Sudden death due to genetic mutation in the heart

2024-03-01 10:58:19

Heart News: “Sudden death due to genetic mutation”

In person under 35 years old The fatal cause is usually linked to structural alterations in the heart with which one is born (valves, size of the heart, arteries that carry blood) or is linked to hereditary heart diseases, but it is almost never due to an ischemic problem.

“In many family pathologies, in addition, the triggering gene or genes is unknown, and cases linked to a single genetic mutation are also rare,” emphasizes Dr. Macaya, professor of Cardiology at the Complutense University of Madrid.

A particularly striking disease is found in the arrhythmogenic right ventricular cardiomyopathyresponsible for around 20% of sudden deaths among athletes, as was the case of the Sevilla player Antonio Puerta in 2007.

“We have all seen news in the media about people who die unexpectedly, usually soccer players and marathon runners, who are the paradigm of health in our global society,” says the cardiologist at the San Carlos Clinical Hospital.

These people are unaware that they are carriers of a potentially lethal disease in their heart muscle; A situation that is even more notable in the case of elite athletes, who undergo various special medical checks during their professional life.

Genetic mutation in the heart muscle: from syncope to sudden death

From the headquarters of the Interhospital Cardiovascular Research Foundation (FIC) In the capital of Spain, Dr. Carlos Macaya focuses the Cardiology videoblog on the genetic mutation, of one or more genes, that can cause syncope and sudden death in some cases.

“What is the underlying cause of this disease of the heart muscle that can end with a totally unexpected death?… Well, we are entering the almost unknown universe of the human genome, although research reveals new genetic mysteries every day,” he says. ask and answer.

And what are genes?

People have more than 20,000 different types of genes and they are all part of DNA. Each gene, therefore, is “a little piece” of this deoxyribonucleic acid. And all of us are made up of one copy of our mother’s DNA and another of our father’s DNA.

DNA is included in the 23 pairs of chromosomes and forms codes using nucleotides, four chemicals (A -adenine-, T -thymine-, G -guamina, C -cytosine-) that join together forming base pairs to connect the two strands of DNA.

And approximately 2% of the 3.2 billion letters in the human genome are dedicated to proteins.

Even so, the main function of all genes would consist of regulating the decoding process of genes that express proteins.

“In addition, each gene constantly replicates, making copies of itself inside cells: millions and millions of copies that are not completely exact,” explains Dr. Macaya.

“When these abnormal copies exceed around 5% of the total copies, that is when we talk about a genetic mutation,” he points out.

So what happens if a gene in the cell mutates?

“The mutated gene will produce a protein similar to the original, but not exactly the same. And that erroneous protein, if it fulfills a fundamental organic function, as happens in cardiac muscle cells, will generate dysfunction,” he details.

In arrhythmogenic cardiomyopathy the problem is detected in the cardiomyocytes (the cells that make up the heart muscle tissue).

“These cells must contract in an orderly manner with each heartbeat. And for them to contract in an orderly manner, a specific protein is needed, the desmosomes, which manage to unite all of these cells (myocardiocytes),” he comments.

If these proteins, desmosomes, function poorly due to the genetic mutation, the cells will not contract, remaining isolated, generating fatty, fibrotic tissue, and may necrotize.

“When you practice physical exercise, more intense contractions of the heart muscle are needed. If the heart suffers this type of mutation in the right ventricle, heart failure with all its symptoms will manifest,” he describes.

“But there will also be malignant arrhythmias that can lead to syncope (loss of consciousness and collapse, not a simple dizziness) even the possibility of sudden death, even more so in competitive sports,” he highlights.

However, scientific research is constantly advancing in revealing all the secrets of cardiovascular diseases, such as arrhythmogenic cardiomyopathy.

A team from the National Cardiovascular Research Center (CNIC), led by scientist Juan Antonio Bernal, director of the Viral Vectors Unit, has discovered a possible treatment, which has not existed to date, that would serve to recover the contraction capacity of the heart muscle. .

Study published in the journal Nature Comunications in October 2023.

By studying mutations in the protein responsible for this condition, researchers have described for the first time an unknown function that controls the binding of heart muscle cells.

The study – the researchers indicate – has made it possible to understand why the muscle cells of the heart do not contract correctly and how to solve this functional problem.

At the moment, more than 350 mutations have been described in that protein Plakophilin-2 (PKP2), although it is unknown which are pathological and which are not; and if they are, if they will be more or less aggressive.

This work identifies a group of mutants that are always associated with severe contractile problems and that respond to pharmacological treatment with an activator of regulatory myosins, 4-hydroxyacetophenone (4-HAP).

The results – the CNIC emphasizes – are a proof of concept that demonstrates that it is possible to generate a complete atlas of all PKP2 mutations and categorize patients susceptible to suffering from syncope or sudden death.

What is known for certain is that extreme exercise accelerates the development of this heart muscle disease caused by a genetic mutation.

Preventive conclusions: Anyone who has a history of syncope and especially sudden death in immediate family members should be evaluated as soon as possible by a cardiology specialist.

We must assess the origin of these syncope and its possible relationship with malignant arrhythmias, which can lead to sudden death.

An irreversible event that haunts athletes while they practice their favorite hobby or during the hours after finishing the competition.

Research leads us to discover more genetic mutations and, therefore, more abnormal proteins; path that facilitates the search for therapeutic targets that resolve diseases, especially those of the cardiovascular system.

Dr. Carlos Macaya Miguel, cardiologist at the San Carlos Clinical Hospital and professor of Medicine at the Complutense University of Madrid.