Netherlands Heart Journal Supplements
Vo l u m e 2 4
A p r i l 2 01 6
Journal of the Netherlands Society of Cardiology
Abstracts of the Scientific Spring
Congress of the Netherlands
Society of Cardiology 2016
NHJ 1604 Abstracts NVVC incl omslag_proef5.indd 1
31 March and 1 April 2016, NH Leeuwenhorst, Noordwijkerhout
De medisch specialist
is (g)een alleskunner
Over het functioneren van
specialisten en maatschappen
Prof. dr. Douwe H. Biesma
DE MEDISCH SPECIALIST
IS (G)EEN ALLESKUNNER
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maar dat kan niet zonder goede context.
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internist Berend en MDL-arts Marlies, gevolgd door korte commentaren en ontwikkelingen. Daarnaast
laat hij enkele toonaangevende experts aan het woord over hun visie op de maatschap.
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NVVC incl omslag_proef5.indd
Spring Congress of the Netherlands
Society of Cardiology 2016
31 March and 1 April 2016,
NH Leeuwenhorst, Noordwijkerhout
We are pleased to present here the abstracts of the Scientific Spring Congress of the Netherlands Society of
Cardiology which will be held on 31 March and 1 April in NH Leeuwenhorst, Noordwijkerhout.
We hope that you will enjoy reading the abstracts.
On behalf of the Chief Editorial Board
Prof. Dr. E.E. van der Wall
Netherlands Heart Journal, Volume 24, Supplement, April 2016
NHJ 1604 Abstracts NVVC incl omslag_proef5.indd 1
Session 1: Cardiovascular Imaging
DIFFERENCES IN ATHEROSCLEROTIC BURDEN BETWEEN SOUTH ASIANS AND
CAUCASIANS WITH TYPE 2 DIABETES MELLITUS AND COMPARABLE 10 YEAR
PREDICTED CARDIOVASCULAR RISK
S.N. Gobardhan (LUMC, Leiden); A.C. Dimitriu-Leen (LUMC, Leiden); A.R. van Rosendael
(LUMC, Leiden); E.W. van Zwet (LUMC, Leiden); C.J. Roos (LUMC, Leiden); P.V. Oemrawsingh
(MCH, Den Haag); A.V. Kharagjitsingh (MCH, Den Haag); J.W. Jukema (LUMC, Leiden); M.J.
Schalij (LUMC, Leiden); J.J. Bax (LUMC, Leiden); A.J.H.A. Scholte (LUMC, Leiden);
The aim of this study was to explore the association of 10 year predicted cardiovascular
(CV) risk assessed with different risk models and the presence of coronary artery disease
(CAD) and coronary artery calcium (CAC) score in South Asians with type 2 diabetes
mellitus in comparison with matched Caucasians.
Asymptomatic type 2 diabetic South Asians and Caucasians were matched on age, gender,
BMI, hypertension and hypercholesterolemia. Several diabetes risk scores (UKPDS, FRS,
ASCVD and JBS3) were calculated and the presence of CAC and obstructive CAD (≥50%
stenosis) were assessed with coronary computed tomography angiography. In addition, the
association of South Asian ethnicity with the presence of CAC and obstructive CAD was
corrected for different CV risk models in multivariate analysis.
UKPDS, FRS and ASCVD showed no differences in estimated risk scores between 159
South Asians and 159 matched Caucasians. In contrast, JBS3 showed a significant higher
risk score in South Asians (17.6% vs 13.7%, p<0.01). Higher presence of CAC score > 0
(69% vs 55%, p<0.05) and obstructive CAD (39% vs 27%, p<0.05) was observed in South
Asians. In multivariate analysis, JBS3 corrected best for South Asian ethnicity in the
predictive CV risk for the presence of CAC score > 0 and obstructive CAD (Figure 1).
Asymptomatic South Asians with type 2 diabetes mellitus had more frequently CAC and
obstructive CAD compared with matched Caucasians with similar predictive CV risk scores.
JBS3 is recommended as predictive CV risk estimator in South Asians with type 2 DM.
Figure 1 Association between the South Asian ethnicity adjusted for cardiovascular risk scores and the
presence of coronary artery disease and coronary artery calcium on coronary computed tomography
WOMEN WITH SUSPECTED CORONARY ARTERY DISEASE BENEFIT MOST FROM
CARDIAC CT: RESULTS FROM THE MULTICENTER, RANDOMIZED CRESCENT TRIAL
Marisa Lubbers (Erasmus MC, Rotterdam), Adriaan Coenen (Erasmus MC, Rotterdam),
Tobias Bruning (Maasstad ziekenhuis, Rotterdam), Tjebbe Galema (Erasmus MC,
Rotterdam), Jurgen Akkerhuis (Sint Franciscus Gasthuis, Rotterdam), Boudewijn
Krenning (Haven ziekenhuis Rotterdam), Paul Musters (Erasmus MC, Rotterdam),
Mohamed Ouhlous (Erasmus MC, Rotterdam), Ahno Liem (Sint Franciscus Gasthuis,
Rotterdam), Andre Niezen (Maasstad ziekenhuis, Rotterdam), Admir Dedic (Erasmus MC,
Rotterdam), Ron van Domburg (Erasmus MC, Rotterdam), Miriam Hunink (Erasmus MC,
Rotterdam), Koen Nieman (Erasmus MC, Rotterdam)
To assess the sex-based differences in the effectiveness and safety of a cardiac CT strategy
versus standard functional testing in patients with symptoms suggestive of coronary artery
Cardiac CT to detect CAD in women may provide an alternative strategy with potential
benefits in terms of effectiveness and cost-efficiency.
Patients with stable angina were prospectively randomized between cardiac CT and
functional testing. The tiered cardiac CT protocol included a calcium scan followed by CT
angiography if the Agatston calcium score was between 1 and 400. Patients with test
specific contra-indications were not excluded from study participation.
In this pre-specified sub-analysis of the CRESCENT trial, which randomized 350 patients
(55% women) pre-dominantly middle-aged (55 ± 8 years) and the majority with an
intermediate pre-test probability of CAD, women presented more often with atypical chest
pain symptoms (58% vs. 46%, p=0.029). In both men and women CAD could be ruled out
more frequently by cardiac CT (women 84% vs. 48%, p<0.001; men 71% vs. 55%,
p=0.017). Women were more likely to have a zero calcium score (48% vs. 35%, p=0.036).
After one year women randomized to CT reported fewer anginal symptoms in comparison
to the functional testing group (40% vs. 22%, p=0.026). For both men and women
randomized to CT the diagnosis was reached faster, with less frequently required additional
diagnostic testing in women in the CT group (16% vs. 57%, p<0.001). For men this
difference just failed to reach statistical significance (27% vs. 41%, p=0.057). This resulted
in lower mean cumulative diagnostic costs for women (€270 vs. € 211, p<0.001). In men
there was no difference in overall diagnostic costs.
Cardiac CT is a safe, clinically more effective and cost-efficient alternative to functional
testing in the diagnostic workup of suspected coronary artery disease in women.
CAD = Presence of Coronary Artery Disease >50%. CAC = Presence of Coronary Artery Calcium,
calciumscore >0. JBS3 = Joint British Societies for the prevention of cardiovascular disease.
ASCVD = atherosclerotic cardiovascular disease. FRS = Framingham Risk Score. UKPDS = United Kingdom
Prospective Diabetes Study. OR = Odds Ratio. Cl = Confidence interval
LONG-TERM PROGNOSTIC VALUE OF DOBUTAMINE STRESS SPECT IN ELDERLY PATIENTS
UNABLE TO PERFORM EXERCISE TESTING
Figure 1. Kaplan-Meier curves for all-cause mortality. Event-free survival was significantly lower in patients with
an abnormal SPECT compared to patients with normal SPECT.
S. Roest (Erasmus MC, Rotterdam); H.J. Boiten (Erasmus MC, Rotterdam); R.T. van Domburg
(Erasmus MC, Rotterdam); R. Valkema (Erasmus MC, Rotterdam); A.F.L. Schinkel (Erasmus
Dobutamine stress myocardial perfusion imaging (MPI) is a feasible alternative for the
evaluation of coronary artery disease (CAD) in patients unable to perform an exercise test.
