Publications by authors named "Gabe B Bleeker"

78 Publications

Targeted Temperature Management in Out-of-Hospital Cardiac Arrest With Shockable Rhythm: A Post Hoc Analysis of the Coronary Angiography After Cardiac Arrest Trial.

Crit Care Med 2021 Sep 22. Epub 2021 Sep 22.

Department of Cardiology, Amsterdam University Medical Center, location VUmc, Amsterdam, The Netherlands. Department of Cardiology, Erasmus Medical Center, Rotterdam, The Netherlands. Department of Intensive Care Medicine, Erasmus Medical Center, Rotterdam, The Netherlands. Department of Cardiology, Amphia Hospital, Breda, The Netherlands. Department of Intensive Care Medicine, Amphia Hospital, Breda, The Netherlands. Department of Cardiology, Rijnstate Hospital, Arnhem, The Netherlands. Department of Intensive Care Medicine, Rijnstate Hospital, Arnhem, The Netherlands. Department of Cardiology, HAGA Hospital, Den Haag, The Netherlands. Department of Intensive Care Medicine, HAGA Hospital, Den Haag, The Netherlands. Department of Cardiology, Maasstad Hospital, Rotterdam, The Netherlands. Department of Cardiology, University Medical Centre Utrecht, Utrecht, The Netherlands. Department of Intensive Care Medicine, Maasstad Hospital, Rotterdam, The Netherlands. Department of Intensive Care Medicine, Amsterdam University Medical Center, location VUmc, Amsterdam, The Netherlands. Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands. Department of Intensive Care Medicine, Maastricht University Medical Center, University Maastricht, Maastricht, The Netherlands. Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht, The Netherlands. Department of Intensive Care Medicine, Medisch Spectrum Twente, Enschede, The Netherlands. Department of Cardiology, Medisch Spectrum Twente, Enschede, The Netherlands. Department of Cardiology, Radboud University Medical Center, Nijmegen, The Netherlands. Department of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, The Netherlands. Department of Cardiology, Amsterdam University Medical Center, location AMC, Amsterdam, The Netherlands. Department of Intensive Care Medicine, Amsterdam University Medical Center, location AMC, Amsterdam, The Netherlands. Department of Cardiology, OLVG, Amsterdam, The Netherlands. Department of Intensive Care Medicine, OLVG, Amsterdam, The Netherlands. Department of Cardiology, Noord West Ziekenhuisgroep, Alkmaar, The Netherlands. Department of Intensive Care Medicine, Noord West Ziekenhuisgroep, Alkmaar, The Netherlands. Department of Cardiology, Maastricht University Medical Center, Maastricht, The Netherlands. Department of Cardiology, Scheper Hospital, Emmen, The Netherlands. Department of Cardiology, Haaglanden Medical Center, Den Haag, The Netherlands. Department of Cardiology, Isala Hospital, Zwolle, The Netherlands. Department of Cardiology, Tergooi Hospital, Blaricum, The Netherlands. Department of Cardiology, Elisabeth-Tweesteden Hospital, Tilburg, The Netherlands. Department of Epidemiology and Data Science, Amsterdam University Medical Center, location VUmc, Amsterdam, The Netherlands.

Objectives: The optimal targeted temperature in patients with shockable rhythm is unclear, and current guidelines recommend targeted temperature management with a correspondingly wide range between 32°C and 36°C. Our aim was to study survival and neurologic outcome associated with targeted temperature management strategy in postarrest patients with initial shockable rhythm.

Design: Observational substudy of the Coronary Angiography after Cardiac Arrest without ST-segment Elevation trial.

Setting: Nineteen hospitals in The Netherlands.

Patients: The Coronary Angiography after Cardiac Arrest trial randomized successfully resuscitated patients with shockable rhythm and absence of ST-segment elevation to a strategy of immediate or delayed coronary angiography. In this substudy, 459 patients treated with mild therapeutic hypothermia (32.0-34.0°C) or targeted normothermia (36.0-37.0°C) were included. Allocation to targeted temperature management strategy was at the discretion of the physician.

Interventions: None.

Measurements And Main Results: After 90 days, 171 patients (63.6%) in the mild therapeutic hypothermia group and 129 (67.9%) in the targeted normothermia group were alive (hazard ratio, 0.86 [95% CI, 0.62-1.18]; log-rank p = 0.35; adjusted odds ratio, 0.89; 95% CI, 0.45-1.72). Patients in the mild therapeutic hypothermia group had longer ICU stay (4 d [3-7 d] vs 3 d [2-5 d]; ratio of geometric means, 1.32; 95% CI, 1.15-1.51), lower blood pressures, higher lactate levels, and increased need for inotropic support. Cerebral Performance Category scores at ICU discharge and 90-day follow-up and patient-reported Mental and Physical Health Scores at 1 year were similar in the two groups.

Conclusions: In the context of out-of-hospital cardiac arrest with shockable rhythm and no ST-elevation, treatment with mild therapeutic hypothermia was not associated with improved 90-day survival compared with targeted normothermia. Neurologic outcomes at 90 days as well as patient-reported Mental and Physical Health Scores at 1 year did not differ between the groups.
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http://dx.doi.org/10.1097/CCM.0000000000005271DOI Listing
September 2021

The effect of immediate coronary angiography after cardiac arrest without ST-segment elevation on left ventricular function. A sub-study of the COACT randomised trial.

Resuscitation 2021 07 28;164:93-100. Epub 2021 Apr 28.

Department of Intensive care medicine, Noord West Ziekenhuisgroep, Alkmaar, The Netherlands.

Background: The effect of immediate coronary angiography and percutaneous coronary intervention (PCI) in patients who are successfully resuscitated after cardiac arrest in the absence of ST-segment elevation myocardial infarction (STEMI) on left ventricular function is currently unknown.

Methods: This prespecified sub-study of a multicentre trial evaluated 552 patients, successfully resuscitated from out-of-hospital cardiac arrest without signs of STEMI. Patients were randomized to either undergo immediate coronary angiography or delayed coronary angiography, after neurologic recovery. All patients underwent PCI if indicated. The main outcomes of this analysis were left ventricular ejection fraction and end-diastolic and systolic volumes assessed by cardiac magnetic resonance imaging or echocardiography.

Results: Data on left ventricular function was available for 397 patients. The mean (± standard deviation) left ventricular ejection fraction was 45.2% (±12.8) in the immediate angiography group and 48.4% (±13.2) in the delayed angiography group (mean difference: -3.19; 95% confidence interval [CI], -6.75 to 0.37). Median left ventricular end-diastolic volume was 177 ml in the immediate angiography group compared to 169 ml in the delayed angiography group (ratio of geometric means: 1.06; 95% CI, 0.95-1.19). In addition, mean left ventricular end-systolic volume was 90 ml in the immediate angiography group compared to 78 ml in the delayed angiography group (ratio of geometric means: 1.13; 95% CI 0.97-1.32).

Conclusion: In patients successfully resuscitated after out-of-hospital cardiac arrest and without signs of STEMI, immediate coronary angiography was not found to improve left ventricular dimensions or function compared with a delayed angiography strategy.

