Matthew Ginks

Patient-specific electromechanical models of the heart for the prediction of pacing acute effects in CRT: a preliminary clinical validation.

Cardiac resynchronisation therapy (CRT) is an effective treatment for patients with congestive heart failure and a wide QRS complex. However, up to 30% of patients are non-responders to therapy in terms of exercise capacity or left ventricular reverse remodelling. A number of controversies still remain surrounding patient selection, targeted lead implantation and optimisation of this important treatment. The development of biophysical models to predict the response to CRT represents a potential strategy to address these issues. In this article, we present how the personalisation of an electromechanical model of the myocardium can predict the acute haemodynamic changes associated with CRT. In order to introduce such an approach as a clinical application, we needed to design models that can be individualised from images and electrophysiological mapping of the left ventricle. In this paper the personalisation of the anatomy, the electrophysiology, the kinematics and the mechanics are described. The acute effects of pacing on pressure development were predicted with the in silico model for several pacing conditions on two patients, achieving good agreement with invasive haemodynamic measurements: the mean error on dP/dt(max) is 47.5±35mmHgs(-1), less than 5% error. These promising results demonstrate the potential of physiological models personalised from images and electrophysiology signals to improve patient selection and plan CRT.

Length-dependent tension in the failing heart and the efficacy of cardiac resynchronization therapy

AIMS Cardiac resynchronization therapy (CRT) has emerged as one of the few effective and safe treatments for heart failure. However, identifying patients that will benefit from CRT remains controversial. The dependence of CRT efficacy on organ and cellular scale mechanisms was investigated in a patient-specific computer model to identify novel patient selection criteria. METHODS AND RESULTS A biophysically based patient-specific coupled electromechanics heart model has been developed which links the cellular and sub-cellular mechanisms which regulate cardiac function to the whole organ function observed clinically before and after CRT. A sensitivity analysis of the model identified lack of length dependence of tension regulation within the sarcomere as a significant contributor to the efficacy of CRT. Further simulation analysis demonstrated that in the whole heart, length-dependent tension development is key not only for the beat-to-beat regulation of stroke volume (Frank-Starling mechanism), but also the homogenization of tension development and strain. CONCLUSIONS In individuals with effective Frank-Starling mechanism, the length dependence of tension facilitates the homogenization of stress and strain. This can result in synchronous contraction despite asynchronous electrical activation. In these individuals, synchronizing electrical activation through CRT may have minimal benefit.

Invasive Acute Hemodynamic Response to Guide Left Ventricular Lead Implantation Predicts Chronic Remodeling in Patients Undergoing Cardiac Resynchronization Therapy

OBJECTIVES We evaluated the relationship between acute hemodynamic response (AHR) and reverse remodeling (RR) in cardiac resynchronization therapy (CRT). BACKGROUND CRT reduces mortality and morbidity in heart failure patients; however, up to 30% of patients do not derive symptomatic benefit. Higher proportions do not remodel. Multicenter trials have shown echocardiographic techniques are poor at improving response rates. We hypothesized the degree of AHR at implant can predict which patients remodel. METHODS Thirty-three patients undergoing CRT (21 dilated and 12 ischemic cardiomyopathy) were studied. Left ventricular (LV) volumes were assessed before and after CRT. The AHR (maximum rate of left ventricular pressure [LV-dP/dt(max)]) was assessed at implant with a pressure wire in the LV cavity. Largest percentage rise in LV-dP/dt(max) from baseline (atrial antibradycardia pacing or right ventricular pacing with atrial fibrillation) to dual-chamber pacing (DDD)-LV was used to determine optimal coronary sinus LV lead position. Reverse remodeling was defined as reduction in LV end systolic volume ≥15% at 6 months. RESULTS The LV-dP/dt(max) increased significantly from baseline (801 ± 194 mm Hg/s to 924 ± 203 mm Hg/s, p < 0.001) with DDD-LV pacing for the optimal LV lead position. The LV end systolic volume decreased from 186 ± 68 ml to 157 ± 68 ml (p < 0.001). Eighteen (56%) patients exhibited RR. There was a significant relationship between percentage rise in LV-dP/dt(max) and RR for DDD-LV pacing (p < 0.001). A similar relationship for AHR and RR in dilated cardiomyopathy and ischemic cardiomyopathy (p = 0.01 and p = 0.006) was seen. CONCLUSIONS Acute hemodynamic response to LV pacing is useful for predicting which patients are likely to remodel in response to CRT both for dilated cardiomyopathy and ischemic cardiomyopathy. Using AHR has the potential to guide LV lead positioning and improve response rates.

