Publications by authors named "Mathias Meine"

75 Publications

Optimizing lead placement for pacing in dyssynchronous heart failure: The patient in the lead.

Heart Rhythm 2021 Feb 16. Epub 2021 Feb 16.

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

Cardiac resynchronization therapy (CRT) greatly reduces morbidity and mortality in patients with dyssynchronous heart failure. However, despite tremendous efforts, response has been variable and can be further improved. Although optimizing left ventricular lead placement (LVLP) is arguably the cornerstone of CRT, the procedure of LVLP using the transvenous approach has remained largely unchanged for more than 2 decades. Improvements have been developed using scar location and electrical and/or mechanical mapping. Interest in conduction system pacing as an alternative to biventricular pacing has emerged recently. Conduction system pacing is promising but may not be suitable for all patients with dyssynchronous heart failure. This review underscores the importance of a patient-tailored approach and discusses the potential applications of both conduction system pacing and targeted biventricular CRT.
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http://dx.doi.org/10.1016/j.hrthm.2021.02.011DOI Listing
February 2021

Development and external validation of prediction models to predict implantable cardioverter-defibrillator efficacy in primary prevention of sudden cardiac death.

Europace 2021 Feb 14. Epub 2021 Feb 14.

Department of Cardiology, Amsterdam UMC, Location AMC, University of Amsterdam, Heart Center, Amsterdam, the Netherlands.

Aims: This study was performed to develop and externally validate prediction models for appropriate implantable cardioverter-defibrillator (ICD) shock and mortality to identify subgroups with insufficient benefit from ICD implantation.

Methods And Results: We recruited patients scheduled for primary prevention ICD implantation and reduced left ventricular function. Bootstrapping-based Cox proportional hazards and Fine and Gray competing risk models with likely candidate predictors were developed for all-cause mortality and appropriate ICD shock, respectively. Between 2014 and 2018, we included 1441 consecutive patients in the development and 1450 patients in the validation cohort. During a median follow-up of 2.4 (IQR 2.1-2.8) years, 109 (7.6%) patients received appropriate ICD shock and 193 (13.4%) died in the development cohort. During a median follow-up of 2.7 (IQR 2.0-3.4) years, 105 (7.2%) received appropriate ICD shock and 223 (15.4%) died in the validation cohort. Selected predictors of appropriate ICD shock were gender, NSVT, ACE/ARB use, atrial fibrillation history, Aldosterone-antagonist use, Digoxin use, eGFR, (N)OAC use, and peripheral vascular disease. Selected predictors of all-cause mortality were age, diuretic use, sodium, NT-pro-BNP, and ACE/ARB use. C-statistic was 0.61 and 0.60 at respectively internal and external validation for appropriate ICD shock and 0.74 at both internal and external validation for mortality.

Conclusion: Although this cohort study was specifically designed to develop prediction models, risk stratification still remains challenging and no large group with insufficient benefit of ICD implantation was found. However, the prediction models have some clinical utility as we present several scenarios where ICD implantation might be postponed.
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http://dx.doi.org/10.1093/europace/euab012DOI Listing
February 2021

Acute recoordination rather than functional hemodynamic improvement determines reverse remodelling by cardiac resynchronisation therapy.

Int J Cardiovasc Imaging 2021 Feb 5. Epub 2021 Feb 5.

University Medical Center Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, The Netherlands.

Purpose: Cardiac resynchronisation therapy (CRT) improves left ventricular (LV) function acutely, with further improvements and reverse remodelling during chronic CRT. The current study investigated the relation between acute improvement of LV systolic function, acute mechanical recoordination, and long-term reverse remodelling after CRT.

Methods: In 35 patients, LV speckle tracking longitudinal strain, LV volumes & ejection fraction (LVEF) were assessed by echocardiography before, acutely within three days, and 6 months after CRT. A subgroup of 25 patients underwent invasive assessment of the maximal rate of LV pressure rise (dP/dt) during CRT-implantation. The acute change in dP/dt, LVEF, systolic discoordination (internal stretch fraction [ISF] and LV systolic rebound stretch [SRSlv]) and systolic dyssynchrony (standard deviation of peak strain times [2DS-SD18]) was studied, and their association with long-term reverse remodelling were determined.

Results: CRT induced acute and ongoing recoordination (ISF from 45 ± 18 to 27 ± 11 and 23 ± 12%, p < 0.001; SRS from 2.27 ± 1.33 to 0.74 ± 0.50 and 0.71 ± 0.43%, p < 0.001) and improved LV function (dP/dt 668 ± 185 vs. 817 ± 198 mmHg/s, p < 0.001; stroke volume 46 ± 15 vs. 54 ± 20 and 52 ± 16 ml; LVEF 19 ± 7 vs. 23 ± 8 and 27 ± 10%, p < 0.001). Acute recoordination related to reverse remodelling (r = 0.601 and r = 0.765 for ISF & SRSlv, respectively, p < 0.001). Acute functional improvements of LV systolic function however, neither related to reverse remodelling nor to the extent of acute recoordination.

Conclusion: Long-term reverse remodelling after CRT is likely determined by (acute) recoordination rather than by acute hemodynamic improvements. Discoordination may therefore be a more important CRT-substrate that can be assessed and, acutely restored.
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http://dx.doi.org/10.1007/s10554-021-02174-7DOI Listing
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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http://dx.doi.org/10.1111/jce.14910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986123PMC
March 2021

Segment length in cine (SLICE) strain analysis: a practical approach to estimate potential benefit from cardiac resynchronization therapy.

J Cardiovasc Magn Reson 2021 Jan 11;23(1). Epub 2021 Jan 11.

Department of Cardiology, Amsterdam Cardiovascular Sciences (ACS), Amsterdam University Medical Centers (AUMC), Location VU University Medical Center, De Boelelaan 1118, 1081 HV, Amsterdam, The Netherlands.

Background: Segment length in cine (SLICE) strain analysis on standard cardiovascular magnetic resonance (CMR) cine images was recently validated against gold standard myocardial tagging. The present study aims to explore predictive value of SLICE for cardiac resynchronization therapy (CRT) response.

