Localized Structural Alterations Underlying a Subset of Unexplained Sudden Cardiac Death

Abstract

Background: Sudden cardiac death because of ventricular fibrillation (VF) is commonly unexplained in younger victims. Detailed electrophysiological mapping in such patients has not been reported.

Methods: We evaluated 24 patients (29±13 years) who survived idiopathic VF. First, we used multielectrode body surface recordings to identify the drivers maintaining VF. Then, we analyzed electrograms in the driver regions using endocardial and epicardial catheter mapping during sinus rhythm. Established electrogram criteria were used to identify the presence of structural alterations.

Results: VF occurred spontaneously in 3 patients and was induced in 16, whereas VF was noninducible in 5. VF mapping demonstrated reentrant and focal activities (87% versus 13%, respectively) in all. The activities were dominant in one ventricle in 9 patients, whereas they had biventricular distribution in others. During sinus rhythm areas of abnormal electrograms were identified in 15/24 patients (62.5%) revealing localized structural alterations: in the right ventricle in 11, the left ventricle in 1, and both in 3. They covered a limited surface (13±6 cm²) representing 5±3% of the total surface and were recorded predominantly on the epicardium. Seventy-six percent of these areas were colocated with VF drivers (P<0.001). In the 9 patients without structural alteration, we observed a high incidence of Purkinje triggers (7/9 versus 4/15, P=0.033). Catheter ablation resulted in arrhythmia-free outcome in 15/18 patients at 17±11 months follow-up.

Conclusions: This study shows that localized structural alterations underlie a significant subset of previously unexplained sudden cardiac death. In the other subset, Purkinje electrical pathology seems as a dominant mechanism.

Keywords: catheter ablation; endocardium; epicardial mapping; incidence; sudden cardiac death; ventricular fibrillation.

Figure 1.

Identification and location of reentrant drivers. A, Phase mapping and activation mapping. Left, Shows the color-coded phases of wave propagation. Reentrant activity is shown as full phase progression around a center-point in the anterior right ventricle (RV). Right, Shows raw unipolar electrograms recorded around the reentry trajectory which indicate corroborated sequential activation. B, Regions of epicardial heart surface. The epicardial surface is divided into 3 regions to describe anatomic distribution of driver activity. 1, Right ventricle. 2, Septum (interventricular groove). 3, Left ventricle (LV). LAD indicates left anterior descending artery.

Figure 2.

Location of driver regions in 3 patients. ECG examples of ventricular fibrillation (VF) onset (Stars) are shown from 3 patients (from top to bottom, patients no. 4, 11, and 5): the upper 2 patients (A) and (B) had spontaneously occurring VF in-hospital and case (C) had VF induced by electrical stimulation. Maps are shown on the body surface ventricular projection on anterior, inferior, and left lateral views. The locations of reentries are shown in red and vary among the 3 patients. Patient A presents drivers dominantly located in the right ventricle; patient B harbors drivers dominantly in the left ventricle (middle), whereas patient C shows a biventricular distribution (no dominant ventricle). Left descending artery (LAD) on the surface of the interventricular groove separating right and left ventricle.

Figure 3.

Spatial location of abnormal signal areas with those of the drivers identified during ventricular fibrillation (VF). Twelve-lead ECGs and intracardiac electrograms are recorded during sinus rhythm in 2 patients. The maps indicate the regions of reentry activities during VF and the clusters of abnormal electrograms in sinus rhythm are indicated by the dotted contour. Note the prolonged fragmented electrograms within an overall low-voltage electrogram. A, Patient 14, epicardial electrograms shows 2 abnormal areas over the anterior and inferior right ventricle, in close proximity with location of reentry activities, whereas other regions did not show abnormal electrograms. B, Patient 4, recordings from the right and left ventricles show colocation of abnormal electrograms in sinus rhythm, with the main VF driver in the posterior left ventricle. LAD indicates left descending artery.

Figure 4.

Example of healthy signals during sinus rhythm (patient no. 5). Left, Maps, in anterior, inferior, and left lateral views, show focal breakthroughs (blue points in upper blue) and reentry areas (red areas in lower). The pattern of ventricular fibrillation (VF) activities shows no specific distribution. Middle, Shows the 12-lead ECG in sinus rhythm. Right, Shows the presence of normal narrow signals in all sites of epicardium indicating healthy local tissue. LV indicates left ventricle; and RV, right ventricle.

Figure 5.

Example of abnormal signals during sinus rhythm in the right ventricle (RV, patient no. 16). Left, Maps of ventricular fibrillation (VF) sources, in anterior, inferior, and left lateral views, show focal breakthroughs in the inferior RV (blue points in blue upper) and reentry areas in the anterior RV (red areas in lower). These sources are largely dominant in the RV. Middle, Shows the 12-lead ECG before and after infusion of ajmaline demonstrating the absence of the Brugada pattern (maximal ST elevation is 0.07 mV in V1 or V2). Right, Shows the presence of abnormal signals during epicardial mapping in 3 areas in the RV; note also the heterogeneous signal timing indicating localized conduction abnormality. Abnormal signals are recorded within the black dotted contours; which colocated strikingly with those of VF drivers (red areas and blue points). No abnormal electrograms are recorded in the (smaller) left ventricular (LV) driver areas.

Figure 6.

Effect of ablation on abnormal signals. A, Location of electrical in the right ventricle (RV, red) during fibrillation in patient no. 19. B, Epicardial sites harboring fragmented signals (black points) which delineate the ablation area. Note the contiguity of these sites with the areas of ventricular fibrillation (VF) drivers (red spots). C, Baseline signals showing abnormal late fragmented components (stars) and their abolition after radiofrequency ablation (9 min of radiofrequency [RF] delivery).