An inherited sudden cardiac arrest syndrome may be based on primary myocardial and autonomic nervous system abnormalities.

Background: A recently discovered sudden cardiac arrest (SCA) syndrome is linked to a risk haplotype that harbors the dipeptidyl-peptidase 6 (DPP6) gene as a plausible culprit.

Objective: Because DPP6 impacts both cardiomyocyte and neuronal function, we hypothesized that ventricular fibrillation (VF) in risk haplotype carriers arises from functional changes in both the heart and autonomic nervous system.

Methods: We studied 6 risk haplotype carriers with previous VF (symptomatic), 8 carriers without VF (asymptomatic), and 7 noncarriers (controls). We analyzed supine and standing heart rate variability, baroreflex sensitivity, pre-VF heart rate changes, and myocardial I-meta-iodobenzylguanide (I-mIBG) scintigraphy.

Results: Carriers had longer interbeat intervals than controls (1.03 ± 0.11 seconds vs 0.81 ± 0.07 seconds; P <.001), lower low-frequency (LF) and higher high-frequency (HF) activity, and lower LF/HF ratio (0.68 ± 0.50 vs 2.11 ± 1.10; P = .013) in the supine position. Upon standing up, carriers had significantly larger decrease in interbeat interval and increase in LF than controls (standing-to-supine ratio: 0.78 ± 0.07 vs 0.90 ± 0.07; P = .002; and 1.94 ± 1.03 vs 1.17 ± 0.34; P = .022, respectively), and nonsignificantly larger decrease in HF (0.62 ± 0.36 vs 0.97 ± 0.42; P = .065) and increase in LF/HF ratio (5.55 ± 6.79 vs 1.62 ± 1.24; P = .054). Sixteen of 17 VF episodes occurred at rest. Heart rate immediately before VF was 110 ± 25 bpm. Symptomatic carriers had less heterogeneous I-mIBG distribution in the left ventricle than asymptomatic carriers (single-photon emission computed tomography score ≥3 in 7 asymptomatic and 1 symptomatic carrier; P = .008).

Conclusion: It can be speculated that these data are consistent with more labile autonomic tone in carriers, suggesting that the primary abnormalities may reside in both the heart and the autonomic nervous system.