However, no data exist regarding the long-term prognostic value of stress MPI in elderly patients
unable to perform an exercise test.
We examined the outcome of 247 elderly patients ≥65 years old who underwent dobutamine
stress single-photon emission computed tomography (SPECT) MPI. End points were all-cause
mortality, cardiac mortality, and nonfatal myocardial infarction (MI). Hard cardiac events were
the combined endpoint of cardiac mortality and nonfatal MI. Kaplan-Meier curves were
constructed and univariable and multivariable Cox proportional hazards regression models
were used to examine the additional value of MPI parameters with the endpoints of interest.
During a mean follow-up of 8.2±5 years, 168 (68%) patients died (all-cause mortality), of which
56 (23%) were due to cardiac causes. Nonfatal MI occurred in 19 (8%) patients. Kaplan-Meier
survival curves showed that MPI provided optimal risk stratification in patients with normal and
abnormal MPI. Multivariable analysis identified an abnormal MPI as the strongest independent
predictor of all-cause mortality [HR 1.85, (95% CI 1.28-2.69), P<0.001] and hard cardiac
events [HR 2.66, (95% CI 1.54-4.61), P<0.001]. A reversible defect and the summed stress
score (SSS) were also strong long-term predictors of cardiac events.
Dobutamine stress MPI is useful in risk classifying elderly patients and provides incremental
prognostic information for the prediction of long-term survival and cardiovascular outcomes in
elderly patients, unable to perform exercise testing.
NHJ 1604 Abstracts NVVC incl omslag_proef5.indd 2
Netherlands Heart Journal, Volume 24, Supplement, April 2016
Session 1: Cardiovascular Imaging (continued)
ANOMALOUS CORONARY ARTERY ORIGINATING FROM THE OPPOSITE SINUS OF
VALSALVA; FRACTIONAL FLOW RESERVE- AND INTRAVASCULAR ULTRASOUND-GUIDED
MANAGEMENT IN 17 CONSECUTIVE PATIENTS
B.W. Driesen (UMC Utrecht); G.J. Krings (WKZ Utrecht); P.A.F.M. Doevendans (UMC Utrecht);
M. Voskuil (UMC Utrecht).
To describe the use of fractional flow reserve (FFR) and intravascular ultrasound (IVUS) in the
assessment of anomalous coronary arteries originating from the opposite sinus of Valsalva
We retrospectively studied 17 consecutive patients with ACAOS who received IVUS- and FFRguided treatment at our institution between October 2010 and October 2015. FFR was
performed using adenosine and if normal also dobutamine was given. IVUS was performed
using Volcano Revolution catheter.
FFR was abnormal in only 3 patients. IVUS showed the typical slit-like anatomy of the origo in
12 patients. Based on either one of these measurements and the clinical presentation,
intervention by unroofing of the coronary artery (n=6) was performed. No periprocedural
complications occurred. In all other patients a conservative strategy was executed. No adverse
events occurred after a mean of 20 months of follow-up.
Conservative treatment is justifiable in patients with ACAOS in presence of non-significant FFR
and IVUS results and absence of suspicious clinical symptoms. We recommend to use FFR
and/or IVUS in standard work-up for ACAOS.
AVNRT with positive troponin
Slitlike orifice, coronary compression
SIMILAR OUTCOME AFTER A NEGATIVE TEST RESULT FOR ALL NON-INVASIVE
CARDIAC IMAGING MODALITIES IN PATIENTS WITH SUSPECTED OR KNOWN
CORONARY ARTERY DISEASE – A META-ANALYSIS
M.W. Smulders (MUMC, Maastricht)*; C. Jaarsma (MUMC, Maastricht)*; P.J. Nelemans
(MUMC, Maastricht); S.C.A.M. Bekkers (MUMC, Maastricht); J. Bucerius (MUMC,
Maastricht); T. Leiner (UMC, Utrecht); H.J.G.M. Crijns (MUMC, Maastricht); J.E. Wildberger
(MUMC, Maastricht); S. Schalla (MUMC, Maastricht). *these authors contributed
The prognostic value is one of the most robust features of non-invasive cardiac imaging.
However, comparison of prognosis between all available tests and the influence of the pretest probability has not been explored before in a single study.
MEDLINE, EMBASE and Cochrane Library were searched for studies investigating the
prognostic value of coronary computed tomographic angiography, cardiovascular magnetic
resonance, exercise electrocardiographic testing, positron emission tomography, stressechocardiography, and single-photon emission tomography in patients with suspected or
known coronary artery disease (CAD). Studies were included if a (derivable) annual event
rate (AER) of non-fatal myocardial infarction and cardiac death for a negative test result
165 studies (122,721 patients) were included. A negative test result was associated with
an overall pooled AER of 0.94% (0.81-1.09) ranging from 0.32% [0.22-0.43] for computed
tomography angiography to 1.66% [1.22-2.16] for stress-echocardiography during 2.7
years follow-up. A lower AER after a negative test result was significantly correlated with the
baseline risk of events (Figure 1). After correcting for the baseline risk and presence of CAD
(pre-test probability) using meta-regression analysis, the prognosis after a negative test
result was similar between all non-invasive imaging modalities.
This meta-analysis is the first study comparing all available non-invasive cardiac imaging
modalities. It shows that a negative test result, regardless of the selected modality, conveys
an excellent prognosis for patients with suspected or known CAD. Differences between
modalities in the number of events after a negative test result may be explained by
differences in pre-test probability.
THE ASSOCIATION OF LEFT ATRIAL DIMENSIONS AND FUNCTION WITH AGE AND
LEFT VENTRICULAR DIASTOLIC FUNCTION IN A HEALTHY DUTCH POPULATION
R.W.J. van Grootel (Erasmus MC, Rotterdam); M.E. Menting (Erasmus MC, Rotterdam);
A.E. van den Bosch (Erasmus MC, Rotterdam); J.S. McGhie (Erasmus MC, Rotterdam);
W.B. Vletter (Erasmus MC, Rotterdam); M. Strachinaru (Erasmus MC, Rotterdam); M.L.
Geleijnse (Erasmus MC, Rotterdam); J.W. Roos-Hesselink (Erasmus MC, Rotterdam).
Left atrial (LA) volume is associated with adverse cardiovascular events and outcome. We
aim to determine the relationship between LA dimensions and function with
anthropomorphic factors and left ventricular (LV) diastolic function, to propose normative
values in a healthy Dutch population.
A cohort of 155 prospectively recruited healthy subjects, aged 20-72 years (at least 28
subjects per decade, equally distributed for sex) underwent physical examination and
2D-echocardiography. LA minimum, maximum and pre-A volumes (PAV) were measured
using the method-of-disk-summation-technique. LA reservoir, conduit and pump function
were assessed with total, passive and active emptying volumes (TEV, PEV, AEV) and
corresponding fractions (TEF, PEF, AEF). LV diastolic function was assessed with peak Eand A-velocities, TDI E’ and deceleration time.
147 subjects were included (age 44±14 years, 50% female). Normal values are presented
in figure per age group. Variables pertaining LA dimension and function were significantly
correlated with age (LA-min r=0.252, PAV r=0.437, TEF r=-0.279, PEF r=-0.613, AEF
r=0.281). This was also true for LV diastolic function parameters (E-wave r=-0.457, A-wave
r=0.582, E/A-ratio r= -0.680, deceleration time r=0.313, E’(septal) r=-0.756, E/E’-ratio
r=0.472). Multivariate analysis showed that age was an independent predictor for LA
dimensions, function and LV diastolic function. Peak E- and A-velocities were strong
independent predictors for LA conduit and pump function.
This study provides echocardiographic reference ranges for LA dimensions and function
which can be utilized to enhance accuracy of echocardiographic diagnostics. The results
emphasize the need for age-specific assessment.
Figure 1. Left atrial volume & function
Figure 1. Correlation of the prognosis after a negative test result and the index risk of the referred
population for all non-invasive cardiac imaging modalities.
LA: Left Atrial. Volumes are indexed with BSA. *: p < 0.05. **: p < 0.001.
