Quantitative analysis of lead position vs. correction of electrical dyssynchrony in an experimental model of LBBB/CRT

International audienceCardiac resynchronization therapy (CRT) is a recommended treatment in patients with electrical dyssynchrony such as left bundle branch block (LBBB). The determination of the optimal leads position, and the quantification of the changes in electrical activation are two current major challenges. In this paper, we investigate these aspects through electroanatomical data from a controlled experimental protocol, which studied pigs with no structural disease under LBBB and CRT conditions. We propose to use a quasi-conformal mapping technique to standardize electroanatomical maps of endo- and epi-cardial walls of both ventricles to a common reference geometry, in which simple quantitative indices can be computed. Then, we investigate the relation between leads and simple surrogates of the recovery of the electrical activation based either on total activation times or on the spatial distribution of the patterns. Our methodology allows a better understanding of the complex electrical activation patterns in LBBB and CRT, and confirms hypotheses about the optimal leads position from previous studies

Branching out:CRT beyond current concepts

Patients suffering from heart failure and delay in electrical activation of the heart can be treated with cardiac resynchronization therapy (CRT). This treatment restores the synchronous contraction of the two large cardiac chambers (ventricles) using a pacemaker. In this PhD thesis some relatively unexplored facets of CRT are investigated. One of these facets concerns the effects of CRT on electrical recovery of the cardiac cells (repolarization). A good and more or less simultaneous repolarization is important in the prevention of arrhythmias. Measurements in patients showed that important changes in the part of the electrocardiogram that represents repolarization already occurred within two weeks of starting CRT. Using a computer model, we demonstrated that these changes were indicative of more simultaneous repolarization. Moreover, we found that a bigger change in repolarization was linked to a larger improvement in cardiac function. These results can contribute to (research into) better treatment of patients with heart failure

Meshless electrophysiological modeling of cardiac resynchronization therapy—benchmark analysis with finite-element methods in experimental data

Computational models of cardiac electrophysiology are promising tools for reducing the rates of non-response patients suitable for cardiac resynchronization therapy (CRT) by optimizing electrode placement. The majority of computational models in the literature are mesh-based, primarily using the finite element method (FEM). The generation of patient-specific cardiac meshes has traditionally been a tedious task requiring manual intervention and hindering the modeling of a large number of cases. Meshless models can be a valid alternative due to their mesh quality independence. The organization of challenges such as the CRT-EPiggy19, providing unique experimental data as open access, enables benchmarking analysis of different cardiac computational modeling solutions with quantitative metrics. We present a benchmark analysis of a meshless-based method with finite-element methods for the prediction of cardiac electrical patterns in CRT, based on a subset of the CRT-EPiggy19 dataset. A data assimilation strategy was designed to personalize the most relevant parameters of the electrophysiological simulations and identify the optimal CRT lead configuration. The simulation results obtained with the meshless model were equivalent to FEM, with the most relevant aspect for accurate CRT predictions being the parameter personalization strategy (e.g., regional conduction velocity distribution, including the Purkinje system and CRT lead distribution). © 2022 by the authors. Licensee MDPI, Basel, Switzerland

Caractérisation et traitement du substrat électrique pour la thérapie de resynchronisation cardiaque

