Diagnostics & Imaging Week

In matters of the heart, it's accepted that men and women can be vastly different. And the more researchers dig into gender anomalies related to cardiac care, the more they realize that treatment practices for women need to change.

New research highlights those differences, particularly as they pertain to arrhythmias and the potential benefit derived from defibrillators. What may result from this new research – Compugen (Tel Aviv, Israel) reported the discovery and experimental verification of CGEN-327, a novel molecular biomarker candidate for the diagnosis of ovarian cancer. CGEN-327 is a previously unknown splice variant of the HE4 (Human Epididymis Protein 4) gene, which is a known biomarker for ovarian cancer. The company also said that it has entered into a research and license option agreement for the product candidate with an unidentified diagnostic company. Patent coverage for this discovery is being pursued by Compugen. VP of R&D Anat Cohen-Dayag said, "This is an excellent example of Compugen's 'discovery on demand' capabilities. In this case, we were approached by a leading company developing and commercializing immunoassay panels for rapid diagnosis of challenging diseases. Their specific interest was to determine whether any unknown splice variants exist for this known biomarker for ovarian cancer, an objective with a high level of industry interest and past research activity." as quickly as this year – is a new test that would determine if a women is at high risk for arrhythmias because existing tests, designed based on men's physiology, just don't do the job.

Data from a new study proves that increased QT variability is an independent predictor of ventricular tachycardia (VT) or ventricular fibrillation (VF) in men, while in women, QT variability alone does not pose a risk of arrhythmic events.

"Women don't seem to derive as big a benefit from defibrillators as men do," Mark Haigney, MD, of the Division of Cardiology at the Uniformed Services University of the Health Sciences (Bethesda, Maryland), told Diagnostics & Imaging Week. "This is probably due to the fact that they have fewer arrhythmias. The other thing that is probably impacting on the estimate of benefit of defibrillators for women is that there are fewer women in these trials."

Results from a study led by Haigney may help to develop a test that's uniquely effective in women because even though they have fewer arrhythmias than men, those who do get defibrillators implanted tend to be sicker with more incidences of hypertension and diabetes.

"Right now we believe defibrillators are beneficial in women with reduced systolic function, but we don't have proof," Haigney said. "Part of the problem is that we're not good at identifying women at high risk. The most exciting thing is that we may have identified a test that's suited to identify women at highest risk."

The actual focus of Haigney's study was to see if the beat-to-beat electrical behavior with defibrillators are different in women compared with men and to see if the things that predict arrhythmias in men are the same for women.

The study, which appears in the current issue of HeartRhythm Journal, a publication of the Heart Rhythm Society (Washington), confirms that gender plays a significant role in predicting the risk of VT/VF. It also highlights the fact that QT variability, when not correlated to heart rate variability, is a significant predictor of arrhythmic events in women.

QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. The QT interval is dependent on the heart rate in an obvious way (the faster the heart rate, the shorter the QT interval) and has to be adjusted to aid interpretation.

The study included a patient population of 1,232 (with 805 usable recordings identified; 663 men and 142 women) from those enrolled in the Multicenter Automatic Defibrillator Trial (MADIT) II. Patients of the MADIT II study underwent 10-minute, resting digitized recordings at study entry and both QT and heart rate were measured for each beat with a semi-automated method.

Haigney compared QT variability and heart rate in both men and women to determine if these values influence the occurrence of VT/VF and whether or not gender impacts the risk.

In a 2.6-year follow-up period, study analysis found increase QT variability or heart rate variance was associated with a significantly higher risk of VT/VF in men, but not in women.

Haigney said the findings confirm that different measures of variability in QT and heart rate determine the level of risk for men and women.

"Our primary goal in this study was to see whether the things that predicated arrhythmias in men also worked in women," he said. "We had reason to believe that it wouldn't. We already knew women have fewer arrhythmias. The repolarization phase of the cardiac cycle in women is different from men. So we were trying to see if the difference would be reflected in electrical behavior of the heart.

"We found that women's hearts manifest enough of the same electrical abnormalities as men, but they don't seem to be as well correlated with arrhythmias," he said. "It was a complicated finding and not exactly what we expected to find. But we think it may be a clue to point us in the direction to develop better tests to find women at greatest risk."

A new test for women wouldn't be entirely new, just a different application of existing technology.

"It takes a Holter recording of ECG, a pretty conventional test," Haigney said. "But it analyzes the beat-to-beat changes in heart rate and QT interval in a novel way. The algorithm we used was created at Johns Hopkins University (Baltimore) and requires no unusual hardware and no expensive investment in infrastructure."

Haigney said his team now wants to see these findings confirmed in at least one or two other studies before they suggest a change to standard cardiac practice.

"We need to do a better job of identifying who is at risk for arrhythmias so that we can put defibrillators in the people who will get the biggest benefit. More studies coming out in the next year could have a big impact on the behavior of practicing physicians."