Netherlands Heart Journal, Volume 24, Supplement, April 2016
NHJ 1604 Abstracts NVVC incl omslag_proef5.indd 3
Session 1: Cardiovascular Imaging (continued)
THE IMPACT OF HYBRID CORONARY CT ANGIOGRAPHY AND ADENOSINE STRESS CT
PERFUSION IMAGING ON REFERRAL FOR CATHETERIZATION AND SUBSEQUENT
REVASCULARIZATION IN PATIENTS WITH NEW-ONSET CHEST PAIN
A.R. van Rosendael (LUMC, Leiden); A.C. Dimitriu-Leen (LUMC, Leiden); E.W. van Zwet (LUMC,
Leiden); J.W. Jukema (LUMC, Leiden); J.J. Bax (LUMC, Leiden); L.J. Kroft (LUMC, Leiden); A.J.
Scholte (LUMC, Leiden)
The aim of this study was to assess the impact of a protocol consisting of coronary artery
calcium (CAC) score and coronary computed tomography angiography (CTA), added with
adenosine stress computed tomography perfusion (CTP) in case of ≥ 50% stenosis (cardiac CT
imaging protocol), on the downstream performance of catheterization and revascularization in
patients presenting with new-onset stable chest pain.
384 patients with new-onset stable chest pain were enrolled in the cardiac CT imaging
protocol. Patients with lesions ≥ 50% stenosis underwent subsequentially stress CTP.
Perfusion scans were considered abnormal if a defect was observed in ≥ 1 segment.
Downstream performance of catheterizations and revascularization was assessed within 3
In total, 115 patients showed ≥ 50% stenosis on coronary CTA; the stress CTP was normal in
48 patients, abnormal in 38 patients and not performed in 29 patients. After normal stress
CTP, 13 (27%) patients underwent catheterization and 8 (17%) underwent revascularization.
After abnormal stress CTP, 36 (95%) underwent catheterization and 29 (76%)
revascularizations were performed. No or non-obstructive CAD was observed in 269 patients
among whom 8 underwent catheterization; none underwent revascularization. The rate of
finding ≥ 50% stenosis at catheterization was 80%.
The cardiac CT imaging protocol consisting of CAC score and coronary CTA, added with stress
CTP in case of ≥ 50% stenosis effectively serves as a gatekeeper to catheterization and
revascularization for patients with new onset chest pain. In patients with ≥ 50% stenosis,
stress CTP could direct clinical decision making regarding downstream catheterization and
EKOSONIC ULTRASOUND ENDOVASCULAR SYSTEM FOR THE TREATMENT OF
HEMODYNAMICALLY UNSTABLE PULMONARY EMBOLISM
Hart, E (UMC Utrecht, Utrecht); Leenders, GEH (UMC Utrecht, Utrecht); Carpaij, N (UMC
Utrecht, Utrecht); Klöpping, C (UMC Utrecht, Utrecht); Bronsveld, I (UM Utrecht, Utrecht);
Stella, PR (UMC Utrecht, Utrecht); Voskuil, M (UMC Utrecht, Utrecht); Chamuleau, SAJ
(UMC Utrecht, Utrecht); Kraaijeveld, AO (UMC Utrecht, Utrecht)
To assess the initial experience with the EkoSonic Ultrasound Endovascular System
(EKOS), a novel local ultrasound assisted low-dose thrombolysis system for the treatment
of hemodynamically unstable pulmonary embolism (PE).
Patients with hemodynamically unstable PE that were treated with EKOS from December
2014 until February 2016 in the University Medical Center Utrecht were included in a
registry. Efficacy outcomes were clinical improvement at discharge and reduction in right
ventricular pressure and/or remission of PE as assessed by echocardiography or CT
angiography (CTA), respectively. Safety outcomes were all-cause mortality, bleeding
(International Society on Thrombosis and Haemostasis criteria), hospitalization time and
Eight patients with CTA confirmed PE were included. All patients showed significant
obstructive PE upon diagnosis. Following EKOS, 6 patients (75%) showed clinical improve
ment, 2 patients (25%) died. One patient died from cerebral infarction accompanied by
septic shock, 1 patient died due to right-sided heart failure.
Six patients underwent CTA follow-up; all showed remission of pulmonary emboli. Of the
two patients without CTA follow-up, 1 patient showed an echocardiographic decrease in
right ventricular dilation and pressure and 1 patient showed no improvement.
Two patients (25%) developed a bleed. One bleed consisted of a post-traumatic rib
hematoma with a significant Hb drop of ≥1.24 mmol/L (major bleed), the other consisted
of a post-traumatic periocular hematoma (clinically relevant non-major bleed).
Median hospitalization time was 7 days, no recurrence of PE was observed.
EKOS therapy for the treatment of hemodynamically unstable PE seems to be effective at
reducing thrombus load without inducing clinically significant bleeding complications.
NHJ 1604 Abstracts NVVC incl omslag_proef5.indd 4
Netherlands Heart Journal, Volume 24, Supplement, April 2016
Session II: Atrial fibrillation/Anticoagulants
ECHOCARDIOGRAPHIC ASSOCIATES OF ATRIAL FIBRILLATION IN END-STAGE RENAL
PERIATRIAL EPICARDIAL ADIPOSE TISSUE DOES NOT PREDICT OUTCOME IN HYBRID
ATRIAL FIBRILLATION ABLATION
L.C.R. Hensen (LUMC, Leiden); V. Delgado (LUMC, Leiden); S.E. van Wijgaarden
Leiden); M. Leung (LUMC, Leiden); M.K. de Bie (LUMC, Leiden); M.S. Buiten
Leiden); M.J. Schalij (LUMC, Leiden); J.J. Van de Kerkhof (Bernhoven Medical
Uden); J.W. Jukema (LUMC, Leiden); T.J. Rabelink (LUMC, Leiden); J.I. Rotmans
Leiden); J.J. Bax (LUMC, Leiden)
M.Vroomen (MUMC, Maastricht); B. Maesen (MUMC, Maastricht); V. L’Espoir (MUMC,
Maastricht); S. Verheule (MUMC, Maastricht); M. La Meir (UZ Brussel, Brussel); U.
Schotten (MUMC, Maastricht); J.G. Maessen (MUMC, Maastricht); H.J.G.M. Crijns (MUMC,
Maastricht); L. Pison (MUMC, Maastricht).
The prevalence of atrial fibrillation (AF) in end-stage renal disease (ESRD) patients is high.
Changes in the atrium, such as an increased size and myocardial fibrosis, may lead to
delayed conduction and are known substrates for AF. PA-TDI duration, a parameter derived
from tissue Doppler imaging, measures delay between electrical conduction and
mechanical activation of the atrial myocardium. This is a surrogate for detecting substrates
in the left atrial wall. The present study evaluated whether atrial substrates differ between
ESRD patients with and without AF.
ESRD patients enrolled in the Implantable Cardioverter Defibrillators in Dialysis patients
(ICD2) trial until June 2015 were included. Clinical and echocardiographic characteristics
were evaluated. Based on ICD remote monitoring or clinical records, the occurrence of AF
Of 171 patients, 47 (27%) patients experienced AF. There were no differences in left
ventricular ejection fraction or mitral regurgitation between ESRD patients with and without
AF. However, patients with AF had significantly larger left atrial volume index (LAVI), reduced
late diastolic mitral annular velocity and longer PA-TDI duration compared to patients
without AF (Table 1). Larger LAVI and longer PA-TDI duration were independently associated
with the presence of AF (OR 1.05, 95% CI 1.02-1.09, p=0.004 and OR 1.02, 95% CI 1.001.03, p=0.023) after correcting for age and left ventricular filling pressure.
ESRD patients with AF show increased LAVI and delay of atrial conduction (based on PA-TDI
duration) compared to ESRD patients without AF, suggesting more advanced changes in
the LA substrate. Purpose:
Epicardial adipose tissue volume (EAT-V) is greater in patients with a recurrence after a
catheter ablation compared to those who maintained sinus rhythm. The aim of the present
study is to explore the relation between periatrial EAT-V and outcome after a hybrid AF
ablation (epicardial surgical and endocardial catheter ablation).