We aimed to characterize the electrical substrate amenable to biventricular pacing (BVP) and to assess the actual value of electrical resynchronization. We showed, both with respect to surface ECG and detailed ventricular electrocardiographic mapping (ECM), a strong relationship between the baseline electrical dyssnchrony and the hemodynamic response to BIV pacing. Compared with standard ECG, ECM allows a more detailed analysis of the ventricular dyssynchrony and better predicts clinical outcomes after BVP. A minimal amount of electrical dyssynchrony, in particular a sufficient LV activation delay relative to right ventricular activation, is a prerequisite to the hemodynamic response to BVP. Due to their advanced electrical dyssynchrony, patients with left bundle branch block present potential for BVP positive response which acts by electrical resynchronization. Conversely, BVP worsens the electrical activation (iatrogenic dyssynchrony) and hemodynamics in patients with narrow QRS suffering from insufficient electrical dyssynchrony at baseline. Patients with unspecified conduction disorders show variable levels of electrical dyssynchrony and as a consequence mixed results to BVP. Similarly, ECM reveals a variable degree of left ventricular activation delay in patients chronically paced in the right ventricle. Beside the electrical resynchronization, other mechanisms are involved in the cardiac pump function improvement such as the redistribution of the mechanical work over the right and left ventricles. Through ventricular interaction, the RV myocardium importantly contributes to the improvement in LV pump function induced by single site LV pacing.L'objectif de ce travail était de mieux appréhender les mécanismes impliqués dans la réponse à la resynchronisation biventriculaire (BIV) en insistant sur la caractérisation du substrat électrique éligible à la thérapie et l'intérêt de la resynchronisation électrique. Nous avons démontré qu'il existe une relation forte entre l'asynchronisme électrique de base défini tant par l'ECG de surface que par cartographie détaillée de l'activation ventriculaire (ECM) et la réponse hémodynamique à la stimulation BIV. Par rapport à l'ECG de surface, l'ECM permet une caractérisation plus fine de l'asynchronisme électrique ventriculaire avec une meilleure prédiction de la réponse clinique à la stimulation BIV. La présence d'un asynchronisme de base minimum, en particulier d'un retard d'activation ventriculaire gauche (VG) par rapport au ventricule droit (typiquement >SOms), est un prérequis à l'efficacité de la thérapie. Les patients avec bloc de branche gauche présentent un haut degré d'asynchronisme et la stimulation BIV agit sur ce substrat par resynchronisation de l'activation électrique. A contrario, la stimulation BIV dégrade la séquence d'activation ainsi que l'hémodynamique des patients à QRS fins (dyssynchronie iatrogène). Les patients présentant un trouble de conduction aspécifique présentent des degrés variables d'asynchronie électrique et en conséquence des réponses contrastées à la stimulation BIV. De même, l'analyse ECM de l'asynchronisme des patients chroniquement stimulés sur le ventricule droit a permis de mettre en évidence des degrés variables de retard d'activation du VG. Si la resynchronisation électrique est garante d'une amélioration de la fonction cardiaque, d'autres mécanismes sont impliqués telle la redistribution du travail segmentaire au sein du myocarde ventriculaire. L'efficacité de la stimulation mono-VG implique une participation accrue du ventricule droit au travail global (interaction ventriculaire)

Coupling of ventricular action potential duration and local strain patterns during reverse remodeling in responders and non-responders to cardiac resynchronization therapy

BACKGROUND: The high risk of ventricular arrhythmias in heart failure patients remains despite the benefit of cardiac resynchronization therapy (CRT). An electromechanical interaction between regional myocardial strain patterns and the electrophysiological substrate is thought to be important. OBJECTIVE: We investigated the in-vivo relation between left ventricular (LV) activation recovery interval (ARI), as a surrogate measure of activation potential duration (APD), and local myocardial strain patterns in responders and non-responders to CRT. METHODS: ARI were recorded from the left ventricular epicardium in 20 CRT patients 6 weeks and 6 months post implant. Two-dimensional speckle tracking echocardiography was performed at the same time to assess myocardial strains. Patients with ≥15% reduction in end-systolic volume at 6-months were classified as responders. RESULTS: ARI reduced in responders, 263±46ms vs. 246±47ms, p145ms and QRS shortening with biventricular pacing was associated with ARI shortening during CRT. CONCLUSIONS: Changes in ventricular wall mechanics predict local APD lengthening or shortening during CRT. Non-responders have a worsening of myocardial strain and local APD. Baseline QRS >145ms and QRS shortening on biventricular pacing identified patients who exhibited improvement in APD