Clinical Trial Registration: Netherlands Trial Register number, NTR4973.
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http://dx.doi.org/10.1016/j.resuscitation.2021.04.020DOI Listing
July 2021

VA-ECMO With IABP is Associated With Better Outcome Than VA-ECMO Alone in the Treatment of Cardiogenic Shock in ST-Elevation Myocardial Infarction.

J Invasive Cardiol 2021 05 20;33(5):E387-E392. Epub 2021 Apr 20.

Koopvaardersplantsoen 83, 1034KE, Amsterdam, The Netherlands.

Objective: To assess whether combining venoarterial extracorporeal membrane oxygenation (VA-ECMO) with intra-aortic balloon pump (IABP) improves outcomes in ST-segment elevation myocardial infarction (STEMI) over VA-ECMO alone.

Background: VA-ECMO is an upcoming technique in the treatment of cardiogenic shock (CS); however, it increases afterload. IABP + VA-ECMO has been suggested to reduce afterload and increase survival.

Methods: A multicenter in-hospital registry was maintained on all patients undergoing VA-ECMO or VA-ECMO + IABP treatment for CS in STEMI.

Results: Between 2015 and 2018, a total of 18 patients with STEMI underwent VA-ECMO ± IABP treatment for CS. The majority (n = 14; 78%) were male and median age was 59 years (interquartile range, 47-75 years). VA-ECMO + IABP was performed in 7 patients (39%) and VA-ECMO alone was performed in 11 patients (61%). The VA-ECMO + IABP group had more complex coronary anatomy and a higher number of patients with left main (LM) disease, LM + 3-vessel disease, or 3-vessel disease (VA-ECMO + IABP 86% vs VA-ECMO alone 18%; P=.03). The Survival After Veno-Arterial Extracorporeal Membrane Oxygenation (SAVE) score did not differ between the groups (VA-ECMO alone -5.9 ± 2.4 vs VA-ECMO + IABP -6.1 ± 2.6; P=.88). The SYNTAX score was higher in the VA-ECMO + IABP group (32 ± 13 vs 22 ± 14 in the VA-ECMO alone group). In the total group, a SAVE score of -6 had a predicted survival of 25%-35%. Survival in the VA-ECMO + IABP group was 100% (7/7) and survival in the VA-ECMO group was 55% (6/11); P=.04. Good neurological outcome was achieved in more patients in the VA-ECMO + IABP group (VA-ECMO alone 45% vs VA-ECMO + IABP 100%; P=.04).

Conclusion: In STEMI complicated by CS, VA-ECMO + IABP leads to a lower observed mortality and higher observed good neurological outcome.
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May 2021

Data on sex differences in one-year outcomes of out-of-hospital cardiac arrest patients without ST-segment elevation.

Data Brief 2020 Dec 12;33:106521. Epub 2020 Nov 12.

Department of Intensive care medicine, Maastricht University Medical Center, University Maastricht, Maastricht, the Netherlands.

Sex differences in out-of-hospital cardiac arrest (OHCA) patients are increasingly recognized. Although it has been found that post-resuscitated women are less likely to have significant coronary artery disease (CAD) than men, data on follow-up in these patients are limited. Data for this data in brief article was obtained as a part of the randomized controlled Coronary Angiography after Cardiac Arrest without ST-segment elevation (COACT) trial. The data supplements the manuscript "Sex differences in out-of-hospital cardiac arrest patients without ST-segment elevation: A COACT trial substudy" were it was found that women were less likely to have significant CAD including chronic total occlusions, and had worse survival when CAD was present. The dataset presented in this paper describes sex differences on interventions, implantable-cardioverter defibrillator (ICD) shocks and hospitalizations due to heart failure during one-year follow-up in patients successfully resuscitated after OHCA. Data was derived through a telephone interview at one year with the patient or general practitioner. Patients in this randomized dataset reflects a homogenous study population, which can be valuable to further build on research regarding long-term sex differences and to further improve cardiac care.
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http://dx.doi.org/10.1016/j.dib.2020.106521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691722PMC
December 2020

Sex differences in patients with out-of-hospital cardiac arrest without ST-segment elevation: A COACT trial substudy.

Resuscitation 2021 01 12;158:14-22. Epub 2020 Nov 12.

Department of Intensive care medicine, Maastricht University Medical Centre, University Maastricht, Maastricht, the Netherlands.

Background: Whether sex is associated with outcomes of out-of-hospital cardiac arrest (OHCA) is unclear.

Objectives: This study examined sex differences in survival in patients with OHCA without ST-segment elevation myocardial infarction (STEMI).

Methods: Using data from the randomized controlled Coronary Angiography after Cardiac Arrest (COACT) trial, the primary point of interest was sex differences in OHCA-related one-year survival. Secondary points of interest included the benefit of immediate coronary angiography compared to delayed angiography until after neurologic recovery, angiographic and clinical outcomes.

Results: In total, 522 patients (79.1% men) were included. Overall one-year survival was 59.6% in women and 63.4% in men (HR 1.18; 95% CI: 0.76-1.81;p = 0.47). No cardiovascular risk factors were found that modified survival. Women less often had significant coronary artery disease (CAD) (37.0% vs. 71.3%;p < 0.001), but when present, they had a worse prognosis than women without CAD (HR 3.06; 95% CI 1.31-7.19;p = 0.01). This was not the case for men (HR 1.05; 95% CI 0.67-1.65;p = 0.83). In both sexes, immediate coronary angiography did not improve one-year survival compared to delayed angiography (women, odds ratio (OR) 0.87; 95% CI 0.58-1.30;p = 0.49; vs. men, OR 0.97; 95% CI 0.45-2.09;p = 0.93).

Conclusion: In OHCA patients without STEMI, we found no sex differences in overall one-year survival. Women less often had significant CAD, but when CAD was present they had worse survival than women without CAD. This was not the case for men. Both sexes did not benefit from a strategy of immediate coronary angiography as compared to delayed strategy with respect to one-year survival.

Clinical Trial Registration Number: Netherlands trial register (NTR) 4973.
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http://dx.doi.org/10.1016/j.resuscitation.2020.10.026DOI Listing
January 2021

Coronary Angiography After Cardiac Arrest Without ST Segment Elevation: One-Year Outcomes of the COACT Randomized Clinical Trial.

JAMA Cardiol 2020 Dec;5(12):1358-1365

Department of Cardiology, Scheper Hospital, Emmen, the Netherlands.

Importance: Ischemic heart disease is a common cause of cardiac arrest. However, randomized data on long-term clinical outcomes of immediate coronary angiography and percutaneous coronary intervention (PCI) in patients successfully resuscitated from cardiac arrest in the absence of ST segment elevation myocardial infarction (STEMI) are lacking.

Objective: To determine whether immediate coronary angiography improves clinical outcomes at 1 year in patients after cardiac arrest without signs of STEMI, compared with a delayed coronary angiography strategy.

Design, Setting, And Participants: A prespecified analysis of a multicenter, open-label, randomized clinical trial evaluated 552 patients who were enrolled in 19 Dutch centers between January 8, 2015, and July 17, 2018. The study included patients who experienced out-of-hospital cardiac arrest with a shockable rhythm who were successfully resuscitated without signs of STEMI. Follow-up was performed at 1 year. Data were analyzed, using the intention-to-treat principle, between August 29 and October 10, 2019.

Interventions: Immediate coronary angiography and PCI if indicated or coronary angiography and PCI if indicated, delayed until after neurologic recovery.