Fifty patients referred for a hybrid ablation were studied. On preoperative CT-scans, left
atrial (LA) and right atrial (RA) EAT-V were identified by a window of -30 to -190 Hounsfield
Units, using custom-made imageJ. Also myocardial mass (10 to 120 Hounsfield Units) and
LA volumes (LAV) were assessed. Follow-up in 49 patients (1 lost to follow-up) at 1 year was
conducted according the HRS expert consensus statement.
Detailed results are depicted in the table. EAT-V was not significantly different between
paroxysmal and persistent AF patients. EAT-V was not predictive of acute conduction block
in the epicardial surgical box lesion, neither of AF recurrence at 1 year. LA EAT-V did not
correlate with LAV determined on echocardiography (r=0.22, P=ns), but did correlate with
LAV determined on CT (r=0.42, P<0.01). Overall, LAV determined on CT correlated to but
was systematically smaller than LAV determined on echocardiography (r=0.40, P<0.01).
In patient with a complex underlying AF substrate undergoing hybrid AF ablation, total EAT-V
is not predictive of recurrence at 1 year. LA EAT-V does increase with LAV, and thus could
fatty infiltration play a role in early substrate development, but less in the domestication of
Type of AF
Table 1. Clinical and echocardiographic characteristics of ESRD patients with and without AF
No AF (n=124)
Heart rate (beats/min)
67 ± 10
72 ± 12
56 ± 8
54 ± 8
Moderate/severe MR, n (%)
29 ± 11
23 ± 10
Lateral A’ (cm/s)
7.1 ± 2.8
8.2 ± 2.4
144 ± 30
131 ± 27
EAT-V LA (mL)
EAT-V RA (mL)
10.6±5.7 0.44 9.6±5.3
Outcome 1 year
12.7±6.1 0.17 8.5±1.9
Total EAT-V (mL) 16.5±8.9 18.8±9.8 0.39 17.4±9.9 21.8±8.7 0.28 15.9±5.4 17.8±9.9 0.67
EAT-V = Epicardial Adipose Tissue, LA = Left Atrium, RA = Right Atrium, AF = Atrial Fibrillation, PAF =
Paroxysmal AF, persAF = persistent + long-standing persistent AF, SR = Sinus Rhythm.
Continuous data are presented as mean ± SD. Categorical data are presented as numbers and
percentages. LAVI, left atrial volume index; LVEF, left ventricular ejection fraction; MR, mitral
regurgitation; TDI, tissue doppler imaging
SURGICAL VERSUS PERCUTANEOUS AF ABLATION; A RANDOMIZED CONTROLLED
GALECTIN-3 DOES NOT REFLECT PROGRESSION OF THE FIBROTIC SUBSTRATE IN
THE HUMAN ATRIA AND SERUM OF PATIENTS WITH ATRIAL FIBRILLATION
A. Adiyaman (Isala Klinieken, Zwolle); L. Schreuder (Isala Klinieken, Zwolle); R. Beukema
(Isala Klinieken, Zwolle); P.P. Delnoy (Isala Klinieken, Zwolle); J.J.J Smit (Isala Klinieken,
Zwolle); H. Sie (Isala Klinieken, Zwolle); A.R. Ramdat Misier (Isala Klinieken, Zwolle); A.
Elvan (Isala Klinieken, Zwolle).
W.R. Berger (AMC, Amsterdam), B. Jagu (AMC, Amsterdam), N.W.E. van den Berg (AMC,
Amsterdam), D.R.P.P. Chan Pin Yin (Spaarne Gasthuis, Zaandam), J. Neefs (AMC,
Amsterdam), J.P. van Straalen (AMC, Amsterdam), A.H.G. Driessen (AMC, Amsterdam),
S.P.J. Krul (AMC, Amsterdam), W. J. van Boven (AMC, Amsterdam), J.R. de Groot (AMC,
The cornerstone of invasive AF treatment is pulmonary vein isolation (PVI). Both minimally
invasive thoracoscopic epicardial PVI (MIPI) and percutaneously performed endocardial PVI
are accepted treatments. As no randomized data is present for patients undergoing a first
ablation, it is yet unclear which approach is most effective.
We conducted a randomized controlled trial in patients with lone, paroxysmal or persistent
AF, undergoing a first ablation. Patients were randomized to MIPI with LAA excision or
percutaneous PVI (PVI). RF energy was used for all ablations. All patients were monitored
with implanted continuous loop monitors from 6 months before up to 2 years after the
procedure. The primary outcome measure was freedom of atrial tachyarrhythmia. Results
were analyzed on an intention to treat basis. The safety endpoint was freedom of
complications, and was analyzed on an as treated basis.
Between 2007 and 2013, fifty patients with drug-refractory AF were randomized to CA
(n=25) or MIPI (n=25). Median age was 57 years (range 37-75), 78% were male and 74%
had paroxysmal AF. All patients had 2 years of follow-up. No significant differences were
present for the primary endpoint after 6 and 12 months follow-up. After 2 years, more
patients were free of atrial tachyarrhythmia after PVI versus MIPI (12/27, 44% versus 6/22
27%, P=0.047). More procedure related major complications occurred after MIPI than after
CA (0% versus 22%, p=0.016).
Percutaneous PVI results in lower long-term AF recurrence rates than surgical PVI with LAA
Netherlands Heart Journal, Volume 24, Supplement, April 2016
NHJ 1604 Abstracts NVVC incl omslag_proef5.indd 5
Galectin-3(Gal-3), a soluble lectin expressed in a variety of tissues, appears to be an
important mediator of cardiac fibrosis, particularly in heart failure. Gal-3 levels are
associated with increased risk of developing atrial fibrillation(AF) and may reflect atrial
fibrotic remodeling. Therefore, Gal-3 may be a biomarker for AF progression. We
investigated the relation between atrial fibrosis and Gal-3 concentrations in atrial tissue
and serum of AF patients.
Left atrial appendages(LAAs) and serum were collected from patients undergoing
thoracoscopic pulmonary vein isolation (TPVI) for treatment of AF. Gal-3 concentrations in
tissue and serum were measured with ELISA and normalized for total protein concentration.
Picrosirius red staining was performed for quantification of interstitial collagen.
Ninety-eight patients(76% male, mean age 60±9 years) underwent TPVI for paroxysmal
(PAF,n=44) or persistent AF(PeAF,n=54). The percentage of left atrial fibrosis was 5.1 and
5.0% (p=1.0), and did not correspond to local Gal-3 expression (93.6±28.6ug/l and
91.9±28.4ug/l, p=0.08 in PAF and PeAF respectively). Serum Gal-3 levels were not
significantly different in PAF and PeAF (14.4±4.1 and 14.1±3.6 ug/l p=0.97) and did not
correlate with tissue Gal-3 (p=0.3) or actual atrial fibrosis (p=0.2).
Atrial fibrosis does not correspond to circulating Galecin-3 in patients with AF, and neither
correlates with local Galectin-3 expression in atrial tissue. Our data suggest that changes
in Galectin-3 may reflect remote processes and are not mechanistically related to AF
progression. This may limit the clinical applicability of circulating Gal-3 as a biomarker for
progression of the fibrotic substrate of AF.
