Three-dimensional dominant frequency mapping using autoregressive spectral analysis of atrial electrograms of patients in persistent atrial fibrillation

Background: Areas with high frequency activity within the atrium are thought to be ‘drivers’ of the rhythm in patients with atrial fibrillation (AF) and ablation of these areas seems to be an effective therapy in eliminating DF gradient and restoring sinus rhythm. Clinical groups have applied the traditional FFT-based approach to generate the three-dimensional dominant frequency (3D DF) maps during electrophysiology (EP) procedures but literature is restricted on using alternative spectral estimation techniques that can have a better frequency resolution that FFT-based spectral estimation. Methods: Autoregressive (AR) model-based spectral estimation techniques, with emphasis on selection of appropriate sampling rate and AR model order, were implemented to generate high-density 3D DF maps of atrial electrograms (AEGs) in persistent atrial fibrillation (persAF). For each patient, 2048 simultaneous AEGs were recorded for 20.478 s-long segments in the left atrium (LA) and exported for analysis, together with their anatomical locations. After the DFs were identified using AR-based spectral estimation, they were colour coded to produce sequential 3D DF maps. These maps were systematically compared with maps found using the Fourier-based approach. Results: 3D DF maps can be obtained using AR-based spectral estimation after AEGs downsampling (DS) and the resulting maps are very similar to those obtained using FFT-based spectral estimation (mean 90.23%). There were no significant differences between AR techniques (p=0.62). The processing time for AR-based approach was considerably shorter (from 5.44 to 5.05 s) when lower sampling frequencies and model order values were used. Higher levels of DS presented higher rates of DF agreement (sampling frequency of 37.5Hz). Conclusion: We have demonstrated the feasibility of using AR spectral estimation methods for producing 3D DF maps and characterised their differences to the maps produced using the FFT technique, offering an alternative approach for 3D DF compu- tation in human persAF studies

Prevalence and extent of infarct and microvascular obstruction following different reperfusion therapies in ST-elevation myocardial infarction

Background: Microvascular obstruction (MVO) describes suboptimal tissue perfusion despite restoration of infarct-related artery flow. There are scarce data on Infarct Size (IS) and MVO in relation to the mode and timing of reperfusion. We sought to characterise the prevalence and extent of microvascular injury and IS using Cardiovascular magnetic resonance (CMR), in relation to the mode of reperfusion following acute ST-Elevation Myocardial Infarction (STEMI). Methods: CMR infarct characteristics were measured in 94 STEMI patients (age 61.0 ± 13.1 years) at 1.5 T. Seventy-three received reperfusion therapy: primary percutaneous coronary-intervention (PPCI, n = 47); thrombolysis (n = 12); rescue PCI (R-PCI, n = 8), late PCI (n = 6). Twenty-one patients presented late (>12 hours) and did not receive reperfusion therapy. Results: IS was smaller in PPCI (19.8 ± 13.2% of LV mass) and thrombolysis (15.2 ± 10.1%) groups compared to patients in the late PCI (40.0 ± 15.6%) and R-PCI (34.2 ± 18.9%) groups, p <0.001. The prevalence of MVO was similar across all groups and was seen at least as frequently in the non-reperfused group (15/21, [76%] v 33/59, [56%], p = 0.21) and to a similar magnitude (1.3 (0.0-2.8) v 0.4 [0.0-2.9]% LV mass, p = 0.36) compared to patients receiving early reperfusion therapy. In the 73 reperfused patients, time to reperfusion, ischaemia area at risk and TIMI grade post-PCI were the strongest independent predictors of IS and MVO. Conclusions: In patients with acute STEMI, CMR-measured MVO is not exclusive to reperfusion therapy and is primarily related to ischaemic time. This finding has important implications for clinical trials that use CMR to assess the efficacy of therapies to reduce reperfusion injury in STEMI

Rare and low-frequency coding variants alter human adult heigh

Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways