Publications by authors named "Alwin Zweerink"

25 Publications

  • Page 1 of 1

Crossing of strength-duration curves with His bundle pacing and impact of pacing mode on thresholds.

HeartRhythm Case Rep 2021 Feb 28;7(2):123-126. Epub 2020 Nov 28.

Department of Cardiology, University Hospital of Geneva, Geneva, Switzerland.

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http://dx.doi.org/10.1016/j.hrcr.2020.11.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897745PMC
February 2021

His-Optimized Cardiac Resynchronization Therapy With Ventricular Fusion Pacing for Electrical Resynchronization in Heart Failure.

JACC Clin Electrophysiol 2021 Feb 19. Epub 2021 Feb 19.

Department of Cardiology, University Hospital of Geneva, Geneva, Switzerland. Electronic address:

Objectives: This study sought to evaluate the effectiveness of His-optimized cardiac resynchronization therapy (HOT-CRT) for reducing left ventricular activation time (LVAT) compared to His bundle pacing (HBP) and biventricular (BiV) pacing (including multipoint pacing [MPP]), using electrocardiographic (ECG) imaging.

Background: HBP may correct bundle branch block (BBB) and has shown encouraging results for providing CRT. However, HBP does not correct BBB in all patients and may be combined with univentricular or BiV fusion pacing to deliver HOT-CRT to maximize resynchronization.

Methods: Nineteen patients with a standard indication for CRT, implanted with HBP without correction of BBB and BiV (n = 14) or right ventricular (n = 5) leads, were prospectively enrolled. Patients underwent ECG imaging while pacing in different configurations using different LV electrodes and at different HBP ventricular pacing (VP) delays. The primary endpoint was reduction in LVAT with HOT-CRT, and the secondary endpoints included various other dys-synchrony measurements including right ventricular activation time (RVAT).

Results: Compared to HBP, HOT-CRT reduced LVAT by 21% (-17 ms [95% confidence interval [CI]: -25 to -9 ms]; p < 0.001) and outperformed BiV by 24% (-22 ms [95% CI: -33 to -10 ms]; p = 0.002) and MPP by 13% (-11 ms [95% CI: -21 to -1 ms]; p = 0.035). Relative to HBP, HOT-CRT also reduced RVAT by 7% (-5 ms [95% CI: -9 to -1 ms; p = 0.035) in patients with right BBB, whereas RVAT was increased by BiV. The other electrical dyssynchrony measurements also improved with HOT-CRT.

Conclusions: HOT-CRT acutely improves ventricular electrical synchrony beyond BiV and MPP. The impact of this finding needs to be evaluated further in studies with clinical follow-up. (Electrical Resynchronization and Acute Hemodynamic Effects of Direct His Bundle Pacing Compared to Biventricular Pacing; NCT03452462).
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http://dx.doi.org/10.1016/j.jacep.2020.11.029DOI Listing
February 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

Cryoablation vs. radiofrequency ablation of the atrioventricular node in patients with His-bundle pacing.

Europace 2021 Mar;23(3):421-430

Department of Cardiology, University Hospital of Geneva, Rue Gabrielle-Perret-Gentil 4, CH-1211 Geneva, Switzerland.

Aims: Radiofrequency ablation (RFA) of the atrioventricular node (AVN) with His-bundle pacing (HBP) can cause rise in capture thresholds. Cryoablation (CRYO) may offer reversibility in case of threshold rise but has never been tested for AVN ablation in this setting. Our aim was to compare procedural characteristics and outcome of CRYO compared with RFA for AVN ablation in patients with HBP.