A subject-specific technique for respiratory motion correction in image-guided cardiac catheterisation procedures

We describe a system for respiratory motion correction of MRI-derived roadmaps for use in X-ray guided cardiac catheterisation procedures. The technique uses a subject-specific affine motion model that is quickly constructed from a short pre-procedure MRI scan. We test a dynamic MRI sequence that acquires a small number of high resolution slices, rather than a single low resolution volume. Additionally, we use prior knowledge of the nature of cardiac respiratory motion by constraining the model to use only the dominant modes of motion. During the procedure the motion of the diaphragm is tracked in X-ray fluoroscopy images, allowing the roadmap to be updated using the motion model. X-ray image acquisition is cardiac gated. Validation is performed on four volunteer datasets and three patient datasets. The accuracy of the model in 3D was within 5mm in 97.6% of volunteer validations. For the patients, 2D accuracy was improved from 5 to 13mm before applying the model to 2-4mm afterwards. For the dynamic MRI sequence comparison, the highest errors were found when using the low resolution volume sequence with an unconstrained model.

Coupled personalization of cardiac electrophysiology models for prediction of ischaemic ventricular tachycardia

In order to translate the important progress in cardiac electrophysiology modelling of the last decades into clinical applications, there is a requirement to make macroscopic models that can be used for the planning and performance of the clinical procedures. This requires model personalization, i.e. estimation of patient-specific model parameters and computations compatible with clinical constraints. Simplified macroscopic models can allow a rapid estimation of the tissue conductivity, but are often unreliable to predict arrhythmias. Conversely, complex biophysical models are more complete and have mechanisms of arrhythmogenesis and arrhythmia sustainibility, but are computationally expensive and their predictions at the organ scale still have to be validated. We present a coupled personalization framework that combines the power of the two kinds of models while keeping the computational complexity tractable. A simple eikonal model is used to estimate the conductivity parameters, which are then used to set the parameters of a biophysical model, the Mitchell–Schaeffer (MS) model. Additional parameters related to action potential duration restitution curves for the tissue are further estimated for the MS model. This framework is applied to a clinical dataset derived from a hybrid X-ray/magnetic resonance imaging and non-contact mapping procedure on a patient with heart failure. This personalized MS model is then used to perform an in silico simulation of a ventricular tachycardia (VT) stimulation protocol to predict the induction of VT. This proof of concept opens up possibilities of using VT induction modelling in order to both assess the risk of VT for a given patient and also to plan a potential subsequent radio-frequency ablation strategy to treat VT.

A Simultaneous X-Ray/MRI and Noncontact Mapping Study of the Acute Hemodynamic Effect of Left Ventricular Endocardial and Epicardial Cardiac Resynchronization Therapy in Humans

Background—Cardiac resynchronization therapy (CRT) using endocardial left ventricular (LV) pacing may be superior to conventional CRT. We studied the acute hemodynamic response to conventional CRT and LV pacing from different endocardial sites using a combined cardiac MRI and LV noncontact mapping (NCM) protocol to gain insights into the underlying mechanisms. Methods and Results—Fifteen patients (age, 63±10 years; 12 men) awaiting CRT were studied in a combined x-ray and MRI laboratory. Delayed-enhancement cardiac magnetic resonance was performed to define areas of myocardial fibrosis. Patients underwent an electrophysiological study incorporating endocardial and epicardial LV pacing. Acute hemodynamic response was measured using a pressure wire within the LV cavity to derive LV dP/dt max. NCM was used to define areas of slow conduction. There was a significant improvement in all LV pacing modes versus baseline (P<0.001). LV endocardial CRT from the best endocardial site was superior to conventional CRT, with a 79.8±49.0% versus 59.6±49.5% increase in LV dP/dt max of from baseline (P<0.05). The hemodynamic benefits of pacing were greater when LV stimulation was performed outside of areas of slow conduction defined by NCM (P<0.001). Delayed-enhancement cardiac magnetic resonance was able to delineate zones of slow conduction seen with NCM in ischemic patients but was unreliable in nonischemic patients. Conclusions—Endocardial LV pacing appears superior to conventional CRT, although the optimal site varies between subjects and is influenced by pacing within areas of slow conduction. Delayed-enhancement cardiac magnetic resonance was a poor predictor of zones of slow conduction in nonischemic patients.

