Publications by authors named "Antonius van Stipdonk"

19 Publications

  • Page 1 of 1

Comparing Ventricular Synchrony in Left Bundle Branch and Left Ventricular Septal Pacing in Pacemaker Patients.

J Clin Med 2021 Feb 17;10(4). Epub 2021 Feb 17.

Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre + (MUMC+), 6229 HX Maastricht, The Netherlands.

Background: Left bundle branch area pacing (LBBAP) has recently been introduced as a novel physiological pacing strategy. Within LBBAP, distinction is made between left bundle branch pacing (LBBP) and left ventricular septal pacing (LVSP, no left bundle capture).

Objective: To investigate acute electrophysiological effects of LBBP and LVSP as compared to intrinsic ventricular conduction.

Methods: Fifty patients with normal cardiac function and pacemaker indication for bradycardia underwent LBBAP. Electrocardiography (ECG) characteristics were evaluated during pacing at various depths within the septum: starting at the right ventricular (RV) side of the septum: the last position with QS morphology, the first position with r' morphology, LVSP and-in patients where left bundle branch (LBB) capture was achieved-LBBP. From the ECG's QRS duration and QRS morphology in lead V1, the stimulus- left ventricular activation time left ventricular activation time (LVAT) interval were measured. After conversion of the ECG into vectorcardiogram (VCG) (Kors conversion matrix), QRS area and QRS vector in transverse plane (Azimuth) were determined.

Results: QRS area significantly decreased from 82 ± 29 µVs during RV septal pacing (RVSP) to 46 ± 12 µVs during LVSP. In the subgroup where LBB capture was achieved ( = 31), QRS area significantly decreased from 46 ± 17 µVs during LVSP to 38 ± 15 µVs during LBBP, while LVAT was not significantly different between LVSP and LBBP. In patients with normal ventricular activation and narrow QRS, QRS area during LBBP was not significantly different from that during intrinsic activation (37 ± 16 vs. 35 ± 19 µVs, respectively). The Azimuth significantly changed from RVSP (-46 ± 33°) to LVSP (19 ± 16°) and LBBP (-22 ± 14°). The Azimuth during both LVSP and LBBP were not significantly different from normal ventricular activation. QRS area and LVAT correlated moderately (Spearman's = 0.58).

Conclusions: ECG and VCG indices demonstrate that both LVSP and LBBP improve ventricular dyssynchrony considerably as compared to RVSP, to values close to normal ventricular activation. LBBP seems to result in a small, but significant, improvement in ventricular synchrony as compared to LVSP.
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February 2021

Development and implementation of a cardiac resynchronisation therapy care pathway: improved process and reduced resource use.

BMJ Open Qual 2021 Feb;10(1)

Cardiology, Maastricht Universitair Medisch Centrum+, Maastricht, Netherlands.

Background: Cardiac resynchronisation therapy (CRT) requires intensive, complex and multidisciplinary care to maximize the clinical benefit. In current practice this is typically a task for highly specialised physicians. We report on a novel multidisciplinary, standardised CRT care pathway (CRT-CPW). Experienced clinicians developed a CPW with simple and broadly applicable aids based on clinical evidence and identified shortcomings in the current CRT care. The resulting CPW was implemented at the Maastricht University Medical Center, aiming at a transfer from heterogeneous physician-led care to standardized nurse-led care.

Methods: Two CRT patient cohorts were compared in this analysis. The benchmarked usual care cohort (2012-2014, 122 patients) was compared with the CRT-CPW cohort (2015-2017, 115 patients). The primary outcomes were process-related: number of physician consultations, nurse consultations, length of stay (LOS) at implantation and total hospitalisation days during 1-year follow-up, and referral-to-treatment time. Clinical outcomes were assessed to adress non-inferiority of quality of care.

Results: Patients in the CRT-CPW cohort consulted nurses and technicians significantly more often than patients in the usual care cohort (2.4±1.5 vs 1.7±2.0, p<0.0001 and 4.3±2.5 vs 3.7±1.5, p=0.063, respectively). Patients with CRT-CPW consulted physicians significantly less often (1.7±1.4 vs 2.6±2.1, p<0.001). Referral to treatment time was significantly reduced in the CRT-CPW group (23.6±18.4 vs 37.0±26.3 days, p=0.002). LOS at implantation and total hospitalisation days were significantly reduced in the CRT-CPW group (1.1±1.2 vs 1.5±0.7 days, p<0.0001 and 2.4±4.8 vs 4.8±9.3, p<0.0001, respectively). Clinical outcome analyses showed no significant difference in 12-month all-cause mortality and heart failure hospitalisations.