Methods And Results: Forty-four patients with HBP underwent AVN ablation for an 'ablate and pace' indication. Cryoablation was performed in the first 22 patients and RFA in the following 22 patients. Procedural characteristics, success rates, and change in His capture thresholds were compared between groups. Distance from the ablation site to the His lead was measured using biplane fluoroscopy. Acute success was 100% with both strategies. Median procedural duration was significantly longer for CRYO {50 [interquartile range (IQR) 38-63] min} compared with RFA [36 (IQR, 30-41) min; P = 0.027]. An acute threshold rise of ≥1 V was observed in four CRYO (one complete loss of capture) and three RFA patients (P = 0.38), with all of the applications being within 6 mm of the His lead tip. During follow-up, nine patients had AVN re-conduction (six CRYO vs. three RFA; P = 0.58), but only four patients required a redo procedure (all CRYO; P = 0.09).

Conclusion: Cryoablation does not offer any advantage over RFA for AVN ablation in patients with HBP and tended to require more redo procedures. If possible, a distance of ≥6 mm should be maintained from the His lead tip to avoid a rise in capture thresholds.
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http://dx.doi.org/10.1093/europace/euaa344DOI Listing
March 2021

Next-level examination of His-optimized cardiac resynchronization therapy by noninvasive electrocardiographic activation mapping.

J Cardiovasc Electrophysiol 2020 11 16;31(11):3065-3066. Epub 2020 Sep 16.

Department of Cardiology, University Hospital of Geneva, Geneva, Switzerland.

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http://dx.doi.org/10.1111/jce.14736DOI Listing
November 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

[His bundle pacing : the pursuit of physiologic ventricular stimulation].

Rev Med Suisse 2020 Jun;16(696):1159-1164

Unité de stimulation cardiaque, Département de cardiologie, HUG, 1211 Genève 14.

Traditional right ventricular pacing has been pursued for decades. As the deleterious effects of long-term right ventricular pacing have become evident, there is growing interest in a more physiological type of pacing like His bundle pacing. As it engages conduction over the His-Purkinje system, His bundle pacing results in normal electrical activation of the ventricles and avoids dyssynchrony (and its negative effects on left ventricular function) in the long term. This pacing technique has become a routine procedure at the University Hospital of Geneva. This article overviews our experience with His bundle pacing and aims to familiarize the reader with this novel pacing technique that will be increasingly used in their patients.
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June 2020

Programming and follow-up of patients with His bundle pacing.

Herzschrittmacherther Elektrophysiol 2020 Jun 30;31(2):177-182. Epub 2020 Apr 30.

Cardiac Pacing Unit, Cardiology Departement, University Hospital of Geneva, Rue Gabrielle-Perret-Gentil 4, 1211, Genève, Switzerland.

His bundle pacing (HBP) is being increasingly adopted worldwide, with the aim of providing more physiological stimulation of the heart as opposed to right ventricular pacing or as an alternative to cardiac resynchronization therapy (CRT). Current devices are not specifically designed for HBP, which gives rise to programming challenges. This article aims to provide practical recommendations for HBP programming and follow-up.
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http://dx.doi.org/10.1007/s00399-020-00677-9DOI Listing
June 2020

His bundle pacing to avoid electrical dyssynchrony with traditional right ventricular pacing: Importance of heart size.

Int J Cardiol 2020 07 13;311:54-57. Epub 2020 Apr 13.

Department of Cardiology, University Hospital of Geneva, Geneva, Switzerland. Electronic address:

Background: His Bundle Pacing (HBP) is attracting interest as an alternative to traditional right ventricular pacing (RVP) because it avoids electrical dyssynchrony induced by RVP. This study aims to evaluate the effect of heart size on benefit from HBP compared to RVP in terms of achieving electrical synchrony.

Methods: Fifty-nine patients with HBP and a RVP back-up lead underwent pre-implantation echocardiography to measure left ventricular end-diastolic volume (LVEDV). Electrical benefit from HBP was calculated as the difference in QRS duration (QRSd) between RVP and HPB.

Results: LVEDV was significantly correlated with RVP QRSd (R = 0.53; p < 0.001). In contrast, LVEDV was unrelated to HBP QRSd (R = 0.16; p = 0.24). Electrical benefit of HBP over RVP was directly related with LVEDV (R = 0.43; p = 0.001). In addition, electrical benefit of HBP was larger for patients with LVEDV above median (99 mL) than below (49 ± 27 ms vs. 34 ± 19 ms, p = 0.014).

