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 ¹²³I-meta-iodobenzylguanide (¹²³I-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 ¹²³I-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.

中文翻译：

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遗传性心脏骤停综合征可能基于原发性心肌和自主神经系统异常

背景

最近发现的心脏骤停 (SCA) 综合征与风险单倍型有关，该风险单倍型含有二肽基肽酶 6 (DPP6) 基因作为可能的罪魁祸首。

客观的

因为 DPP6 影响心肌细胞和神经元功能，我们假设风险单倍型携带者的心室颤动 (VF) 是由心脏和自主神经系统的功能变化引起的。

方法

我们研究了 6 名既往有 VF（有症状）的风险单倍型携带者、8 名没有 VF 的携带者（无症状）和 7 名非携带者（对照）。我们分析了仰卧位和站立位心率变异性、压力反射敏感性、VF 前心率变化和心肌¹²³ I-间碘苄基胍 ( ¹²³ I- m IBG) 闪烁显像。

结果

与对照组相比，携带者的心跳间隔更长（1.03 ± 0.11 秒 vs 0.81 ± 0.07 秒；P <.001），低频 (LF) 和高频 (HF) 活动较低，LF/HF 比值较低 (0.68 ± 0.50 vs 2.11 ± 1.10；P = .013）在仰卧位。站立时，携带者的节拍间期减少和 LF 增加明显大于对照组（站立与仰卧比：0.78 ± 0.07 vs 0.90 ± 0.07；P = .002；和 1.94 ± 1.03 vs 1.17 ± 0.34；P = .022，分别为 0.022），HF 下降幅度不显着（0.62 ± 0.36 vs 0.97 ± 0.42；P = .065）和 LF/HF 比率增加（5.55 ± 6.79 vs 1.62 ± 1.24；P= .054)。17 次 VF 发作中有 16 次发生在休息时。VF 前的心率为 110 ± 25 bpm。与无症状携带者相比，有症状携带者在左心室的¹²³ I- m IBG 分布不均匀（7 名无症状携带者和 1 名有症状携带者中的单光子发射计算机断层扫描评分≥3； P = .008）。

结论

可以推测，这些数据与携带者更不稳定的自主神经张力一致，表明原发性异常可能存在于心脏和自主神经系统中。