Session II: Atrial fibrillation/Anticoagulants (continued)
SAFETY AND EFFICACY OF HYBRID ABLATION IN PATIENTS WITH LONGSTANDING
PERSISTENT ATRIAL FIBRILLATION
ADHERENCE TO NON VITAMIN K ORAL ANTICOAGULANTS IN ADULTS WITH
CONGENITAL HEART DISEASE
M.I.H. Al-Jazairi (UMCG, Groningen); T.J. Klinkenberg (UMCG, Groningen); J. Korenstra
(UMCG, Groningen); M. Rienstra (UMCG, Groningen); I.C. Van Gelder (UMCG, Groningen);
M. Mariani (UMCG, Groningen); Y. Blaauw (UMCG, Groningen)
H. Yang (AMC, Amsterdam); G. Scognamiglio (Vincenzo Monaldi Hospital, Naples); M.
Ladouceur (Hôpital Européen Georges Pompidou, Paris); F.J. Meijboom (UMCU, Utrecht);
T. Konings (VU, Amsterdam); R.J.G. Peters (AMC, Amsterdam); B.J. Bouma (AMC,
Amsterdam); B.J.M. Mulder (AMC, Amsterdam)
Catheter ablation of longstanding persistent atrial fibrillation (LS-AF) has high recurrence
rates (even with multiple procedures). Safety and efficacy of combined surgical
thoracoscopic and percutaneous ablation (hybrid), as a promising approach to treat LS-AF,
Consecutive patients undergoing single stage hybrid AF ablation (consisting of
thoracoscopic PVI, roof, inferior line and SVC isolation, LAA exclusion by CHADS-VASc≥2,
endocardial ablation by incomplete surgical lines, CTI-ablation, and CFAEs ablation if AF
persisted). Efficacy was assessed using 3-day Holter at 3, 6 and 12 months. Major adverse
events (MAEs) were prospectively assessed and included death, major bleeding, stroke,
TIA, cardiac tamponade, myocardial infarction and major complications requiring surgical
Thirty-six patients, mean age was 55±8 years, 30 (83%) were men, 33 (92%) had
symptomatic persistent AF, 18 (50%) had prior ablation(s) and total AF history was 5.1
years (2.1-8.7y). Mean BMI was 28.0±3.3, mean LAVI was 39±10ml/m2 and mean LVEF
was 54±6%. Mean procedure time was 339±50 minutes. After a median follow-up of 7
months (3-10m), AF recurrence rate was 3% without AAD and 0% with AAD. Two (6%)
patients had recurrence of atypical atrial flutter, neither requiring additional treatment.
AADs were discontinued in 33 (92%) patients at 6±2 weeks. No re-interventions were
performed or scheduled. Three (8%) patients developed MAEs; one had major bleeding
necessitating sternotomy, one developed pericardial and pleural effusion requiring
drainage and one developed pleural effusion requiring drainage. No death occurred.
Our initial results of single stage hybrid AF ablation in patients with LS-AF demonstrate
efficacy and safety.
RESULTS FROM A DUTCH NOAC/VKA OBSERVATIONAL STUDY
F.R. den Hartog (Ziekenhuis Gelderse Vallei, Ede); R.P. van ‘t Land (Trombosedienst
Neder-Veluwe, Ede); P. van Mourik (Ziekenhuis Gelderse Vallei, Ede); M. Langedijk
(Ziekenhuis Gelderse Vallei, Ede); D.J. Duits-Kroon (Trombosedienst Neder-Veluwe,
Ede); J.Zimmerman (Ziekenhuis Gelderse Vallei, Ede)
In the Gelderse Vallei the introduction of NOAC for atrial fibrillation includes evaluation of
clinical endpoints in our real life patients. The purpose is to attribute to the search for a
good stratification of “real” patients to the right individual anticoagulation therapy.
There was an active registration of thromboembolic events, severe bleeding and intra
cranial bleeding, searched for in our cohorts (VKA 2014;NOAC 2015) as rigorous as in
international NOAC trials. There was no randomization or correction for differences
between our two cohorts. VKA results for 2015 will follow. The time in therapeutic range
(TR) for VKA (INR) was around 85% for the long term patients. The TR was 2,0 – 3,5 INR for
most of patients. Only around 4% of these INR’s was below 2,0.
Regardless of methodological differences and differences in patient characteristics the
data show comparable event risks for our own VKA and NOAC cohorts, both of which in
general perform better than both NOAC and warfarin in the NOAC trials (table, including
1. Our careful, protocolled introduction of NOAC performs better than NOAC and warfarin
in NOAC trials. NOAC performs equal to VKA in our cohorts, set aside differences in
2. VKA in our population performs better than warfarin in NOAC trials.
3. Our data support the recommendation for continued registration to confirm or reject
these figures and to learn to stratify patients to the preferred anticoagulation therapy.
Adherence to non-vitamin K oral anticoagulants (NOACs) is of great concern due to lack of
anticoagulation monitoring and devastating consequences of stroke. Recent data on
patients with acquired heart disease using NOACs demonstrated that 70-75% were
sufficiently adherent. However, adherence to NOACs and vitamin K antagonists (VKA) in
adult congenital heart disease (ACHD) patients with atrial arrhythmias is currently
Patients enrolled in the NOTE registry were included in this study. Adherence was measured
using 1) pharmacy interrogation at 1-year follow-up (n=28) to calculate medication refill
adherence (MRA) and 2) Morisky-8 questionnaire (MMAS-8), obtained at baseline, 6
months and 1-year follow-up (n=58). Adherence was classified as sufficient if MMAS-8
adherence was middle (6-7) to high (8) or MRA adherence was ≥80%. Chi-square test was
used for comparisons.
A total of 58 ACHD patients were included (mean age 51y, 41.4% male, 84.5% moderate/
complex ACHD, median CHA2DS2-VASc 2). Pharmacy data revealed a high overall
adherence of 98% (IQR 88.9-103), with 24 patients (86%) being sufficiently adherent. With
MMAS-8 questionnaire, 70% of the patients scored sufficient adherence at 1-year follow
up. In patients, who previously used VKA (n=37), 84% had sufficient adherence, which did
not change at 6 months (87%, p=0.727) or at 1-year follow-up (81%, p=1.000). Main
reason for low adherence (n=12) was polypharmacy.
In this ongoing study, the first results regarding adherence to NOACs in ACHD patients are
reassuring with sufficient adherence rates, equal to VKA adherence and higher than
reported in patients with acquired heart disease.
ENDO-EPICARDIAL DISSOCIATION OF THE RIGHT ATRIAL WALL DURING ATRIAL
FIBRILLATION IN HUMANS
J.M.E. van der Does (Erasmus MC, Rotterdam); A. Yaksh (Erasmus MC, Rotterdam); P.
Knops (Erasmus MC, Rotterdam); E.A.H. Lanters (Erasmus MC, Rotterdam); C.P. Teuwen
(Erasmus MC, Rotterdam); P.C. van de Woestijne (Erasmus MC, Rotterdam); J.A. Bekkers
(Erasmus MC, Rotterdam); C. Kik (Erasmus MC, Rotterdam); A.J.J.C. Bogers (Erasmus
MC, Rotterdam); M.A. Allessie (Erasmus MC, Rotterdam); N.M.S. de Groot (Erasmus MC,
The purpose of this study is to provide evidence for the occurrence of endo-epicardial
dissociation in human atrial fibrillation (AF) in support of the hypothesis of two layers acting
as drivers for each other during AF.
Intra-operative mapping of the endo- and epicardial right atrial wall was performed during
(induced) AF in 14 patients with (N=10) and without (N=4) a history of AF. Before venous
cannulation, a clamp made of two rectangular 8x16 electrode arrays (inter-electrode
distance 2mm) was inserted into the incision in the right atrial appendage. Recordings of
10 seconds of AF were analysed to determine the incidence of asynchronous endoepicardial activation times (≥15ms) of opposite electrodes.
Patients were surgically treated for coronary heart disease (N=9), mitral valve (N=7),
tricuspid valve (N=4) and/or aortic valve disorders (N=2). Patients with AF prior to surgery
had paroxysmal (N=3), persistent (N=4) or longstanding persistent AF (N=3). Asynchronous
endo-epicardial activation ranged between 0.9-55.9% and seems to occur more often in
patients with AF than without AF (18.9% vs 5.2%). Focal waves appeared equally frequent
at endocardium and epicardium (579 vs 620). Using strict criteria for breakthrough
(presence of an opposite wave within 4mm and ≤14ms before the origin of the focal wave),
the majority (65%) of all focal fibrillation waves could be attributed to endo-epicardial
We provided the first evidence for asynchronous activation of the endo-epicardial wall during
AF in humans. Endo-epicardial asynchrony may play a major role in the pathophysiology of AF.
Tabel: Event risk / patient year in AF
NHJ 1604 Abstracts NVVC incl omslag_proef5.indd 6
Figure 1. Epi- and endocardial activation maps recorded during AF demonstrating endo-epicardial
dissociation. Black/white arrows illustrate the direction of conduction. Isochrones are set at 5ms intervals.