Conclusion: The introduction of a novel CRT-CPW resulted in a successful transition of physician-led to nurse-led care, with a significantly reduced resource use and equal clinical outcomes. Future evaluations will focus on impact on outcomes versus costs, to evaluate cost-effectiveness of the CRT-CPW.
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February 2021

Reduction in the QRS area after cardiac resynchronization therapy is associated with survival and echocardiographic response.

J Cardiovasc Electrophysiol 2021 Mar 28;32(3):813-822. Epub 2021 Jan 28.

Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre+, Maastricht, The Netherlands.

Introduction: Recent studies have shown that the baseline QRS area is associated with the clinical response after cardiac resynchronization therapy (CRT). In this study, we investigated the association of QRS area reduction (∆QRS area) after CRT with the outcome. We hypothesize that a larger ∆QRS area is associated with a better survival and echocardiographic response.

Methods And Results: Electrocardiograms (ECG) obtained before and 2-12 months after CRT from 1299 patients in a multi-center CRT-registry were analyzed. The QRS area was calculated from vectorcardiograms that were synthesized from 12-lead ECGs. The primary endpoint was a combination of all-cause mortality, heart transplantation, and left ventricular (LV) assist device implantation. The secondary endpoint was the echocardiographic response, defined as LV end-systolic volume reduction ≥ of 15%. Patients with ∆QRS area above the optimal cut-off value (62 µVs) had a lower risk of reaching the primary endpoint (hazard ratio: 0.43; confidence interval [CI] 0.33-0.56, p < .001), and a higher chance of echocardiographic response (odds ratio [OR] 3.3;CI 2.4-4.6, p < .0001). In multivariable analysis, ∆QRS area was independently associated with both endpoints. In patients with baseline QRS area ≥109 µVs, survival, and echocardiographic response were better when the ∆QRS area was ≥62 µVs (p < .0001). Logistic regression showed that in patients with baseline QRS area ≥109 µVs, ∆QRS area was the only significant predictor of survival (OR: 0.981; CI: 0.967-0.994, p = .006).

Conclusion: ∆QRS area is an independent determinant of CRT response, especially in patients with a large baseline QRS area. Failure to achieve a large QRS area reduction with CRT is associated with a poor clinical outcome.
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March 2021

Heart Size Corrected Electrical Dyssynchrony and Its Impact on Sex-Specific Response to Cardiac Resynchronization Therapy.

Circ Arrhythm Electrophysiol 2021 Jan 9;14(1):e008452. Epub 2020 Dec 9.

Department of Cardiology (O.A.E.S., M.J.C., M.M.), University Medical Center Utrecht, Utrecht University, the Netherlands.

Background: Women are less likely to receive cardiac resynchronization therapy, yet, they are more responsive to the therapy and respond at shorter QRS duration. The present study hypothesized that a relatively larger left ventricular (LV) electrical dyssynchrony in smaller hearts contributes to the better cardiac resynchronization therapy response in women. For this, the vectorcardiography-derived QRS area is used, since it allows for a more detailed quantification of electrical dyssynchrony compared with conventional electrocardiographic markers.

Methods: Data from a multicenter registry of 725 cardiac resynchronization therapy patients (median follow-up, 4.2 years [interquartile range, 2.7-6.1]) were analyzed. Baseline electrical dyssynchrony was evaluated using the QRS area and the corrected QRS area for heart size using the LV end-diastolic volume (QRSarea/LVEDV). Impact of the QRSarea/LVEDV ratio on the association between sex and LV reverse remodeling (LV end-systolic volume change) and sex and the composite outcome of all-cause mortality, LV assist device implantation, or heart transplantation was assessed.

Results: At baseline, women (n=228) displayed larger electrical dyssynchrony than men (QRS area, 132±55 versus 123±58 μVs; =0.043), which was even more pronounced for the QRSarea/LVEDV ratio (0.76±0.46 versus 0.57±0.34 μVs/mL; <0.001). After multivariable analyses, female sex was associated with LV end-systolic volume change (β=0.12; =0.003) and a lower occurrence of the composite outcome (hazard ratio, 0.59 [0.42-0.85]; =0.004). A part of the female advantage regarding reverse remodeling was attributed to the larger QRSarea/LVEDV ratio in women (25-fold change in β from 0.12 to 0.09). The larger QRSarea/LVEDV ratio did not contribute to the better survival observed in women. In both volumetric responders and nonresponders, female sex remained strongly associated with a lower risk of the composite outcome (adjusted hazard ratio, 0.59 [0.36-0.97]; =0.036; and 0.55 [0.33-0.90]; =0.018, respectively).