Main Outcomes And Measures: Survival, myocardial infarction, revascularization, implantable cardiac defibrillator shock, quality of life, hospitalization for heart failure, and the composite of death or myocardial infarction or revascularization after 1 year.

Results: At 1 year, data on 522 of 552 patients (94.6%) were available for analysis. Of these patients, 413 were men (79.1%); mean (SD) age was 65.4 (12.3) years. A total of 162 of 264 patients (61.4%) in the immediate angiography group and 165 of 258 patients (64.0%) in the delayed angiography group were alive (odds ratio, 0.90; 95% CI, 0.63-1.28). The composite end point of death, myocardial infarction, or repeated revascularization since the index hospitalization was met in 112 patients (42.9%) in the immediate group and 104 patients (40.6%) in the delayed group (odds ratio, 1.10; 95% CI, 0.77-1.56). No significant differences between the groups were observed for the other outcomes at 1-year follow-up. For example, the rate of ICD shocks was 20.4% in the immediate group and 16.2% in the delayed group (odds ratio, 1.32; 95% CI, 0.66-2.64).

Conclusions And Relevance: In this trial of patients successfully resuscitated after out-of-hospital cardiac arrest and without signs of STEMI, a strategy of immediate angiography was not found to be superior to a strategy of delayed angiography with respect to clinical outcomes at 1 year. Coronary angiography in this patient group can therefore be delayed until after neurologic recovery without affecting outcomes.

Trial Registration: trialregister.nl Identifier: NTR4973.
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http://dx.doi.org/10.1001/jamacardio.2020.3670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489423PMC
December 2020

Coronary Angiography after Cardiac Arrest without ST-Segment Elevation.

N Engl J Med 2019 Apr 18;380(15):1397-1407. Epub 2019 Mar 18.

From the Departments of Cardiology (J.S.L., G.N.J., N.W.H., N.R.), Intensive Care Medicine (P.W.G.E., H.M.O.-S.), and Epidemiology and Biostatistics (P.M.V.), Amsterdam University Medical Center VUmc, the Departments of Cardiology (J.P.H.) and Intensive Care Medicine (A.P.J.V.), Amsterdam University Medical Center AMC, and the Departments of Cardiology (M.A.V.) and Intensive Care Medicine (B.B.), Onze Lieve Vrouwe Gasthuis, Amsterdam, the Thorax Center, Erasmus Medical Center (L.S.D.J., E.A.D.), and the Departments of Cardiology (G.J.V.) and Intensive Care Medicine (B.J.W.E.), Maasstad Hospital, Rotterdam, the Departments of Cardiology (M. Meuwissen) and Intensive Care Medicine (T.A.R.), Amphia Hospital, Breda, the Departments of Cardiology (H.A.B.) and Intensive Care Medicine (M.J.B.), Rijnstate Hospital, Arnhem, the Departments of Cardiology (G.B.B.) and Intensive Care Medicine (R.B.), Haga Hospital, and the Department of Cardiology, Haaglanden Medical Center (P.V.O.), The Hague, the Departments of Cardiology (P.H.) and Intensive Care Medicine (I.C.C.H.), University of Groningen, Groningen, the Departments of Cardiology (M.V.) and Intensive Care Medicine (J.J.H.), University Medical Center Utrecht, Utrecht, the Departments of Intensive Care Medicine (A.B.) and Cardiology (M.S.), Medisch Spectrum Twente, Enschede, the Departments of Cardiology (C.C., N.R.) and Intensive Care Medicine (H.H.), Radboud University Medical Center, Nijmegen, the Departments of Cardiology (T.A.C.M.H.) and Intensive Care Medicine (W.R.), Noordwest Ziekenhuisgroep, Alkmaar, the Departments of Intensive Care Medicine (T.S.R.D.) and Cardiology (H.J.G.M.C.), Maastricht University Medical Center, Maastricht, the Department of Cardiology, Scheper Hospital, Emmen (G.A.J.J.), the Department of Cardiology, Isala Hospital, Zwolle (M.T.M.G.), the Department of Cardiology, Tergooi Hospital, Blaricum (K.P.), and the Department of Cardiology, Elisabeth-Tweesteden Hospital, Tilburg (M. Magro) - all in the Netherlands.

Background: Ischemic heart disease is a major cause of out-of-hospital cardiac arrest. The role of immediate coronary angiography and percutaneous coronary intervention (PCI) in the treatment of patients who have been successfully resuscitated after cardiac arrest in the absence of ST-segment elevation myocardial infarction (STEMI) remains uncertain.

Methods: In this multicenter trial, we randomly assigned 552 patients who had cardiac arrest without signs of STEMI to undergo immediate coronary angiography or coronary angiography that was delayed until after neurologic recovery. All patients underwent PCI if indicated. The primary end point was survival at 90 days. Secondary end points included survival at 90 days with good cerebral performance or mild or moderate disability, myocardial injury, duration of catecholamine support, markers of shock, recurrence of ventricular tachycardia, duration of mechanical ventilation, major bleeding, occurrence of acute kidney injury, need for renal-replacement therapy, time to target temperature, and neurologic status at discharge from the intensive care unit.

Results: At 90 days, 176 of 273 patients (64.5%) in the immediate angiography group and 178 of 265 patients (67.2%) in the delayed angiography group were alive (odds ratio, 0.89; 95% confidence interval [CI], 0.62 to 1.27; P = 0.51). The median time to target temperature was 5.4 hours in the immediate angiography group and 4.7 hours in the delayed angiography group (ratio of geometric means, 1.19; 95% CI, 1.04 to 1.36). No significant differences between the groups were found in the remaining secondary end points.

Conclusions: Among patients who had been successfully resuscitated after out-of-hospital cardiac arrest and had no signs of STEMI, a strategy of immediate angiography was not found to be better than a strategy of delayed angiography with respect to overall survival at 90 days. (Funded by the Netherlands Heart Institute and others; COACT Netherlands Trial Register number, NTR4973.).
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http://dx.doi.org/10.1056/NEJMoa1816897DOI Listing
April 2019

Coronary angiography after cardiac arrest: Rationale and design of the COACT trial.

Am Heart J 2016 Oct 14;180:39-45. Epub 2016 Jul 14.

Department of Cardiology, VU University Medical Centre, Amsterdam, the Netherlands.

Background: Ischemic heart disease is a major cause of out-of-hospital cardiac arrest. The role of immediate coronary angiography (CAG) and percutaneous coronary intervention (PCI) after restoration of spontaneous circulation following cardiac arrest in the absence of ST-segment elevation myocardial infarction (STEMI) remains debated.

Hypothesis: We hypothesize that immediate CAG and PCI, if indicated, will improve 90-day survival in post-cardiac arrest patients without signs of STEMI.

Design: In a prospective, multicenter, randomized controlled clinical trial, 552 post-cardiac arrest patients with restoration of spontaneous circulation and without signs of STEMI will be randomized in a 1:1 fashion to immediate CAG and PCI (within 2 hours) versus initial deferral with CAG and PCI after neurological recovery. The primary end point of the study is 90-day survival. The secondary end points will include 90-day survival with good cerebral performance or minor/moderate disability, myocardial injury, duration of inotropic support, occurrence of acute kidney injury, need for renal replacement therapy, time to targeted temperature control, neurological status at intensive care unit discharge, markers of shock, recurrence of ventricular tachycardia, duration of mechanical ventilation, and reasons for discontinuation of treatment.

