Predicting arrhythmia recurrence following catheter ablation for ventricular tachycardia using late gadolinium enhancement magnetic resonance imaging: Implications of varying scar ranges.

BACKGROUND: Thresholding-based analysis of late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) can create scar maps and identify corridors that might provide a reentrant substrate for ventricular tachycardia (VT). Current recommendations use a full-width-at-half-maximum approach, effectively classifying areas with a pixel signal intensity (PSI) >40% as border zone (BZ) and >60% as core. OBJECTIVE: The purpose of this study was to investigate the impact of 4 different threshold settings on scar and corridor quantification and to correlate this with postablation VT recurrence. METHODS: Twenty-seven patients with ischemic cardiomyopathy who had undergone catheter ablation for VT were included for retrospective analysis. LGE-CMR images were analyzed using ADAS3D LV. Scar maps were created for 4 PSI thresholds (40-60, 35-65, 30-70, and 45-55), and the extent of variation in BZ and core, as well as the number and weight of conduction corridors, were quantified. Three-dimensional representations were reconstructed from exported segmentations and used to quantify the surface area between healthy myocardium and scar (BZ + core), and between BZ and core. RESULTS: A wider PSI threshold was associated with an increase in BZ mass and decrease in scar (P <.001). No significant differences were observed for the total number of corridors and their mass with increasing PSI threshold. The best correlation in predicting arrhythmia recurrence was observed for PSI 45-55 (area under the curve 0.807; P = .001). CONCLUSION: Varying PSI has a significant impact on quantification of LGE-CMR parameters and may have incremental clinical value in predicting arrhythmia recurrence. Further prospective investigation is warranted to clarify the functional implications of these findings for LGE-CMR-guided ventricular ablation.

Modelling the interaction between stem cells derived cardiomyocytes patches and host myocardium to aid non-arrhythmic engineered heart tissue design.

Application of epicardial patches constructed from human-induced pluripotent stem cell- derived cardiomyocytes (hiPSC-CMs) has been proposed as a long-term therapy to treat scarred hearts post myocardial infarction (MI). Understanding electrical interaction between engineered heart tissue patches (EHT) and host myocardium represents a key step toward a successful patch engraftment. EHT retain different electrical properties with respect to the host heart tissue due to the hiPSC-CMs immature phenotype, which may lead to increased arrhythmia risk. We developed a modelling framework to examine the influence of patch design on electrical activation at the engraftment site. We performed an in silico investigation of different patch design approaches to restore pre-MI activation properties and evaluated the associated arrhythmic risk. We developed an in silico cardiac electrophysiology model of a transmural cross section of host myocardium. The model featured an infarct region, an epicardial patch spanning the infarct region and a bath region. The patch is modelled as a layer of hiPSC-CM, combined with a layer of conductive polymer (CP). Tissue and patch geometrical dimensions and conductivities were incorporated through 10 modifiable model parameters. We validated our model against 4 independent experimental studies and showed that it can qualitatively reproduce their findings. We performed a global sensitivity analysis (GSA) to isolate the most important parameters, showing that the stimulus propagation is mainly governed by the scar depth, radius and conductivity when the scar is not transmural, and by the EHT patch conductivity when the scar is transmural. We assessed the relevance of small animal studies to humans by comparing simulations of rat, rabbit and human myocardium. We found that stimulus propagation paths and GSA sensitivity indices are consistent across species. We explored which EHT design variables have the potential to restore physiological propagation. Simulations predict that increasing EHT conductivity from 0.28 to 1-1.1 S/m recovered physiological activation in rat, rabbit and human. Finally, we assessed arrhythmia risk related to increasing EHT conductivity and tested increasing the EHT Na+ channel density as an alternative strategy to match healthy activation. Our results revealed a greater arrhythmia risk linked to increased EHT conductivity compared to increased Na+ channel density. We demonstrated that our modeling framework could capture the interaction between host and EHT patches observed in in vitro experiments. We showed that large (patch and tissue dimensions) and small (cardiac myocyte electrophysiology) scale differences between small animals and humans do not alter EHT patch effect on infarcted tissue. Our model revealed that only when the scar is transmural do EHT properties impact activation times and isolated the EHT conductivity as the main parameter influencing propagation. We predicted that restoring physiological activation by tuning EHT conductivity is possible but may promote arrhythmic behavior. Finally, our model suggests that acting on hiPSC-CMs low action potential upstroke velocity and lack of IK1 may restore pre-MI activation while not promoting arrhythmia.

Thirty years of the World Health Organization's target caesarean section rate: time to move on.

It has been 30 years since the World Health Organization first recommended a "maximum" caesarean section (CS) rate of 15%. There are demographic differences across the 194 WHO member countries; recent analyses suggest the optimal global CS rate is almost 20%. Attempts to reduce CS rates in developed countries have not worked. The strongest predictor of caesarean delivery for the first birth of "low risk" women appears to be maternal age; a factor that continues to increase. Most women whose first baby is born by caesarean delivery will have all subsequent children by caesarean delivery. Outcomes that informed the WHO recommendation primarily relate to maternal and perinatal mortality, which are easy to measure. Longer term outcomes, such as pelvic organ prolapse and urinary incontinence, are closely related to mode of birth, and up to 20% of women will undergo surgery for these conditions. Pelvic floor surgery is typically undertaken for older women who are less fit for surgery. Serious complications such as placenta accreta occur with repeat caesarean deliveries, but the odds only reach statistical significance at the third or subsequent caesarean delivery. However, in Australia, parity is falling, and only 20% of women will have more than two births. We should aim to provide CS to women in need and to continue including women in the conversation about the benefits and disadvantages, both short and long term, of birth by caesarean delivery.

Integrating parental leave into specialist training: experience of trainees and recently graduated RANZCOG Fellows.

OBJECTIVES: To ascertain the views of trainees and recently graduated Fellows of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists on their experiences of taking parental leave during specialist training. DESIGN: An anonymous online survey, conducted over a 1-month period from 16 August 2012 to 14 September 2012, of participants' experiences of taking parental leave and of the effects of parental leave taken by trainee colleagues on participants' own training. SETTING AND PARTICIPANTS: All trainees undertaking training for the Fellowship of the College, and all Fellows who had graduated in the past 6 years were invited to take part. Of the total 1051 invitees, 261 responded to the survey. MAIN OUTCOME MEASURES: Ease with which parental leave was granted, ability to return to a training post after taking leave, and participants' experiences of views expressed about parental leave in the work environment. RESULTS: Most participants requesting parental leave were able to access it and return to a training post; however, a small proportion experienced difficulties. Among female respondents who had taken parental leave, 28 (26.2%) reported being asked about their intentions for future pregnancy during the training application process, and 45 (42.1%) reported receiving negative comments about this in the work environment. CONCLUSIONS: While in most instances parental leave is accessible automatically, a small but significant number of trainees reported encountering difficulties. These matters are being addressed within our own College, and our results are likely to be relevant to all bodies involved in postgraduate medical training, particularly given the increasing feminisation of the medical workforce.