Conclusions: Greater electrical dyssynchrony in smaller hearts contributes, in part, to more reverse remodeling observed in women after cardiac resynchronization therapy, but this does not explain their better long-term outcomes.
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January 2021

Cardiac Inflammation Impedes Response to Cardiac Resynchronization Therapy in Patients With Idiopathic Dilated Cardiomyopathy.

Circ Arrhythm Electrophysiol 2020 11 30;13(11):e008727. Epub 2020 Sep 30.

Cardiovascular Research Institute (CARIM), Departments of Cardiology (J.A.J.V., J.J.M., A.M.W.v.S., M.T.H.M.H., V.P.M.v.E., C.K., J.G.L.M.L., H.J.G.M.C., H.-P.B.-L.R., K.V., S.R.B.H., M.R.H.), Maastricht University Medical Center, the Netherlands.

Background: Cardiac resynchronization therapy (CRT) is an established therapy in patients with dilated cardiomyopathy (DCM) and conduction disorders. Still, one-third of the patients with DCM do not respond to CRT. This study aims to depict the underlying cardiac pathophysiological processes of nonresponse to CRT in patients with DCM using endomyocardial biopsies.

Methods: Within the Maastricht and Innsbruck registries of patients with DCM, 99 patients underwent endomyocardial biopsies before CRT implantation, with histological quantification of fibrosis and inflammation, where inflammation was defined as >14 infiltrating cells/mm. Echocardiographic left ventricular end-systolic volume reduction ≥15% after 6 months was defined as response to CRT. RNA was isolated from cardiac biopsies of a representative subset of responders and nonresponders.

Results: Sixty-seven patients responded (68%), whereas 32 (32%) did not respond to CRT. Cardiac inflammation before implantation was negatively associated with response to CRT (25% of responders, 47% of nonresponders; odds ratio 0.3 [0.12-0.76]; =0.01). Endomyocardial biopsies fibrosis did not relate to CRT response. Cardiac inflammation improved the robustness of prediction beyond well-known clinical predictors of CRT response (likelihood ratio test <0.001). Cardiac transcriptomic profiling of endomyocardial biopsies reveals a strong proinflammatory and profibrotic signature in the hearts of nonresponders compared with responders. In particular, , and were significantly higher expressed in the hearts of nonresponders.

Conclusions: Cardiac inflammation along with a transcriptomic profile of high expression of combined proinflammatory and profibrotic genes are associated with a poor response to CRT in patients with DCM.
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November 2020

Association of ECG characteristics with clinical and echocardiographic outcome to CRT in a non-LBBB patient population.

J Interv Card Electrophysiol 2020 Sep 12. Epub 2020 Sep 12.

Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre+, Maastricht, the Netherlands.

Purpose: Effectiveness of cardiac resynchronization therapy (CRT) in patients without left bundle branch block (non-LBBB) QRS morphology is limited. Additional selection criteria are needed to identify these patients.

Methods: Seven hundred ninety consecutive patients with non-LBBB morphology, who received a CRT-device in 3 university centers in the Netherlands, were selected. Pre-implantation 12-lead ECGs were evaluated on morphology, duration, and area of the QRS complex, as well as on PR interval, left ventricular activation time (LVAT), and the presence of fragmented QRS (fQRS). Association of these ECG features with the primary endpoint: a combination of left ventricular assist device (LVAD) implantation, cardiac transplantation and all-cause mortality, and secondary endpoint-echocardiographic reduction of left ventricular end-systolic volume (LVESV)-were evaluated.

Results: The primary endpoint occurred more often in non-LBBB patients with with PR interval ≥ 230ms, QRS area < 109μVs, and with fQRS. Multivariable regression analysis showed independent associations of QRS area (HR 2.33 [1.44, 3.77], p = 0.001) and PR interval (HR 2.03 [1.51, 2.74], p < 0.001) only. Mean LVESV reduction was significantly lower in patients with baseline RBBB, QRS duration < 150 ms, PR interval ≥ 230 ms, and in QRS area < 109 μVs. Multivariable regression analyses only showed significant associations between QRS area ≥ 109 μVs (OR 2.00 [1.09, 3.66] p = 0.025) and probability of echocardiographic response to CRT.