Conclusions: This study is the first to demonstrate that patients with larger LV size may benefit most from HBP as a replacement of traditional RVP to avoid electrical dyssynchrony. Our results indicate that LV size impacts QRSd during RVP with slow cell-to-cell conduction, whereas it does not affect electrical synchrony during HBP with fast His-Purkinje conduction.
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http://dx.doi.org/10.1016/j.ijcard.2020.04.025DOI Listing
July 2020

Shifting diastolic filling from right to left in non-obstructive hypertrophic cardiomyopathy: exploring new indications for biventricular pacing.

Eur J Heart Fail 2020 07 24;22(7):1273-1275. Epub 2020 Feb 24.

Department of Cardiology, University Hospital of Geneva, Geneva, Switzerland.

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http://dx.doi.org/10.1002/ejhf.1775DOI Listing
July 2020

Correlation between septal midwall late gadolinium enhancement on CMR and conduction delay on ECG in patients with nonischemic dilated cardiomyopathy.

Int J Cardiol Heart Vasc 2020 Feb 25;26:100474. Epub 2020 Jan 25.

Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Cardiology, Amsterdam Cardiovascular Sciences, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.

Background: Septal midwall late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) is a characteristic finding in nonischemic dilated cardiomyopathy (DCM) and is associated with adverse cardiac events. QRS-prolongation in DCM is also frequently present and a predictor of arrhythmic events and mortality. Since the His-Purkinje fibres are located in the interventricular septum, QRS-prolongation may directly result from septal fibrosis, visualized by LGE. Our aim was to study the correlation of the presence and extent of septal midwall LGE and QRS-duration.

Methods: DCM-patients with left ventricular (LV) dysfunction (LVEF < 50%) were included. LV volumes, systolic function and nonischemic septal midwall LGE, defined as patchy or stripe-like LGE in the septal segments, were quantified. QRS-duration on standard 12-lead ECG was measured.

Results: 165 DCM-patients were included (62% male, mean age 59 ± 15 years) with a median LVEF of 36% [24-44]. Fifty-one patients (31%) demonstrated septal midwall LGE with a median extent of 8.1 gram [4.3-16.8]. Patients with midwall LGE had increased LV end-diastolic volumes (EDV) 248 mL [193-301] vs. 193 mL [160-239], p < 0.001) and lower LVEF (26% [18-35] vs. 40% [32-45], p < 0.001). Median QRS-duration was 110 ms [95-146] without a correlation to the presence nor extent of midwall LGE. QRS-duration was moderately correlated with LV-dilation and mass (respectively r = 0.35, p < 0.001 and r = 0.30, p < 0.001).

Conclusion: In DCM-patients, QRS-prolongation and septal midwall LGE are frequently present and often co-exist. However, they are not correlated. This suggests that the assessment of LGE-CMR has complementary value to ECG evaluation in the clinical assessment and risk stratification of DCM-patients.
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http://dx.doi.org/10.1016/j.ijcha.2020.100474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6994302PMC
February 2020

Efficiency is key.

Eur Heart J Cardiovasc Imaging 2020 02;21(2):154-156

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

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http://dx.doi.org/10.1093/ehjci/jez260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029764PMC
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

Myocardial adaptation after surgical therapy differs for aortic valve stenosis and hypertrophic obstructive cardiomyopathy.

Int J Cardiovasc Imaging 2019 Jun 1;35(6):1089-1100. Epub 2019 Mar 1.

Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Cardiovascular Sciences, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.

