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

Noninvasive Multi-Modality Studies of Cardiac Electrophysiology, Mechanics, and Anatomical Substrate in Healthy Adults, Arrhythmogenic Cardiomyopathy, and Heart Failure

Heart disease is a leading cause of death and disability and is a major contributor to healthcare costs. Many forms of heart disease are caused by abnormalities in the electrical function of heart muscle cells or the cardiac conduction system. Electrocardiographic Imaging (ECGI) is a noninvasive modality for imaging cardiac electrophysiology. By combining recordings of the voltage distribution on the torso surface with anatomical images of the heart-torso geometry, ECGI reconstructs voltages on the epicardium. This thesis applies ECGI to novel studies of human heart function and disease and explores new combinations of ECGI with additional imaging modalities. ECGI was applied in combination with late gadolinium enhancement (LGE) scar imaging MRI in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). ARVC carries a high risk of sudden cardiac death, and the hallmark feature of ARVC is the progressive replacement of healthy myocardium with fibrous and fatty tissue. By combining ECGI and LGE in ARVC patients we found that there are signs of conduction abnormalities before structural abnormalities can be detected in ARVC patients. Electrical and structural abnormalities in ARVC patients co-localized. We also found that PVCs, potential triggers for arrhythmia, originated in regions of structural and electrical abnormalities. ECGI was applied in combination with speckle tracking echocardiography (STE) to longitudinally image heart failure patients undergoing cardiac resynchronization therapy (CRT). STE is an echocardiographic technique for measuring strain (contraction) in the heart. CRT is a highly effective treatment for heart failure, however, around 30% of patients do not respond to the treatment. ECGI was more effective for predicting response to CRT than the current standard ECG criteria or STE indices. The timing of peak contraction in STE did not accurately reflect the electrical activation sequence. CRT caused improvements in contraction that persisted even when pacing was disabled. CRT prolonged repolarization at the site of the LV pacing lead, which may increase the risk of arrhythmia in CRT patients. The above studies contribute novel observations of human disease physiology and demonstrate the clinical feasibility and effectiveness of ECGI for noninvasive assessment of ARVC and CRT

196 Non response after cardiac resynchronisation therapy is associated with a more severe cardiomyopathy

BackgroundCardiac resynchronisation therapy (CRT) has been shown to improve clinical status in heart failure patients. Some patients treated by CRT fail to respond to the treatment. Predisposing factors for non-response should be investigated to optimize patient selection.ObjectiveThe purpose of the study was to evaluate before device implantation and 3, 6 and 12 month after, echocardiographic and biological parameters with respect to CRT response.MethodsThirty two patients with heart failure (72% of men; age 66±10 years; 59% non-ischaemic cardiomyopathy; NYHA III–IV; left ventricular ejection fraction (LVEF) 22.7±6.7%; QRS width 146±26ms) were implanted with CRT device and followed during twelve month. Responders (R) were defined as patients with improvement of one or more NYHA functional class, with a significant improvement in quality of life and without episode nor hospitalization for heart failure during follow-up.Results34% of the patients constitute the non-responder group (NR). No difference between R and NR was observed in LVEF, QRS width, NYHA, cardiovascular risk factors nor drug medication. Non-ischaemic dilated cardiomyopathy was significantly more present in R (71% vs 27%; p=0.03). Before CRT, NR had more important left ventricular end-diatolic diameter, left ventricular end-systolic diameter and more elevated left pressions. Atrioventricular dyssynchrony was significantly more observed in R (66% vs 9%; p=0.006) so as intraventricular dyssynchrony (95% vs 27%; p=0.001).BNP is significantly more elevated in NR (602±385 vs 320±361; p=0.03) before CRT.After 3 and 6 month, a significant decrease in left ventricular end-diatolic and end-systolic diameters, LVEF and normalisation of left and right pressions occur in R. Likewise, BNP levels were lower in R.ConclusionsNR patients have before implantation a more severe cardiomyopathy. At follow-up, left ventricular remodelling could only be observed in R patients. These data suggest that cardiac CRT should not be proposed too late so that left ventricular remodelling could be expected

Radial dyssynchrony assessed by cardiovascular magnetic resonance in relation to left ventricular function, myocardial scarring and QRS duration in patients with heart failure

Radial dyssynchrony is almost universal in patients with heart failure. This vies against the notion that a lack of response to CRT is related to a lack of dyssynchrony

Cardiac Resynchronisation Therapy: The Role of Echocardiography in Patient Selection and Follow-up

Resynchronisation of segmental left ventricular mechanics as well as re-coordination of both atrioventricular and interventricular mechanics are potential mechanisms for the clinical improvement observed in patients undergoing cardiac resynchronisation therapy (CRT) for heart failure. Resynchronisation therapy is approved in patients with refractory heart failure symptoms despite optimal medical therapy. The presence of a prolonged QRS duration has been the main criterion used to identify ventricular dyssynchrony. However, based on the current selection criteria, about 20% to 30% of patients do not improve after biventricular pacing. Using echocardiography, dyssynchrony may be absent in some heart failure patients with a wide QRS, or present in those with a normal QRS interval. Echocardiography, and especially the more sophisticated techniques based on Tissue Doppler Imaging, may improve patient selection by identifying inter- and intra-ventricular dyssynchrony. Echocardiography can also be used to optimise lead placement. Following pacemaker implantation, various echocardiographic techniques can be used to ensure optimal cardiac resynchronisation and to monitor improvements in left ventricular function and hemodynamics. In this review, the different echocardiographic approaches to predict patient response to CRT are discussed. In addition, the use of echocardiography to guide lead positioning and to optimise pacemaker settings following pacemaker implantation is discussed

Echocardiographic assessment of inter and intra ventricular dyssynchrony in heart failure patients with normal QRS duration.

