Medical Device Daily Executive Editor

"Predictive" medicine is a growing enthusiasm in healthcare, but the cardiovascular sector may be furthest behind this particular R&D curve. While plenty of standard behavioral and associated disease signs and symptoms obviously point to impending heart disease, the technologies for the earliest prediction of those at highest risk for sudden cardiac death are not yet available.

That is perhaps most obvious in the case of sudden cardiac arrest (SCA) — as opposed to myocardial infarction (MI) — which the new SCA Coalition has decided to attack more aggressively and more publicly (see adjacent story, this page). And it is clear that the primary effort of this group should be in identifying those most likely to need implantable cardioverter defibrillators (ICDs), since getting to the victims and applying the necessary CPR/automated cardioverter defibrillator (AED) shock in four to six minutes (that is, less than 360 seconds) will always be dicey, if not impossible.

The burden of reducing the high rate of fatality thus lands on the development of new diagnostics to develop more sensitive assays for determining who most needs an ICD implant.

But from the broad range of studies rolling out of last week's scientific sessions of the Heart Rhythm Society (HRS; Washington), it seems clear that the diagnostic emphasis of cardiovascular science is on detecting and specifying the heart disease that a person already has, not what asymptomatic or mildly symptomatic patients are most likely to succumb to SCA. And without the needed financial support (read, profit motive), this is unlikely to change, given the lengthy follow-up time and large populations needed to investigate mortality.

The other side of the coin suggests this as well, since there were some studies at the HRS conference — but very few — describing the newest methods for predicting unexpected mortality from cardiovascular disease. (And only four studies were listed in the abstract index under "Risk factor.") Additionally, most of these still depend on evaluating patients who have already experienced a heart "event" of some sort.

In a Finnish study, researchers combined bicycle ergometer exercise testing with T-wave alternans (TWA) to predict mortality in 1,047 patients referred for exercising testing but not having an MI. TWA is a noninvasive method for analyzing beat-to-beat variance in the T-wave portion of the ECG, and is most often used to determine risk of death following MI.

Digital ECGs were recorded and TWA was analyzed with a method called time-domain modified moving average. The maximum TWA value at heart rate was derived and analyzed for its ability to stratify risk for all-cause cardiovascular death and for risk of sudden cardiac death.

In a 44-month follow-up, 59 of those enrolled died of either SCA or as the result of some other heart failure. Analysis showed that the relative TWA risk was 7.4 for sudden cardiac death, 6 for cardiovascular mortality, and 3.3 for all-cause mortality, and the researchers concluded that the testing method "powerfully predicts mortality" in a population undergoing exercise testing combined with TWA.

A study from Poland used microvolt TWA (MTWA, a TWA variant measuring one-millionth of a volt) to determine if it can be used as a universal marker for "cardiac events" after acute MI.

The researchers said that when it looked at all of the negative events from a population of 115 post-MI patients who had suffered negative events — deaths, sudden deaths, reinfarctions, ventricular tachycardia and rehospitalizations — the only common factor was "a not negative MTWA," and thus a "powerful predictor" of such events, but not predictive of which events are the worst — sudden death.

A Japanese study appeared to offer a specific negative concerning a combination of TWA systems for identification of risk.

The researchers studied the use of MTWA as an index of risk for ventricular arrhythmias or sudden cardiac death and combined this with ambulatory ECG-based tracking of TWA (called A-TWA), which is also used for risk stratification.

The study employed the two methods, using the same voltage power, to look at 68 patients with serious cardiac disorders or syncope but found no linear correlation between the two methods.

Another study out of the University of Utah (Salt Lake City) examining the prediction of death following an MI, used two new predictive systems: heart rate turbulence (HRT) and deceleration capacity (DC).

The study enrolled 2,292 patients that had acute revascularization and found 185 deaths in this population in a five-year follow-up. The researchers said that the methods of analysis correlated with the high risk of left ventricular ejection fraction (LVEF) — with depressed LVEF being a high-risk predictor — and so the two methods are "feasible" for identifying those patients at highest risk for death, the research report concludes.

Sleep apnea has long been associated with cardiovascular disease and perhaps sudden cardiac death. Researchers from two universities in Japan said that sleep apnea clearly has been proven to be associated with death in those with CHF, but that there has been no definitive relationship shown to cause sudden death in these CHF patients.

The study followed 95 patients with CHF receiving treatment for sleep apnea, with an average of 17 months follow-up, and it reported 18 patients of the group dying, 10 experiencing ventricular tachyarrhythmia.

It said the results supported the need for the management of sleep apnea in these patients, and that the risk factors identified were independent of hemodynamic parameters.

All of these studies were interesting, but so technically specific and limited to such narrow populations over relatively short periods, that they appear to provide only the narrowest of pathways to what the SCA Coalition needs in terms of preventing SCA in the near term. This is an observation likely to be made by government budget authorities and may raise continuing doubts concerning the cost-effectiveness of making any inroads vs. this lethal event.

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