Knowledge discovery on the integrative analysis of electrical and mechanical dyssynchrony to improve cardiac resynchronization therapy

Cardiac resynchronization therapy (CRT) is a standard method of treating heart failure by coordinating the function of the left and right ventricles. However, up to 40% of CRT recipients do not experience clinical symptoms or cardiac function improvements. The main reasons for CRT non-response include: (1) suboptimal patient selection based on electrical dyssynchrony measured by electrocardiogram (ECG) in current guidelines; (2) mechanical dyssynchrony has been shown to be effective but has not been fully explored; and (3) inappropriate placement of the CRT left ventricular (LV) lead in a significant number of patients. In terms of mechanical dyssynchrony, we utilize an autoencoder to extract new predictive features from nuclear medicine images, characterizing local mechanical dyssynchrony and improving the CRT response rate. Although machine learning can identify complex patterns and make accurate predictions from large datasets, the low interpretability of these black box methods makes it difficult to integrate them with clinical decisions made by physicians in the healthcare setting. Therefore, we use visualization techniques to enable physicians to understand the physical meaning of new features and the reasoning behind the clinical decisions made by the artificial intelligent model. For electrical dyssynchrony, we use short-time Fourier transform (STFT) to transform one-dimensional waveforms into two-dimensional frequency-time spectra. And transfer learning is used to leverage the knowledge learned from a large arrhythmia ECG dataset of related medical conditions to improve patient selection for CRT with limited data. This improves prediction accuracy, reduces the time and resources required, and potentially leads to better patient outcomes. Furthermore, an innovative approach is proposed for using three-dimensional spatial VCG information to describe the characteristics of electrical dyssynchrony, locate the latest activation site, and combine it with the latest mechanical contraction site to select the optimal LV lead position. In addition, we apply deep reinforcement learning to the decision-making problem of CRT patients. We investigate discrete state space/specific action space models to find the best treatment strategy, improve the reward equation based on the physician\u27s experience, and learn the approximation of the best action-value function that can improve the treatment policy used by clinicians and provide interpretability

Cardiac Resynchronisation Therapy and its effects on systolic heart failure

Cardiac Resynchronisation Therapy (CRT) is now an established therapeutic option for patients with symptomatic left ventricular systolic dysfunction, broad QRS duration (>120 milliseconds on surface electrocardiogram) and on optimal tolerated medical therapy. The numbers of implants are rising throughout the Westernised world. The United Kingdom has also had a rapid increase in CRT implantation. Despite the large randomised trials which prove clinical effectiveness, there is a realisation that a significant minority of patients who undergo CRT implantation do not derive the anticipated clinical benefit. This has been labelled as non-response with up to 40 percent of patients being affected depending on diagnostic criteria. However potential solutions to a lack of clinical benefit do exist. These include medical optimisation of the patient’s heart failure pharmacotherapy following CRT implantation, and device based optimisation adjusting atrioventricular and ventriculo-ventricular (AV and VV) intervals. Other reasons for a lack of clinical improvement may be explained on pathophysiology which is currently not accounted for in the guidelines and selection criteria. The thesis is therefore dedicated to the exploration of these issues using the dataset from the specialist heart failure pacing clinic at the Royal Brompton Hospital. The study of medical optimisation following CRT implantation observed increased rates of neurohormonal antagonists and anticoagulants when a systematic structured clinical approach was adopted. One potential method of evaluating device based optimisation is impedance cardiography and within chapter V, a cohort of 44 patients underwent device based optimisation with either conventional echocardiographic techniques or impedance cardiography. Though underpowered and a pilot study, the impedance cardiographic method within this cohort performed adequately. Heart failure remains a complex syndrome with complex pathophysiology. One of the potential reasons for non-response is the lack of acknowledgement of other physiological criteria in the selection criteria. The study performed using cardiac magnetic resonance (CMR) imaging to evaluate right ventricular function on cardiovascular outcomes in patients following CRT implantation. Here it was demonstrated that right ventricular dysfunction as assessed by CMR is a powerful predictor of adverse outcomes and of a failure to undergo left ventricular remodelling. The last study chapter was a small pilot study which compared impedance cardiographic performance to echocardiography within an intensive care setting. Whilst the numbers of patients recruited were small (n=6), the adjustment of atrioventricular and ventriculo-ventricular delays did induce a change in haemodynamics. In conclusion the thesis represents studies and work focussed on the problem of lack of clinical benefit experienced by patients following CRT implantation. It has covered a prognosticator and two potential methods for improving the rate of clinical response following CRT implantation.Open Acces