Thick black lines indicate conduction block (<18 cm/s). A focal wave appears at the white star. Four
examples of corresponding endo-epicardial electrograms show the
Netherlands Heart Journal, Volume 24, Supplement, April 2016
Session III: Electrophysiology
ANALYSIS OF CIRCADIAN REPOLARIZATION IDENTIFIES QTC DIURNALITY AS A
NOVEL CLINICAL PARAMETER ASSOCIATED WITH HERG CHANNEL DYSFUNCTION
AND VENTRICULAR ARRHYTHMIAS
B.C. du Pré (UMC Utrecht, Utrecht); L.W. Van Laake (UMC Utrecht, Utrecht); M. Meine
(UMC Utrecht, Utrecht); J.F. van der Heijden (UMC Utrecht, Utrecht); P.A. Doevendans
(UMC Utrecht, Utrecht); M.A. Vos (UMC Utrecht, Utrecht); A.A.B Van Veen (UMC Utrecht,
Cardiac repolarisation abnormalities are among the major causes of ventricular
arrhythmias and sudden cardiac death. In humans, cardiac repolarisation duration has a
24-hour rhythm and peaks in the early morning. Previous studies showed that in mice, the
amplitude (diurnality) of this rhythm is associated with hERG channel dysfunction. Here, we
investigated whether in man 1) 24-hour rhythms in repolarisation are associated with hERG
channel dysfunction and 2) 24-hour rhythms in repolarisation are associated with
in 2 retrospective studies, 24-hour rhythms in repolarisation (QT and QTc diurnality) were
derived from Holter analyses and compared between groups: 1) 5 genetic (LQTS2) and 16
drug (Sotalol)-induced hERG channel dysfunction patients vs 22 controls and 2) 64 postinfarct patients, 26 with and 38 without a history of ventricular arrhythmias.
QT and QTc diurnality were increased in patients with genetic or drug-induced hERG
channel dysfunction. In post-infarct patients with a reduced (<35%) left ventricular ejection
fraction, QT diurnality was 2-fold higher in patients with a history of ventricular arrhythmias
compared to controls.
QT and QTc diurnality present novel clinical repolarisation parameters that can be derived
from Holter registrations. Both are associated with hERG channel dysfunction and
ventricular arrhythmias in patients at risk.
Figure 1. QTc diurnality in an example patient
NON-INVASIVE TESTING CANNOT IDENTIFY A TYPICAL SUBSTRATE FOR LIFETHREATENING RE-ENTRY VT IN ATHLETES
J. Venlet (Leids Universitair Medisch Centrum, Leiden); S.R.D. Piers (Leids Universitair
Medisch Centrum, Leiden); M. De Riva Silva (Leids Universitair Medisch Centrum,
Leiden;), Y. Naruse (Leids Universitair Medisch Centrum, Leiden); D.C.Q.M. BargeSchaapveld (Leids Universitair Medisch Centrum, Leiden); M.J. Schalij (Leids Universitair
Medisch Centrum, Leiden); K. Zeppenfeld (Leids Universitair Medisch Centrum, Leiden).
Two electroanatomical (EA) scar pattern for VT from the RV have been identified: a
dominant subtricuspid and an isolated epicardial RVOT scar, typical for endurance athletes
with inferior axis VT. The latter pattern may not be identified by non-invasive testing.
Consecutive symptomatic patients (pts) with scar-related re-entry VT from the RV, who
underwent endocardial ± epicardial EA mapping were included.
Among 57 patients (48±15 years, 83% male) 46 (81%) had a dominant subtricuspid scar.
All had features suggestive for structural heart disease (SHD); T-wave inversion (TWI) >V2
in 17 (37%), prolonged TAD 25/35, epsilon waves 10 (21%), wall motion abnormalities
(WMA) 27 (59%), and 25/45 (56%) had an ARVC associated pathogenic mutation. Based
on non-invasive testing, 33 had definite ARVC, 3 borderline ARVC, 5 cardiac sarcoidosis, 4
scar of unknown origin and 1 myocarditis. All 11 patients with isolated RVOT scar were
endurance athletes (15 [IQR 10 – 20] hours/week); 9/11 (82%) presented with exercise
related palpitations including syncope in 6 (55%). Only 1 had increased TAD, 2 (18%) TWI
V1-V2, but none TWI > V2, epsilon waves, WMA, or a pathogenic mutation. Based on noninvasive testing the diagnosis was idiopathic RVOT VT in 8/11 (81%) and possible SHD
based on additional minor criteria in 3.
The majority of endurance athletes with isolated RVOT scar has no features for SHD on
non-invasive testing and may be misdiagnosed as idiopathic VT. Considering the potentially
life threatening VT EA mapping should be considered in symptomatic athletes.
AGE AND GENDER RELATED DIFFERENCES IN CORRECTED QT INTERVAL IN
CHILDREN AND ADOLESCENTS WITH LQT1 AND LQT2
A.S. Vink (AMC, Amsterdam); S.A.B. Clur (AMC, Amsterdam); R.B. Geskus (AMC,
Amsterdam); A.C. Blank (UMCU, Utrecht); C.C.A. de Kezel (ETZ, Tilburg); R.R. Loontjens
(AMC, Amsterdam); M. Bruijn (MCA, Alkmaar); N. Hofman (AMC, Amsterdam); A.A.M.
Wilde (AMC, Amsterdam); and N.A. Blom (AMC, Amsterdam).
Children and adolescents constitute an important risk group in patients with congenital
Long QT Syndrome (LQTS). Age-, gender- and genotype related differences in QTc intervals
have been observed in young LQTS patients, but these observations were only based on
the comparison of baseline QTc interval measurements between large age groups.
Therefore, we aimed to evaluate age and gender related differences in QTc intervals in a
longitudinal cohort of children and adolescents with LQTS type 1 and 2 (LQT1 and LQT2).
OUTPATIENT TREATMENT WITH THE WEARABLE CARDIOVERTER DEFIBRILLATOR;
CLINICAL EXPERIENCE IN 2 CENTERS
V.F. van Dijk (St Antonius, Nieuwegein); A.F.B.E. Quast (AMC, Amsterdam); A.A.M. Wilde
(AMC, Amsterdam); L.V.A. Boersma (St Antonius, Nieuwegein); R.E. Knops (AMC,
An implantable cardioverter defibrillator (ICD) is indicated for the prevention of sudden
cardiac death in patients at risk of ventricular arrhythmia. In case of a possible transient
ICD indication or if an ICD temporarily cannot be implanted, a wearable cardioverter
defibrillator (WCD) can be an alternative to long-term hospitalization.
All patients treated with the WCD were included from both centers and retrospectively
analysed. Events and compliance were collected from the home monitoring system and
adjudicated by the investigators.
Between 2009 and 2016, 79 patients were treated with a WCD. Most common indications
were awaiting improvement of left ventricular function after either revascularization or de
novo cardiomyopathy diagnosis in 46 patients (58,2%), or bridge to implant in 33 patients
(41,8%). Two patients (2,6%) received an appropriate shock(calculated appropriate annual
shock rate 13,%), there was 1 inappropriate shock. In 21 patients (26,6%) ICD indication
proved to be transient. 14(17,7%) patients did not receive an ICD for other reasons. A total
of 44 patients were implanted with ICD’s after WCD(55,7%). The WCD was worn for
70±6,41 days. As bridge to implant, the WCD saved 79±10,59 admission days.
All available electrocardiograms of genetically confirmed LQT1 and LQT2 patients born
after January 1985 were retrospectively collected. QTc intervals were measured and
analysed using a linear mixed-effect model.
All 2116 electrocardiograms of 278 patients from 100 different families were analysed.
The study population consisted of 130 LQT1 patients (54% females) and 148 LQT2
patients (55% females) with a median follow-up duration of 4 years (IQR 1-9). LQT1 females
had significantly longer QTc intervals after the age of 10 compared to LQT1 males. LQT2
males had significantly shorter QTc intervals during the first years of life and significantly
longer QTc intervals between the ages of 8 - 11 years compared to LQT2 females (Figure 1).
There is an age- depended gender difference in QTc interval among LQT1 and LQT2
patients, with different patterns in both genotypes. Our data suggests that changes in
these gender differences occur after the age of 10-11 years which correspond with the
onset of puberty.
Figure 1 Age and gender related changes in QTc interval among LQT1 and LQT2 patients. Solid lines are
males and dashed lines are females. 95% confidence intervals in grey.