Methods And Results: Fifty-seven patients with heart failure and left bundle branch block (LBBB) were prospectively enrolled in this multi-center study and underwent CMR examination before CRT implantation. Circumferential strains of the septal and lateral wall were measured by SLICE on short-axis cine images. In addition, timing and strain pattern parameters were assessed. After twelve months, CRT response was quantified by the echocardiographic change in left ventricular (LV) end-systolic volume (LVESV). In contrast to timing parameters, strain pattern parameters being systolic rebound stretch of the septum (SRS), systolic stretch index (SSI), and internal stretch factor (ISF) all correlated significantly with LVESV change (R - 0.56; R - 0.53; and R - 0.58, respectively). Of all strain parameters, end-systolic septal strain (ESS) showed strongest correlation with LVESV change (R - 0.63). Multivariable analysis showed ESS to be independently related to LVESV change together with age and QRS.

Conclusion: The practicable SLICE strain technique may help the clinician to estimate potential benefit from CRT by analyzing standard CMR cine images without the need for commercial software. Of all strain parameters, end-systolic septal strain (ESS) demonstrates the strongest correlation with reverse remodeling after CRT. This parameter may be of special interest in patients with non-strict LBBB morphology for whom CRT benefit is doubted.
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http://dx.doi.org/10.1186/s12968-020-00701-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798189PMC
January 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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http://dx.doi.org/10.1161/CIRCEP.120.008452DOI Listing
January 2021

Short-Term Variability of the QT Interval Can be Used for the Prediction of Imminent Ventricular Arrhythmias in Patients With Primary Prophylactic Implantable Cardioverter Defibrillators.

J Am Heart Assoc 2020 12 20;9(23):e018133. Epub 2020 Nov 20.

Department of Medical Physiology University Medical Center Utrecht Utrecht The Netherlands.

Background Short-term variability of the QT interval (STV) has been proposed as a novel electrophysiological marker for the prediction of imminent ventricular arrhythmias in animal models. Our aim is to study whether STV can predict imminent ventricular arrhythmias in patients. Methods and Results In 2331 patients with primary prophylactic implantable cardioverter defibrillators, 24-hour ECG Holter recordings were obtained as part of the EU-CERT-ICD (European Comparative Effectiveness Research to Assess the Use of Primary Prophylactic Implantable Cardioverter Defibrillators) study. ECG Holter recordings showing ventricular arrhythmias of >4 consecutive complexes were selected for the arrhythmic groups (n=170), whereas a control group was randomly selected from the remaining Holter recordings (n=37). STV was determined from 31 beats with fiducial segment averaging and calculated as [Formula: see text], where represents the QT interval. STV was determined before the ventricular arrhythmia or 8:00 am in the control group and between 1:30 and 4:30 am as baseline. STV at baseline was 0.84±0.47 ms and increased to 1.18±0.74 ms (<0.05) before the ventricular arrhythmia, whereas the STV in the control group remained unchanged. The arrhythmic patients were divided into three groups based on the severity of the arrhythmia: (1) nonsustained ventricular arrhythmia (n=32), (2) nonsustained ventricular tachycardia (n=134), (3) sustained ventricular tachycardia (n=4). STV increased before nonsustained ventricular arrhythmia, nonsustained ventricular tachycardia, and sustained ventricular tachycardia from 0.80±0.43 ms to 1.18±0.78 ms (<0.05), from 0.90±0.49 ms to 1.14±0.70 ms (<0.05), and from 1.05±0.22 ms to 2.33±1.25 ms (<0.05). This rise in STV was significantly higher in sustained ventricular tachycardia compared with nonsustained ventricular arrhythmia (+1.28±1.05 ms versus +0.24±0.57 ms [<0.05]) and compared with nonsustained ventricular arrhythmia (+0.34±0.87 ms [<0.05]). Conclusions STV increases before imminent ventricular arrhythmias in patients, and the extent of the increase is associated with the severity of the ventricular arrhythmia.
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http://dx.doi.org/10.1161/JAHA.120.018133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763775PMC
December 2020

Evaluation of a Fully Automatic Measurement of Short-Term Variability of Repolarization on Intracardiac Electrograms in the Chronic Atrioventricular Block Dog.

Front Physiol 2020 21;11:1005. Epub 2020 Aug 21.

Department of Medical Physiology, University Medical Center Utrecht, Utrecht, Netherlands.

: Short-term variability (STV) of repolarization of the monophasic action potential duration (MAPD) or activation recovery interval (ARI) on the intracardiac electrogram (EGM) increases abruptly prior to the occurrence of ventricular arrhythmias in the chronic AV-block (CAVB) dog model. Therefore, this parameter might be suitable for continuous monitoring of imminent arrhythmias using the EGM stored on an implanted device. However, 24/7 monitoring would require automatic STV measurement by the device. : To evaluate a newly developed automatic measurement of STV for prediction of dofetilide-induced torsade de pointes (TdP) arrhythmias in the CAVB-dog. : Two retrospective analyses were done on data from recently performed dog experiments. (1) In seven anesthetized CAVB-dogs, the new automatic STV method was compared with the gold standard STV at baseline and after dofetilide administration (0.025 mg/kg in 5 min). (2) The predictive value of the automatic method was compared to currently used STV methods, i.e., slope method and fiducial segment averaging (FSA) method, in 11 inducible (≥3 TdP arrhythmias) and 10 non-inducible CAVB-dogs. : (1) The automatic measurement of STV had good correlation with STV ( = 0.89; < 0.001). Bland-Altman analysis showed a small bias of 0.06 ms with limits of agreement between -0.63 and 0.76 ms. (2) STV of all three methods was significantly different between inducible and non-inducible dogs after dofetilide. The automatic method showed the highest predictive performance with an area under the ROC-curve of 0.93, compared to 0.85 and 0.87 of the slope and FSA methods, respectively. With a threshold of STV set at 1.69 ms, STV measured with the automatic method had a sensitivity of 0.91 and specificity of 0.90 in differentiating inducible from non-inducible subjects. : We developed a fully-automatic method for measurement of STV on the intracardiac EGM that can accurately predict the occurrence of ventricular arrhythmias in the CAVB-dog. Future integration of this method into implantable devices could provide the opportunity for 24/7 monitoring of arrhythmic risk.
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http://dx.doi.org/10.3389/fphys.2020.01005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7472439PMC
August 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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http://dx.doi.org/10.1007/s10840-020-00866-zDOI Listing
September 2020

High-rate pacing guided by short-term variability of repolarization prevents imminent ventricular arrhythmias automatically by an implantable cardioverter-defibrillator in the chronic atrioventricular block dog model.