Conclusions: In the heterogeneous non-LBBB patient population, QRS area and PR prolongation rather than traditional QRS duration and morphology are associated to both clinical and echocardiographic outcomes of CRT.
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September 2020

Evaluating Electrocardiography-Based Identification of Cardiac Resynchronization Therapy Responders Beyond Current Left Bundle Branch Block Definitions.

JACC Clin Electrophysiol 2020 02 27;6(2):193-203. Epub 2019 Nov 27.

Department of Cardiology, Maastricht University Medical Center, Maastricht, the Netherlands; Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands; Department of Cardiology, Radboud University Medical Centre, Nijmegen, the Netherlands.

Objectives: This study aimed to evaluate the association of 4 left bundle branch block (LBBB) definitions and their individual ECG characteristics with clinical outcome. Furthermore, it aimed to combine relevant outcome-associated electrocardiographic (ECG) characteristics into a novel outcome-based definition.

Background: LBBB morphology is associated with positive response to cardiac resynchronization therapy. However, there are multiple LBBB definitions. Associations with outcomes may differ between definitions and depend on varying contributions of the individual ECG characteristics that these LBBB definitions are composed of.

Methods: A retrospective multicenter study was conducted in 1,492 cardiac resynchronization therapy patients. Patients were classified as LBBB or non-LBBB according to definitions provided by the European Society of Cardiology, American Heart Association, MADIT-CRT (Multicenter Automatic Defibrillator Implantation with Cardiac Resynchronization Therapy) trial, and according to Strauss et al., the primary endpoint was left ventricular assist device implantation, cardiac transplantation, and all-cause mortality.

Results: LBBB classification differed significantly between the 4 definitions (kappa coefficients ranging from 0.09 to 0.92). The American Heart Association definition correlated the least (0.09 to 0.12) with the other definitions. Only 13.8% of patients were classified as LBBB by all definitions. During a follow-up period of 3.4 ± 2.4 years, 472 (32%) patients experienced the primary endpoint. For each LBBB definition survival analysis showed a significant association of LBBB with outcome, with relative risk reduction ranging from 39% to 43%. Each LBBB definition included characteristics that were not associated with outcome. Combining outcome-associated ECG characteristics into a novel prediction model did not significantly improve diagnostic performance (relative risk reduction 43%).

Conclusions: The classification of LBBB is highly dependent on the LBBB definition used. However, each LBBB definition provides a comparable difference in risk of adverse clinical events between LBBB and non-LBBB patients. Combining individual outcome-associated ECG-characteristics into a novel prediction model does not improve association with outcome.
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February 2020

Strategies to Improve Selection of Patients Without Typical Left Bundle Branch Block for Cardiac Resynchronization Therapy.

JACC Clin Electrophysiol 2020 02;6(2):129-142

Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands.

Cardiac resynchronization therapy (CRT) is becoming increasingly controversial in patients without typical left bundle branch block (LBBB). Yet, several recent studies displayed that a distinct subpopulation of patients with non-LBBB does benefit from CRT. Patients with non-LBBB should, therefore, not as a group be withheld from a potentially very beneficial therapy. Unfortunately, current clinical practice lacks validated selection criteria that may identify possible CRT responders in the non-LBBB subgroup. Consequently, clinical decision making in these patients is often challenging. A few studies, strongly differing in design, have proposed additive selection criteria for improved response prediction in patients with non-LBBB. There is accumulating evidence that more sophisticated echocardiographic dyssynchrony markers, taking into account the underlying electrical substrate responsive to CRT, can aid in the selection of patients with a non-LBBB who may benefit more favorably from CRT. Furthermore, it is important that cardiologists are aware of the shortcomings of current electrocardiographic selection criteria for CRT. Whereas these criteria provide an evidence-based approach for selecting patients for CRT, they do not necessarily guarantee the most optimal strategy for patient selection. Parameters obtained with vectorcardiography, such as QRS area, show potential to overcome the shortcomings of conventional electrocardiographic selection criteria and may improve response prediction regardless of QRS morphology.
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February 2020

Association between heart failure aetiology and magnitude of echocardiographic remodelling and outcome of cardiac resynchronization therapy.

