Table 2.
Clinical Studies With the Modified Moving Average Method
| Test Setting First Author (Trial) (Ref. #) | Patient Population (Enrollment, Disease, Mean Age) | Mean LVEF | Hazard Ratios (95% CI) for TWA; NPV and PPV |
|---|---|---|---|
| Routine exercise testing | |||
| Nieminen et al. (FINCAVAS) (64) | 1,037 consecutive patients referred for routine exercise testing; 58 ± 13 yrs (patients included in Leino et al. [66]) | Mostly preserved | 6.0 (2.8–12.8) for CV death, 7.4 (2.8–19.4) for SCD at 44 ± 7 months for 65-μV TWA cutpoint; NPV for CV death = 97.6; PPV = 12.6; NPV for SCD = 98.6, PPV = 8.0 |
| Minkkinen et al. (FINCAVAS) (65) | 2,119 consecutive patients referred for routine exercise testing; 57 ± 13 yrs (patients included in Leino et al. [66]) | Mostly preserved | 4.6 (2.2–9.9) for CV death, 4.4 (1.5–12.7) for SCD at 47 months for 65-μV cutpoint; NPV for CV death = 97.4; PPV = 10.2 |
| Leino et al. (FINCAVAS) (66) | 3,598 consecutive patients referred for routine exercise testing; 56 ± 13 yrs | Mostly preserved | 1.55 (1.150–2.108, p < 0.004) for CV death; 1.58 (1.041–2.412; p < 0.033) for SCD at 55 months per 20 μV TWA in lead V5. |
|
| |||
| Exercise recovery | |||
| Exner et al. (REFINE) (54) | 322 post-MI patients; 62 (interquartile range: 53–70) yrs | Moderately depressed (38%–48%) | 2.94 (1.10–7.87) monitored at 10–14 weeks after event for CV death or resuscitated cardiac arrest (primary endpoint) at 47 months; NS when monitored at 2–4 weeks after MI. For primary endpoint for TWA, AUC = 0.62; for combination of TWA + HRT, AUC = 0.71. |
| Slawnych et al. (REFINE/FINCAVAS) (67) | 322 post-MI patients (from REFINE) and 681 CAD patients (from FINCAVAS); 69 (interquartile range: 57–76) yrs | Moderately depressed (38%–48%) and preserved (56%–63%) groups | 2.5 (1.1–6.0) for CV death at 48 months for 60-μV cutpoint; NPV = 96%; PPV= 13%. AUC for CV mortality = 0.69. |
| Leino et al. (FINCAVAS) (68) | 1,972 consecutive patients referred for routine exercise testing; 57 ± 13 yrs (patients included in Leino et al. [66]) | Mostly preserved | 3.5 (1.6–7.9) for CV death at 48 months for 60-μV cutpoint. For CV death for TWA alone, C-statistic = 0.550–0.606; for combination of TWA + HRR, C-statistic = 0.671–0.691. |
|
| |||
| Ambulatory ECG monitoring | |||
| Verrier et al. (ATRAMI) (69) | Acute post-MI; case: control analysis (15 cases: 29 control subjects) from 1,284 ATRAMI patients, monitored at 15 ± 10 days post-MI; 60–62 yrs | Moderately depressed (42 ± 3%) | 7.9 (1.9–33.1) for cardiac arrest or arrhythmic death at 21 months for a priori 75th percentile cutpoint (47 μV); patients were monitored at 15 ± 10 days post-MI |
| Stein et al. (EPHESUS) (70) | Acute post-MI, LVEF ≤40%, and heart failure; case: control analysis (46 cases: 92 control subjects) from 6,632 EPHESUS patients, monitored at 2–10 days post-MI; 68 ± 11 yrs | Depressed (34 ± 5%) | 5.5 (2.2–13.8) for SCD at 16.4 months for 47-μV cutpoint; patients were monitored at 2–10 days post- MI. For SCD, AUC = 0.73 for TWA in lead V1 and = 0.70 in lead V3 (p < 0.001). |
| Sakaki et al. (71) | 295 consecutive cardiomyopathy patients with ischemic or nonischemic left ventricular dysfunction; 66 ± 16 yrs | Depressed (34 ± 6%) | 17.1 (6.3–46.6) for CV death, 22.6 (2.6–193.7) for witnessed SCD at 1 yr for 65-μV cutpoint; NPV for CV death = 97%; PPV = 37% |
| Maeda et al. (72) | 63 consecutive patients including 21 control subjects, 21 post-MI patients without VT, and 21 post-MI patients with VT; 65 ± 11 yrs | Depressed (36%–43%) for post-MI group | 6.1 (1.1–34.0) for sustained VT or VF at 6 yrs for 65-μV cutpoint |
| Stein et al. (CHS) (73) | General population patients age ≥65 yrs; case: control analysis (49 cases: 98 control subjects) from 1,649 CHS patients | Not tested, assumed preserved | 4.8 (1.48–15.81) for SCD at 14 yrs |
| Hou et al. (74) | 219 consecutive acute post-MI patients; 55 yrs | >35% in 201; ≤35% in 18 | 17.78 (3.75–84.31) for SCD within 16 months for 47-μV cutpoint; patients were monitored at 1–15 days post-MI; NPV = 99%; PPV = 17% |
This table is based on searches of the published medical data on the terms alternans and alternation for all clinical studies that reported hazard ratios in PubMed (National Library of Medicine, National Institutes of Health, Bethesda Maryland) and Paperchase (Bedford Massachusetts) databases. Reference lists from these studies and from recent reviews (4–7) were also scanned.
ATRAMI = Autonomic Tone and Reflexes after Myocardial Infarction; CHS = Cardiovascular Health Study; CV = cardiovascular; EPHESUS = Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study; FINCAVAS = Finnish Cardiovascular Study; HRR = heart rate recovery; NPV = negative predictive value; PPV = positive predictive value; other abbreviations as in Table 1.