Surgical therapies in aortic valve stenosis (AVS) and hypertrophic obstructive cardiomyopathy (HOCM) aim to relief intraventricular pressure overload and improve clinical outcome. It is currently unknown to what extent myocardial adaptation concurs with restoration of intraventricular pressures, and whether this is similar in both patient groups. The aim of this study was to investigate changes in myocardial adaptation after surgical therapies for AVS and HOCM. Ten AVS and ten HOCM patients were enrolled and underwent cardiac magnetic resonance cine imaging and myocardial tagging prior to, and 4 months after aortic valve replacement (AVR) and septal myectomy, respectively. Global left ventricular (LV) analyses were derived from cine images. Circumferential strain was assessed from myocardial tagging images at the septal and lateral wall of the mid ventricle. Pressure gradients significantly decreased in both AVS and HOCM after surgery (p < 0.01), with a concomitant decrease in left atrial volume (p < 0.05) suggesting lower diastolic filling pressures. Also, LV volumes, mass and septal wall thickness decreased in both, but to a larger extent in AVS than in HOCM patients. AVR improved wall thickening (p < 0.05) and did not change systolic strain rate. Myectomy did not affect wall thickening and reduced septal systolic strain rate (p = 0.03). Both AVR and myectomy induced positive structural remodeling in line with a reduction of pressure overload. A concomitant recovery in systolic function however was found in AVR only. The systolic functional deterioration in HOCM patients seems to be inherent to myectomy and the ongoing and irreversible disease.
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http://dx.doi.org/10.1007/s10554-019-01563-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534665PMC
June 2019

Size Matters: Normalization of QRS Duration to Left Ventricular Dimension Improves Prediction of Long-Term Cardiac Resynchronization Therapy Outcome.

Circ Arrhythm Electrophysiol 2018 12;11(12):e006767

Department of Cardiology, Amsterdam Cardiovascular Sciences, VU University Medical Center, Amsterdam, the Netherlands (ACS) (A.Z., C.V., S.B., A.C.v.R., R.N., C.P.A.).

Background: In patients with left bundle branch block (LBBB), QRS duration (QRSd) depends on left ventricular (LV) dimension. Previously, we demonstrated that normalizing QRSd to LV dimension, to adjust for variations in LV size, improved prediction of hemodynamic response to cardiac resynchronization therapy (CRT). In addition, sex-specific differences in CRT outcome have been attributed to normalized QRSd. The present study evaluates the effect of normalization of QRSd to LV dimension on prediction of survival after CRT implantation.

Methods: In this 2-center study, we studied 250 heart failure patients with LV ejection fraction ≤35% and QRSd ≥120 ms who underwent cardiac magnetic resonance imaging before CRT implantation. LV end-diastolic volumes were used for QRSd normalization (ie, QRSd/LV end-diastolic volumes). The primary end point was a combined end point of death, LV assist device, or heart transplantation.

Results: During a median follow-up of 3.9 years, 79 (32%) patients reached the primary end point. Using univariable Cox regression, unadjusted QRSd was unrelated to CRT outcome ( P=0.116). In contrast, normalized QRSd was a strong predictor of survival (hazard ratio, 0.81 per 0.1 ms/mL; P=0.008). Women demonstrated higher normalized QRSd than men (0.62±0.17 versus 0.55±0.17 ms/mL; P=0.003) and showed better survival after CRT (hazard ratio, 0.52; P=0.018). A multivariable prognostic model included normalized QRSd together with age, atrial fibrillation, renal function, and heart failure cause, whereas sex, diabetes mellitus, strict left bundle branch block morphology, and LV end-diastolic volumes were expelled from the model.

Conclusions: Normalization of QRSd to LV dimension improves prediction of survival after CRT implantation. In addition, sex-specific differences in CRT outcome might be attributed to the higher QRSd/LV end-diastolic volumes ratio that was found in selected women, indicating more conduction delay.
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http://dx.doi.org/10.1161/CIRCEP.118.006767DOI Listing
December 2018

Chronotropic Incompetence in Chronic Heart Failure.

Circ Heart Fail 2018 08;11(8):e004969

Department of Cardiology, Amsterdam Cardiovascular Sciences, VU University Medical Center, the Netherlands.