ESC Heart Fail 2020 04 28;7(2):645-653. Epub 2020 Jan 28.

Department of Cardiology, University of Groningen, University Medical Centre Groningen, PO Box 30.001, Groningen, 9700, RB, The Netherlands.

Aims: Echocardiographic response after cardiac resynchronization therapy (CRT) is often lesser in ischaemic cardiomyopathy (ICM) than non-ischaemic dilated cardiomyopathy (NIDCM) patients. We assessed the association of heart failure aetiology on the amount of reverse remodelling and outcome of CRT.

Methods And Results: Nine hundred twenty-eight CRT patients were retrospectively included. Reverse remodelling and endpoint occurrence (all-cause mortality, heart transplantation, or left ventricular assist device implantation) was assessed. Two response definitions [≥15% reduction left ventricular end systolic volume (LVESV) and ≥5% improvement left ventricular ejection fraction] and the most accurate cut-off for the amount of reverse remodelling that predicted endpoint freedom were assessed. Mean follow-up was 3.8 ± 2.4 years. ICM was present in 47%. ICM patients who were older (69 ± 7 vs. 63 ± 11), more often men (83% vs. 58%), exhibited less LVESV reduction (13 ± 31% vs. 23 ± 32%) and less left ventricular ejection fraction improvement (5 ± 11% vs. 10 ± 12%) than NIDCM patients (all P < 0.001). Nevertheless, every 1% LVESV reduction was associated with a relative reduction in endpoint occurrence: NIDCM 1.3%, ICM 0.9%, and absolute risk reduction was similar (0.4%). The most accurate cut-off of LVESV reduction that predicted endpoint freedom was 17.1% in NIDCM and 13.2% in ICM.

Conclusions: ICM patients achieve less reverse remodelling than NIDCM, but the prognostic gain in terms of survival time is the same for every single percentage of reverse remodelling that does occur. The assessment and expected magnitude of reverse remodelling should take this effect of heart failure aetiology into account.
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April 2020

Fully automated QRS area measurement for predicting response to cardiac resynchronization therapy.

J Electrocardiol 2020 Nov - Dec;63:159-163. Epub 2019 Jul 9.

Department of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, the Netherlands. Electronic address:

Background: Cardiac resynchronization therapy (CRT) is an established treatment in patients with heart failure and conduction abnormalities. However, a significant number of patients do not respond to CRT. Currently employed criteria for selection of patients for this therapy (QRS duration and morphology) have several shortcomings. QRS area was recently shown to provide superior association with CRT response. However, its assessment was not fully automated and required the presence of an expert.

Objective: Our objective was to develop a fully automated method for the assessment of vector-cardiographic (VCG) QRS area from electrocardiographic (ECG) signals.

Methods: Pre-implantation ECG recordings (N = 864, 695 left-bundle-branch block, 589 men) in PDF files were converted to allow signal processing. QRS complexes were found and clustered into morphological groups. Signals were converted from 12‑lead ECG to 3‑lead VCG and an average QRS complex was built. QRS area was computed from individual areas in the X, Y and Z leads. Practical usability was evaluated using Kaplan-Meier plots and 5-year follow-up data.

Results: The automatically calculated QRS area values were 123 ± 48 μV.s (mean values and SD), while the manually determined QRS area values were 116 ± 51 ms; the correlation coefficient between the two was r = 0.97. The automated and manual methods showed the same ability to stratify the population (hazard ratios 2.09 vs 2.03, respectively).

Conclusion: The presented approach allows the fully automatic and objective assessment of QRS area values.

Significance: Until this study, assessing QRS area values required an expert, which means both additional costs and a risk of subjectivity. The presented approach eliminates these disadvantages and is publicly available as part of free signal-processing software.
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July 2019

QRS Area Is a Strong Determinant of Outcome in Cardiac Resynchronization Therapy.

Circ Arrhythm Electrophysiol 2018 12;11(12):e006497

Department of Cardiology, Maastricht University Medical Centre, The Netherlands (A.M.W.v.S., H.J.G.M.C., K.V.).

Background: The combination of left bundle branch block (LBBB) morphology and QRS duration is currently used to select patients for cardiac resynchronization therapy (CRT). These parameters, however, have limitations. This study evaluates the value of QRS area compared with that of QRS duration and morphology in the association with clinical and echocardiographic outcomes in a large cohort of CRT patients.