INTRODUCTION : The management of patients with heart failure is an important issue in cardiology. The cost of healthcare associated with management and hospitalization is substantial. Device therapy for patients refractory to medical therapy focuses on improving the clinical outcome and quality of life. Normally Electrical activation and conduction through the His Purkinje network occurs fast. This results in synchronous mechanical contraction of the heart. Many diseases of the heart produce changes in the temporal sequence of early and late systolic contraction of different regions of the myocardium1. This results in abnormal contraction pattern due to the resultant electromechanical dyssynchrony. This causes an increase in the duration of QRS on ECG. Some studies report mechanical dyssynchrony in a subgroup of patients with diastolic heart failure2 too. Dyssynchrony has also been reported in some patients with heart failure and decreased ejection fraction and a normal QRS duration3. The differential regional activation and dyssynchronous left ventricular contraction by decreasing ejection and relaxation has the net effect of reduced cardiac output. Work efficiency of the myocardium is also decreased because of the dyssynchrony. Heart failure is associated with alterations in the local and systemic neuro hormonal milieu playing an important role in pathological remodeling and changes at the cellular level1,4. Superimposition of electrical conduction delay and mechanical dyssynchrony over this setting results in additive effects and creates complex pathological changes and increased propensity to arrhythmias. AIMS & OBJECTIVES : To assess the prevalence of inter and intraventricular dyssynchrony in patients with heart failure and Normal QRS duration echocardiographically using M mode and Tissue Doppler imaging (TDI). CONCLUSION ; 1. Intra and interventricular dyssynchrony occur in a significant proportion of heart failure patients with a QRS duration of 120 ms or less. The prevalence of intra ventricular electromechanical dyssynchrony was 23% and interventricular dyssynchrony 16 % 2. Among the indices of intraventricular dyssynchrony, The dyssynchrony index(Ts-SD) and peak velocity difference (Ts diff ) show good inter parameter correlation compared to septal posterior wall motion delay SPWMD. 3. There is no association between the QRS duration and the dyssynchrony parameters in the study. 4. There is no association between interventricular dyssynchrony and intraventricular dyssynchrony

Relationship between QRS complex notch and ventricular dyssynchrony in patients with heart failure and prolonged QRS duration

Background: Cardiac resynchronization therapy (CRT) has been accepted as an established therapy for advanced systolic heart failure. Electrical and mechanical dyssynchrony are usually evaluated to increase the percentage of CRT responders. We postulated that QRS notch can increase mechanical LV dyssynchrony independently of other known predictors such as left ventricular ejection fraction and QRS duration. Methods: A total of 87 consecutive patients with advanced systolic heart failure and QRS duration more than 120 ms with an LBBB-like pattern in V1 were prospectively evaluated. Twelve-lead electrocardiogram was used for detection of QRS notch. Complete echocardiographic examination including tissue Doppler imaging, pulse wave Doppler and M-mode echocardiography were done for all patients. Results: Eighty-seven patients, 65 male (75%) and 22 female (25%), with mean (SD) age of 56.7 (12.3) years were enrolled the study. Ischemic cardiomyopathy was the underlying heart disease in 58% of the subjects, and in the others it was idiopathic. Patients had a mean (SD) QRS duration of 155.13 (23.34) ms. QRS notch was seen in 49.4% of the patients in any of two precordial or limb leads. Interventricular mechanical delay was the only mechanical dyssynchrony index that was significantly longer in the group of patients with QRS notch. Multivariate analysis revealed that the observed association was actually caused by the effect of QRS duration, rather than the presence of notch per se. Conclusions: QRS notch was not an independent predictor of higher mechanical dyssynchrony indices in patients with wide QRS complex and symptomatic systolic heart failure; however, there was a borderline association between QRS notch and interventricular delay

Cardiac resynchronization therapy in heart failure patients: An update

Heart failure continues to be a major public health problem with high morbidity and mortality rates, despite the advances in medical treatment. Advanced heart failure patients have severe persistent symptoms and a poor quality of life. Cardiac resynchronization therapy (CRT), an invasive therapy which involves synchronized pacing of both right and left ventricles, improves ventricular conduction delay and left ventricular performance. Several clinical trials of CRT in medically refractory heart failure patients with wide QRS (> 120 ms), left ventricular ejection fraction &#163; 35% and New York Heart Association (NYHA) class III and IV have shown improved quality of life, NYHA class, left ventricular ejection fraction and reduced mortality. About 30% of heart failure patients who receive CRT do not respond to treatment. Mechanical dyssynchrony may play a role in identifying patients who may respond better to CRT treatment. However, recent large scale clinical trials PROSPECT and RethinQ have challenged this concept. The role of CRT in heart failure patients with narrow QRS (< 120 ms), NYHA class I and II, atrioventricular nodal ablation in patients with atrial fibrillation and triple site pacing are evolving. Our review discusses the current evidence, indications, upcoming trials and future directions

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