Expiration-Triggered Sinus Arrhythmia May Be Considered Post-Infarction Risk Marker

The association of expiration-triggered sinus arrhythmia with mortality remained statistically significant even after taking into account respiratory rate, left ventricular ejection fraction, GRACE score, and diabetes.

Expiration-triggered sinus arrhythmia (ETA) can be considered an independent post-myocardial infarction (MI) risk marker, according to new data published in the Journal of the American College of Cardiology.

As the authors explained, “Various parameters have been proposed for RSA [respiratory sinus arrhythmia] quantification and its use as a predictor for subsequent mortality in cardiac patients … We present a method that addresses heart rate changes mediated by the expiration-driven increase of vagal activity.” They sought to improve RSA determination by quantifying the amount of sinus arrhythmia related to expiration based on short-term electrocardiogram (ECG) and respiration chest excursion recordings.

Patients included in the study were survivors of acute MI (n=941), ≤80 years of age, presented in sinus rhythm, and did not meet criteria for implantable cardioverter defibrillator implantation for secondary prevention before hospital discharge. The short-term ECGs (30 minutes) were performed within 2 weeks of patients’ index MIs and during their initial hospitalizations.

Heartbeat intervals starting between ᶲ1 and ᶲ2 were identified as anchors for computing ETA and RR interval segments around the anchors were selected and averaged. RR interval average change was quantified by Haar wavelet analysis with a scale of 2. Then, the numeral values of ᶲ1 and ᶲ2 (0.6 and -0.1, respectively) were optimized with respect to 5-year all-cause mortality prediction, as assessed by receiver-operating characteristic (ROC) analysis.

MI diagnosis was confirmed via the following criteria: typical chest pain for at least 20 minutes, creatine kinase twice above the normal limit, and ST-segment elevation ≥0.1 mV in at least 2 limb leads or ≥0.2 mV in at least 2 contiguous precordial leads. In addition, left ventricular ejection fraction (LVEF) was determined via angiography (n=445; 47.3%) or biplane ECG according to Simpson’s method (n=496; 52.7%).

The GRACE score (a clinical score combining age, serum creatinine, previous MI, previous heart failure, in-hospital percutaneous coronary intervention, heart rate, systolic blood pressure, ST-segment deviation, and positive enzymes) was used for the prediction of long-term prognosis.

The median ETA was 0.54 ms (interquartile range [IQR]: -0.25 to 1.66 ms), and those patients who died during follow-up had significantly smaller ETAs compared with survivors (-0.35 ms; IQR: -1.33 to 0.30 vs 0.64 ms; IQR: -0.16 to 1.75; P<.0001). The area under the ROC curve was 0.72 (95% confidence interval [CI]: 0.67-0.78) for all-cause mortality prediction via ETA.

ETA was a significant predictor of outcome in univariable Cox analysis—an increase of 1 ms was associated with a hazard ratio (HR) of 0.94 (95% CI: 0.90-0.97; P=.001). GRACE score, LVEF, diabetes, and respiratory rate were also significant predictors of all-cause mortality. Furthermore, in multivariable Cox analysis considering all of those risk predictors, the association of ETA with mortality remained statistically significant (HR: 0.95; 95% CI: 0.91-0.99; P=.035).

Adding ETA to a model composed of respiratory rate, LVEF, diabetes, and the GRACE score, significantly increased the area under the ROC curve from 0.79 to 0.82 (P=.02).

However, performance of standard methods for RSA quantification was weaker—areas under the ROC curve were 0.57 (95% CI: 0.49-0.64) and 0.62 (95% CI: 0.55-0.69) for RSAHF and RSAPT, respectively.

“The primary end point of the study was all-cause mortality. With respect to cardiac mortality, we obtained similar results as with all-cause mortality, albeit at a lower statistical significance level,” researchers explained.

Nonetheless, since ETA appears to be associated with mortality independent of other risk factors, including it in these models will most likely improve their predictive power.

“Future investigations should address the mechanisms relating ETA to clinical outcomes among MI survivors and explore interventions that might reduce mortality in those with impaired reflex activity,” researchers concluded.


Sinnecker D, Dommasch M, Steger A, et al. Expiration-triggered sinus arrhythmia predicts outcome in survivors of acute myocardial infarction. J Am Coll Cardiol. 2016;67(19):2213-2220. doi: 10.1016.j.jacc.2016.03.484.