Methods: A retrospective multicentre study was conducted in 1492 CRT patients. LBBB morphology, QRS duration, and QRS area in the baseline 12-lead ECG were evaluated for their association with the occurrence of the combined primary end point of all-cause mortality, cardiac transplantation, and left ventricular assist device implantation. Secondary end points were heart failure hospitalization within the first year after implantation and echocardiographic reduction in left ventricular end-systolic volume.

Results: During a mean follow-up period of 3.4 years, 32% of patients reached the primary end point. The association of QRS area with all outcomes was stronger than that of LBBB morphology and QRS duration separately and at least as strong as their combination. QRS area identified patients who did not experience the primary end point better than QRS morphology and QRS duration (area under the curve, 0.61 versus 0.55 and 0.51, respectively; P<0.001). Furthermore, QRS area identifies patients with echocardiographic remodeling in response to CRT better than QRS morphology and duration (area under the curve, 0.69 versus 0.58 and 0.58, respectively; P<0.001). QRS area was the only independent electrocardiographic determinant associated with the primary end point; hazard ratio, 0.50 (0.35-0.71). Furthermore, QRS area showed significant association with outcomes in both patients with and without LBBB and QRS ≥150 ms.

Conclusions: QRS area has a strong association to clinical and echocardiographic response to CRT, at least as strong as current patient selection parameters. QRS area may be particularly useful to predict CRT response in patients without a wide LBBB.
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December 2018

The definition of left bundle branch block influences the response to cardiac resynchronization therapy.

Int J Cardiol 2018 Oct 17;269:165-169. Epub 2018 Jul 17.

Fondazione Cardiocentro Ticino, Lugano, Switzerland.

Background: CRT has been proven to achieve most benefit in patients with left bundle branch block morphology (LBBB). However, ECG criteria to define LBBB significantly differ from each other. Objective of the study was to evaluate the impact of different ECG criteria for LBBB definition on survival, hospitalization for heart failure and reverse remodelling in patients who received cardiac resynchronization therapy (CRT).

Methods And Results: Three-hundred-sixteen consecutive patients were included in the analysis. Six different classifications were assessed in baseline ECGs of patients who received a CRT device: a QRS duration of ≥150 ms and LBBB according to AHA/ACC/HRS, ESC 2006, ESC 2009, ESC 2013 and the classification proposed by Strauss and colleagues. In univariate analysis, the ESC 2009 and 2013 and the Strauss classifications were significantly associated with a reduction in cumulative probability for heart failure (HF) and mortality (HR 0.60, 95%CI 0.42-0.86, HR 0.61, 95% CI 0.43-0.87 and HR 0.57, 95% CI 0.40-0.80, respectively). In multivariate analysis, the association with the combined endpoint was confirmed only for ESC 2009 and 2013 classifications and for Strauss. Moreover, the cumulative probability of all-cause death and HF hospitalizations was higher in patients who were negative for all the 5 LBBB classifications.

Conclusions: This study shows that the strength of the association of LBBB to outcome in CRT depends on the ECG classifications used to define LBBB, the simplest criteria (ESC 2009 and 2013) providing the best association with clinical endpoints in CRT.
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October 2018

Tailoring device settings in cardiac resynchronization therapy using electrograms from pacing electrodes.

Europace 2018 07;20(7):1146-1153

Department of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands.

Aims: Left ventricular (LV) fusion pacing appears to be at least as beneficial as biventricular pacing in cardiac resynchronization therapy (CRT). Optimal LV fusion pacing critically requires adjusting the atrioventricular (AV)-delay to the delay between atrial pacing and intrinsic right ventricular (RV) activation (Ap-RV). We explored the use of electrogram (EGM)-based vectorloop (EGMV) derived from EGMs of implanted pacing leads to achieve optimal LV fusion pacing and to compare it with conventional approaches.