The WCD is a safe and effective treatment in patients in whom the indication for an ICD is
to be postponed or device implantation is temporarily contra-indicated.
Table 1. Results WCD therapy.
Patients (n = 79)
Number of days WCD is worn (median, IQ1-IQ3)
70,00 (43,00 – 94,00)
Average hours a day WCD is worn (median, IQ1-IQ3)
23,30 (22,62 – 23,71)
Appropriate therapy given by WCD (n, %)
Inappropriate therapy given by WCD (n,%)
Number of altered ICD indications after WCD (n,%)
Number hospitalization days prevented in ‘bridge-to-ICD patients’ (median)
79,00 (54,75 – 102,25)
Netherlands Heart Journal, Volume 24, Supplement, April 2016
NHJ 1604 Abstracts NVVC incl omslag_proef5.indd 7
Session III: Electrophysiology (continued)
QRS-COMPLEX FRAGMENTATION IS ASSOCIATED WITH SUDDEN CARDIAC DEATH IN
ADULTS WITH CONGENITAL HEART DISEASE
PREDILECTION SITES FOR ELECTROPATHOLOGY DURING SINUS RHYTHM IN
PATIENTS WITH A CONGENITAL HEART DISEASE
J.T. Vehmeijer (Academisch Medisch Centrum, Amsterdam); Z. Koyak (Academisch
Medisch Centrum, Amsterdam); B.J.M. Mulder (Academisch Medisch Centrum,
Amsterdam); B.J. Bouma (Academisch Medisch Centrum, Amsterdam); J.R. de Groot
(Academisch Medisch Centrum, Amsterdam)
E.A.H. Lanters (Erasmus Medical Center, Rotterdam); C.P. Teuwen (Erasmus Medical
Center, Rotterdam); A. Yaksh (Erasmus Medical Center, Rotterdam), P. Knops (Erasmus
Medical Center, Rotterdam), J.W. Roos-Hesselink (Erasmus Medical Center, Rotterdam),
P.C. van de Woestijne (Erasmus Medical Center, Rotterdam), A.J.J.C. Bogers (Erasmus
Medical Center, Rotterdam), M.A. Allessie (Erasmus Medical Center, Rotterdam), N.M.S.
de Groot (Erasmus Medical Center, Rotterdam)
Sudden cardiac death (SCD) is a major cause of mortality in adult congenital heart disease
(ACHD) patients. However, identification of high-risk patients remains challenging.
Fragmented QRS-complexes (fQRS) are a marker for SCD in patients with acquired heart
disease, but data in ACHD patients is lacking. We evaluated the prognostic value of fQRS for
SCD in ACHD patients.
This was a multicenter case-controlled study. From a cohort of 25,790 ACHD patients, we
included 165 SCD cases and 310 matched controls. We defined fQRS as ≥1 additional
notch in the QRS-complex, not part of a bundle branch block, in two contiguous ECG-leads.
We calculated odds ratios (OR) with corresponding P-values using generalized linear mixed
For 150 SCD cases (66% male, median age at death 34 years), and 271 controls, the ECG
was of sufficient quality. fQRS was present in 49% of cases and 34% of controls (OR 1.9,
P=0.002). In multivariable analysis, adjusted for QRS-duration, heart failure symptoms and
impaired systemic ventricular function, fQRS was independently associated with SCD (OR
1.7, P=0.026). fQRS in the anterior leads was more strongly associated with SCD (21% in
cases vs. 11% in controls; OR 2.1, P=0.02), compared to lateral (12% vs. 7%; OR 1.3,
P=0.44), inferior (28% vs 23%; OR 1.2, P=0.48) and other leads (14% vs. 15%; OR 0.8,
fQRS is associated with SCD in ACHD patients. Independently, its prognostic value is too
limited to warrant ICD implantation. However, when combined with other clinical
parameters, it may contribute to the indication for ICD implantation.
Figure 1. Multivariable logistic regression of fQRS and SCD, corrected for QRS width >120ms, heart failure
symptoms and impaired systemic ventricular function (SVF): ejection fraction ≤ 39% or at least moderately
Congenital heart diseases (CHD) such as atrial septal defects are associated with right
atrial (RA) volume overload and subsequently atrial stretch resulting in intra-atrial
conduction abnormalities which may be involved in the pathophysiology of atrial
tachyarrhythmias. We tested the hypothesis that heterogeneity in conduction during sinus
rhythm (SR) in CHD patients with RA overload occurs mainly in the right atrium.
Intra-operative, high-resolution (128/192 electrodes, inter-electrode distances 2mm)
epicardial mapping studies of the RA, Bachmann’s Bundle(BB), left atrioventricular
groove(LAVG) and pulmonary vein area(PVA) during SR were performed in 12 CHD patients
with RA volume overload. Three patients had paroxysmal atrial fibrillation. Unipolar
voltages, conduction delay(CD) and conduction block (CB) were quantified per 1 cm2
Unipolar signals were recorded from 22,965 sites (1,914±329 signals/patient). Median
atrial voltage was 2.5;2.5(1.4-3.5)mV; there were no differences between unipolar
voltages/cm2 of the RA, BB, LAVG and PVA(P=0.461). Voltages ≤0.5mV were measured in
6(50%) patients at 12(2.9%) quadrants, mainly at the superior RA(N=5) and at BB(N=4).
Median amount of CD and CB were 1.6;1.3(0.9-2.9)% and 1.6;1.3(0.7-3.5)% respectively.
CD and CB occurred most frequently at BB(52% and 41% respectively). Also, the amount of
CD (2.4%, P=0.027) and CB (3.2%, P=0.004) was highest at BB.
In CHD patients with RA volume overload, low voltages and conduction disorders during SR
occurred throughout the entire atria, showing considerable regional differences. A
predilection site was observed at BB. Consequently, the arrhythmogenic substrate involved
in the pathogenesis of atrial tachyarrhythmias may not only be confined to the RA.
REASONS FOR ‘FAILING’ AUTOMATED EXTERNAL DEFIBRILLATORS OPERATED BY
J.A. Zijlstra (Academisch Medisch Centrum, Amsterdam); L.E. Bekkers (Academisch
Medisch Centrum, Amsterdam); M. Hulleman (Academisch Medisch Centrum,
Amsterdam); S.G. Beesems (Academisch Medisch Centrum, Amsterdam); R.W. Koster
(Academisch Medisch Centrum, Amsterdam)
CARDIOLOGY UNLIMITED : TOWARDS A SMART AED?
VF WAVEFORM ANALYSIS TO PREDICT DEFIBRILLATION SUCCESS IN CARDIAC
R. Starreveld (Radboudumc, Nijmegen); J. Nas (Radboudumc, Nijmegen); J.L. Bonnes
(Radboudumc, Nijmegen); J. Thannhauser (Radboudumc, Nijmegen); G. Meinsma
(University of Twente, Enschede); P.M. van Grunsven (Ambulance Emergency Services
Gelderland-South, Nijmegen); M.J. de Boer (Radboudumc, Nijmegen); Marc A. Brouwer
Recent studies have demonstrated that information from the VF waveform can be used in
AEDs to contribute to the prediction of survival during out-of-hospital cardiac arrest (OHCA).
A combined measure of amplitude and frequency, the Amplitude Spectral Area (AMSA), is
regarded the most promising predictor of early shock success. Its impact in later phases of
the resuscitation is unknown. We therefore sought to investigate whether the AMSA is able
to predict shock success during early (shock 1–2) and later stages of a resuscitation
(shocks > 2).
Paddle-ECG recordings of OHCA patients from the Nijmegen area (2008–2011) with VF as
first observed rhythm were studied (n=108, 392 shocks). The AMSA was calculated from
three-second chest compression free segments of VF prior to each shock. Univariate
analysis and receiver operating characteristic curves were used to evaluate the association
of the pre-shock AMSA with shock success (i.e. return of organized rhythm).
For shock 1–2 (success 44%), the AMSA was significantly higher prior to successful
compared to unsuccessful shocks. The discriminative value of the AMSA for shock success
of shock 1 and 2 was 0.72 (p<0.001). The AMSA prior to shock 3–8 (success 53%) did not
differ between successful and unsuccessful shocks. Also, the discriminative value of the
AMSA was lower (0.58, p=0.054) for these shocks.