Heart Rhythm 2020 12 22;17(12):2078-2085. Epub 2020 Jul 22.

Department of Medical Physiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address:

Background: The anesthetized, complete chronic atrioventricular block (CAVB) dog model allows reproducible inducibility of torsades de pointes (TdP) arrhythmias due to ventricular remodeling and after a challenge with an I blocker. High-rate pacing (HRP) prevents ventricular arrhythmias but has long-term detrimental effects on cardiac function when applied continuously. Temporal dispersion of repolarization, quantified as short-term variability (STV), increases before ventricular arrhythmias and has been proposed as a marker to guide HRP.

Objective: The purpose of this proof-of-principle study was to show that automatically determined STV can guide HRP to prevent imminent ventricular arrhythmias.

Methods: Eight CAVB dogs were implanted with an implantable cardioverter-defibrillator (ICD) with software to automatically determine STV (STV) in real time. During HRP, STV was measured offline from right ventricular (RV) electrograms (EGMs) and left ventricular (LV) monophasic action potential durations (MAPDs) (STV). The CAVB dogs were challenged twice with dofetilide (0.025 mg/kg intravenously over 5 minutes or until the first TdP). In experiment 1, the individual STV threshold before the first arrhythmic event was determined and programmed into the ICD. In experiment 2, HRP with 100 bpm was initiated automatically once the STV threshold was reached.

Results: In experiment 1, 8 of 8 dogs had repetitive TdP, and STV increased from 0.96 ± 0.42 ms to 2.10 ± 1.26 ms (P <.05). In experiment 2, all dogs reached the STV threshold. HRP decreased STV from 2.02 ± 1.12 ms to 0.78 ± 0.28 ms, which was accompanied by prevention of TdP in 7 of 8 dogs.

Conclusion: STV can guide HRP automatically by an ICD to prevent ventricular arrhythmias.
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http://dx.doi.org/10.1016/j.hrthm.2020.07.023DOI Listing
December 2020

The value of septal rebound stretch analysis for the prediction of volumetric response to cardiac resynchronization therapy.

Eur Heart J Cardiovasc Imaging 2021 Jan;22(1):37-45

Department of Cardiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands.

Aims: Patient selection for cardiac resynchronization therapy (CRT) may be enhanced by evaluation of systolic myocardial stretching. We evaluate whether systolic septal rebound stretch (SRSsept) derived from speckle tracking echocardiography is a predictor of reverse remodelling after CRT and whether it holds additive predictive value over the simpler visual dyssynchrony assessment by apical rocking (ApRock).

Methods And Results: The association between SRSsept and change in left ventricular end-systolic volume (ΔLVESV) at 6 months of follow-up was assessed in 200 patients. Subsequently, the additive predictive value of SRSsept over the assessment of ApRock was evaluated in patients with and without left bundle branch block (LBBB) according to strict criteria. SRSsept was independently associated with ΔLVESV (β 0.221, P = 0.002) after correction for sex, age, ischaemic cardiomyopathy, QRS morphology and duration, and ApRock. A high SRSsept (≥optimal cut-off value 2.4) also coincided with more volumetric responders (ΔLVESV ≥ -15%) than low SRSsept in the entire cohort (70.0% and 56.4%), in patients with strict LBBB (83.3% vs. 56.7%, P = 0.024), and non-LBBB (70.7% vs. 46.3%, P = 0.004). Moreover, in non-LBBB patients, SRSsept held additional predictive information over the assessment of ApRock alone since patients that showed ApRock and high SRSsept were more often volumetric responder than those with ApRock but low SRSsept (82.8% vs. 47.4%, P = 0.001).

Conclusion: SRSsept is strongly associated with CRT-induced reduction in left ventricular end-systolic volume and holds additive prognostic information over QRS morphology and ApRock. Our data suggest that CRT patient selection may be improved by assessment of SRSsept, especially in the important subgroup without strict LBBB.

Clinical Trial Registration: The MARC study was registered at clinicaltrials.gov: NCT01519908.
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http://dx.doi.org/10.1093/ehjci/jeaa190DOI Listing
January 2021

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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http://dx.doi.org/10.1016/j.jacep.2019.10.009DOI Listing
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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http://dx.doi.org/10.1016/j.jacep.2019.11.018DOI Listing
February 2020

Hemodynamic Optimization in Cardiac Resynchronization Therapy: Should We Aim for dP/dt or Stroke Work?

JACC Clin Electrophysiol 2019 09 31;5(9):1013-1025. Epub 2019 Jul 31.

Department of Cardiology, and Amsterdam Cardiovascular Sciences (ACS), Amsterdam University Medical Centers, Vrije Universiteit, Amsterdam, the Netherlands. Electronic address:

Objectives: This study evaluated the acute effect of dP/dt- versus stroke work (SW)-guided cardiac resynchronization therapy (CRT) optimization and the related acute hemodynamic changes to long-term CRT response.

Background: Hemodynamic optimization may increase benefit from CRT. Typically, maximal left ventricular (LV) pressure rise dP/dt is used as an index of ventricular performance. Alternatively, SW can be derived from pressure-volume (PV) loops.

Methods: Forty-one patients underwent CRT implantation followed by invasive PV loop measurements. The stimulation protocol included 16 LV pacing configurations using each individual electrode of the quadripolar lead with 4 atrioventricular (AV) delays. Conventional CRT was defined as pacing from the distal electrode with an AV delay of approximately 120 ms.

