Bernus, Olivier

Background: Increased sympathetic drive resulting in decreased heart rate variability (HRV), has been linked to cardiovascular diseases such as heart failure and myocardial infarction (MI). Dynamic electrophysiological changes due to acute ischemia and chronic MI are known to be pro-arrhythmic. Objective: Evaluate the changes in autonomic tone resulting from substrate remodeling during the development of chronic MI in an in-vivo ovine model. Methods: ECG recordings were collected at baseline, post occlusion and 6 weeks post MI, in young adult sheep (n=16). Time domain, frequency domain and non-linear measures of HRV were evaluated from 10 minutes of ECG data at the 3 time points. RR interval, heart rate, SDRR (standard deviation of the RR intervals), RMSSD (root mean square of successive differences between normal heartbeats), QTc interval, pNN 50 , LF/HF ratio and SD1/SD2 ratio were calculated and compared between baseline, post acute coronary artery occlusion and after 6 weeks of chronic MI. 24-hour telemetry was also performed in an ambulatory animal for 6 weeks to monitor the progression of alterations in the T-wave morphology or duration, i.e. T-wave alternans, a known marker of ventricular tachyarrhythmias, with chronic MI. Results: Chronic MI led to significantly decreased RR interval (Fig.1A) and increased heart rate (Fig.1B), along with a significant prolongation of the QTc interval (Fig.1C). Significant rise was also observed in the SDRR (Fig1D) and LF/HF ratio (Fig1E) indicating a shift towards increased sympathetic tone and reduced parasympathetic drive. In addition to the autonomic changes, a significant rise in T-wave alternans burden (Fig1F) and localized action potential alternans inducibility was observed with progression of MI indicating increased arrhythmogenicity. Conclusion: Skewed autonomic balance is evident in chronic MI and may be closely linked to increased arrhythmogenicity.

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 cm 2 ) 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.