Early prediction of cardiac resynchronization therapy response by non-invasive electrocardiogram markers

[EN] Cardiac resynchronization therapy (CRT) is an effective treatment for those patients with severe heart failure. Regrettably, there are about one third of CRT "non-responders", i.e. patients who have undergone this form of device therapy but do not respond to it, which adversely affects the utility and cost-effectiveness of CRT. In this paper, we assess the ability of a novel surface ECG marker to predict CRT response. We performed a retrospective exploratory study of the ECG previous to CRT implantation in 43 consecutive patients with ischemic (17) or non-ischemic (26) cardiomyopathy. We extracted the QRST complexes (consisting of the QRS complex, the S-T segment, and the T wave) and obtained a measure of their energy by means of spectral analysis. This ECG marker showed statistically significant lower values for non-responder patients and, joint with the duration of QRS complexes (the current gold-standard to predict CRT response), the following performances: 86% accuracy, 88% sensitivity, and 80% specificity. In this manner, the proposed ECG marker may help clinicians to predict positive response to CRT in a non-invasive way, in order to minimize unsuccessful procedures.This work was supported by MINECO under grants MTM2013-43540-P and MTM2016-76647-P.Ortigosa, N.; Pérez-Roselló, V.; Donoso, V.; Osca Asensi, J.; Martínez-Dolz, L.; Fernández Rosell, C.; Galbis Verdu, A. (2018). Early prediction of cardiac resynchronization therapy response by non-invasive electrocardiogram markers. Medical & Biological Engineering & Computing. 56(4):611-621. https://doi.org/10.1007/s11517-017-1711-1S611621564Boggiatto P, Fernández C, Galbis A (2009) A group representation related to the stockwell transform. Indiana University Mathematics Journal 58(5):2277–2296Brignole M, Auricchio A, Baron-Esquivias G, Bordachar P, Boriani G et al (2013) 2013 ESC guidelines on cardiac pacing and cardiac resynchronization therapy. Europace 15:1070–1118Brown RA, Lauzon ML, Frayne R (2010) A general description of linear time-frequency transforms and formulation of a fast, invertible transform that samples the continuous s-transform spectrum nonredundantly. IEEE Trans Signal Process 58(1): 281–290Carità P, Corrado E, Pontone G, Curnis A, Bontempi L et al (2016) Non-responders to cardiac resynchronization therapy: insights from multimodality imaging and electrocardiography. A brief review. Int J Cardiol 225:402–407Cazeau S, Leclercq C, Lavergne T, Walker S, Varma C, Linde C et al (2001) Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay. N Engl J Med 344:873–880Chang CC, Lin CJ (2011) LIBSVM: a library for support vector machines. ACM Trans Intell Syst Technol 2(3):27:1–27:27Chawla NV, Bowyer KW, Hall LO, Kegelmeyer WP (2002) SMOTE: synthetic minority over-sampling technique. J Artif Intell Res 16(1):321–357Cleland JGF, Abraham WT, Linde C, Gold MR, Young J et al (2013) An individual patient meta-analysis of five randomized trials assessing the effects of cardiac resyn- chronization therapy on morbidity and mortality in patients with symptomatic heart failure. Eur Heart Journal 34(46):3547–3556Cleland JGF, Calvert MJ, Verboven Y, Freemantle N (2009) Effects of cardiac resynchronization therapy on long-term quality of life: an analysis from the Cardiac Resynchronisation-Heart Failure (CARE-HF) study. Am Heart J 157:457–466Cleland JGF, Freemantle N, Erdmann E, Gras D, Kappenberger L et al (2012) Long-term mortality with cardiac resynchronization therapy in the Cardiac Resynchronization-Heart Failure (CARE-HF) trial. Eur J Heart Fail 14:628–634Egoavil CA, Ho RT, Greenspon AJ, Pavri BB (2005) Cardiac resynchronization therapy in patients with right bundle branch block: analysis of pooled data from the MIRACLE and Contak CD trials. Heart Rhythm 2(6):611–615Engels EB, Mafi-Rad M, van Stipdonk AM, Vernooy K, Prinzen FW (2016) Why QRS duration should be replaced by better measures of electrical activation to improve patient selection for cardiac resynchronization therapy. J