Results: Compared with conventional CRT, dP/dt-guided optimization resulted in a one-third additional dP/dt increase (17 ± 11% vs. 12 ± 9%; p < 0.001). Similarly, SW-guided optimization resulted in a one-third additional SW increase (80 ± 55% vs. 53 ± 48%; p < 0.001). Comparing both optimization strategies, dP/dt favored contractility (8 ± 12% vs. 5 ± 10%; p = 0.015), whereas SW optimization improved ventricular-arterial (VA) coupling (45% vs. 32%; p < 0.001). After 6 months, mean LV ejection fraction (LVEF) change was 10 ± 9% with 23 (56%) patients becoming super-responders to CRT (≥10% LVEF improvement). Although acute changes in SW were predictive for long-term CRT response (area under the curve: 0.78; p = 0.002), changes in dP/dt were not (area under the curve: 0.65; p = 0.112).

Conclusions: PV-guided hemodynamic optimization in CRT results in approximately one-third SW improvement on top of conventional CRT, caused by a mechanism of enhanced VA coupling. In contrast, dP/dt optimization favored LV contractility. Ultimately, acute changes in SW showed larger predictive value for long-term CRT response compared with dP/dt.
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http://dx.doi.org/10.1016/j.jacep.2019.05.020DOI Listing
September 2019

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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http://dx.doi.org/10.1016/j.jelectrocard.2019.07.003DOI Listing
July 2019

Effect of remote monitoring on patient-reported outcomes in European heart failure patients with an implantable cardioverter-defibrillator: primary results of the REMOTE-CIED randomized trial.

Europace 2019 Sep;21(9):1360-1368

Department of Cardiology, University Medical Centre Utrecht, Heidelberglaan 100, GA Utrecht, Utrecht, The Netherlands.

Aims: The European REMOTE-CIED study is the first randomized trial primarily designed to evaluate the effect of remote patient monitoring (RPM) on patient-reported outcomes in the first 2 years after implantation of an implantable cardioverter-defibrillator (ICD).

Methods And Results: The sample consisted of 595 European heart failure patients implanted with an ICD compatible with the Boston Scientific LATITUDE® RPM system. Patients were randomized to RPM plus a yearly in-clinic ICD check-up vs. 3-6-month in-clinic check-ups alone. At five points during the 2-year follow-up, patients completed questionnaires including the Kansas City Cardiomyopathy Questionnaire and Florida Patient Acceptance Survey (FPAS) to assess their heart failure-specific health status and ICD acceptance, respectively. Information on clinical status was obtained from patients' medical records. Linear regression models were used to compare scores between groups over time. Intention-to-treat and per-protocol analyses showed no significant group differences in patients' health status and ICD acceptance (subscale) scores (all Ps > 0.05). Exploratory subgroup analyses indicated a temporary improvement in device acceptance (FPAS total score) at 6-month follow-up for secondary prophylactic in-clinic patients only (P < 0.001). No other significant subgroup differences were observed.

Conclusion: Large clinical trials have indicated that RPM can safely and effectively replace most in-clinic check-ups of ICD patients. The REMOTE-CIED trial results show that patient-reported health status and ICD acceptance do not differ between patients on RPM and patients receiving in-clinic check-ups alone in the first 2 years after ICD implantation.ClinicalTrials.gov Identifier: NCT01691586.
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http://dx.doi.org/10.1093/europace/euz140DOI Listing
September 2019

Multimodality imaging for real-time image-guided left ventricular lead placement during cardiac resynchronization therapy implantations.

Int J Cardiovasc Imaging 2019 Jul 7;35(7):1327-1337. Epub 2019 Mar 7.

Department of Cardiology, University Medical Center Utrecht, Heidelberglaan 100, P.O. Box 85500, 3584 CX, Utrecht, The Netherlands.

This study was performed to evaluate the feasibility of intra-procedural visualization of optimal pacing sites and image-guided left ventricular (LV) lead placement in cardiac resynchronization therapy (CRT). In fifteen patients (10 males, 68 ± 11 years, 7 with ischemic cardiomyopathy and ejection fraction of 26 ± 5%), optimal pacing sites were identified pre-procedurally using cardiac imaging. Cardiac magnetic resonance (CMR) derived scar and dyssynchrony maps were created for all patients. In six patients the anatomy of the left phrenic nerve (LPN) and coronary sinus ostium was assessed via a computed tomography (CT) scan. By overlaying the CMR and CT dataset onto live fluoroscopy, aforementioned structures were visualized during LV lead implantation. In the first nine patients, the platform was tested, yet, no real-time image-guidance was implemented. In the last six patients real-time image-guided LV lead placement was successfully executed. CRT implant and fluoroscopy times were similar to previous procedures and all leads were placed close to the target area but away from scarred myocardium and the LPN. Patients that received real-time image-guided LV lead implantation were paced closer to the target area compared to patients that did not receive real-time image-guidance (8 mm [IQR 0-22] vs 26 mm [IQR 17-46], p = 0.04), and displayed marked LV reverse remodeling at 6 months follow up with a mean LVESV change of -30 ± 10% and a mean LVEF improvement of 15 ± 5%. Real-time image-guided LV lead implantation is feasible and may prove useful for achieving the optimal LV lead position.
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http://dx.doi.org/10.1007/s10554-019-01574-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6598949PMC
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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http://dx.doi.org/10.1161/CIRCEP.118.006497DOI Listing
December 2018

Remote monitoring of implantable cardioverter defibrillators: Patient experiences and preferences for follow-up.

Pacing Clin Electrophysiol 2019 02 2;42(2):120-129. Epub 2019 Jan 2.

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

Background: Patient satisfaction with remote patient monitoring (RPM) of implantable cardioverter defibrillators (ICDs) seems to be high, yet knowledge on long-term patient experiences is limited. The European REMOTE-CIED study explored patients' experiences with RPM, examined patient's preferences for ICD follow-up, and identified determinants of patient's preferences in the first 2 years postimplantation.