Methods And Results: During CRT-device implantation, 28 patients were prospectively studied. During atrial-LV pacing (Ap-LVp) at various AV-delays, LV dP/dtmax, 12-lead electrocardiogram (ECG), and unipolar EGMs were recorded. Electrocardiogram and electrogram were used to reconstruct a vectorcardiogram (VCG) and EGMV, respectively, from which the maximum QRS amplitude (QRSampl), was extracted. Ap-RV was determined: (i) conventionally as the longest AV-delay at which QRS morphology was visually unaltered during RV pacing at increasing AV-delays(Ap-RVvis; reference-method); (ii) 70% of delay between atrial pacing and RV sensing (Ap-RVaCRT); and (iii) the delay between atrial pacing and onset of QRS (Ap-QRSonset). In both the EGMV and VCG, the longest AV-delay showing an unaltered QRSampl as compared with Ap-LVp with a short AV-delay, corresponded to Ap-RVvis. In contrast, Ap-QRSonset and Ap-RVaCRT were larger. The Ap-LVp induced increase in LV dP/dtmax was larger at Ap-RVvis, Ap-RVEGMV, and Ap-RVVCG than at Ap-QRSonset (all P < 0.05) and Ap-RVaCRT (P = 0.02, P = 0.13, and P = 0.03, respectively).

Conclusion: In this acute study, it is shown that the EGMV QRSampl can be used to determine optimal and individual CRT-device settings for LV fusion pacing, possibly improving long-term CRT response.
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July 2018

Evaluation of the use of unipolar voltage amplitudes for detection of myocardial scar assessed by cardiac magnetic resonance imaging in heart failure patients.

PLoS One 2017 5;12(7):e0180637. Epub 2017 Jul 5.

Center for Computational Medicine in Cardiology, Institute of Computational Science, Università della Svizzera italiana, Lugano, Switzerland.

Background: Validation of voltage-based scar delineation has been limited to small populations using mainly endocardial measurements. The aim of this study is to compare unipolar voltage amplitudes (UnipV) with scar on delayed enhancement cardiac magnetic resonance imaging (DE-CMR).

Methods: Heart failure patients who underwent DE-CMR and electro-anatomic mapping were included. Thirty-three endocardial mapped patients and 27 epicardial mapped patients were investigated. UnipV were computed peak-to-peak. Electrograms were matched with scar extent of the corresponding DE-CMR segment using a 16-segment/slice model. Non-scar was defined as 0% scar, while scar was defined as 1-100% scar extent.

Results: UnipVs were moderately lower in scar than in non-scar (endocardial 7.1 [4.6-10.6] vs. 10.3 [7.4-14.2] mV; epicardial 6.7 [3.6-10.5] vs. 7.8 [4.2-12.3] mV; both p<0.001). The correlation between UnipV and scar extent was moderate for endocardial (R = -0.33, p<0.001), and poor for epicardial measurements (R = -0.07, p<0.001). Endocardial UnipV predicted segments with >25%, >50% and >75% scar extent with AUCs of 0.72, 0.73 and 0.76, respectively, while epicardial UnipV were poor scar predictors, independent of scar burden (AUC = 0.47-0.56). UnipV in non-scar varied widely between patients (p<0.001) and were lower in scar compared to non-scar in only 9/22 (41%) endocardial mapped patients and 4/19 (21%) epicardial mapped patients with scar.

Conclusion: UnipV are slightly lower in scar compared to non-scar. However, significant UnipV differences between and within patients and large overlap between non-scar and scar limits the reliability of accurate scar assessment, especially in epicardial measurements and in segments with less than 75% scar extent.
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October 2017

A novel approach for left ventricular lead placement in cardiac resynchronization therapy: Intraprocedural integration of coronary venous electroanatomic mapping with delayed enhancement cardiac magnetic resonance imaging.

Heart Rhythm 2017 01 20;14(1):110-119. Epub 2016 Sep 20.

Department of Cardiology, Maastricht University Medical Center, Maastricht, the Netherlands.

Background: Placing the left ventricular (LV) lead at a site of late electrical activation remote from scar is desired to improve cardiac resynchronization therapy (CRT) response.

Objective: The purpose of this study was to integrate coronary venous electroanatomic mapping (EAM) with delayed enhancement cardiac magnetic resonance (DE-CMR) enabling LV lead guidance to the latest activated vein remote from scar.

Methods: Eighteen CRT candidates with focal scar on DE-CMR were prospectively included. DE-CMR images were semi-automatically analyzed. Coronary venous EAM was performed intraprocedurally and integrated with DE-CMR to guide LV lead placement in real time. Image integration accuracy and electrogram parameters were evaluated offline.