Summary: The COACT trial is a multicenter, randomized, controlled clinical study that will evaluate the effect of an immediate invasive coronary strategy in post-cardiac arrest patients without STEMI on 90-day survival.
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http://dx.doi.org/10.1016/j.ahj.2016.06.025DOI Listing
October 2016

Effect of cardiac resynchronization therapy in patients without left intraventricular dyssynchrony.

Eur Heart J 2012 Apr 24;33(7):913-20. Epub 2012 Jan 24.

Department of Cardiology, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.

Aims: To evaluate the effects of cardiac resynchronization therapy (CRT) on long-term survival of patients without baseline left ventricular (LV) mechanical dyssynchrony.

Methods And Results: A total of 290 heart failure patients (age 67 ± 10 years, 77% males) without significant baseline LV dyssynchrony (<60 ms as assessed with tissue Doppler imaging) were treated with CRT. Patients were divided according to the median LV dyssynchrony measured after 48 h of CRT into two groups. All-cause mortality was compared between the subgroups. In addition, the all-cause mortality rates of these subgroups were compared with the all-cause mortality of 290 heart failure patients treated with CRT who showed significant LV dyssynchrony (≥60 ms) at baseline. In the group of patients without significant LV dyssynchrony, median LV dyssynchrony increased from 22 ms (inter-quartile range 16-34 ms) at baseline to 40 ms (24-56 ms) 48 h after CRT. The cumulative mortality rates at 1-, 2-, and 3-year follow-up of patients with LV dyssynchrony ≥40 ms 48 h after CRT implantation were significantly higher when compared with patients with LV dyssynchrony <40 ms (10, 17, and 23 vs. 3, 8, and 10%, respectively; log-rank P< 0.001). Finally, the cumulative mortality rates at 1-, 2-, and 3-year follow-up of patients with baseline LV dyssynchrony were 3, 8, and 11%, respectively (log-rank P= 0.375 vs. patients with LV dyssynchrony <40 ms). Induction of LV dyssynchrony after CRT was an independent predictor of mortality (hazard ratio: 1.247; P= 0.009).

Conclusion: In patients without significant LV dyssynchrony, the induction of LV dyssynchrony after CRT may be related to a less favourable long-term outcome.
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http://dx.doi.org/10.1093/eurheartj/ehr468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3345550PMC
April 2012

Cardiac resynchronization therapy in patients with ischemic versus non-ischemic heart failure: Differential effect of optimizing interventricular pacing interval.

Am Heart J 2009 Nov;158(5):769-76

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

Background: Whether sequential biventricular pacing provides substantial benefits over conventional simultaneous stimulation remains unclear, particularly regarding the differences between ischemic and non-ischemic patients. The purpose of this study was to evaluate the acute effect of interventricular pacing interval (V-V) optimization on left ventricular (LV) systolic performance and dyssynchrony in ischemic versus non-ischemic patients.

Methods: Sixty-nine consecutive patients underwent cardiac resynchronization therapy. Within 3 days after implantation, V-V was optimized by measuring (every 20-millisecond interval) LV systolic performance (LV outflow-tract velocity-time-integral, LVOT VTI) and LV dyssynchrony (using tissue Doppler imaging). Optimal pacing configuration was the one achieving maximal increase in LVOT VTI.

Results: Optimized sequential pacing provided a significant improvement in LVOT VTI compared to simultaneous stimulation (from 138 +/- 42 to 163 +/- 38 mm, P < .001) and was associated with a significant reduction in LV dyssynchrony (from 33 +/- 31 to 19 +/- 24 milliseconds, P < .001). The increase in LVOT VTI and LV ejection fraction after implantation was greater in non-ischemic as compared to ischemic patients (P < .001). However, V-V optimization yielded a larger improvement in LV systolic performance in ischemic patients (P = .03). Consequently, the 2 groups showed comparable response after V-V optimization. A significant correlation was observed between LV scar tissue and optimal V-V interval (r = 0.58, P < .001), with a larger extent of scar related to a larger level of LV preactivation, probably reflecting slow intra-LV conduction.

Conclusions: Optimized sequential biventricular pacing further increased LV systolic performance as compared to simultaneous stimulation, particularly in ischemic patients where the presence of a large scar was correlated with a larger LV preactivation.
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http://dx.doi.org/10.1016/j.ahj.2009.09.004DOI Listing
November 2009

Limited effects of growth hormone replacement in patients with GH deficiency during long-term cure of acromegaly.

Pituitary 2009 12;12(4):339-46. Epub 2009 Jun 12.

Department of Endocrinology and Metabolic Diseases C4-R, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands.

The aim of this study was to assess the effects of replacement with recombinant human growth hormone (rhGH) in patients with GH deficiency (GHD) after treatment of acromegaly. Intervention study. Sixteen patients (8 men, age 56 years), treated for acromegaly by surgery and radiotherapy, with an insufficient GH response to insulin-induced hypoglycaemia, were treated with 1 year of rhGH replacement. Study parameters were assessed at baseline and after 1 year of rhGH replacement. Study parameters were cardiac function, body composition, bone mineral density (BMD), fasting lipids, glucose, bone turnover markers, and Quality of Life (QoL). During rhGH replacement IGF-I concentrations increased from -0.4 +/- 0.7 to 1.0 +/- 1.5 SD (P = 0.001), with a mean daily dose of 0.2 +/- 0.1 mg in men and 0.3 +/- 0.2 mg in women. Nonetheless, rhGH replacement did not alter cardiac function, lipid and glucose concentrations, body composition or QoL. Bone turnover markers (PINP and beta crosslaps) levels increased (P = 0.005 and P = 0.021, respectively), paralleled by a small, but significant decrease in BMD of the hip. The beneficial effects of rhGH replacement in patients with GHD during cure from acromegaly are limited in this study.
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http://dx.doi.org/10.1007/s11102-009-0186-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2764055PMC
February 2010

Comparison of time course of response to cardiac resynchronization therapy in patients with ischemic versus nonischemic cardiomyopathy.

Am J Cardiol 2009 Mar 26;103(5):690-4. Epub 2008 Dec 26.

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

The time course of the effects of cardiac resynchronization therapy (CRT) on left ventricular (LV) systolic function and reverse remodeling is still unknown and was the subject of this study. In particular, whether the acute benefit of CRT translates in late response was explored. Furthermore, the time course of response was compared between ischemic and nonischemic patients. A total of 222 consecutive patients with heart failure (135 ischemic) scheduled for CRT were included. Standard echocardiography was performed before, immediately after CRT, and at 6-month follow-up to measure LV end-systolic volume (ESV), LV end-diastolic volume (EDV), and ejection fraction. Immediately after CRT, significant improvements in LV ejection fraction (from 25 +/- 8% to 31 +/- 9%, p <0.001) and LVESV (from 163 +/- 68 to 149 +/- 63 ml, p <0.001) were observed, followed by an additional improvement at 6-month follow-up (to 34 +/- 9% and 132 +/- 62 ml, respectively, p <0.001 for the 2 comparisons). A significant decrease in LVEDV was observed only at 6-month follow-up (from 217 +/- 73 to 194 +/- 72 ml, p <0.001). An acute decrease in LVESV of 6% could predict response to CRT at 6-month follow-up (defined as a decrease >or=15% in LVESV) with a sensitivity and specificity of 79% and 75%, respectively. The time course of response to CRT was similar in ischemic and nonischemic patients, but decreases in LVESV and LVEDV were significantly greater in nonischemic patients (p <0.001). In conclusion, the beneficial effect of CRT on LV systolic function occurs immediately after CRT, with additional improvement at 6-month follow-up. An acute decrease in LVESV can predict response to CRT at 6-month follow-up. Nonischemic patients show significantly greater LV reverse remodeling compared with ischemic patients.
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http://dx.doi.org/10.1016/j.amjcard.2008.11.008DOI Listing
March 2009

Long-term prognosis after cardiac resynchronization therapy is related to the extent of left ventricular reverse remodeling at midterm follow-up.