Methods: European heart failure patients (N = 300; median age = 66 years [interquartile range (IQR) = 59-73], and 22% female) with a first-time ICD received a Boston Scientific LATITUDE RPM system (Marlborough, MA, USA) and had scheduled in-clinic follow-ups once a year. Patients completed questionnaires at 1-2 weeks and also at 3, 6, 12, and 24 months postimplantation and clinical data were obtained from their medical records. Patient evaluation data were analyzed descriptively, and Student's t-tests/Man-Whitney U tests or Chi-square tests/Fisher's exact tests were performed to examine determinants of patient preferences.

Results: At 2 years postimplantation, the median patient satisfaction score with the RPM system was 9 out of 10 (IQR = 8-10), despite 53% of the patients experiencing issues (eg, failure to transmit data). Of the 221 patients who reported their follow-up preferences, 43% preferred RPM and 19% preferred in-clinic follow-up. Patients with a preference for RPM were more likely to be higher educated (P = 0.04), employed (P = 0.04), and equipped with a new LATITUDE model (P = 0.04), but less likely to suffer from chronic obstructive pulmonary disease (P = 0.009).

Conclusion: In general, patients were highly satisfied with RPM, but a subgroup preferred in-clinic follow-up. Therefore, physicians should include patients' concerns and preferences in the decision-making process, to tailor device follow-up to individual patients' needs and preferences.
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http://dx.doi.org/10.1111/pace.13574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849564PMC
February 2019

Atrioventricular optimization in cardiac resynchronization therapy with quadripolar leads: should we optimize every pacing configuration including multi-point pacing?

Europace 2019 Jan;21(1):e11-e19

Department of Cardiology, University Medical Center Utrecht, Heidelberglaan 100, CX Utrecht, The Netherlands.

Aims: This study aims to define an atrioventricular (AV) delay optimization method for cardiac resynchronization therapy (CRT) with a quadripolar left ventricular (LV) lead based on intrinsic conduction intervals.

Methods And Results: Heart failure patients with a left bundle branch block underwent CRT implantation with a quadripolar LV lead. Invasive LV pressure-volume loops were recorded during four biventricular and three multi-point pacing (MPP) settings, using four patient-specific paced AV delays. Haemodynamic response was defined as change in stroke work (Δ%SW) compared to intrinsic rhythm and was related to the following conduction intervals: right atrial pacing to right ventricular sensing interval (RAp-RVs), Q to LV sensing interval normalized to QRS duration (QLV/QRSd), PR-interval, and P-wave duration. In 44 patients, the largest Δ%SW (104 ± 76%) occurred at a paced AV delay of 128 ± 32 ms, at 47 ± 9% of RAp-RVs. Optimal AV delay of biventricular pacing (126 ± 26 ms) did not differ from MPP (126 ± 21 ms, P = 0.29). Intra-class correlation coefficient between optimal AV delays of different pacing configurations was 0.64 (0.45-0.78, P < 0.001). Although not statistically significant, Δ%SW at 50% of RAp-RVs (98 ± 74%) was closer to the maximal achievable Δ%SW increase than a fixed interval of 120 ms (96 ± 73%, P = 0.60). RAp-RVs, QLV/QRSd, PR interval, and P-wave duration were associated with the optimal AV delay in univariate analysis, but only RAp-RVs remained significantly associated in multivariate analysis (R = 0.69).

Conclusion: The AV delay that provides highest haemodynamic response is similar for various LV pacing configurations and for MPP. An AV delay ∼50% of RAp-RVs creates an acute haemodynamic response close to the maximal patient-specific response.
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http://dx.doi.org/10.1093/europace/euy138DOI Listing
January 2019

Strain imaging to predict response to cardiac resynchronization therapy: a systematic comparison of strain parameters using multiple imaging techniques.

ESC Heart Fail 2018 12 26;5(6):1130-1140. Epub 2018 Jul 26.

Department of Cardiology, and Amsterdam Cardiovascular Sciences (ACS), VU University Medical Center, Amsterdam, The Netherlands.

Aims: Various strain parameters and multiple imaging techniques are presently available including cardiovascular magnetic resonance (CMR) tagging (CMR-TAG), CMR feature tracking (CMR-FT), and speckle tracking echocardiography (STE). This study aims to compare predictive performance of different strain parameters and evaluate results per imaging technique to predict cardiac resynchronization therapy (CRT) response.

Methods And Results: Twenty-seven patients were prospectively enrolled and underwent CMR and echocardiographic examination before CRT implantation. Strain analysis was performed in circumferential (CMR-TAG, CMR-FT, and STE-circ) and longitudinal (STE-long) orientations. Regional strain values, parameters of dyssynchrony, and discoordination were calculated. After 12 months, CRT response was measured by the echocardiographic change in left ventricular (LV) end-systolic volume (LVESV). Twenty-six patients completed follow-up; mean LVESV change was -29 ± 27% with 17 (65%) patients showing ≥15% LVESV reduction. Measures of dyssynchrony (SD-TTP ) and discoordination (ISF ) were strongly related to CRT response when using CMR-TAG (R 0.61 and R 0.57, respectively), but showed poor correlations for CMR-FT and STE (all R  ≤ 0.32). In contrast, the end-systolic septal strain (ESS ) parameter showed a consistent high correlation with LVESV change for all techniques (CMR-TAG R 0.60; CMR-FT R 0.50; STE-circ R 0.43; and STE-long R 0.43). After adjustment for QRS duration and QRS morphology, ESS remained an independent predictor of response per technique.

Conclusions: End-systolic septal strain was the only parameter with a consistent good relation to reverse remodelling after CRT, irrespective of assessment technique. In clinical practice, this measure can be obtained by any available strain imaging technique and provides predictive value on top of current guideline criteria.
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http://dx.doi.org/10.1002/ehf2.12335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6300826PMC
December 2018

Pressure-Volume Loop Analysis of Multipoint Pacing With a Quadripolar Left Ventricular Lead in Cardiac Resynchronization Therapy.

