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Left ventricular hypertrophy (LVH) is common among older adults. Amidst all causes, Fabry disease (FD) should be considered when LVH occurs with family history, specific clinical manifestations, or cardiac alert signs. Here, we report a case of a 76-year-old male who presented late onset concentric LVH with symptomatic high-grade atrioventricular (AV) block. After dual-chamber pacemaker implantation, interrogation revealed frequent right ventricular (RV) pacing with a wide QRS duration. The patient developed heart failure symptoms with rapid deterioration of LV systolic function. Pacing-induced cardiomyopathy (PICM) was suspected, and the pacemaker was upgraded to biventricular pacing. Further FD surveys were performed, including biochemical examinations, cardiac biopsies, and genetic sequencing, and the patient was ultimately diagnosed with a cardiac variant of FD. Particularly, we strongly suggest that physiologic pacing should be initially considered for patients with FD who have symptomatic high-grade AV block, rather than traditional RV pacing to prevent PICM.

Yu, Tzu-Ping and Cui-Wei Xie. Orphanin FQ/nociceptin inhibits synaptic transmission and long-term potentiation in the rat dentate gyrus through postsynaptic mechanisms. J. Neurophysiol. 80: 1277–1284, 1998. Orphanin FQ/nociceptin (OFQ), a recently characterized natural ligand for the opioid receptor-like 1 (ORL1) receptor, shares structural similarity to the endogenous opioids. Our previous study found that OFQ, like classical opioids, modulated synaptic transmission and long-term potentiation (LTP) in the hippocampal CA1 region, suggesting a modulatory role for OFQ in synaptic plasticity involved in learning and memory. In the present study we investigated the action of OFQ in the dentate gyrus and explored possible underlying cellular mechanisms. Field potential recordings showed that OFQ significantly inhibited excitatory synaptic transmission and LTP induction in the dentate lateral perforant path. In the presence of OFQ, the excitatory postsynaptic potential (EPSP) slope-population spike (E-S) curve was shifted to the right, and no significant change was found in paired-pulse facilitation, suggesting a postsynaptic mechanism responsible for the inhibition of synaptic transmission. Under whole cell voltage-clamp conditions, bath application of OFQ activated K+ currents in most granule cells tested at a holding potential of −50 mV, suggesting that OFQ could reduce the excitability of dentate granule cells by hyperpolarizing cell membranes. OFQ also inhibited the amplitude of N-methyl-d-aspartate (NMDA) receptor–mediated excitatory postsynaptic currents (EPSCs) without affecting α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor–mediated EPSCs. This inhibition was not blocked by opioid receptor antagonists. Furthermore, the inward currents evoked by focal application of NMDA to granule cells were suppressed by OFQ in a dose-dependent manner, suggesting that OFQ may suppress LTP by inhibiting the function of postsynaptic NMDA receptors. These results demonstrate that OFQ may negatively modulate synaptic transmission and plasticity in the dentate gyrus through postsynaptic mechanisms, including hyperpolarization of granule cells as well as inhibition of the function of postsynaptic NMDA receptors/channels in dentate granule cells.