J Am Coll Cardiol 2009 Feb;53(6):483-90

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

Objectives: The aim of the current study was to evaluate the relation between the extent of left ventricular (LV) reverse remodeling and clinical/echocardiographic improvement after 6 months of cardiac resynchronization therapy (CRT) as well as long-term outcome.

Background: Despite the current selection criteria, individual response to CRT varies significantly. Furthermore, it has been suggested that reduction in left ventricular end-systolic volume (LVESV) after CRT is related to outcome.

Methods: A total of 302 CRT candidates were included. Clinical status and echocardiographic evaluation were performed before implantation and after 6 months of CRT. Long-term follow-up included all-cause mortality and hospitalizations for heart failure.

Results: Based on different extents of LV reverse remodeling, 22% of patients were classified as super-responders (decrease in LVESV > or =30%), 35% as responders (decrease in LVESV 15% to 29%), 21% as nonresponders (decrease in LVESV 0% to 14%), and 22% negative responders (increase in LVESV). More extensive LV reverse remodeling resulted in more clinical improvement, with a larger increase in LV function and more reduction in mitral regurgitation. In addition, more LV reverse remodeling resulted in less heart failure hospitalizations and lower mortality during long-term follow-up (22 +/- 11 months); 1- and 2-year hospitalization-free survival rates were 90% and 70% in the negative responder group compared with 98% and 96% in the super-responder group (log-rank p value <0.001).

Conclusions: The extent of LV reverse remodeling at midterm follow-up is predictive for long-term outcome in CRT patients.
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http://dx.doi.org/10.1016/j.jacc.2008.10.032DOI Listing
February 2009

Noninvasive imaging in cardiac resynchronization therapy--Part 2: Follow-up and optimization of settings.

Pacing Clin Electrophysiol 2008 Dec;31(12):1628-39

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

Cardiac resynchronization therapy (CRT) has become a therapeutic option for drug-refractory heart failure. Several noninvasive imaging techniques play an increasingly important role before and after device implantation. This review highlights the acute and long-term CRT benefits after implantation as assessed with echocardiography and nuclear imaging. Furthermore, optimization of CRT settings, in particular atrioventricular and interventricular delay, will be discussed using echocardiography and other (device-based) techniques.
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http://dx.doi.org/10.1111/j.1540-8159.2008.01237.xDOI Listing
December 2008

Magnetic resonance imaging and computed tomography in assessing cardiac veins and scar tissue.

Europace 2008 Nov;10 Suppl 3:iii110-3

Department of Cardiology, Leiden University Medical Center, Postbox 9600, 2300 RC Leiden, The Netherlands.

The success of cardiac resynchronization therapy is influenced by several issues including cardiac venous anatomy and myocardial scar tissue. This article discusses non-invasive imaging modalities that could contribute significantly to the selection process of cardiac resynchronization therapy (CRT) candidates: multi-slice computed tomography to depict the coronary sinus tributaries and magnetic resonance imaging to identify scar tissue.
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http://dx.doi.org/10.1093/europace/eun236DOI Listing
November 2008

Noninvasive imaging in cardiac resynchronization therapy--part 1: selection of patients.

Pacing Clin Electrophysiol 2008 Nov;31(11):1475-99

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

Cardiac resynchronization therapy (CRT) is an established therapy for patients with advanced heart failure, depressed left ventricular function, and wide QRS complex. However, individual response varies, and a substantial amount of patients do not respond to CRT. Recent studies observed that assessment of inter- and particularly intraventricular dyssynchrony may allow identification of potential responders to CRT. In addition, presence of scar tissue and venous anatomy may play a role in the selection of candidates. In this review, an extensive overview of the available dyssynchrony measurements is provided using echocardiography as well as magnetic resonance imaging (MRI) and nuclear imaging. Furthermore, other information derived from MRI, nuclear imaging, and computed tomography useful for the selection of potential candidates for CRT will be discussed.
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http://dx.doi.org/10.1111/j.1540-8159.2008.01212.xDOI Listing
November 2008

Optimal left ventricular lead position predicts reverse remodeling and survival after cardiac resynchronization therapy.

J Am Coll Cardiol 2008 Oct;52(17):1402-9

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

Objectives: The aim of the current study was to evaluate echocardiographic parameters after 6 months of cardiac resynchronization therapy (CRT) as well as long-term outcome in patients with the left ventricular (LV) lead positioned at the site of latest activation (concordant LV lead position) as compared with that seen in patients with a discordant LV lead position.

Background: A nonoptimal LV pacing lead position may be a potential cause for nonresponse to CRT.

Methods: The site of latest mechanical activation was determined by speckle tracking radial strain analysis and related to the LV lead position on chest X-ray in 244 CRT candidates. Echocardiographic evaluation was performed after 6 months. Long-term follow-up included all-cause mortality and hospitalizations for heart failure.

Results: Significant LV reverse remodeling (reduction in LV end-systolic volume from 189 +/- 83 ml to 134 +/- 71 ml, p < 0.001) was noted in the group of patients with a concordant LV lead position (n = 153, 63%), whereas patients with a discordant lead position showed no significant improvements. In addition, during long-term follow-up (32 +/- 16 months), less events (combined for heart failure hospitalizations and death) were reported in patients with a concordant LV lead position. Moreover, a concordant LV lead position appeared to be an independent predictor of hospitalization-free survival after long-term CRT (hazard ratio: 0.22, p = 0.004).

Conclusions: Pacing at the site of latest mechanical activation, as determined by speckle tracking radial strain analysis, resulted in superior echocardiographic response after 6 months of CRT and better prognosis during long-term follow-up.
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http://dx.doi.org/10.1016/j.jacc.2008.06.046DOI Listing
October 2008

Cardiac manifestations of GH deficiency after treatment for acromegaly: a comparison to patients with biochemical remission and controls.

Eur J Endocrinol 2008 Dec 11;159(6):705-12. Epub 2008 Sep 11.

Department of Endocrinology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.

Objective: Both GH excess and GH deficiency (GHD) lead to specific cardiac pathology. The aim of this study was to evaluate cardiac morphology and function in patients with GHD after treatment for acromegaly.

Design: Cross-sectional study.

Patients And Methods: Cardiac parameters were studied by conventional two-dimensional echocardiography and tissue Doppler imaging in 53 patients with acromegaly (16 patients with GHD, 20 patients with biochemical remission, and 17 patients with active disease). Patients with GHD were also compared with age- and gender-matched controls.