JACC Clin Electrophysiol 2018 07 28;4(7):881-889. Epub 2018 Mar 28.

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

Objectives: This study aimed to compare multipoint pacing (MPP) to optimal biventricular pacing with a quadripolar left ventricular (LV) lead and find factors associated with hemodynamic response to MPP.

Background: MPP with a quadripolar LV lead may increase response to cardiac resynchronization therapy.

Methods: Heart failure patients with a left bundle branch block underwent cardiac resynchronization therapy implantation. Q to LV sensing interval divided by the intrinsic QRS duration was measured. Invasive pressure-volume loops were assessed during 4 biventricular pacing settings and 3 MPP settings, using 4 atrioventricular delays. Hemodynamic response was defined as change in stroke work (Δ%SW) compared with baseline measurements during intrinsic conduction. Δ%SW of MPP was compared with conventional biventricular pacing using the distal electrode and the electrode with highest Δ%SW (BIV-OPT).

Results: Forty-three patients were analyzed (age 66 ± 10 years, 63% men, 30% ischemic cardiomyopathy, LV ejection fraction 29 ± 8%, and QRS duration 175 ± 13 ms). Q to local LV sensing interval corrected for QRS duration was 84 ± 8%, and variation between LV electrodes was 9 ± 5%. Compared with conventional biventricular pacing using the distal electrode, MPP showed a significant higher increase of SW (Δ%SW +15 ± 35%; p < 0.05) with a large interindividual variation. There was no significant difference in Δ%SW with MPP compared with BIV-OPT (-5 ± 24%; p = 0.19). Male sex and low LV ejection fraction were associated with increase in Δ%SW due to MPP versus BIV-OPT in multivariate analysis, while ischemic cardiomyopathy was only associated in univariate analysis.

Conclusions: Optimization of the pacing site of a quadripolar LV lead is more important than to program MPP. However, specific subgroups (i.e., especially men) may benefit substantially from MPP.
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http://dx.doi.org/10.1016/j.jacep.2018.02.005DOI Listing
July 2018

Can We Use the Intrinsic Left Ventricular Delay (QLV) to Optimize the Pacing Configuration for Cardiac Resynchronization Therapy With a Quadripolar Left Ventricular Lead?

Circ Arrhythm Electrophysiol 2018 03;11(3):e005912

From the Department of Cardiology, University Medical Center Utrecht, The Netherlands (W.M.v.E., M.J.C., P.A.D., M.M.); Department of Cardiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (A.Z., A.C.v.R., C.P.A.); Department of Cardiology, Maastricht University Medical Center, The Netherlands (U.C.N., K.V.); and Department of Physiology, CARIM (Cardiovascular Research Institute Maastricht), Maastricht University, The Netherlands (U.C.N., F.W.P.).

Background: Previous studies indicated the importance of the intrinsic left ventricular (LV) electric delay (QLV) for optimal benefit to cardiac resynchronization therapy. We investigated the use of QLV for achieving optimal acute hemodynamic response to cardiac resynchronization therapy with a quadripolar LV lead.

Methods And Results: Forty-eight heart failure patients with a left bundle branch block were prospectively enrolled (31 men; age, 66±10 years; LV ejection fraction, 28±8%; QRS duration, 176±14 ms). Immediately after cardiac resynchronization therapy implantation, invasive LV pressure-volume loops were recorded during biventricular pacing with each separate electrode at 4 atrioventricular delays. Acute cardiac resynchronization therapy response, measured as change in stroke work (Δ%SW) compared with intrinsic conduction, was related to intrinsic interval between Q on the ECG and LV sensing delay (QLV), normalized for QRS duration (QLV/QRSd), and electrode position. QLV/QRSd was 84±9% and variation between the 4 electrodes 9±5%. Δ%SW was 89±64% and varied by 39±36% between the electrodes. In univariate analysis, an anterolateral or lateral electrode position and a high QLV/QRSd had a significant association with a large Δ%SW (all <0.01). In a combined model, only QLV/QRSd remained significantly associated with Δ%SW (<0.05). However, a direct relation between QLV/QRSd and Δ%SW was only seen in 24 patients, whereas 24 patients showed an inverse relation.

Conclusions: The large variation in acute hemodynamic response indicates that the choice of the stimulated electrode on a quadripolar lead is important. Although QLV/QRSd was associated with acute hemodynamic response at group level, it cannot be used to select the optimal electrode in the individual patient.
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http://dx.doi.org/10.1161/CIRCEP.117.005912DOI Listing
March 2018

Nationwide Longitudinal Follow-Up of Riata Leads Under Advisory at 3 Annual Screenings: Report From the Netherlands Heart Rhythm Association Device Advisory Committee.

JACC Clin Electrophysiol 2017 08 1;3(8):887-893. Epub 2017 Mar 1.

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

Objectives: This study sought to determine prospectively the rate of conductor externalization (CE), and whether this was associated with electrical failure.

Background: The Riata family of defibrillator leads was placed under U.S. Food and Drug Administration advisory as of November 28, 2011 because of high rates of CE.

Methods: A nationwide cohort established in 2012 of 1,029 patients with recalled Riata leads with 147 CE were followed until death, lead discontinuation, or 3 annual screenings with fluoroscopy and device interrogation.

Results: Follow-up of 882 patients with normal baseline fluoroscopy revealed incident overt CE in 95 leads (11%) after median risk time of 2.9 years, yielding an incidence rate of 4.9 (95% confidence interval [CI]: 3.9 to 5.9) per 100 patient-years. The incidence rate was significantly higher in 8-F Riata leads than in 7-F Riata ST leads (7.0 vs. 3.2 per 100 patient-years; p < 0.001). Electrical follow-up demonstrated electrical abnormality in 77 leads, resulting in an incidence rate of 4.0 (95% CI: 3.2 to 5.0) per 100 patient-years. The incidence rate of electrical abnormalities was not different between leads without CE and those with CE (3.9 vs. 5.2 per 100 patient-years; p = 0.39).