Chronotropic incompetence (CI) is generally defined as the inability to increase the heart rate (HR) adequately during exercise to match cardiac output to metabolic demands. In patients with heart failure (HF), however, this definition is unsuitable because metabolic demands are unmatched to cardiac output in both conditions. Moreover, HR dynamics in patients with HF differ from those in healthy subjects and may be affected by β-blocking medication. Nevertheless, it has been demonstrated that CI in HF is associated with reduced functional capacity and poor survival. During exercise, the normal heart increases both stroke volume and HR, whereas in the failing heart, contractility reserve is lost, thus rendering increases in cardiac output primarily dependent on cardioacceleration. Consequently, insufficient cardioacceleration because of CI may be considered a major limiting factor in the exercise capacity of patients with HF. Despite the profound effects of CI in this specific population, the issue has drawn limited attention during the past years and is often overlooked in clinical practice. This might partly be caused by a lack of standardized approach to diagnose the disease, further complicated by changes in HR dynamics in the HF population, which render reference values derived from a normal population invalid. Cardiac implantable electronic devices (implantable cardioverter defibrillator; cardiac resynchronization therapy) now offer a unique opportunity to study HR dynamics and provide treatment options for CI by rate-adaptive pacing using an incorporated sensor that measures physical activity. This review provides an overview of disease mechanisms, diagnostic strategies, clinical consequences, and state-of-the-art device therapy for CI in HF.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.118.004969DOI Listing
August 2018

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

Long-Term Prognostic Implications of Previous Silent Myocardial Infarction in Patients Presenting With Acute Myocardial Infarction.

JACC Cardiovasc Imaging 2018 12 18;11(12):1773-1781. Epub 2018 Apr 18.

Department of Cardiology, VU University Medical Center, Amsterdam, the Netherlands. Electronic address:

Objectives: This study investigated the prevalence of silent myocardial infarction (MI) in patients presenting with first acute myocardial infarction (AMI), and its relation with mortality and major adverse cardiovascular events (MACE) at long-term follow-up.

Background: Up to 54% of MI occurs without apparent symptoms. The prevalence and long-term prognostic implications of previous silent MI in patients presenting with seemingly first AMI are unclear.

Methods: A 2-center observational longitudinal study was performed in 392 patients presenting with first AMI between 2003 and 2013, who underwent late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) examination within 14 days post-AMI. Silent MI was assessed on LGE-CMR images by identifying regions of hyperenhancement with an ischemic distribution pattern in other territories than the AMI. Mortality and MACE (all-cause death, reinfarction, coronary artery bypass grafting, and ischemic stroke) were assessed at 6.8 ± 2.9 years follow-up.

Results: Thirty-two patients (8.2%) showed silent MI on LGE-CMR. Compared with patients without silent MI, mortality risk was higher in patients with silent MI (hazard ratio: 3.87; 95% confidence interval: 1.21 to 12.38; p = 0.023), as was risk of MACE (hazard ratio: 3.10; 95% confidence interval: 1.22 to 7.86; p = 0.017), both independent from clinical and infarction-related characteristics.

Conclusions: Silent MI occurred in 8.2% of patients presenting with first AMI and was independently related to poorer long-term clinical outcome, with a more than 3-fold risk of mortality and MACE. Silent MI holds prognostic value over important traditional prognosticators in the setting of AMI, indicating that these patients represent a high-risk subgroup warranting clinical awareness.
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http://dx.doi.org/10.1016/j.jcmg.2018.02.009DOI Listing
December 2018

Additional diagnostic value of CMR to the European Society of Cardiology (ESC) position statement criteria in a large clinical population of patients with suspected myocarditis.

Eur Heart J Cardiovasc Imaging 2018 12;19(12):1397-1407

Department of Cardiology, VU University Medical Center, De Boelelaan 1117, HV Amsterdam, The Netherlands.

Aims: To determine the diagnostic yield of tissue characterization by cardiovascular magnetic resonance (CMR) in a large clinical population of patients with suspected acute myocarditis (AM) and to establish its diagnostic value within the 2013 European Society of Cardiology position statement criteria (ESC-PSC) for clinically suspected myocarditis.