Results: Left ventricular (LV) dimensions, wall thickness, and mass did not differ between the three groups, or between the patients with GHD and healthy controls. Systolic function, assessed by LV ejection fraction, tended to be lower in patients with GHD compared with patients with biochemical remission (65.9+/-7.3% vs 72.4+/-8.5%, P=0.070), but was higher when compared with active acromegaly (58.8+/-9.3%, P=0.047). No differences were found with healthy controls. Diastolic function, measured with early diastolic velocity (E'), was lower in patients with GHD when compared with both patients with biochemical remission (6.0+/-2.1 cm/s vs 8.3+/-1.5 cm/s, P=0.005) and healthy controls (8.1+/-1.9 cm/s, P=0.006).

Conclusion: GHD after acromegaly results in a specific decrease in diastolic function compared with patients with biochemical remission of acromegaly and healthy controls. In addition, systolic function tends to be decreased in patients with GHD compared with patients with biochemical remission, but was higher than that in patients with active acromegaly.
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http://dx.doi.org/10.1530/EJE-08-0496DOI Listing
December 2008

Real-time three-dimensional echocardiography as a novel approach to assess left ventricular and left atrium reverse remodeling and to predict response to cardiac resynchronization therapy.

Heart Rhythm 2008 Sep 6;5(9):1257-64. Epub 2008 Aug 6.

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

Background: Real-time 3-dimensional echocardiography (RT3DE) is a novel promising technique for the assessment of left ventricular (LV) dyssynchrony.

Objective: This study sought to explore the value of RT3DE to assess LV and left atrium (LA) reverse remodeling and to predict response to cardiac resynchronization therapy (CRT).

Methods: A total of 57 consecutive heart failure patients scheduled for CRT were included, and RT3DE was performed before and 6 months after implantation. LV dyssynchrony was defined as the standard deviation of the time to reach the minimum systolic volume for 16 LV segments, expressed in percentage of cardiac cycle (systolic dyssynchrony index, SDI). Patients were divided into responders or nonresponders, based on a reduction >or=15% in LV end-systolic volume after CRT.

Results: Six patients (10%) were excluded from further analysis because of suboptimal images. Of the remaining 51 patients, 34 (67%) were classified as responders. Baseline characteristics were similar between responders and nonresponders, except for the SDI, which was larger in responders (9.7% +/- 3.6% versus 5.1% +/- 1.8%, P <.0001). ROC curve analysis revealed that a cutoff value for SDI of 6.4% yielded a sensitivity of 88% with a specificity of 85% to predict response to CRT. In responders, RT3DE also showed beneficial effects of CRT on LA: (1) significant LA reverse remodeling; (2) significant improvement in LA total emptying fraction and in LA conduit and reservoir function.

Conclusion: RT3DE allows assessment of changes in LV and LA volumes and function after CRT, and it is highly predictive for response to CRT.
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http://dx.doi.org/10.1016/j.hrthm.2008.05.021DOI Listing
September 2008

Effects of interruption of long-term cardiac resynchronization therapy on left ventricular function and dyssynchrony.

Am J Cardiol 2008 Sep 18;102(6):718-21. Epub 2008 Jun 18.

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

Interruption of short-term cardiac resynchronization therapy (CRT) has been shown to acutely worsen left ventricular (LV) function, mitral regurgitation, and LV dyssynchrony. The present study aims to assess whether LV reverse remodeling influences interruption of CRT, and, more practically, whether long-term continuous pacing is necessary in patients with reverse LV remodeling. A total of 135 recipients of CRT were selected after showing LV reverse remodeling defined as a decrease in LV end-systolic volume > or =15% after 6 months of CRT ("responders"). Echocardiography was performed at baseline and after 6 months with intermittent CRT on and off. LV dyssynchrony was determined using tissue Doppler imaging. During interruption of CRT, an acute deterioration in LV function, mitral regurgitation, and LV desynchronization were noted in responder patients. Of note, worsening of these echocardiographic measurements was observed, but they did not return to baseline values. For comparison, 100 nonresponder patients (without LV reverse remodeling) showed no significant echocardiographic changes during interruption. In conclusion, despite the presence of LV reverse remodeling, interruption of CRT resulted in worsening of LV function and desynchronization. Therefore, continuous long-term pacing is warranted to maintain the beneficial effects.
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http://dx.doi.org/10.1016/j.amjcard.2008.05.009DOI Listing
September 2008

Myocardial collagen metabolism in failing hearts before and during cardiac resynchronization therapy.

Eur J Heart Fail 2008 Sep 2;10(9):878-83. Epub 2008 Sep 2.

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

Background: In patients with heart failure cardiac resynchronization therapy (CRT) leads to reverse ventricular remodelling.

Aim: To evaluate whether myocardial collagen metabolism in patients with heart failure is implicated in adverse ventricular remodelling and response to CRT.

Methods: Collagen synthesis and degradation were assessed from the concentrations of aminoterminal propeptides of type I and type III collagen (PINP and PIIINP) and carboxyterminal telopeptide of type I collagen (ICTP), respectively, in serum of 64 patients with heart failure before and after 6 months of CRT. Forty-six patients (72%) showed a > 10% reduction in LV end-systolic volume at follow-up and were classified as responders to CRT, the other 18 patients (28%) were classified as non-responders.

Results: Responders demonstrated a mean (+/-SEM) increase of serum PINP and PIIINP during follow-up, from 32.9+/-2.2 to 46.7+/-4.0 microg/L (p < 0.001) and from 4.59+/-0.24 to 5.13+/-0.36 microg/L (p < 0.05), respectively. In non-responders, serum PINP and PIIINP remained unchanged during follow-up. At baseline, responders had significantly lower serum PINP than non-responders (32.9+/-2.2 vs. 41.8+/-4.3 microg/L; p < 0.05). ICTP levels of responders at baseline tended to be higher than in non-responders (3.54+/-0.56 vs. 2.08+/-0.37 microg/L, p = ns), and in both groups ICTP levels did not change upon CRT.

Conclusion: Reverse LV remodelling following CRT is associated with increased collagen synthesis rate in the first 6 months of follow-up.
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http://dx.doi.org/10.1016/j.ejheart.2008.06.019DOI Listing
September 2008

Increased aortic root diameters in patients with acromegaly.

Eur J Endocrinol 2008 Aug 21;159(2):97-103. Epub 2008 May 21.

Departments of Endocrinology, C4-R, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.

Objective: The clinical manifestations of acromegalic cardiomyopathy include arrhythmias, valvular regurgitation, concentric left ventricular (LV) hypertrophy, and LV systolic and diastolic dysfunction. At present, it is unknown whether acromegaly also affects the aortic root.

Design: Aortic root diameters were prospectively assessed in 37 acromegalic patients (18 patients with active disease and 19 with controlled disease) by conventional two-dimensional and Doppler echocardiography before, and after, an observation period of 1.9 years (range 1.5-3.0 years). Baseline parameters were compared with healthy controls.