Implantable cardioverter defibrillators for the treatment of arrhythmias and cardiac resynchronisation therapy for the treatment of heart failure: systematic review and economic evaluation

Background This assessment updates and expands on two previous technology assessments that evaluated implantable cardioverter defibrillators (ICDs) for arrhythmias and cardiac resynchronisation therapy (CRT) for heart failure (HF). Objectives To assess the clinical effectiveness and cost-effectiveness of ICDs in addition to optimal pharmacological therapy (OPT) for people at increased risk of sudden cardiac death (SCD) as a result of ventricular arrhythmias despite receiving OPT; to assess CRT with or without a defibrillator (CRT-D or CRT-P) in addition to OPT for people with HF as a result of left ventricular systolic dysfunction (LVSD) and cardiac dyssynchrony despite receiving OPT; and to assess CRT-D in addition to OPT for people with both conditions. Data sources Electronic resources including MEDLINE, EMBASE and The Cochrane Library were searched from inception to November 2012. Additional studies were sought from reference lists, clinical experts and manufacturers’ submissions to the National Institute for Health and Care Excellence. Review methods Inclusion criteria were applied by two reviewers independently. Data extraction and quality assessment were undertaken by one reviewer and checked by a second. Data were synthesised through narrative review and meta-analyses. For the three populations above, randomised controlled trials (RCTs) comparing (1) ICD with standard therapy, (2) CRT-P or CRT-D with each other or with OPT and (3) CRT-D with OPT, CRT-P or ICD were eligible. Outcomes included mortality, adverse events and quality of life. A previously developed Markov model was adapted to estimate the cost-effectiveness of OPT, ICDs, CRT-P and CRT-D in the three populations by simulating disease progression calculated at 4-weekly cycles over a lifetime horizon. Results A total of 4556 references were identified, of which 26 RCTs were included in the review: 13 compared ICD with medical therapy, four compared CRT-P/CRT-D with OPT and nine compared CRT-D with ICD. ICDs reduced all-cause mortality in people at increased risk of SCD, defined in trials as those with previous ventricular arrhythmias/cardiac arrest, myocardial infarction (MI) > 3 weeks previously, non-ischaemic cardiomyopathy (depending on data included) or ischaemic/non-ischaemic HF and left ventricular ejection fraction ≤ 35%. There was no benefit in people scheduled for coronary artery bypass graft. A reduction in SCD but not all-cause mortality was found in people with recent MI. Incremental cost-effectiveness ratios (ICERs) ranged from £14,231 per quality-adjusted life-year (QALY) to £29,756 per QALY for the scenarios modelled. CRT-P and CRT-D reduced mortality and HF hospitalisations, and improved other outcomes, in people with HF as a result of LVSD and cardiac dyssynchrony when compared with OPT. The rate of SCD was lower with CRT-D than with CRT-P but other outcomes were similar. CRT-P and CRT-D compared with OPT produced ICERs of £27,584 per QALY and £27,899 per QALY respectively. The ICER for CRT-D compared with CRT-P was £28,420 per QALY. In people with both conditions, CRT-D reduced the risk of all-cause mortality and HF hospitalisation, and improved other outcomes, compared with ICDs. Complications were more common with CRT-D. Initial management with OPT alone was most cost-effective (ICER £2824 per QALY compared with ICD) when health-related quality of life was kept constant over time. Costs and QALYs for CRT-D and CRT-P were similar. The ICER for CRT-D compared with ICD was £27,195 per QALY and that for CRT-D compared with OPT was £35,193 per QALY. Limitations Limitations of the model include the structural assumptions made about disease progression and treatment provision, the extrapolation of trial survival estimates over time and the assumptions made around parameter values when evidence was not available for specific patient groups. Conclusions In people at risk of SCD as a result of ventricular arrhythmias and in those with HF as a result of LVSD and cardiac dyssynchrony, the interventions modelled produced ICERs of < £30,000 per QALY gained. In people with both conditions, the ICER for CRT-D compared with ICD, but not CRT-D compared with OPT, was < £30,000 per QALY, and the costs and QALYs for CRT-D and CRT-P were similar. A RCT comparing CRT-D and CRT-P in people with HF as a result of LVSD and cardiac dyssynchrony is required, for both those with and those without an ICD indication. A RCT is also needed into the benefits of ICD in non-ischaemic cardiomyopathy in the absence of dyssynchrony. Study registration This study is registered as PROSPERO number CRD42012002062. Funding The National Institute for Health Research Health Technology Assessment programme

Pacing the heart:one site fits all?

