Author + information
- Alan H. Kadish, MD∗ ( and )
- Jason T. Jacobson, MD
- President's office and the Department of Medicine, Division of Cardiology, New York Medical College, Valhalla, New York
- ↵∗Address for correspondence:
Dr. Alan H. Kadish, New York Medical College, 500 7th Avenue, New York, New York 10018.
Sudden cardiac arrest (SCA) due to fatal ventricular arrhythmia (VA) after the acute phase is one of the most feared sequelae of myocardial infarction (MI). Randomized trials have proven the efficacy of implantable cardioverter-defibrillators (ICD) for the primary prevention of SCA in this population. Early studies required a left ventricular ejection fraction (LVEF) of ≤35% to 40% and nonsustained ventricular tachycardia and inducible sustained ventricular tachycardia at electrophysiology study (1,2). Subsequent studies identified the fact that subjects with LVEF ≤35% with mild to moderate congestive heart failure symptoms, or LVEF ≤30% alone, were well served by primary prevention ICD insertion (3,4). These initial trials enrolled patients in the chronic phase post-MI. Some of these trials excluded patients within 90 days of revascularization, but most trials did not have this exclusion. Alternatively, when investigating the utility of prophylactic ICD insertion in the subacute phase post-MI (within 35 to 40 days after) in patients with LVEF ≤35% to 40%, 2 separate trials found no protective benefit against mortality (5,6). Although there was a benefit in preventing sudden death due to VA, there was higher non-SCA mortality in the ICD groups. The current guidelines (7) and appropriate use criteria (8) state that primary prevention ICD cannot be inserted within 40 days after a first acute MI or 90 days after revascularization, whichever is longer if both apply. Part of the rationale for this delay is that an improvement in LVEF may occur, either because of positive remodeling due to medical therapy, revascularization, or both.
Unfortunately, many patients experience SCA during this waiting period. Although the wearable defibrillator does offer some protection while awaiting ICD insertion, its utility and cost effectiveness have yet to be proven in a randomized trial. Additional features that identify increased risk early post-MI are needed to improve the selection of patients who will most likely benefit from primary prevention ICD. In this issue of JACC: Clinical Electrophysiology, Chew et al. (9) present a reanalysis of 3 independent MI cohort studies, exploring the prognostic value of changes in LVEF after first MI as it pertains to SCA. These cohorts included those in the REFINE (Risk Estimation Following Infarction Noninvasive Evaluation) study, the CARISMA (Cardiac Arrhythmia and Risk Stratification after Myocardial Infarction) study, and the ISAR (Improved Stratification of Autonomy Regulation) study.
The authors analyzed these cohorts separately, because the heterogeneity among studies did not allow for pooled analysis. Patients with a history of previous MI before enrollment in their respective studies were not included for analysis. Each cohort was divided into 3 groups based on LVEF change: those who experienced a decline or no increase; those who had a modest increase (1% to 9%); and those who had a large increase (≥10%).
In the REFINE cohort, 31% had no recovery, 33% had a modest improvement, and 36% had large improvement. Initial LVEF did not predict improvement. Rate of fatal and nonfatal SCAs decreased with degree of LVEF improvement (none: 15.6%; modest: 4.8%; large: 1.1%), with a 6-fold higher (unadjusted hazard ratio [HR]: 5.8; 95% confidence interval [CI]: 2.1 to 16.6; p = 0.001) in patients with no LVEF recovery versus those who had a modest or large improvement in LVEF, similarly when follow-up LVEF was evaluated (adjusted HR: 5.1; 95% CI: 1.1 to 23.7; p=0.04).
In the CARISMA cohort, repeated assessments were performed by 6 weeks post-MI: 47% had no recovery, 28% had a modest improvement, and 25% had large improvement. Like the REFINE cohort, a relationship between LVEF recovery and SCA (fatal and nonfatal) was seen: none: 12.4%; modest recovery: 7.7%; and large recovery: 0% with a 3-fold higher (unadjusted HR: 3.2; 95% CI: 1.0 to 10.2; p = 0.04) in patients with no LVEF recovery versus those with a modest or large improvement in LVEF. Although the p value is <0.05, the inclusion of an HR of 1 in 95% CI calls into question the significance of this finding.
In the ISAR cohort, where LVEF was reassessed by 3 months, 21% had no recovery, 41% had a modest improvement, and 38% had large improvement. Although there was no relationship between total mortality, cardiac mortality, and sudden cardiac death, when stratified by timing of LVEF reassessment (≥14 days), patients with no LVEF recovery had a nonsignificant 2-fold higher risk of cardiac mortality (unadjusted HR: 2.3; 95% CI: 0.9 to 6.3; p = 0.09).
Although the authors should be commended for identifying a novel, significant association between SCA and lack of LVEF improvement in the REFINE cohort, the findings in the other 2 cohorts were borderline or did not reach significance. Nonetheless, the trends in the 3 studies were similar.
In summary, a lack of change in ejection fraction during recovery from MI portends an increased risk of SCD regardless of the level of ejection fraction. Presumably, the positive remodeling that allows for recovery of LVEF parallels positive electrical remodeling that prevents VA. Further work is needed to determine the interaction between remodeling and the electrophysiologic substrate that underlies this observation. Does an improved ejection fraction as opposed to a fixed higher ejection fraction indicate a different border zone configuration that may be less arrhythmogenic?
Even if this association remained robust throughout all the cohorts, how would this help us clinically? It is not clear that a lack of improvement in LVEF would help identify those who would benefit early from primary prevention ICD insertion (<40 days) post-MI, because the follow-up assessment occurred at 8 to 10 weeks. Perhaps the novel findings reported by Chew et al. (9) could be used to risk stratify those post-MI patients with LVEF greater than the threshold for primary prevention ICD, given their clinical features. For instance, a patient with an LVEF of 45% immediately and 90 days post-MI would benefit from a primary prevention ICD, whereas a patient that started at 35% but improved to 45% would not.
The serial measurement of LVEF alone remains an imprecise measurement of the true substrate subtending these processes, and the immediate post-MI LVEF alone is not predictive of improvement or SCD. Other techniques such as cardiac magnetic resonance that can differentiate scar from stunned myocardium may provide added value. However, at this point, the novel findings reported by Chew et al. (9) will not prevent the clinician faced with SCD from shaking her head and saying, “If I knew then what I know now….”
↵∗ Editorials published in JACC: Clinical Electrophysiology reflect the views of the authors and do not necessarily represent the views of JACC: Clinical Electrophysiology or the American College of Cardiology.
Dr. Jacobson is a consultant for St. Jude Medical. Dr. Kadish has reported that he has no relationships relevant to the contents of this paper to disclose.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page.
- 2018 American College of Cardiology Foundation
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