because so little was known about how the condition changes this part of the heart at the molecular level, the researchers set out to map the molecules and fats in right atrium tissue from patients with significant tricuspid regurgitation. They expected to find a distinct chemical pattern showing that the heart cells were breaking down less sugar for energy, that their energy-producing machinery was under strain, that the balance of fats in their membranes was disrupted, and that harmful fats were building up.¹

How Was the Study Carried Out?

The researchers collected small samples of tissue from a little pouch on the right atrium during heart surgery in 24 adults. Eleven of these patients had severe or worse tricuspid regurgitation, and the other 13, who did not have the condition, served as a comparison group. Along with the laboratory techniques described above, the team used several statistical methods to compare the two groups and pick out the overall patterns of molecules and fats that best told them apart.¹

What Did the Study Reveal About Changes in the Heart Tissue of Patients with Tricuspid Regurgitation?

Patients with tricuspid regurgitation showed a distinct chemical pattern in their heart tissue. They had lower levels of several molecules involved in breaking down sugar for energy. They also had changes in molecules linked to oxidative stress, a type of cell damage, and to the breakdown of amino acids, the building blocks of proteins. The fat analysis revealed widespread changes in the fats that make up cell membranes, along with signs pointing to changes in mitochondria, the parts of cells that produce energy. These included a shift in the balance between two major types of membrane fats and lower levels of certain other fats.¹

When the researchers looked at all the measurements together, the two groups clearly separated from one another, and the same molecules consistently stood out as the most important differences between them. This led the researchers to conclude that TR is associated with coordinated metabolic and lipidomic reprogramming in the RA, a pattern compatible with, though not direct evidence of, mitochondrial stress, impaired bioenergetics, and membrane destabilization.¹

“These findings,” write the authors of the paper,¹ “support a model in which RA remodeling is tightly linked to TR pathophysiology, highlighting candidate molecular features for future validation. Multi-omics biomarkers may enhance risk stratification, inform the timing of intervention, and guide the development of future point-of-care molecular diagnostics.”

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References

1. Alma, M.; Aydın, A.; Sezer, A. et al. Multi-omics Analysis of Human Right Atrial Tissue Identifies Molecular Signatures of Remodeling in Tricuspid Regurgitation. BMC Cardiovasc Disord. 2026, 26 (1), 962. DOI: 10.1186/s12872-026-06320-8
2. Nath, J.; Foster, E.; Heidenreich, P. A. Impact of Tricuspid Regurgitation on Long-term Survival. J Am Coll Cardiol. 2004, 43 (3), 405-409. DOI: 10.1016/j.jacc.2003.09.036
3. Topilsky, Y.; Nkomo, V. T.; Vatury, O. et al. Clinical Outcome of Isolated Tricuspid Regurgitation. JACC Cardiovasc Imaging 2014, 7 (12), 1185-94. X DOI: 10.1016/j.jcmg.2014.07.018
4. Utsunomiya, H.; Itabashi, Y.; Mihara, H. et al. Functional Tricuspid Regurgitation Caused by Chronic Atrial Fibrillation: A Real-Time 3-Dimensional Transesophageal Echocardiography Study. Circ Cardiovasc Imaging 2017, 10 (1), e004897. DOI: 10.1161/CIRCIMAGING.116.004897