Results: Integration of EAM and DE-CMR was achieved using 8.9 ± 2.8 anatomic landmarks and with accuracy of 4.7 ± 1.1 mm (mean ± SD). Maximal electrical delay ranged between 72 and 197ms (57%-113% of QRS duration) and was heterogeneously located among individuals. In 12 patients, the latest activated vein was located outside scar, and placing the LV lead in the latest activated vein remote from scar was accomplished in 10 patients and prohibited in 2 patients. In the other 6 patients, the latest activated vein was located in scar, and targeting alternative veins was considered. Unipolar voltages were on average lower in scar compared to nonscar (6.71 ± 3.45 mV vs 8.18 ± 4.02 mV [median ± interquartile range), P <.001) but correlated weakly with DE-CMR scar extent (R -0.161, P <.001) and varied widely among individual patients.

Conclusion: Integration of coronary venous EAM with DE-CMR can be used during CRT implantation to guide LV lead placement to the latest activated vein remote from scar, possibly improving CRT.
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January 2017

Why QRS Duration Should Be Replaced by Better Measures of Electrical Activation to Improve Patient Selection for Cardiac Resynchronization Therapy.

J Cardiovasc Transl Res 2016 08 26;9(4):257-65. Epub 2016 May 26.

Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.

Cardiac resynchronization therapy (CRT) is a well-known treatment modality for patients with a reduced left ventricular ejection fraction accompanied by a ventricular conduction delay. However, a large proportion of patients does not benefit from this therapy. Better patient selection may importantly reduce the number of non-responders. Here, we review the strengths and weaknesses of the electrocardiogram (ECG) markers currently being used in guidelines for patient selection, e.g., QRS duration and morphology. We shed light on the current knowledge on the underlying electrical substrate and the mechanism of action of CRT. Finally, we discuss potentially better ECG-based biomarkers for CRT candidate selection, of which the vectorcardiogram may have high potential.
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August 2016

ECG Patterns In Cardiac Resynchronization Therapy.

J Atr Fibrillation 2015 Apr-May;7(6):1214. Epub 2015 Apr 30.

Department of Cardiology, Maastricht University Medical Center.

Cardiac resynchronization therapy is an established treatment modality in heart failure. Though non-response is a serious issue. To address this issue, a good understanding of the electrical activation during underlying intrinsic ventricular activation, biventricular as well as right- and left ventricular pacing is needed. By interpreting the 12-lead electrocardiogram, possible reasons for suboptimal treatment can be identified and addressed. This article reviews the literature on QRS morphology in cardiac resynchronization therapy and its role in optimization of therapy.
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April 2015

Electrocardiographic factors playing a role in ischemic ventricular fibrillation in ST elevation myocardial infarction are related to the culprit artery.

Heart Rhythm 2008 Jan 19;5(1):71-8. Epub 2007 Sep 19.

Department of Cardiology, University Hospital Maastricht, Maastricht, The Netherlands.

Background: Sudden cardiac death caused by ischemic ventricular fibrillation (VF) associated with ST elevation myocardial infarction (STEMI) is one of the most frequent causes of death.

Objective: We hypothesized that electrocardiographic (ECG) characteristics differ between STEMI patients with and without ischemic VF.

Methods: Fifty-five first STEMI patients with at least one 12-lead ECG recorded before ischemic VF were compared with 110 first STEMI patients without ischemic VF. Patients with bundle branch blocks or high-degree atrioventricular blocks with escape rhythms were not included. ECG measurements were performed manually after scanning the ECG with the most prominent ST deviation into a software environment and magnifying it 4 times.

Results: Mean age was 57 +/- 12 years, and 126 patients were male. No differences were present between the VF and control group regarding baseline, enzymatic, and angiographic data. In left circumflex artery and right coronary artery myocardial infarction, a longer QRS interval (109 +/- 23 ms vs. 91 +/- 16 ms, P = .02 and 107 +/- 24 ms vs. 93 +/- 19, P = .02) was present. In the latter the PR interval (211 +/- 64 ms vs. 160 +/- 36 ms, P <.001) and ST deviation score (3.6 +/- 1.0 mV vs. 1.7 +/- 1.5 mV, P <.001) were also increased. In the left anterior descending artery group no differences in conduction intervals and ST deviation score were present.

Conclusion: Longer PR and QRS intervals in right coronary artery and left circumflex artery MI fit with the perfusion and activation pattern of the atrioventricular node and the ventricular myocardium. Myocardium perfused by the left anterior descending artery is activated earliest, hiding any intraventricular conduction delay within the QRS complex. Intramural slowed conduction could be a substrate for ischemic VF.
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January 2008