Methods And Results: In this retrospective study, CMR examinations of 303 hospitalized patients referred for work-up of suspected AM in two tertiary referral centres were analysed. CMR was performed at median 7 days (interquartile range 4-20 days) after clinical presentation and included cine imaging, T2-weighted imaging, and late gadolinium enhancement. CMR images were evaluated to assign each patient to a diagnosis. By using non-CMR criteria only, the 2013 ESC-PSC were positive for suspected myocarditis in 151 patients and negative in 30. In the remaining 122 patients, there was insufficient information available for ESC-PSC assessment, mostly due to lack of coronary angiography (CAG) before the CMR examination (n = 116, 95%). There were no in-hospital deaths. CMR provided a diagnosis in 158 patients (52%), including myocarditis in 104 (34%), myocardial infarction in 44 (15%), and other pathology in 10 patients (3%). Non-urgent CAG (>24 h after presentation) was performed before the CMR examination in 85 patients, of which 20 (24%) were done in patients with subsequently confirmed AM, which could potentially have been avoided if CMR was performed first. ESC-PSC was correct in diagnosing AM before the CMR in 50 of the 151 patients (33%) and was correct in ruling out AM in all the 30 patients (100%). However, ESC-PSC provided an incorrect diagnosis of AM in 27 of the 151 patients (18%), which was corrected by CMR through the identification of new cardiac disease that could explain the clinical syndrome. Patients with insufficient ESC-PSC information had a relatively low pre-test probability of coronary artery disease. In this group, CMR confirmed the diagnosis of AM in a relatively high percentage (44%) but still revealed myocardial infarction in 8% of them.

Conclusion: Tissue characterization by CMR provided a good diagnostic yield in this large clinical population of patients with suspected AM. CMR provided incremental diagnostic value to the ESC-PSC by ruling out the diagnosis of AM on one hand and by potentially sparing AM patients from CAG on the other.
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http://dx.doi.org/10.1093/ehjci/jex308DOI Listing
December 2018

Comparison of strain imaging techniques in CRT candidates: CMR tagging, CMR feature tracking and speckle tracking echocardiography.

Int J Cardiovasc Imaging 2018 Mar 17;34(3):443-456. Epub 2017 Oct 17.

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

Parameters using myocardial strain analysis may predict response to cardiac resynchronization therapy (CRT). As the agreement between currently available strain imaging modalities is unknown, three different modalities were compared. Twenty-seven CRT-candidates, prospectively included in the MARC study, underwent cardiac magnetic resonance (CMR) imaging and echocardiographic examination. Left ventricular (LV) circumferential strain was analysed with CMR tagging (CMR-TAG), CMR feature tracking (CMR-FT), and speckle tracking echocardiography (STE). Basic strain values and parameters of dyssynchrony and discoordination obtained with CMR-FT and STE were compared to CMR-TAG. Agreement of CMR-FT and CMR-TAG was overall fair, while agreement between STE and CMR-TAG was often poor. For both comparisons, agreement on discoordination parameters was highest, followed by dyssynchrony and basic strain parameters. For discoordination parameters, agreement on systolic stretch index was highest, with fair intra-class correlation coefficients (ICC) (CMR-FT: 0.58, STE: 0.55). ICC of septal systolic rebound stretch (SRS) was poor (CMR-FT: 0.41, STE: 0.30). Internal stretch factor of septal and lateral wall (ISF) showed fair ICC values (CMR-FT: 0.53, STE: 0.46), while the ICC of the total LV (ISF) was fair for CMR-FT (0.55) and poor for STE (ICC: 0.32). The CURE index had a fair ICC for both comparisons (CMR-FT: 0.49, STE 0.41). Although comparison of STE to CMR-TAG was limited by methodological differences, agreement between CMR-FT and CMR-TAG was overall higher compared to STE and CMR-TAG. CMR-FT is a potential clinical alternative for CMR-TAG and STE, especially in the detection of discoordination in CRT-candidates.
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http://dx.doi.org/10.1007/s10554-017-1253-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5847211PMC
March 2018

Strain analysis in CRT candidates using the novel segment length in cine (SLICE) post-processing technique on standard CMR cine images.