Results: The diameters of the aortic root at the sino-tubular junction and the ascending aorta were increased in patients with acromegaly: 30+/-4 vs 26+/-3 mm (P=0.0001) and 33+/-5 vs 30+/-4 mm (P=0.006) respectively. The diameter of the aortic root at the aortic annulus and aortic sinus were not different from controls. During follow-up, the aortic root diameters increased at the levels of the annulus and the sinotubular junction (P=0.025 and P=0.024 respectively), whereas there was no change in the diameters at the levels of the sinus and the ascending aorta during follow-up. Baseline aortic root diameters were not influenced by disease duration, current disease activity, or blood pressure. When patients with active and inactive disease were analyzed separately, only the diameter of the sinotubular junction increased in patients with inactive acromegaly during follow-up (P=0.031).

Conclusion: Aortic root diameters are increased in patients with acromegaly compared with healthy controls.
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http://dx.doi.org/10.1530/EJE-08-0138DOI Listing
August 2008

Assessment of left ventricular dyssynchrony by speckle tracking strain imaging comparison between longitudinal, circumferential, and radial strain in cardiac resynchronization therapy.

J Am Coll Cardiol 2008 May;51(20):1944-52

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

Objectives: The objective of this study was to assess the usefulness of each type of strain for left ventricular (LV) dyssynchrony assessment and its predictive value for a positive response after cardiac resynchronization therapy (CRT). Furthermore, changes in extent of LV dyssynchrony for each type of strain were evaluated during follow-up.

Background: Different echocardiographic techniques have been proposed for assessment of LV dyssynchrony. The novel 2-dimensional (2D) speckle tracking strain analysis technique can provide information on radial strain (RS), circumferential strain (CS), and longitudinal strain (LS).

Methods: In 161 patients, 2D echocardiography was performed at baseline and after 6 months of CRT. Extent of LV dyssynchrony was calculated for each type of strain. Response to CRT was defined as a decrease in LV end-systolic volume >/=15% at follow-up.

Results: At follow-up, 88 patients (55%) were classified as responders. Differences in baseline LV dyssynchrony between responders and nonresponders were noted only for RS (251 +/- 138 ms vs. 94 +/- 65 ms; p < 0.001), whereas no differences were noted for CS and LS. A cut-off value of radial dyssynchrony >/=130 ms was able to predict response to CRT with a sensitivity of 83% and a specificity of 80%. In addition, a significant decrease in extent of LV dyssynchrony measured with RS (from 251 +/- 138 ms to 98 +/- 92 ms; p < 0.001) was demonstrated only in responders.

Conclusions: Speckle tracking radial strain analysis constitutes the best method to identify potential responders to CRT. Reduction in LV dyssynchrony after CRT was only noted in responders.
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http://dx.doi.org/10.1016/j.jacc.2008.02.040DOI Listing
May 2008

Noninvasive imaging of cardiac venous anatomy with 64-slice multi-slice computed tomography and noninvasive assessment of left ventricular dyssynchrony by 3-dimensional tissue synchronization imaging in patients with heart failure scheduled for cardiac resynchronization therapy.

Am J Cardiol 2008 Apr 6;101(7):1023-9. Epub 2008 Feb 6.

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

Objectives of this study were to perform a prospective head-to-head comparison between multi-slice computed tomography (MSCT) venography and invasive venography in cardiac resynchronization therapy (CRT) candidates as well as to evaluate the relation between left ventricular (LV) lead position and effect on LV dyssynchrony and immediate response to CRT. Twenty-one consecutive heart failure patients scheduled for CRT implantation were prospectively enrolled to undergo 64-slice MSCT to visualize the venous system, invasive venography during device implantation, and tri-plane tissue synchronization imaging (TSI) before and after implantation. Excellent agreement between MSCT and invasive venography was noted. No significant differences were observed between both techniques regarding vessel diameters. In 12 patients, a match was observed between the area of latest mechanical activation (on TSI) and LV lead position. These patients showed a significant decrease in LV dyssynchrony (43 +/- 7 ms to 11 +/- 9 ms, p <0.0001) with acute reduction in LV end-systolic volume (188 +/- 54 ml to 162 +/- 48 ml, p <0.01) and improvement in LV ejection fraction (22% +/- 9% to 34% +/- 9%, p <0.01). Patients with a mismatch between area of latest activation and LV lead position remained dyssynchronous without improvement in LV function. In conclusion, visualization of major tributaries of the coronary sinus was comparable between invasive venography and MSCT venography. Optimal LV lead positioning in a vein draining the area of latest mechanical activation (determined from tri-plane TSI) resulted in acute improvement of LV dyssynchrony and systolic function after CRT implantation.
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http://dx.doi.org/10.1016/j.amjcard.2007.11.052DOI Listing
April 2008

Mechanism of improvement in mitral regurgitation after cardiac resynchronization therapy.

Eur Heart J 2008 Mar 27;29(6):757-65. Epub 2008 Feb 27.

Department of Cardiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.

Aims: The aim of the current study was to evaluate the relationship between the presence of left ventricular (LV) dyssynchrony at baseline and acute vs. late improvement in mitral regurgitation (MR) after cardiac resynchronization therapy (CRT).

Methods And Results: Sixty eight patients consecutive (LV ejection fraction 23 +/- 8%) with at least moderate MR (>or=grade 2+) were included. Echocardiography was performed at baseline, 1 day after CRT initiation and at 6 months follow-up. Speckle tracking radial strain was used to assess LV dyssynchrony at baseline. The majority of patients improved in MR after CRT, with 43% improving immediately after CRT, and 20% improving late (after 6 months) after CRT. Early and late responders had similar extent of LV dyssynchrony (209 +/- 115 ms vs. 190 +/- 118 ms, P = NS); however, the site of latest activation in early responders was mostly inferior or posterior (adjacent to the posterior papillary muscle), whereas the lateral wall was the latest activated segment in late responders.

Conclusion: Current data suggest that the presence of baseline LV dyssynchrony is related to improvement in MR after CRT. LV dyssynchrony involving the posterior papillary muscle may lead to an immediate reduction in MR, whereas LV dyssynchrony in the lateral wall resulted in late response to CRT.
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http://dx.doi.org/10.1093/eurheartj/ehn063DOI Listing
March 2008

Real-time three-dimensional echocardiography as a novel approach to quantify left ventricular dyssynchrony: a comparison study with phase analysis of gated myocardial perfusion single photon emission computed tomography.

J Am Soc Echocardiogr 2008 Jul 28;21(7):801-7. Epub 2008 Jan 28.

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

Background: Different imaging modalities have been explored for assessment of left ventricular (LV) dyssynchrony. Gated myocardial perfusion single photon emission computed tomography (GMPS) with phase analysis is a reliable technique to quantify LV dyssynchrony and predict response to cardiac resynchronization therapy.

Objective: Real-time 3-dimensional echocardiography (RT3DE) is a novel imaging technique that provides a LV systolic dyssynchrony index, based on regional volumetric changes as a function of time and calculated as the SD of time to minimum systolic volume of 16 standard myocardial segments expressed in percentage of cardiac cycle. The aim of this study was to compare LV dyssynchrony evaluated with GMPS with LV dyssynchrony assessed with RT3DE.

Methods: The study population consisted of 40 patients with heart failure who underwent both GMPS and RT3DE.