Haemodynamic optimization of cardiac resynchronization therapy

Heart failure carries a very poor prognosis, unless treated with the appropriate pharmacological agents which, have been evaluated in large randomized clinical trials and have demonstrated improvements in morbidity and mortality of this cohort of patients. A significant proportion of these patients develop conduction abnormalities involving both the atrioventricular node and also the specialised conduction tissue (bundle of His and Purkinje fibers) of the ventricular myocardium which is most commonly evidenced by the presence of a wide QRS, typically left bundle branch block. The net effect of these conduction abnormalities is inefficient filling and contraction of the left ventricle. The presence of these conduction abnormalities is an additional strong marker of poor prognosis. Over the last 15 years pacing treatments have been developed aimed at mitigating the conduction disease. Large scale randomized multicentre trials have repeatedly demonstrated the effectiveness of cardiac pacing, officially recognized as cardiac resynchronization therapy (CRT). This mode of pacing therapy has undoubtedly had a positive impact on both the morbidity and mortality of these patients. Despite the large advancement in the management of heart failure patients by pacing therapies, a significant proportion of patients (30%) being offered CRT are classed as non-responders. Many explanations have been put forward for the lack of response. The presence of scar at the pacing site with failure to capture or delayed capture of myocardium, too much left ventricular scar therefore minimal contractile response, incorrect pacing site due to often limited anatomical options of lead placement and insufficient programming i.e optimization, of pacemaker settings such as the AV and VV delay are just some of the suggested areas perceived to be responsible for the lack of patients’ response to cardiac resynchronization therapy. The effect of optimization of pacemaker settings is a field that has been investigated extensively in the last decade. Disappointingly, current methods of assessing the effect of optimization of pacemaker settings on several haemodynamic parameters, such as cardiac output and blood pressure, are marred with very poor reproducibility, so measurement of any effect of optimization is close to being meaningless. Moreover, detailed understanding of the effects of CRT on coronary physiology and cardiac mechanoenergetics is equally, disappointingly, lacking. In this thesis, I investigated the acute effects of cardiac resynchronization therapy and AV optimization on coronary physiology and cardiac mechanoenergetics. This was accomplished using very detailed and demanding series of invasive catheterization studies. I used novel analytical mathematical techniques, such as wave intensity analysis, which have been developed locally and this provided a unique insight of the important physiological entities defining coronary physiology and cardiac mechanics. I explored in detail the application and reliability of photoplethysmography as a tool for non-invasive optimization of the AV delay. Photoplethysmography has the potential of miniaturization and therefore implantation alongside pacemaker devices. I compared current optimization techniques (Echocardiography and ECG) of VV delay against beat-to-beat blood pressure using the Finometer device and defined the criteria that a technique requires if such a technique can be used meaningfully for the optimization of pacemaker settings both in clinical practice and in clinical trials. Finally, I investigated the impact of atrial pacing and heart rate on the optimal AV delay and attempted to characterize the mechanisms underlying any changes of the optimal AV delay under these varying patient and pacing states. In this thesis I found that optimization of AV delay of cardiac resynchronization therapy not only improved cardiac contraction and external cardiac work, but also cardiac relaxation and coronary blood flow, when compared against LBBB. I found that most of the increase in coronary blood flow occurred during diastole and that the predominant drive for this was ventricular microcirculatory suction as evidenced by the increased intracoronary diastolic backward-travelling decompression wave. I showed that non-invasive haemodynamic optimization using the plethysmograph signal of an inexpensive pulse oximeter is as reliable as using the Finometer. Appropriate processing of the oximetric signal improved the reproducibility of the optimal AV delay. The advantage of this technology is that it might be miniaturized and implanted to provide automated optimization. In this thesis I found that other commonly used modalities of VV optimization such as echocardiography and ECG lack internal validity as opposed to non-invasive haemodynamic optimization using blood pressure. This finding will encourage avoidance of internally invalid modalities, which may cause more harm than good. In this thesis I found that the sensed and paced optimal AV delays have, on average, a bigger difference than the one assumed by the device manufacturers and clinicians. As a significant proportion of patients will be atrially paced, especially during exercise, optimization during this mode of pacing is equally crucial as it is during atrial sensing. Finally, I found that the optimal AV delay decreases with increasing heart rate, and the slope of this is within the range of existing pacemaker algorithms used for rate adaptation of AV delay, strengthening the argument for the rate adaptation to be programmed on.Imperial Users Onl

The effect of biventricular pacing as compared to single - side left - ventricular pacing and bifocal pacing of the right ventricle in patients with chronic heart failure

Srdeční resynchronizační terapie (CRT) představuje akceptovanou formu terapie některých nemocných s pokročilým CHSS, jejíž akutní i dlouhodobý efekt byl potvrzen v řadě klinických studií. Nedávno bylo rovněz potvrzeno, že CRT příznivě ovlivňuje i mortalitu a výskyt hospitalizace pro srdeční selhaní. Efekt CRT je však značně interindividuálně variabilní a u řady nemocných ke zlepšení nedochází vůbec. Ačkoliv je identifikace vhodných kandidátů zřejmě klíčovým předpokladem redukujícím množství těchto CRT non-responderů, existují i další faktory, peri- i postimplantační, ovlivňující finální efekt CRT. Tato disertace byla zaměřena na některé z těchto proměnných: 1/ První z nich je selekce vhodného stimulačního režimu. V této disertaci jsme hodnotili efekt 3 z nich, které se jevily být rovnocennými alternativami CRT - biventrikulární stimulace (BiV), izolovaná stimulace LK (LVP) a bifokální stimulace PK (Bif). Ukázalo se, že první dva stimulační režimy, tj. BiV (simultánni stimulace obou komor) a LVP, vedou ke srovnatelnému akutnímu hemodynamickému zlepšení v klidu. Studie 2 této disertace rovněž prokázala srovnatelný efekt obou při zátěži. Studie 1 navíc pomohla vysvětlit příčinu tohoto ekvivalentního efektu BiV a LVP díky popisu aktivační sekvence komor, která se díky fúzi 2 aktivačních vln nad LK přibližuje...Cardiac resynchronization therapy (CRT) represents an accepted treatment modality in patients with advance chronic heart failure, acute and long-term benefit of which was confirmed in several clinical trials. Recently, reduced mortality and rate of hospitalization for heart failure were also demonstrated. However, response to CRT is interindividually highly variable with a substantial proportion of CRT recipients who do not respond to this therapy. Although the identification of suitable candidates is probably the most important factor in the reduction of the rate of non-responders, some other determinants, peri- and post-implant, may substantially affect the final effect of CRT. The present PhD focused on some of these variables: 1/ First of them is a selection of the appropriate pacing mode. This PhD evaluated effect of 3 pacing modalities that have been proposed as alternatives of CRT - biventricular pacing (BiV), single-site left-ventricular pacing (LVP) and rightventricular bifocal pacing (Bif). It was clearly shown that the first two pacing strategies, BiV (it is simultaneous pacing of both ventricles) and LVP, cause comparable acute hemodynamic improvement at rest. Study No.2 of this PhD confirms that the comparable effect of BiV and LVP is preserved also during the exercise. In addition, study No.1...Institute for Clinical and Experimental MedicineInstitut klinické a experimentální medicínyFirst Faculty of Medicine1. lékařská fakult