A comparison of left ventricular endocardial, multisite, and multipolar epicardial cardiac resynchronization: an acute haemodynamic and electroanatomical study

AIMS Alternative forms of cardiac resynchronization therapy (CRT), including biventricular endocardial (BV-Endo) and multisite epicardial pacing (MSP), have been developed to improve response. It is unclear which form of stimulation is optimal. We aimed to compare the acute haemodynamic response (AHR) and electrophysiological effects of BV-Endo with MSP via two separate coronary sinus (CS) leads or a single-quadripolar CS lead. METHODS AND RESULTS Fifteen patients with a previously implanted CRT system received a second temporary CS lead and left ventricular (LV) endocardial catheter. A pressure wire and non-contact mapping array were placed into the LV cavity to measure LVdP/dtmax and perform electroanatomical mapping. Conventional CRT, BV-Endo, and MSP were then performed (MSP-1 via two epicardial leads and MSP-2 via a single-quadripolar lead). The best overall AHR was found using BV-Endo pacing with a 19.6 ± 13.6% increase in AHR at the optimal endocardial site over baseline (P < 0.001). There was an increase in LVdP/dtmax with MSP-1 and MSP-2 compared with conventional CRT, but this was not statistically significant. Biventricular endocardial pacing from the optimal site was significantly superior to conventional CRT (P = 0.039). The AHR achieved when BV-Endo pacing was highly site specific. Within individuals, the best pacing modality varied and was affected by the underlying substrate. Left ventricular activation times did not predict the optimal haemodynamic configuration. CONCLUSION Biventricular endocardial pacing and not MSP was superior to conventional CRT, but was highly site specific. Within individuals, however, different methods of stimulation are optimal and may need to be tailored to the underlying substrate.

Relationship between endocardial activation sequences defined by high-density mapping to early septal contraction (septal flash) in patients with left bundle branch block undergoing cardiac resynchronization therapy

AIMS Early inward motion and thickening/thinning of the ventricular septum associated with left bundle branch block is known as the septal flash (SF). Correction of SF corresponds to response to cardiac resynchronization therapy (CRT). We hypothesized that SF was associated with a specific left ventricular (LV) activation pattern predicting a favourable response to CRT. We sought to characterize the spatio-temporal relationship between electrical and mechanical events by directly comparing non-contact mapping (NCM), acute haemodynamics, and echocardiography. METHODS AND RESULTS Thirteen patients (63 ± 10 years, 10 men) with severe heart failure (ejection fraction 22.8 ± 5.8%) awaiting CRT underwent echocardiography and NCM pre-implant. Presence and extent of SF defined visually and with M-mode was fused with NCM bulls eye plots of endocardial activation patterns. LV-dP/dt(max) was measured during different pacing modes. Five patients had a large SF, four small SF, and four no SF. Large SF patients had areas of conduction block in non-infarcted regions, whereas those with small or no SF did not. Patients with large SF had greater acute response to LV and biventricular (BIV) pacing vs. those with small/no SF (% increase dP/dt 28 ± 14 vs. 11 ± 19% for LV pacing and 42 ± 28 vs. 22 ± 21% for BIV pacing) (P < 0.05). This translated into a more favourable chronic response to CRT. The lines of conduction block disappeared with LV/BIV pacing while remaining with right ventricle pacing. CONCLUSION A strong association exists between electrical activation and mechanical deformation of the septum. Correction of both mechanical synchrony and the functional conduction block by CRT may explain the favourable response in patients with SF.

Benefits of endocardial and multisite pacing are dependent on the type of left ventricular electric activation pattern and presence of ischemic heart disease: insights from electroanatomic mapping.

Background—There is considerable heterogeneity in the myocardial substrate of patients undergoing cardiac resynchronization therapy (CRT), in particular in the etiology of heart failure and in the location of conduction block within the heart. This may account for variability in response to CRT. New approaches, including endocardial and multisite left ventricular (LV) stimulation, may improve CRT response. We sought to evaluate these approaches using noncontact mapping to understand the underlying mechanisms. Methods and Results—Ten patients (8 men and 2 women; mean [SD] age 63 [12] years; LV ejection fraction 246%; QRS duration 161 [24] ms) fulfilling conventional CRT criteria underwent an electrophysiological study, with assessment of acute hemodynamic response to conventional CRT as well as LV endocardial and multisite pacing. LV activation pattern was assessed using noncontact mapping. LV endocardial pacing gave a superior acute hemodynamic response compared with conventional CRT (26% versus 37% increase in LV dP/dtmax, respectively; P<0.0005). There was a trend toward further incremental benefit from multisite LV stimulation, although this did not reach statistical significance (P=0.08). The majority (71%) of patients with nonischemic heart failure etiology or functional block responded to conventional CRT, whereas those with myocardial scar or absence of functional block often required endocardial or multisite pacing to achieve CRT response. Conclusions—Endocardial or multisite pacing may be required in certain subsets of patients undergoing CRT. Patients with ischemic cardiomyopathy and those with narrower QRS, in particular, may stand to benefit.

Pacemaker and Defibrillator Lead Extraction: Predictors of Mortality during Follow‐Up

Background: Extraction of cardiac implantable electric devices is an accepted procedure when systems become infected or malfunction. However, there is an associated morbidity and mortality. We report our 5‐year experience and identify predictors of mortality, and long‐term follow‐up.