Conclusions: The development of CE is progressive in nature with an incidence rate of new CE of 4.9 per 100 patient-years, with a higher rate for 8-F Riata leads than for 7-F Riata ST leads. Despite the high rate of structural failure, no association between development of CE and electrical failure was observed.
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http://dx.doi.org/10.1016/j.jacep.2016.12.011DOI Listing
August 2017

Regional Left Ventricular Electrical Activation and Peak Contraction Are Closely Related in Candidates for Cardiac Resynchronization Therapy.

JACC Clin Electrophysiol 2017 08 2;3(8):854-862. Epub 2017 Aug 2.

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

Objectives: This study determined the relationship between the timing of left ventricular (LV) electrical activation and peak contraction at potential LV pacing locations in candidates for cardiac resynchronization therapy (CRT).

Background: Targeting the LV lead to the region of latest electrical activation or the segment of latest peak contraction has both been shown to improve CRT response. Whether these regions correspond within CRT patients is uncertain.

Methods: Twenty-eight consecutive CRT candidates underwent intraprocedural coronary venous electroanatomic mapping using EnSite NavX. Peak contraction time of the mapped LV regions was determined using longitudinal strain derived from speckle tracking echocardiography. Electrical activation and peak contraction times were correlated on a per patient basis, and the regions of latest electrical activation and latest peak contraction were compared.

Results: Successful measurements by both techniques allowed analysis in 23 of 28 patients. There was a strong positive correlation between electrical activation and peak contraction times within each patient (R = 0.85 ± 0.09). However, the magnitude of the electrical activation-peak contraction relationship varied greatly among patients (slope of regression line: 4.05 ± 3.23). The regions of latest electrical activation and latest peak contraction corresponded in 19 of 23 (83%) patients and were adjacent in 4 patients.

Conclusions: There is a close relationship between the timing of LV electrical activation and peak contraction in CRT candidates. This finding suggests that a strategy of determining the latest activated LV region based on speckle tracking echocardiography corresponds to that based on intracardiac measurements of electrical activation.
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http://dx.doi.org/10.1016/j.jacep.2017.03.014DOI Listing
August 2017

Decreased Quality of Life Due to Driving Restrictions After Cardioverter Defibrillator Implantation.

J Cardiovasc Nurs 2018 Sep/Oct;33(5):474-480

Ivy Timmermans, MSc PhD student and Medical Psychologist, Department of Cardiology, University Medical Center Utrecht, and Department of Medical Psychology, Center of Research on Psychology in Somatic Diseases, Tilburg University, The Netherlands. Niels Jongejan, MSc Physician Assistant, Department of Cardiology, University Medical Center Utrecht, The Netherlands. Mathias Meine, MD, PhD Physician, Department of Cardiology, University Medical Center Utrecht, The Netherlands. Pieter Doevendans, MD, PhD Department of Cardiology, University Medical Center Utrecht, and Netherlands Heart Institute, Utrecht, The Netherlands. Anton Tuinenburg, MD, PhD Physician, Department of Cardiology, University Medical Center Utrecht, The Netherlands. Henneke Versteeg, PhD Assistant Professor and Medical Psychologist, Department of Cardiology, University Medical Center Utrecht, The Netherlands.

Background: Driving restrictions for patients with an implantable cardioverter defibrillator (ICD) may require significant lifestyle adjustment and affect patients' psychological well-being. This study explored the prevalence of, and factors associated with, patient-reported decrease in quality of life due to driving restrictions in the first 2 months postimplantation.

Methods: Dutch ICD patients (N = 334; median age, 64 [interquartile range, 55-70) years; 81% male) completed questionnaires at the time of implantation and 4 months postimplantation, assessing their sociodemographic, psychological, and driving-related characteristics. Clinical baseline data were retrieved from patients' medical records.

Results: Nearly half of the patients (49%) reported decreased quality of life due to driving restrictions. Patient-reported reasons included dependency on others/public transport, (social) isolation, and inability to work. Patients reporting decreased quality of life were more likely to be younger (P = .01), to feel that the restriction lasts too long (P = .004), to have considered ICD refusal because of the restrictions (P = .03), and to have Type D personality (P = .02), anxiety (P = .05), depression (P = .003), and ICD-related concerns (P = .02). Multivariable analysis showed that being younger than 60 years (odds ratio [OR], 2.30; 95% confidence interval [CI], 1.09-4.88; P = .03), feeling the driving restriction lasts too long (OR, 1.77; 95% CI, 1.23-2.55; P = .002), and depression (OR, 3.21; 95% CI, 1.09-9.47; P = .035) were independently associated with decreased quality of life due to driving restrictions.

Conclusions: This study indicated that a significant group of ICD patients may experience decreased quality of life because of the driving restrictions postimplantation. The restrictions seem to particularly affect patients who are younger and distressed and patients who feel that the restriction lasts too long.
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http://dx.doi.org/10.1097/JCN.0000000000000474DOI Listing
November 2019

Patient-reported causes of heart failure in a large European sample.

Int J Cardiol 2018 05 6;258:179-184. Epub 2018 Feb 6.

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

Background: Patients diagnosed with chronic diseases develop perceptions about their disease and its causes, which may influence health behavior and emotional well-being. This is the first study to examine patient-reported causes and their correlates in patients with heart failure.

Methods: European heart failure patients (N = 595) completed questionnaires, including the Brief Illness Perceptions Questionnaire. Using deductive thematic analysis, patient-reported causes were categorized into physical, natural, behavioral, psychosocial, supernatural and other. Clinical data were collected from medical records.

Results: Patients who did not report any cause (11%) were on average lower educated and participated less often in cardiac rehabilitation. The majority of the remaining patients reported physical causes (46%, mainly comorbidities), followed by behavioral (38%, mainly smoking), psychosocial (35%, mainly (work-related) stress), and natural causes (32%, mainly heredity). There were socio-demographic, clinical and psychological group differences between the various categories, and large discrepancies between prevalence of physical risk factors according to medical records and patient-reported causes; e.g. 58% had hypertension, while only 5% reported this as a cause. Multivariable analyses indicated trends towards associations between physical causes and poor health status (Odds ratio (OR) = 1.41, 95% confidence interval (95% CI) = 0.95-2.09, p = 0.09), psychosocial causes and psychological distress (OR = 1.54, 95% CI = 0.94-2.51, p = 0.09), and behavioral causes and a less threatening view of heart failure (OR = 0.64, 95% CI = 0.40-1.01, p = 0.06).