The role of feature-tracking cardiovascular magnetic resonance in optimising response to cardiac resynchronisation therapy

Cardiac resynchronisation therapy (CRT) forms part of the established treatment for heart failure, but individual response is variable. Deformation imaging permits assessment of myocardial mechanics. Echocardiography-based techniques are unable to refine patient selection for CRT, although can identify preferential late mechanically activated (LMA) targets for lead placement. Feature-tracking (FT) is a rapid cardiac magnetic resonance (CMR) deformation technique performed on standard acquisition, overcoming the limitations of myocardial tagging (MT). This work aims to validate FT-CMR against MT and establish its role in patient selection and left ventricular (LV) lead deployment in the context of CRT.A validation study performed on healthy volunteers and cardiomyopathy patients demonstrated good intra- and inter-observer variability, and reasonable agreement compared with MT. In a retrospective observational study of CRT recipients, greater baseline dyssynchrony did not predict LV reverse remodelling (LVRR) or symptomatic response at 6 months, but low strain was associated with a high risk of cardiovascular mortality. Furthermore, lead deployment over non-scarred, LMA myocardium, assessed using late gadolinium enhancement (LGE) and FT-CMR was associated with better LVRR and long term survival. FT-CMR showed no ability to enhance patient selection for CRT but, coupled with LGE CMR, has a role in guiding LV lead deployment

Reverse left ventricular remodeling is more likely in non ischemic cardiomyopathy patients upgraded to biventricular stimulation after chronic right ventricular pacing

<p>Abstract</p> <p>Background</p> <p>Chronic right ventricular (RV) apical pacing may lead to left ventricular (LV) dyssynchrony and LV dysfunction. In heart failure due to RV pacing, upgrading to biventricular stimulation (CRT) can improve NYHA Class and LV function. A proportion of patients do not respond to upgrading. Aim was to assess whether etiology of LV dysfunction accounts for responses to CRT in RV-paced patients.</p> <p>Methods</p> <p>Sixty-two patients treated by CRT, under RV pacing from 50.2 ± 5.4 months, were studied. Cause of LV dysfunction was non-ischemic (NIC) in 28 and ischemic cardiomyopathy (IC) in 34 patients. Clinical and conventional echocardiographic parameters were available within 1 month before RV pacing, within 1 month before CRT and at 12 ± 2 months of follow-up (FU).</p> <p>Results</p> <p>Decreased LVEF (from 37.0 ± 8.8 to 25.6 ± 6.1%, p <0.001), increased LV end-systolic dimensions (LVESD) (from 48.1 ± 8.6 to 55.2 ± 7.9 mm, p <0.001) and worsened NYHA Class (from 1.9 ± 1.1 to 3.2 ± .6, p < 0.005) were found before CRT, compared to pre RV-pacing. After CRT, 44/62 patients showed a ≥ 1 NYHA Class improvement; >10% decrease in LVESD was observed in 24 patients: 5 with IC, 19 with NIC (p < .0.001). The association between cause of LV dysfunction with >10% decrease in LVESD remained highly significant (p < 0.001) adjusting for pre-CRT QRS duration, NYHA Class, LVEF, LVESD, treatment or RV pacing duration.</p> <p>Conclusions</p> <p>CRT improves functional class even after long-lasting pacing. Reverse remodeling is evident in a small population, more likely with NIC.</p