The need for and the challenges of measuring renal sympathetic nerve activity.

Renal denervation (RDN) was primarily developed to treat hypertension and is potentially a new method for treating arrhythmias. Because of the lack of a standardized protocol to measure renal sympathetic nerve activity, RDN is administered in a blind manner. This inability to assess efficacy at the time of treatment delivery may be a large contributor to the ambiguity of RDN outcomes reported in the hypertension literature. The advancement of RDN as a treatment of hypertension or arrhythmias will be hampered by the lack of delivery assessment, a deficiency that the cardiovascular electrophysiology community, with its expertise in recording and mapping, may have a role in addressing and overcoming. The development of endovascular recording of renal nerve action potentials may provide a useful accessory tool for RDN. Innovation in this area will be crucial as we as a community reconsider the therapeutic value of RDN.

Generation of human embryonic stem cell-derived mesoderm and cardiac cells using size-specified aggregates in an oxygen-controlled bioreactor.

The ability to generate human pluripotent stem cell-derived cell types at sufficiently high numbers and in a reproducible manner is fundamental for clinical and biopharmaceutical applications. Current experimental methods for the differentiation of pluripotent cells such as human embryonic stem cells (hESC) rely on the generation of heterogeneous aggregates of cells, also called "embryoid bodies" (EBs), in small scale static culture. These protocols are typically (1) not scalable, (2) result in a wide range of EB sizes and (3) expose cells to fluctuations in physicochemical parameters. With the goal of establishing a robust bioprocess we first screened different scalable suspension systems for their ability to support the growth and differentiation of hESCs. Next homogeneity of initial cell aggregates was improved by employing a micro-printing strategy to generate large numbers of size-specified hESC aggregates. Finally, these technologies were integrated into a fully controlled bioreactor system and the impact of oxygen concentration was investigated. Our results demonstrate the beneficial effects of stirred bioreactor culture, aggregate size-control and hypoxia (4% oxygen tension) on both cell growth and cell differentiation towards cardiomyocytes. QRT-PCR data for markers such as Brachyury, LIM domain homeobox gene Isl-1, Troponin T and Myosin Light Chain 2v, as well as immunohistochemistry and functional analysis by response to chronotropic agents, documented the impact of these parameters on cardiac differentiation. This study provides an important foundation towards the robust generation of clinically relevant numbers of hESC derived cells.

Magnetoelectroanatomic mapping of arrhythmias in structural heart disease using a novel multielectrode catheter:.

Electroanatomic mapping with CARTO requires point-by-point acquisition using the mapping catheter's bipolar tip electrode. This study evaluates the utility of a novel 26-electrode catheter (Qwikstar) for electroanatomic mapping of arrhythmias in patients with structural heart disease. The multielectrode catheter acquires activation times and anatomic data simultaneously from its tip and shaft electrodes. Eight patients (6 men, 2 women, age 47 years [37, 65]) with atrial tachycardia (n = 6) and ventricular tachycardia (n = 2) due to congenital heart disease (n = 4) and cardiomyopathy (n = 4) were studied. Using the multielectrode catheter, the electroanatomic map was constructed in two stages: (1) a scout map using the minimum number of tip and shaft electrode data points that covered > 70% of the tachycardia cycle length and/or the majority of the chamber volume, and (2) a complete map using additional tip electrode data points. A total of 36 (28, 510) tip electrode and 38 (34, 42) shaft electrode electroanatomic data points comprised the scout map. The complete map was constructed with a total of 102 (73, 134) tip electrode electroanatomic data points. In three patients, the scout map suggested a cavotricuspid isthmus dependent atrial flutter that was confirmed with the complete map. In another four patients, the scout map identified the earliest site of focal activation, which was also confirmed with the complete map. In comparison, activation mapping using the bipolar catheter (Navistar) in a group of arrhythmia-matched control subjects required 210 (180, 320) electroanatomic data points (P = 0.012 vs multielectrode catheter complete map). In conclusion, for large macroreentrant or focal arrhythmias in patients with structural heart disease, the multielectrode catheter can generate a scout map that accurately guides complete electroanatomic mapping using fewer point-by-point acquisitions than the bipolar catheter.