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Scientists identify genomic 'fingerprint' for alcohol-induced heart failure

May 05, 2008

A person with dilated cardiomyopathy has an enlarged and stretched heart cavity, usually too weak to pump normally; most people will go on to develop heart failure. While clinicians know that up to 36 percent of all cases of dilated cardiomyopathy may be due to excessive drinking, it has been difficult to differentiate between alcohol-induced heart failure and heart failure due to idiopathic dilated cardiomyopathy. A first-of-its-kind study has found a way to both diagnose alcohol-induced heart failure and possibly reverse it through therapeutic interventions.

Results are published in the May issue of Alcoholism: Clinical & Experimental Research.

"Excessive alcohol consumption affects not only heart function but also its structure," said Judith K. Gwathmey, professor of medicine at Boston University School of Medicine, and corresponding author for the study. "These effects can be acute if the exposure is brief, but can become chronic with long-term drinking. Furthermore, long-term effects are more serious since they affect not only the function of heart muscle but also its structure in a non-reversible manner."

Heart failure is an end point rather than an early sign of defect, she added. "Which is why detection of the pathology is so important during the earlier phases of reduced heart function," she said. "With the fingerprinting or profiling that we now have at hand, we can begin to think of diagnostic test(s) or biomarker(s) that would enable earlier and more definitive diagnoses, better monitor clinical outcomes of cessation of drinking, as well as medical interventions."

For this research, study authors employed a microarray, a technique used to sort out which genes change in response to a disease state. They analyzed an array - containing 1,143 heart-specific oligonucleotide probes - that is normally used to screen ribonucleic acid (RNA) samples from transplant recipients and organ donors with alcohol-related heart failure. The researchers then compared messenger RNA (mRNA) from the hearts of persons with alcohol-related heart failure with mRNA from the hearts of persons who did not engage in excessive drinking.

Results indicate a genomic "fingerprint" or profile of de-regulated genes that are associated with alcohol-induced heart failure in humans.

"The etiology of alcohol-induced cardiomyopathy is unique and different from other forms of cardiomyopathy, especially the idiopathic dilated cardiomyopathy," said Gwathmey. "Alcohol-induced cardiomyopathy is associated with changes in contraction and structural components that result in a reduction in the heart's pumping ability as well as the relaxation and filling of the heart. It is also associated with a significant increase in genes that cause cell death."

While cessation of drinking may mitigate some of the alcohol-related damage to the heart, Gwathmey said there is a point at which heart failure becomes irreversible due to "architectural" changes that alcohol has caused in the heart.

"The 'architectural damage' we refer to is related to the decrease in cells which are responsible for holding all the cells together in the heart and keeping the normal structure and shape of the heart," she said. "Heart function is dependent on the tight connections of heart cells in order for it to work synchronously and efficiently. Any slippage in the alignment of the cells can have severe consequences on the function of the heart and result in a large dilated weak heart with poor pumping function. This damage occurs in addition to a high rate of cardiac cell death."

In the early stages of chronic drinking, the heart can be forgiving, Gwathmey noted. "If the person stops drinking, heart failure is often reversible and/or can significantly improve," she said. "In fact, some patients do not even need medication if caught early enough. However, in later stages the architectural damage and cell death become so great that the heart failure becomes irreversible. Heart cells are not mitogenic, which means they cannot divide or replace themselves through cell division. Nevertheless, through recent efforts much progress has been made with stem-cell research. Many investigators have obtained positive results through the injection of stem cells into the heart, although these experiments are preliminary."

One of the best ways to address alcohol-induced heart failure, she added, is through aggressive early intervention. "Now that we have this diagnostic marker or fingerprint, clinicians will be better able to monitor the progress of a patient who is being treated either medically or simply self reporting a cessation of drinking."

Alcoholism: Clinical & Experimental Research