Assessment of myocardial scarring improves risk stratification in patients evaluated for cardiac defibrillator implantation

Abstract

Objectives: We tested whether an assessment of myocardial scarring by cardiac magnetic resonance imaging (MRI) would improve risk stratification in patients evaluated for implantable cardioverter-defibrillator (ICD) implantation.

Background: Current sudden cardiac death risk stratification emphasizes left ventricular ejection fraction (LVEF); however, most patients suffering sudden cardiac death have a preserved LVEF, and many with poor LVEF do not benefit from ICD prophylaxis.

Methods: One hundred thirty-seven patients undergoing evaluation for possible ICD placement were prospectively enrolled and underwent cardiac MRI assessment of LVEF and scar. The pre-specified primary endpoint was death or appropriate ICD discharge for sustained ventricular tachyarrhythmia.

Results: During a median follow-up of 24 months the primary endpoint occurred in 39 patients. Whereas the rate of adverse events steadily increased with decreasing LVEF, a sharp step-up was observed for scar size >5% of left ventricular mass (hazard ratio [HR]: 5.2; 95% confidence interval [CI]: 2.0 to 13.3). On multivariable Cox proportional hazards analysis, including LVEF and electrophysiological-study results, scar size (as a continuous variable or dichotomized at 5%) was an independent predictor of adverse outcome. Among patients with LVEF >30%, those with significant scarring (>5%) had higher risk than those with minimal or no (≤5%) scarring (HR: 6.3; 95% CI: 1.4 to 28.0). Those with LVEF >30% and significant scarring had risk similar to patients with LVEF ≤30% (p = 0.56). Among patients with LVEF ≤30%, those with significant scarring again had higher risk than those with minimal or no scarring (HR: 3.9; 95% CI: 1.2 to 13.1). Those with LVEF ≤30% and minimal scarring had risk similar to patients with LVEF >30% (p = 0.71).

Conclusions: Myocardial scarring detected by cardiac MRI is an independent predictor of adverse outcome in patients being considered for ICD placement. In patients with LVEF >30%, significant scarring (>5% LV) identifies a high-risk cohort similar in risk to those with LVEF ≤30%. Conversely, in patients with LVEF ≤30%, minimal or no scarring identifies a low-risk cohort similar to those with LVEF >30%.

Figure 1. Event Rate Depending on LVEF and Scar Size

The percentage of patients with the primary endpoint of death or appropriate ICD discharge is shown according to different levels of left ventricular ejection fraction (Panel a) and scar size (Panel b). For ejection fraction, the trendline (red line) shows a positive slope over the entire range, indicating that event rate monotonically increases with decreasing LVEF. In contrast, a marked step-up in event rate is noted for scar size greater than 5% of left ventricular mass, which however does not rise further with increasing scar size.

Figure 2. Kaplan-Meier Estimates of Adverse Events in Patients With LVEF >30%

In patients with LVEF >30%, those with significant scarring (>5% of LV mass) had a higher event rate than those with minimal-or-no scarring (≤5%) for both the primary (panel a) and the two secondary endpoints (panels b, c). Those with LVEF >30% and significant scarring had similar event rate to the entire group of patients with LVEF ≤30%. * For the secondary endpoint of death alone, the hazard ratio between scar >5%, LVEF >30% and scar ≤5%, LVEF >30% cannot be calculated because there were no deaths in the latter group.

Figure 3. Kaplan-Meier Estimates of Adverse Events in Patients With LVEF ≤30%

In patients with LVEF ≤30%, those with significant scarring (>5% of LV mass) had a higher event rate than those with minimal-or-no scarring (≤5%) for both the primary (panel a) and the two secondary endpoints (panels b, c). Those with LVEF ≤30% and minimal-or-no scarring had similar event rate to the entire group of patients with LVEF >30%.

Figure 4. Typical CMR Images In Patients With Various Levels Of Myocardial Scarring And Left Ventricular Function

Example CMR images are shown in patients with concordance (Patient A) and discordance (Patient B, C, and D) in the assessment of risk as determined by LVEF and myocardial scarring (yellow arrows). The last column reports findings during follow-up including the ICD electrograms when available. Patient A had poor LVEF and substantial scarring. This patient, who had both parameters concordant for high risk, had an ICD discharge for ventricular tachycardia during the first month of follow-up. Conversely, Patient B had poor LVEF but no myocardial scar, representing discordance in risk between these two parameters. This patient received an ICD based on LVEF criteria, however had no adverse events during follow-up (29 months). Patients C and D represent examples of those with significantly higher LVEF (46% and 49%, respectively) in whom there was discordance in risk in that substantial scarring was found. Patient C had CAD-type scarring (involves LV subendocardium), whereas patient D had non-CAD-type scarring (spares the LV subendocardium). Both patients had events during follow-up (patient C: sudden cardiac death 18 months after study enrollment; patient D: appropriate ICD discharge to terminate VT at one month and again at 10 months of follow-up).