A cohort study points to potential risk markers that may help identify good candidates for implantable cardioverter defibrillator (ICD) therapy among patients with coronary heart disease (CHD) who don’t qualify for a device by current guidelines.
Future trials aiming to extend the devices to such patients without the recommended level of left ventricular (LV) systolic dysfunction might consider age, heart failure (HF) severity, and midrange LV ejection fraction (LVEF) as further arrhythmic-risk stratifiers, the study suggests.
Those criteria tended to differentiate risk for sudden or arrhythmic death (SAD) from risk for death from other causes (non-SAD) in more than 5000 patients with CHD but LVEF greater than 35%, or greater than 30% if they were in NYHA heart failure class I, investigators reported May 2 in JAMA Cardiology.
Across the entire cohort, SAD accounted for about one fifth of deaths, but the proportion varied among subgroups; it was 14% for patients in NYHA class II and 49% in those younger than age 60 years.
Of note, an LVEF of 40% to 49% predicted SAD better than it did non-SAD, but non-SAD was better predicted by age 60 years or older (especially age 70 years or older) and NYHA class II or worse, note the authors, led by Neal A. Chatterjee, MD, MSc, from Brigham and Women’s Hospital, Boston, Massachusetts.
“At every single ejection fraction, at every single heart failure class, nonarrhythmic deaths are going to dwarf arrhythmic deaths,” except in very young patients, senior author, Christine M. Albert, MD, MPH, also from Brigham and Women’s Hospital, told theheart.org | Medscape Cardiology.
Key to further risk stratification, she said, is consideration of both absolute risk and proportional risk for SAD, that is, SAD risk in relation to risk for death from competing causes.
“What you really want is to put these devices in people who would likely live for a long time,” she said. Having risk-stratification criteria to help identify patients at lower risk for sudden death, who aren’t as likely to need an ICD, is something “I don’t know as electrophysiologists we’ve thought about that much. But I think that we’re going to be forced to.”
When a treatment is highly expensive and “only works on one particular mode of death, I think you have to be more selective about who gets it.”
So in future ICD trials, Albert said, “it looks like the older age groups might not be the most fruitful groups to look at. You might want to limit trials to younger age groups.”
Albert noted that the findings aren’t surprising and have been long appreciated at some level; the study’s purpose was to quantify the risks so as to help the design of future trials.
The cohort consisted of 5761 adult patients from 135 centers in the United States and Canada who were part of the prospective Biologic Markers and MRI SCD study, also known as PRE-DETERMINE. Of the total group, 80% were NYHA class I at baseline; their mean LVEF was 52% and the mean age was 62 years.
They were followed for a median of 3.9 years. Their 4-year cumulative incidences of SAD and non-SAD were 2.1% and 7.7%, respectively.
The risk for SAD went up 71% and risk for non-SAD rose 44% for every 10% drop in LVEF. The non-SAD risk went up stepwise with worsening NYHA class and was significant in all four classes. But the risk for SAD was substantially elevated in association with NYHA class III and IV only.
Table. Absolute 4-Year SAD and Non-SAD Risks in Patients With CHD Not Meeting ICD LVEF Criteria, by Subgroups
| Subgroups | SAD Incidence (95% CI) | P Value for Interaction | Non-SAD Incidence (95% CI) | P Value for Interaction |
|---|---|---|---|---|
| Age | .05 | <.001 | ||
| ≤59 y | 2.0 (1.4 – 2.8) | 2.1 (1.4 – 2.9) | ||
| 60-69 y | 1.6 (1.1 – 2.2) | 5.6 (4.5 – 6.9) | ||
| 69 y | 2.9 (2.1 – 3.8) | 15.2 (13.5 – 17.1) | ||
| NYHA class | .02 | <.001 | ||
| I | 2.0 (1.4 – 2.8) | 2.1 (1.4 – 2.9) | ||
| II | 1.6 (1.1 – 2.2) | 5.6 (4.5 – 6.9) | ||
| III and IV | 2.9 (2.1 – 3.8) | 15.2 (13.5 – 17.1) | ||
| LVEF | <.001 | <.001 | ||
| ≥60% | 1.0 (0.5 – 1.6) | 5.2 (4.1 – 6.6) | ||
| 50% – 59% | 1.6 (1.1 – 2.3) | 6.4 (5.2 – 7.7) | ||
| 40% – 49% | 3.2 (2.4 – 4.2) | 10.1 (8.6 – 11.7) | ||
| 30% – 39% | 4.9 (3.0 – 7.6) | 14.5 (10.8 – 18.6) |
Other conditions that could potentially be useful for risk stratification include diabetes and atrial fibrillation, both of which were significant predictors of both SAD and non-SAD, but more than three times as strongly for non-SAD.
Patients with diabetes, for example, are at high absolute risk for both arrhythmic and nonarrhythmic death. Still, nonarrhythmic death becomes more likely with increasing age, so ICDs may be beneficial in younger people with diabetes, Albert speculated.
“If someone’s going to live longer, you might settle for a lower benefit in the short term, because they’re going to receive that benefit over a longer period of time.”
An accompanying editorial from Zian H. Tseng, MD, MAS, University of California San Francisco, highlighted some of the study’s acknowledged limitations. These include their relevance only to ischemic cardiomyopathy, selection biases from registry enrollment of patients, and, especially, variable and sometimes subjective definitions of sudden or arrhythmic death and the low rate of autopsy confirmation of both kinds of death.
“Because SAD is the only type of sudden death rescued by automatic external defibrillators and ICDs and is the intended focus of genetic association and risk studies of SCD, it is essential to distinguish SAD from nonarrhythmic causes,” Tseng concludes. “While comprehensive autopsies are not practical in most clinical trials and population, cohort, or genetic association studies, understanding the limits of current criteria used to define SCD and SAD is important for interpreting results.”
PRE-DETERMINE was supported by the National Heart, Lung, and Blood Institute and St Jude Medical. Chatterjee had no disclosures. Albert discloses receiving grants from St Jude Medical and Roche Diagnostics. Disclosures for the other authors are in the report. Tseng had no relevant disclosures.
JAMA Cardiol. Published online May 2, 2018. Article, Editorial
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