In a healthy heart, contraction/pumping is controlled by an electrical stimulus. This ensures that the heart contracts synchronously. When a problem arises with generating or conducting this electrical stimulus, people are fitted with a pacemaker. Our research shows that - in contrast to current technology - stimulating the ventricular septum is safer and better for the pump function. Stimulation of the ventricular septum can prevent (symptoms of) heart failure. Survival also improves

Sympathetic Blockade for Dysrhythmia Management in Heart Failure: Rationale and Therapeutic Progression to Intervention

Continuous ganglionic blockade is being used increasingly to help manage ventricular tachydysrhythmias. The purpose of this chapter is to discuss the physiologic and anatomic basis of ventricular tachydysrhythmias in detail that are mediated by the sympathetic nervous system and to discuss appropriate indications for the use of sympathetic ganglion blocks. These blocks can be instituted as both destination and bridging therapeutic options to control these dysrhythmias. These blocks therefore have value in the heart failure patient population since they offer a means of controlling the dysrhythmias that can be devastating to an already compromised myocardium

Access routes, devices and guidance methods for intrapericardial delivery in cardiac conditions

Drug deposition into the intrapericardial space is favourable for achieving localised effects and targeted cardiac delivery owing to its proximity to the myocardium as well as facilitating optimised pharmacokinetic profiles and a reduction in systemic side effects. Access to the pericardium requires invasive procedures but the risks associated with this have been reduced with technological advances, such as combining transatrial and subxiphoid access with different guidance methods. A variety of introducer devices, ranging from needles to loop-catheters, have also been developed and validated in pre-clinical studies investigating intrapericardial delivery of therapeutic agents. Access techniques are generally well-tolerated, self-limiting and safe, although some rare complications associated with certain approaches have been reported. This review covers these access techniques and how they have been applied to the delivery of drugs, cells, and biologicals, demonstrating the potential of intrapericardial delivery for treatments in cardiac arrhythmia, vascular damage, and myocardial infarction

Current Issues and Recent Advances in Pacemaker Therapy

Patients with implanted pacemakers or defibrillators are frequently encountered in various healthcare settings. As these devices may be responsible for, or contribute to a variety of clinically significant issues, familiarity with their function and potential complications facilitates patient management. This book reviews several clinically relevant issues and recent advances of pacemaker therapy: implantation, device follow-up and management of complications. Innovations and research on the frontiers of this technology are also discussed as they may have wider utilization in the future. The book should provide useful information for clinicians involved in the management of patients with implanted antiarrhythmia devices and researchers working in the field of cardiac implants

Resurgence of interest in the hemodynamic alterations of advanced heart failure

Historically, cardiac insufficiency has always being allocated to be the culprit lesion of the heart failure syndrome. However, contemporary heart failure pharmacotherapy solely focuses on preservation of neurohormonal homeostasis. The research described in this manuscript is the result of thorough investigation of the hemodynamic alterations of hundreds of patients admitted for advanced decompensated heart failure (ADHF). Firstly, our data suggest that progressive cardiac insufficiency and hemodynamic derangements assessed through invasive hemodynamic monitoring, are still contributing to short- and long-term compromise, and this independent of race or gender. In addition, we demonstrated that restoring an optimal hemodynamic balance with add-on afterload reduction provides incremental intermediate- and long-term benefits over evidence based neurohormonal blockade alone. Indeed parental vasodilator therapy with sodium nitroprusside can be safely administered to achieve more hemodynamic improvement in patients presenting with ADHF. In addition, the institution of a more aggressive oral vasodilator regimen with isosorbide diniatrate / hydralazine over standard neurohormonal antagonists at the time of discharge after an episode of ADHF can safely maintain these hemodynamic improvements leading to improved outcomes. Another novel insight comes from the notice that venous congestion and raised intra-abdominal pressure, more than impaired cardiac output, seem to be related to the development of worsening renal function in patients admitted with ADHF. Treatment strategies with the aim of better renal preservation should therefore focus how to safely reduce this renal venous congestion with diuretic therapy, ultrafiltration or paracentesis whenever indicated. Finally, we demonstrated that cardiac resynchronization therapy (CRT) really acts as a novel "hemodynamic therapy" for advanced heart failure patients even in the patient population previously categorized as "non-responders". Moreover, we have proven that the phenotypic improvement in heart failure status after prolonged CRT is paralleled by a reversed left ventricualr remodeling and recovery of left ventricular contractility. Thus, prolonged (hemodynamic) unloading of the heart will lead to physiological changes on the myocyte level in hearts once destined to only further deteriorate

Cardiovascular imaging 2010 in the International Journal of Cardiovascular Imaging

Cardiovascular Aspects of Radiolog