Cardiovasc Transl Res 9(4):257–265Engels EB, Végh EM, Van Deursen CJ, Vernooy K, Singh JP, Prinzen FW (2015) T-wave area predicts response to cardiac resynchronization therapy in patients with left bundle branch block. J Cardiovasc Electrophysiol 26(2):176–183Eschalier R, Ploux S, Ritter P, Haïssaguerre M, Ellenbogen K, Bordachar P (2015) Nonspecific intraventricular conduction delay: definitions, prognosis, and implications for cardiac resynchronization therapy. Heart Rhythm 12(5):1071–1079Goldenberg I, Kutyifa V, Klein HU, Cannom DS, Brown MW et al (2014) Survival with cardiac-resynchronization therapy in mild heart failure. N Engl J Med 370:1694–1701He H, Bai Y, Garcia EA, Li S (2008) ADASYN: adaptive synthetic sampling approach for imbalanced learning. In: International joint conference on neural networks, pp 1322–1328Jacobsson J, Borgguist R, Reitan C, Ghafoori E, Chatterjee NA et al (2016) Usefulness of the sum absolute QRST integral to predict outcomes in patients receiving cardiac resynchronization therapy. J Cardiovasc Electrophysiol 118(3):389–395McMurray JJ (2010) Clinical practice. Systolic heart failure. N Engl J Med 3623:228–238Meyer CR, Keiser HN (1977) Electrocardiogram baseline noise estimation and removal using cubic splines and state-space computation techniques. Comput Biomed Res 10:459–470Ortigosa N, Giménez VM (2014) Raw data extraction from electrocardiograms with portable document format. Comput Meth Programs Biomed 113(1):284–289Ortigosa N, Osca J, Jiménez R, Rodríguez Y, Fernández C, Galbis A (2016) Predictive analysis of cardiac resynchronization therapy response by means of the ECG. 2016 Comput Cardio 43:753–756. https://doi.org/10.22489/CinC.2016.218-415Ponikowski P, Voors AA, Anker S, Bueno H, Cleland JG, Coats AJ et al (2016) 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 18(8):891–975Rad MM, Wijntjens GW, Engels EB, Blaauw Y, Luermans JG et al (2016) Vectorcardiographic QRS area identifies delayed left ventricular lateral wall activation determined by electroanatomic mapping in candidates for cardiac resynchronization therapy. Heart Rhythm 13(1):217–225Shanks M, Delgado V, Bax JJ (2016) Cardiac resynchronization therapy in non-ischemic cardiomyopathy. Journal of Atrial Fibrillation 8(5):47–52Singh JP, Fan D, Heist EK, Alabiad CR, Taub C et al (2006) Left ventricular lead electrical delay predicts response to cardiac resynchronization therapy. Heart Rhythm 3(11):1285–1292Sohaib SM, Finegold JA, Nijjer SS, Hossain R, Linde C et al (2015) Opportunity to increase life span in narrow QRS cardiac resynchronization therapy recipients by deactivating ventricular pacing: evidence from randomized controlled trials. JACC Heart Fail 3:327–336Stockwell RG, Mansinha L, Lowe RP (1996) Localization of the complex spectrum: the S transform. IEEE Trans Signal Process 44(4):998–1001Tang ASL, Wells GA, Talajic M, Arnold MO, Sheldon R et al (2010) Cardiac-resynchronization therapy for mild-to-moderate heart failure. N Engl J Med 363:2385–2395Tereshchenko LG, Cheng A, Park J, Wold N, Meyer TE, Gold MR et al (2015) Novel measure of electrical dyssynchrony predicts response in cardiac resynchronization therapy: results from the SMART-AV trial. Heart Rhythm 12(2):2402–2410van Deursen CJ, Vernooy K, Dudink E, Bergfeldt L, Crijns HJ et al (2015) Vectorcardiographic QRS area as a novel predictor of response to cardiac resynchronization therapy. J Electrocardiol 48(1):45–52Wang TJ (2003) Natural history of asymptomatic left ventricular systolic dysfunction in the community. Circulation 108:977–982Woods B, Hawkins N, Mealing S, Sutton A, Abraham WT et al (2015) Individual patient data network meta-analysis of mortality effects of implantable cardiac devices. Heart 101:1800–1806Ypenburg C, van Bommel RJ, Borleffs CJ, Bleeker GB, Boersma E et al (2009) Long-term prognosis after cardiac resynchronization therapy is related to the extent of left ventricular reverse remodeling at midterm follow-up. J Am Coll Cardiol 53(6):483–490Yu CM, Hayes DL (2013) Cardiac resynchronization therapy: state of the art 2013. Eur Heart J 34:1396–140

