Continuous ECG Monitoring for Detection of Ischemia After ACS

Abstract & commentary

By Andrew J. Boyle, MBBS, PhD

Source: Scirica BM, et al. Ischemia detected on continuous electrocardiography after acute coronary syndrome: Observations from the MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndrome-Thrombolysis In Myocardial Infarction 36) trial. J Am Coll Cardiol. 2009;53: 1411-1421.

After acute coronary syndromes (ACS), re-currence of ischemia is a harbinger of worse prognosis. Previous studies have suggested that continuous electrocardiograph (cECG) monitoring can detect ischemia, but that this method is associated with poor cardiovascular outcomes. However, recent advances in medical therapy and percutaneous coronary intervention (PCI) for ACS have changed clinical practice significantly. The role of cECG in detecting recurrent ischemia and determining prognosis in the current era of PCI and intensive pharmacotherapy has not been defined. Accordingly, Scirica et al present data from 6,355 patients undergoing cECG monitoring for seven days after ACS as part of the MERLIN-TIMI 36 study.

The MERLIN-TIMI 36 study was a randomized, placebo-controlled study investigating the efficacy of ranolazine in patients with ACS. They enrolled 6,560 patients, of whom 6,355 had cECG performed using two bipolar leads at 128-Hz sampling rate for seven days. The primary endpoint was ischemia determined by 1 mm ST-segment depression lasting at least one minute during a heart rate of < 100 beats/min. Secondary endpoints included ischemia with 0.5 mm ST depression lasting one minute and the incidence of ischemia occurring in the first 72 hours of randomization. cECG endpoints were analyzed by cardiologists blinded to clinical details. Analyses comparing ischemia detected by cECG excluded events that occurred during the time of cECG monitoring.

Twenty percent of the patients (n = 1,271) had at least one episode of ischemia on cECG. The majority of patients had their first episode of ischemia within 48 hours; the median number of ischemic episodes was three per patient. Patients with ischemia detected, compared to those with none detected, were older (mean age 66.6 vs. 62.7 years; p < 0.001), more likely to be female (38.6% vs. 34.2%; p = 0.003), and had lower body mass index (27.6 vs. 28.4; p < 0.001). They had higher prevalence of hypertension, prior angina, prior heart failure, and renal impairment (77.1% vs. 72.9%, p = 0.002; 66.4% vs. 53.0%, p < 0.001; 20.7% vs. 15.9%, p < 0.001; 29.8% vs. 19.4%, p < 0.001, respectively). The presentation and treatment strategy during hospitalization for ACS influenced the likelihood of ischemia detected with cECG. Patients with detectable ischemia were more likely to have presented with ST-segment depression, elevated troponin, elevated BNP, and a higher TIMI risk score (all p < 0.001). Fewer patients with detectable ischemia had been treated with an initial plan for an early invasive strategy (36.4% vs. 41.4%, p < 0.001), but more had actually undergone revascularization (42.3% vs. 38.6%, p = 0.015). Medication use patterns were different between groups, with those having detectable ischemia being less likely to take thienopyridines (48.5% vs. 53.7%, p = 0.001), statins (74.2% vs. 78.0%, p = 0.004), and calcium channel blockers (28.7% vs. 35.4%, p = 0.015), but more likely to be taking nitrates (38.6% vs. 28.3%, p < 0.001) at discharge. Beta-blocker use was not different between groups.

Patients with detectable ischemia on cECG had higher rates of adverse clinical outcomes. The primary endpoint of the trial was a combined endpoint of cardiovascular death, MI, and recurrent ischemia, which was higher in those with ischemia on cECG (28.5% vs. 17.8%, unadjusted HR 1.75; p < 0.001). The individual components of the composite endpoint were also higher in the group with demonstrated ischemia (cardiovascular death: 7.7% vs. 2.7%, HR 2.94, p < 0.001; MI: 9.4% vs. 5.0%, HR 2.0, p < 0.001; recurrent ischemia: 17.5% vs. 12.3%, HR 1.43, p < 0.001). Scirica et al performed a multivariable analysis, including clinical and biomarker data, and ischemia on cECG remained a strong predictor of events (adjusted HR 2.46 p < 0.001 for cardiovascular death, adjusted HR 1.57, p < 0.001 for primary composite endpoint). The relationship between ischemia and increased clinical event rate was consistent whether the events occurred early (within 48 hours) or late, whether the patients received revascularization or not, whether the ischemia was detected before or after revascularization, and even in the presence of no or minimal coronary artery disease on coronary angiography.

Scirica et al also analyzed the outcomes of patients with lesser degrees of ST-segment depression (0.5-1 mm), which occurred in only 3.9% of patients, and those with ST-segment elevation, which occurred in 3.2% of patients. Neither of these findings were associated with an increase in clinical events in these small subgroups. Furthermore, whether patients were randomized to ranolazine or placebo had no influence on the prevalence of ischemia on cECG monitoring. They concluded that detection of ischemia by cECG provides incremental prognostic information with which to assess the risk of recurrent major cardiovascular events in patients after NSTE ACS.


Each year, 1.3 million Americans are hospitalized with non ST-elevation ACS. Scirica et al demonstrate that, in contemporary practice, the addition of cECG monitoring for seven days after ACS adds additional prognostic information. With 20% of their cohort demonstrating ischemia, and this group having worse clinical outcomes, this has the potential to have a significant impact on the risk stratification of large numbers of patients. The strengths of the study include the large number of patients enrolled and the fact that the events that occurred during monitoring were censored, allowing it to be used as a prognostic tool only. However, several limitations must be acknowledged. Firstly, this study is an observational substudy, and no treatment effect has been studied here. Therefore, the results are hypothesis-generating, and one cannot recommend that we should be using cECG monitoring clinically based on these results. Secondly, there were a number of exclusion criteria in the MERLIN-TIMI 36 study, such as baseline ECG abnormalities, so that the results cannot necessarily be extrapolated to all patients. Thirdly, there were significant differences in the medical management between the groups with and without ischemia. Thus, the effects of the ischemia on outcomes may have been related to the differences in treatment. Despite multivariable adjustments, these differences cannot be disregarded, and may have some clinically meaningful effect on the outcomes. Despite these limitations, this is a valuable study, confirming that, in the era of contemporary PCI and optimal medical management, continued ischemia remains an indicator of poor prognosis. Whether cECG will guide more effective treatment strategies remains to be tested in prospective, randomized, controlled clinical trials.