Conclusion: European patients most frequently reported comorbidities, smoking, stress, and heredity as heart failure causes, but their causal understanding may be limited. There were trends towards associations between patient-reported causes and health status, psychological distress, and illness perceptions.
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http://dx.doi.org/10.1016/j.ijcard.2018.01.113DOI Listing
May 2018

Beat-to-beat variations in activation-recovery interval derived from the right ventricular electrogram can monitor arrhythmic risk under anesthetic and awake conditions in the canine chronic atrioventricular block model.

Heart Rhythm 2018 03 13;15(3):442-448. Epub 2017 Nov 13.

Department of Medical Physiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address:

Background: In the chronic atrioventricular block (CAVB) dog model, beat-to-beat variation of repolarization in the left ventricle (LV) quantified as short-term variability of the left monophasic action potential duration (STV) increases abruptly upon challenge with a proarrhythmic drug. This increase occurs before the first ectopic beat (EB), specifically in subjects who demonstrate subsequent repetitive torsades de pointes arrhythmias (TdP).

Objective: The purpose of this study was to demonstrate that STV is feasible to monitor arrhythmic risk through use of the intracardiac electrogram (EGM) derived from the right ventricular (RV) lead from pacemakers or implantable cardioverter-defibrillators.

Methods: In 30 anaesthetized, inducible (≥3 TdP) CAVB dogs, STV between LV and RV monophasic action potential duration (STV and STV) was compared. In prospectively enrolled CAVB dogs, STV of the activation-recovery interval (ARI) derived from the RV EGM (STV) was measured before and after a challenge with dofetilide under anesthesia (2a; n = 10) and cisapride under awake conditions (2b; n = 8).

Results: Both STV and STV increased before the first EB (1.29 ± 0.58 ms to 3.05 ± 1.70 ms and 1.11 ± 0.53 ms to 2.18 ± 1.43 ms, respectively; P = 0.001). STV increased from 2.82 ± 0.33 ms to 3.77 ± 0.69 ms (P = .001). Inducible subjects (4/8) showed an increase in STV from 2.65 ± 0.55 ms to 3.45 ± 0.33 ms (in the first hour; P = .02) and 4.20 ± 1.33 ms (before the first EB; P = .04).

Conclusion: Behavior of STV from the RV and LV is comparable. STV increases significantly before the occurrence of an arrhythmia in awake and anaesthetized conditions. This finding can be integrated into devices to monitor arrhythmic risk.
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http://dx.doi.org/10.1016/j.hrthm.2017.11.011DOI Listing
March 2018

Comparison of strain parameters in dyssynchronous heart failure between speckle tracking echocardiography vendor systems.

Cardiovasc Ultrasound 2017 Oct 18;15(1):25. Epub 2017 Oct 18.

Department of Cardiology, University Medical Centre Utrecht, P.O. Box 855500, 3508, GA, Utrecht, The Netherlands.

Background: Although mechanical dyssynchrony parameters derived by speckle tracking echocardiography (STE) may predict response to cardiac resynchronization therapy (CRT), comparability of parameters derived with different STE vendors is unknown.

Methods: In the MARC study, echocardiographic images of heart failure patients obtained before CRT implantation were prospectively analysed with vendor specific STE software (GE EchoPac and Philips QLAB) and vendor-independent software (TomTec 2DCPA). Response was defined as change in left ventricular (LV) end-systolic volume between examination before and six-months after CRT implantation. Basic longitudinal strain and mechanical dyssynchrony parameters (septal to lateral wall delay (SL-delay), septal systolic rebound stretch (SRSsept), and systolic stretch index (SSI)) were obtained from either separate septal and lateral walls, or total LV apical four chamber. Septal strain patterns were categorized in three types. The coefficient of variation and intra-class correlation coefficient (ICC) were analysed. Dyssynchrony parameters were associated with CRT response using univariate regression analysis and C-statistics.

Results: Two-hundred eleven patients were analysed. GE-cohort (n = 123): age 68 years (interquartile range (IQR): 61-73), 67% male, QRS-duration 177 ms (IQR: 160-192), LV ejection fraction: 26 ± 7%. Philips-cohort (n = 88): age 67 years (IQR: 59-74), 60% male, QRS-duration: 179 ms (IQR: 166-193), LV ejection fraction: 27 ± 8. LV derived peak strain was comparable in the GE- (GE: -7.3 ± 3.1%, TomTec: -6.4 ± 2.8%, ICC: 0.723) and Philips-cohort (Philips: -7.7 ± 2.7%, TomTec: -7.7 ± 3.3%, ICC: 0.749). SL-delay showed low ICC values (GE vs. TomTec: 0.078 and Philips vs. TomTec: 0.025). ICC's of SRSsept and SSI were higher but only weak (GE vs. TomTec: SRSsept: 0.470, SSI: 0.467) (Philips vs. QLAB: SRSsept: 0.419, SSI: 0.421). Comparability of septal strain patterns was low (Cohen's kappa, GE vs. TomTec: 0.221 and Philips vs. TomTec: 0.279). Septal strain patterns, SRSsept and SSI were associated with changes in LV end-systolic volume for all vendors. SRSsept and SSI had relative varying C-statistic values (range: 0.530-0.705) and different cut-off values between vendors.

Conclusions: Although global longitudinal strain analysis showed fair comparability, assessment of dyssynchrony parameters was vendor specific and not applicable outside the context of the implemented platform. While the standardization taskforce took an important step for global peak strain, further standardization of STE is still warranted.
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http://dx.doi.org/10.1186/s12947-017-0116-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5648447PMC
October 2017