Eur Radiol 2017 Dec 27;27(12):5158-5168. Epub 2017 Jun 27.

Department of Cardiology, and Institute for Cardiovascular Research (ICaR-VU), VU University Medical Center, Amsterdam, The Netherlands.

Objectives: Although myocardial strain analysis is a potential tool to improve patient selection for cardiac resynchronization therapy (CRT), there is currently no validated clinical approach to derive segmental strains. We evaluated the novel segment length in cine (SLICE) technique to derive segmental strains from standard cardiovascular MR (CMR) cine images in CRT candidates.

Methods: Twenty-seven patients with left bundle branch block underwent CMR examination including cine imaging and myocardial tagging (CMR-TAG). SLICE was performed by measuring segment length between anatomical landmarks throughout all phases on short-axis cines. This measure of frame-to-frame segment length change was compared to CMR-TAG circumferential strain measurements. Subsequently, conventional markers of CRT response were calculated.

Results: Segmental strains showed good to excellent agreement between SLICE and CMR-TAG (septum strain, intraclass correlation coefficient (ICC) 0.76; lateral wall strain, ICC 0.66). Conventional markers of CRT response also showed close agreement between both methods (ICC 0.61-0.78). Reproducibility of SLICE was excellent for intra-observer testing (all ICC ≥0.76) and good for interobserver testing (all ICC ≥0.61).

Conclusions: The novel SLICE post-processing technique on standard CMR cine images offers both accurate and robust segmental strain measures compared to the 'gold standard' CMR-TAG technique, and has the advantage of being widely available.

Key Points: • Myocardial strain analysis could potentially improve patient selection for CRT. • Currently a well validated clinical approach to derive segmental strains is lacking. • The novel SLICE technique derives segmental strains from standard CMR cine images. • SLICE-derived strain markers of CRT response showed close agreement with CMR-TAG. • Future studies will focus on the prognostic value of SLICE in CRT candidates.
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http://dx.doi.org/10.1007/s00330-017-4890-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5674110PMC
December 2017

Prediction of Acute Response to Cardiac Resynchronization Therapy by Means of the Misbalance in Regional Left Ventricular Myocardial Work.

J Card Fail 2016 Feb 10;22(2):133-42. Epub 2015 Nov 10.

Department of Cardiology Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, the Netherlands.

Background: Patients with left ventricular (LV) dyssynchrony have a marked misbalance in LV myocardial work distribution, with wasted work in the septum and increased work in the lateral wall. We hypothesized that a low septum-to-lateral wall (SL) myocardial work ratio at baseline predicts acute LV pump function improvement during cardiac resynchronization therapy (CRT).

Methods And Results: Twenty patients (age 65 ± 10 y, 15 men) underwent cardiac magnetic resonance (CMR) tagging for regional LV circumferential strain assessment and invasive pressure-volume loop assessment at baseline and during biventricular pacing. Segmental work at baseline was calculated from regional strain rate and LV pressure. Subsequently, the SL work ratio was calculated and related to acute pump function (stroke work [SW]) improvement during CRT. During biventricular pacing, SW increased by 33% (P <.001). SL work ratio at baseline was found to be significantly related to SW improvement by means of CRT (R = -0.54; P = .015). Moreover, it proved to be the only marker that was significantly related to acute response to CRT, whereas QRS duration and other measures of dyssynchrony or dyscoordination were not.

Conclusions: The contribution of the septum to LV work varies widely in CRT candidates with left bundle branch block. The lower the septal contribution to myocardial work at baseline, the higher the acute pump function improvement that can be achieved during CRT.
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http://dx.doi.org/10.1016/j.cardfail.2015.10.020DOI Listing
February 2016