Interpretable Deep Models for Cardiac Resynchronisation Therapy Response Prediction

Advances in deep learning (DL) have resulted in impressive accuracy in some medical image classification tasks, but often deep models lack interpretability. The ability of these models to explain their decisions is important for fostering clinical trust and facilitating clinical translation. Furthermore, for many problems in medicine there is a wealth of existing clinical knowledge to draw upon, which may be useful in generating explanations, but it is not obvious how this knowledge can be encoded into DL models - most models are learnt either from scratch or using transfer learning from a different domain. In this paper we address both of these issues. We propose a novel DL framework for image-based classification based on a variational autoencoder (VAE). The framework allows prediction of the output of interest from the latent space of the autoencoder, as well as visualisation (in the image domain) of the effects of crossing the decision boundary, thus enhancing the interpretability of the classifier. Our key contribution is that the VAE disentangles the latent space based on `explanations' drawn from existing clinical knowledge. The framework can predict outputs as well as explanations for these outputs, and also raises the possibility of discovering new biomarkers that are separate (or disentangled) from the existing knowledge. We demonstrate our framework on the problem of predicting response of patients with cardiomyopathy to cardiac resynchronization therapy (CRT) from cine cardiac magnetic resonance images. The sensitivity and specificity of the proposed model on the task of CRT response prediction are 88.43% and 84.39% respectively, and we showcase the potential of our model in enhancing understanding of the factors contributing to CRT response.Comment: MICCAI 2020 conferenc

Standard care vs. TRIVEntricular pacing in Heart Failure (STRIVE HF): a prospective multicentre randomized controlled trial of triventricular pacing vs. conventional biventricular pacing in patients with heart failure and intermediate QRS left bundle branch block

AIMS: To determine whether triventricular (TriV) pacing is feasible and improves CRT response compared to conventional biventricular (BiV) pacing in patients with left bundle branch block (LBBB) and intermediate QRS prolongation (120-150 ms). METHODS AND RESULTS: Between October 2015 and November 2019, 99 patients were recruited from 11 UK centres. Ninety-five patients were randomized 1:1 to receive TriV or BiV pacing systems. The primary endpoint was feasibility of TriV pacing. Secondary endpoints assessed symptomatic and remodelling response to CRT. Baseline characteristics were balanced between groups. In the TriV group, 43/46 (93.5%) patients underwent successful implantation vs. 47/49 (95.9%) in the BiV group. Feasibility of maintaining CRT at 6 months was similar in the TriV vs. BiV group (90.0% vs. 97.7%, P = 0.191). All-cause mortality was similar between TriV vs. BiV groups (4.3% vs. 8.2%, P = 0.678). There were no significant differences in echocardiographic LV volumes or clinical composite scores from baseline to 6-month follow-up between groups. CONCLUSION: Implantation of two LV leads to deliver and maintain TriV pacing at 6 months is feasible without significant complications in the majority of patients. There was no evidence that TriV pacing improves CRT response or provides additional clinical benefit to patients with LBBB and intermediate QRS prolongation and cannot be recommended in this patient group. CLINICAL TRIAL REGISTRATION NUMBER: Clinicaltrials.gov: NCT02529410

Atrial fibrillation in cardiac resynchronization therapy

Patients with atrial fibrillation (AF) were largely excluded from the major clinical trials of cardiac resynchronization therapy (CRT), despite the presence of AF in up to 40% of patients receiving CRT in clinical practice. AF appears to attenuate the response to CRT, by the combination of a reduction in biventricular pacing and the loss of atrioventricular synchrony. In addition, remodeling secondary to CRT may influence the progression of AF. Management options for patients with AF and CRT include rate control, with drugs or atrioventricular node ablation, or rhythm control, with electrical cardioversion and antiarrhythmic therapy, or AF catheter ablation. The evidence for these therapies in patients with CRT is largely limited to observational studies or inferred from randomized studies in the general heart failure population. In this review, we explore the complex interaction between AF, heart failure, and CRT and discuss the evidence for the treatment options in this difficult patient cohort

Clinical effectiveness of a dedicated cardiac resynchronization therapy pre-assessment clinic incorporating cardiac magnetic resonance imaging and cardiopulmonary exercise testing on patient selection and outcomes

Background: Pre-procedural assessment of patients undergoing cardiac resynchronization therapy (CRT) is heterogenous and patients implanted with unfavorable characteristics may account for non-response. A dedicated CRT pre-assessment clinic (CRT PAC) was developed to standardize the review process and undertake structured pre-procedural evaluation. The aim of this analysis was to determine the effectiveness on patient selection and outcomes. Methods: A prospective database of consecutive patients attending the CRT PAC between 2013 and 2018 was analyzed. Pre-operative assessment included cardiac magnetic resonance (CMR) and cardiopulmonary exercise testing (CPET). Patients were considered CRT responders based on improvement in clinical composite score (CCS) and/or reduction in left ventricular end-systolic volume (LVESV) ≥ 15% at 6-months follow-up. Results: Of 252 patients reviewed in the CRT PAC during the analysis period, 192 fulfilled consensus guidelines for implantation. Of the patients receiving CRT, 82% showed improvement in their CCS and 57% had a reduction in LVESV ≥ 15%. The presence of subendocardial scar on CMR and a peak VO2 ≤ 12 ml/kg/min on CPET predicted CRT non-response. Two patients were unsuitable for CRT as they had end-stage heart failure and died during follow-up. The majority of patients initially deemed unsuitable for CRT did not suffer from unexpected hospitalization for decompensated heart failure or died from cardiovascular disease; only 8 patients (13%) received CRT devices during follow-up because of symptomatic left ventricular systolic impairment. Conclusion: A dedicated CRT PAC is able to appropriately select patients for CRT. Pre-procedural investigation/imaging can identify patients unlikely to respond to, or may not yet be suitable for CRT