Results: Good correlations between LV dyssynchrony assessed with RT3DE and GMPS were demonstrated (r = 0.76 for histogram bandwidth, r = 0.80 for phase SD, P < .0001). Patients with substantial LV dyssynchrony on GMPS (defined as > or = 135 degrees for histogram bandwidth and > or = 43 degrees for phase SD) had significantly higher LV systolic dyssynchrony index than patients without substantial LV dyssynchrony.

Conclusions: The good correlations between LV dyssynchrony assessed with GMPS and with RT3DE provide further support for the use of RT3DE for reliable assessment of LV dyssynchrony.
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http://dx.doi.org/10.1016/j.echo.2007.12.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3048063PMC
July 2008

Real-time three-dimensional echocardiography permits quantification of left ventricular mechanical dyssynchrony and predicts acute response to cardiac resynchronization therapy.

J Cardiovasc Electrophysiol 2008 Apr 20;19(4):392-9. Epub 2007 Dec 20.

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

Objective: To evaluate the value of real-time three-dimensional echocardiography (RT3DE) to predict acute response to cardiac resynchronization therapy (CRT).

Methods: Sixty consecutive heart failure patients scheduled for CRT were included. RT3DE was performed before and within 48 hours after pacemaker implantation to calculate both left ventricular (LV) volumes and LV dyssynchrony. LV dyssynchrony was defined as the standard deviation of the time taken to reach the minimum systolic volume for 16 LV segments (referred to as the systolic dyssynchrony index, SDI). Patients were subsequently divided into acute responders or nonresponders, based on a reduction > or = 15% in LV end-systolic volume immediately after CRT.

Results: Four patients (7%) were excluded from further analysis because of either suboptimal apical acquisitions or significant translation artifacts. Out of the remaining 56 patients, 35 patients (63%) were classified as acute responders. Baseline characteristics were similar between responders and nonresponders, except for the SDI, which was larger in responders. Moreover, responders demonstrated a significant reduction of SDI immediately after CRT (from 9.7 +/- 4.1% to 3.6 +/- 1.8%, P < 0.0001), whereas SDI did not change in nonresponders (3.4 +/- 1.8% vs 3.1 +/- 1.1%, NS). ROC curve analysis revealed that a cut-off value for SDI of 5.6% yielded a sensitivity of 88% with a specificity of 86% to predict acute echocardiographic response to CRT (AUC 0.96).

Conclusion: RT3DE is highly predictive for acute response to CRT (sensitivity 88% and specificity 86%). In addition, RT3DE allows assessment of changes in LV volumes and LV ejection fraction before and after CRT implantation.
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http://dx.doi.org/10.1111/j.1540-8167.2007.01056.xDOI Listing
April 2008

Nuclear imaging in cardiac resynchronization therapy.

J Nucl Med 2007 Dec;48(12):2001-10

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

Recently, cardiac resynchronization therapy (CRT) has become implemented in the treatment of patients with severe heart failure. Although the improvement in systolic function after CRT implantation can be considerable, 20%-30% of patients do not respond to CRT. Evidence is accumulating that the presence of left ventricular (LV) dyssynchrony is mandatory for a response to CRT. Since the early 1980s attempts have been made to assess cardiac dyssynchrony with nuclear imaging, and it has been reported recently that information on LV dyssynchrony can be obtained from gated myocardial perfusion SPECT with phase analysis. Other studies with SPECT have shown that extensive scar tissue will limit the response to CRT; similarly, it has been demonstrated that viable tissue (assessed with SPECT) in the target zone for the LV pacing lead (usually the lateral wall) is needed for a response to CRT. Moreover, studies with PET have provided insight into the changes in myocardial perfusion, metabolism, and efficiency after CRT. In the current review, a comprehensive summary is provided on the potential role of nuclear imaging in the selection of heart failure patients for CRT. The value of other imaging techniques is also addressed.
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http://dx.doi.org/10.2967/jnumed.107.040360DOI Listing
December 2007

Usefulness of QRS duration to predict response to cardiac resynchronization therapy in patients with end-stage heart failure.

Am J Cardiol 2007 Dec 24;100(11):1665-70. Epub 2007 Oct 24.

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

Despite current selection criteria, 20% to 30% of patients treated with cardiac resynchronization therapy (CRT) do not benefit. It has been suggested that QRS duration may not be the optimal criterion to select patients for CRT. The objective of this study was to systematically evaluate the predictive value of QRS duration for response to CRT in a large group of consecutive patients. A total of 242 patients with heart failure scheduled for implantation of a CRT device were studied. Selection criteria for CRT included moderate to severe heart failure (New York Heart Association classes III to IV), left ventricular ejection fraction (LVEF)120 ms. Before CRT implantation, QRS duration and clinical status were assessed, and 2-dimensional echocardiography (LV volumes and LVEF) was performed. Clinical status and changes in LVEF and LV volumes were reassessed at 6-month follow-up. After 6 months of CRT, 68% of patients were classified as clinical responders (improvement of >or=1 grade in New York Heart Association class) and 60% as echocardiographic responders (decrease>10% in LV end-systolic volume). At baseline, no significant differences were observed in QRS duration between clinical responders and nonresponders and between echocardiographic responders and nonresponders. No significant relation was demonstrated between baseline QRS duration and improvement in clinical and echocardiographic variables at 6-month follow-up. In conclusion, baseline QRS duration is not predictive for clinical and echocardiographic responses to CRT at 6-month follow-up. Better predictors for CRT response are needed.
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http://dx.doi.org/10.1016/j.amjcard.2007.06.071DOI Listing
December 2007

Myocardial contractile reserve predicts improvement in left ventricular function after cardiac resynchronization therapy.

Am Heart J 2007 Dec 14;154(6):1160-5. Epub 2007 Sep 14.

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

Background: Myocardial contractile reserve has been shown to provide important prognostic information in patients with heart failure. We hypothesized that myocardial contractile reserve would predict left ventricular (LV) reverse remodeling after cardiac resynchronization therapy (CRT).

Methods: Thirty-one consecutive patients with heart failure (LV ejection fraction [LVEF] 26% +/- 7%, 35% nonischemic cardiomyopathy) underwent echocardiography during low-dose dobutamine infusion before CRT implantation to assess global contractile reserve (improvement in LVEF) and local contractile reserve in the region of the LV pacing lead (assessed by radial strain using speckle tracking analysis). Responders were defined by a decrease in LV end-systolic volume > or = 15% after 6 months of CRT.

Results: During low-dose dobutamine infusion, responders showed a greater increase in LVEF compared with nonresponders (delta 13% +/- 8% vs 3% +/- 4%, P < .001). Furthermore, contractile reserve was directly related to improvement in LVEF after 6 months of CRT (r = 0.80, P < .001). Moreover, a cutoff value of > 7.5% increase in dobutamine-induced LVEF exhibited a sensitivity of 76% and a specificity of 86% to predict response after 6 months of CRT (area under the curve 0.87). Lastly, contractile reserve in the region in the LV pacing lead was present only in responders (delta strain during low-dose dobutamine 6% +/- 5% in responders vs -1% +/- 4% in nonresponders, P = .002).

Conclusions: The current study demonstrates that myocardial contractile reserve (> 7.5% increase in LVEF during low-dose dobutamine infusion) predicts LV reverse remodeling after CRT.
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http://dx.doi.org/10.1016/j.ahj.2007.07.035DOI Listing
December 2007
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