Techniques for Identification of Left Ventricular Asynchrony for Cardiac Resynchronization Therapy in Heart Failure

The most recent treatment option of medically refractory heart failure includes cardiac resynchronization therapy (CRT) by biventricular pacing in selected patients in NYHA functional class III or IV heart failure. The widely used marker to indicate left ventricular (LV) asynchrony has been the surface ECG, but seems not to be a sufficient marker of the mechanical events within the LV and prediction of clinical response. This review presents an overview of techniques for identification of left ventricular intra- and interventricular asynchrony. Both manuscripts for electrical and mechanical asynchrony are reviewed, partly predicting response to CRT. In summary there is still no gold standard for assessment of LV asynchrony for CRT, but both traditional and new echocardiographic methods have shown asynchronous LV contraction in heart failure patients, and resynchronized LV contraction during CRT and should be implemented as additional methods for selecting patients to CRT

Useful Electrocardiographic Signs to Support the Prediction of Favorable Response to Cardiac Resynchronization Therapy

Cardiac resynchronization therapy (CRT) is a cornerstone therapeutic opportunity for selected patients with heart failure. For optimal patient selection, no other method has been proven to be more effective than the 12-lead ECG, and hence ECG characteristics are extensively researched. The evaluation of particular ECG signs before the implantation may improve selection and, consequently, clinical outcomes. The definition of a true left bundle branch block (LBBB) seems to be the best starting point with which to select patients for CRT. Although there are no universally accepted definitions of LBBB, using the classical LBBB criteria, some ECG parameters are associated with CRT response. In patients with non-true LBBB or non-LBBB, further ECG predictors of response and non-response could be analyzed, such as QRS fractionation, signs of residual left bundle branch conduction, S-waves in V6, intrinsicoid deflection, or non-invasive estimates of Q-LV which are described in newer publications. The most important and recent study results of the topic are summarized and discussed in this current review

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

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

Noninvasive evaluation of patients with coronary artery disease and heart failure

In dit proefschrift worden patiënten bestudeerd met een voorgeschiedenis van coronair lijden en hartfalen. De thesis is onderverdeeld in drie delen: 1. Niet-invasieve inschatting van vuldrukken door middel van geavanceerde echocardiografische technieken 2. Selectie van kandidaten voor cardiale resynchronizatietherapie met echocardiografie, nucleaire technieken en multi slice CT 3. Nietinvasieve prognostische markers waaronder nuchtere glycemie en determinanten van inspanningscapacitei

Echocardiographic Assessment of Right Ventriculo-arterial Coupling: Clinical Correlates and Prognostic Impact in Heart Failure Patients Undergoing Cardiac Resynchronization Therapy

Background: Right ventriculo-arterial coupling (RV-PA) can be estimated by echocardiography using the ratio between tricuspid annular plane systolic excursion (TAPSE) and pulmonary artery systolic pressure (PASP) and it has prognostic value in the general heart failure (HF) population. We aimed to study the clinical correlates and prognostic value of RV-PA in HF patients undergoing cardiac resynchronization therapy (CRT). Methods: We retrospectively studied 70 HF patients undergoing CRT implantation. Results: RV-PA coupling was estimated by TAPSE/PASP ratio using baseline echocardiography. Non-response to CRT was defined as improvement of left ventricular ejection fraction < 5% in a follow-up echo 6-12 months after CRT. Those with lower TAPSE/PASP ratios (worse RV-PA coupling) had higher NT-proBNP concentrations and increased E/e' ratio. TAPSE/PASP ratio and PASP, but not TAPSE, predicted nonresponse to CRT with TAPSE/PASP ratio showing the best discriminative ability with a sensitivity of 76% and specificity of 71%. Among these parameters, PASP independently predicted all-cause mortality. Conclusions: RV-PA coupling estimated by TAPSE/PASP ratio was associated with established prognostic markers in HF. It numerically outperformed PASP and TAPSE in predicting the response to CRT. Our data suggest that this simple and widely available echocardiographic parameter conveys significant pathophysiological and prognostic meaning in HF patients undergoing CRT.info:eu-repo/semantics/publishedVersio