In The Netherlands, an increasing number of apparently failing automated external
defibrillators (AEDs) is reported: AEDs not giving a shock or other malfunction. We assessed
to what extent AEDs are ‘failing’ and whether this had a device-related or operator-related
We studied analysis periods from AEDs used between January 2012 and December 2014.
For each analysis period we assessed the correctness of the (no)-shock advice (sensitivity/
specificity) and reasons for an incorrect (no)-shock advice. If no shock was delivered after a
shock advice, we assessed the reason for no-shock delivery.
We analyzed 1114 electrocardiograms with 3288 analysis periods (1080 shock advices;
2208 no-shock advices). Sensitivity for coarse ventricular fibrillation and specificity for nonshockable rhythm detection was both 99%. The AED gave an incorrect shock advice in 3%
(33/1080) of all shock advices (false positive rate), due to device-related (n=11) and
operator-related errors (n=21) (one unknown error). Of these 33 shock advices, 22 shocks
were given with one causing a harmful rhythm change. In 1% (21/2208) of all no-shock
advices, this advice was incorrect (false negative rate), due to device-related (n=16) and
operator-related errors (n=5). In 5% (52/1080) of the analysis periods, a shock advice was
given but no shock was delivered: operator failed to deliver shock (n=26), electrodes were
removed (n=16), operator pushed ‘off’ button (n=8) and other reasons (n=2).
Errors associated with AED use occur in ≤5% of cases and are mainly caused by the
operator. Fully automated AEDs may prevent the majority of these errors.
Figure 1 Erroneously detecting a (non)-shockable heart rhythm (AED analysis, left part) and no shock
delivery after a shock advice (operator performance, right part).
The present analysis demonstrates that during OHCA, the predictive value of the AMSA for
shock success is restricted to the early phase of resuscitation. This challenges the concept
of continuous ECG waveform analysis for guidance of the entire resuscitation.
Table 1. Median AMSA and corresponding p-values, C-statistic of ROC analysis
AMSA Shocks 1-2
0.72 (95% CI 0.64-0.79)
AMSA Shocks 3-8
0.58 (95% CI 0.50-0.66)
NHJ 1604 Abstracts NVVC incl omslag_proef5.indd 8
Netherlands Heart Journal, Volume 24, Supplement, April 2016
Session IV: Valvular and aortic disease
RATIONALE AND DESIGN OF THE EDWARDS SAPIEN-3 PERIPROSTHETIC LEAKAGE
EVALUATION VERSUS MEDTRONIC COREVALVE IN TRANSFEMORAL AORTIC VALVE
IMPLANTATION (ELECT) TRIAL: A RANDOMIZED COMPARISON OF BALLOONEXPANDABLE VERSUS SELF-EXPANDING TRANSCATHETER AORTIC VALVE
M. Abawi (UMC-Utrecht, Utrecht); P. Agostoni (UMC-Utrecht, Utrecht and St. Antonius
Hospital, Nieuwegein); P. Stella (UMC-Utrecht, Utrecht).
Differences between transcatheter balloon-expandable and self-expanding heart valves
have been suggested where a reduction of periprosthetic aortic regurgitation (PPR) seems
to be crucial.
The current randomized study aims to evaluate potential differences between the balloonexpandable Edwards SAPIEN-3™ and self-expanding Medtronic CoreValve® system with
main focus on post-TAVI PPR by novel imaging endpoints and additional focus on other
clinical endpoints. Primary endpoint of this study is quantitative assessment of difference
in the severity of post-TAVI PPR, using different novel imaging modalities ((3D)
transesophageal echocardiography, x-ray contrast angiography and magnetic resonance
imaging). Secondary objectives of the study include clinical outcomes including cerebral
and kidney injury related to TAVI and quality of life.
Methods and design:
The ELECT study is a single-center, prospective, two-arm randomized controlled trial. For the
purpose of this study, 108 consecutive adult patients will be randomly allocated to receive
the SAPIEN- 3 (n= 54) or the CoreValve system (n= 54). Randomization will be performed
using sealed envelopes. Only patients with aortic annulus diameter between ≥18 and ≤29
mm and anatomy suitable for transfemoral TAVI will be included.
The ELECT-trial is the first randomised controlled trial to quantitatively compare the extent
of post-TAVI PPR between SAPIEN-3 and CoreValve. Furthermore, it will evaluate potential
differences between the two prostheses with regard to mid-term clinical outcome and
quality of life. (ClinicalTrials.gov number NCT01982032).
CLINICAL PERFORMANCE OF A NOVEL BIOENGINEERED DRUG-ELUTING STENT WITH
A SHORT DURATION OF DUAL ANTIPLATELET THERAPY IN PATIENTS AT RISK FOR
MAJOR BLEEDING, FIRST RESULTS OF THE COMBO-TAVI REGISTRY
R. Rozemeijer (Universitair Medisch Centrum Utrecht, Utrecht); Masieh Abawi (Universitair
Medisch Centrum Utrecht, Utrecht); M. Voskuil (Universitair Medisch Centrum Utrecht,
Utrecht); A.O. Kraaijeveld (Universitair Medisch Centrum Utrecht, Utrecht); P.R. Stella
(Universitair Medisch Centrum Utrecht, Utrecht).
Currently, DES require mandatory prolonged dual antiplatelet therapy(DAPT). We studied
the clinical performance of a novel bioengineered DES with a short DAPT regimen(1 month)
in patients at high risk for bleeding.
From April 2015 to January 2016, 22 coronary lesions in 16 patients at risk for major
bleeding were treated by PCI with the bioengineered Combo Dual Therapy Stent prior to TAVIprocedure. The bioengineered Combo Stent is designed to combine pro-healing endothelialprogenitor-cell-capture technology for rapid endothelial strut coverage along with sustainedrelease of sirolimus to control neointimal proliferation. Coronary lesions were treated with
standard interventional techniques and use of FFR, without any restrictions(lesion type/
lesion length). After index-PCI, 8 patients received triple therapy for 1 month whereas the
remainder received 1-month of DAPT prior to TAVI-procedure followed by 3 months of DAPT
after TAVI-procedure. Patients were evaluated during regular hospital visits and by medical
records. The Combo Stent showed a technical success rate of 100% and procedural success
rate of 87.5%. According to (B)ARC, no stent thrombosis occurred and 1 patient suffered
from a significant bleeding BARC≥3 bleeding. The major adverse cardiac event-free survival
(any death/-myocardial infarction/-target-vessel revascularization/-bleeding BARC≥3
bleeding) was 75% after a median follow-up of 4 months [interquartile range 2.5-7.5] and
included the TAVI-procedure.
FIRST CLINICAL EXPERIENCE WITH THE 3RD GENERATION TRIGUARD® DEVICE FOR
CEREBRAL EMBOLIC PROTECTION DURING TRANSCATHETER AORTIC VALVE
M. Abawi (UMC-Utrecht, Utrecht); M. Voskuil (UMC-Utrecht, Utrecht); P. Stella (UMCUtrecht, Utrecht); F.C. Riess (AlbertinenHeart Center, Hamburg, Germany).
Silent brain infarcts are seen in 60 to 100 % of patients undergoing transcatheter aortic
valve implantation (TAVI) and are associated with neurocognitive decline, a 2 fold risk of
dementia and a >3 fold risk of stroke. The TriGuard cerebral embolic protection system is a
highly flexible nitinol frame and mesh that is positioned in the aortic arch to cover all major
cerebral branches to prevent cerebral embolization. The 1st and 2nd generation has been
tested in clinical trials.
To evaluate the clinical performance of the 3rd generation TriGuard device in 2 centers in
Methods and Preliminary Results:
The device was used in 31 patients ( 78.8± 8.7 yrs, 45.2% male) with symptomatic aortic
valve stenosis, who underwent transfemoral TAVI because of high risk for open heart
surgery (EuroSCORE II 7.6±6.3, STS Score 2.4±0.9). The TriGuard covered all 3 vessels with
no device interference in all patients. Pre-TAVI balloon dilatation was performed in 67.7%,
post dilatation in 22.6%, valve in valve implantation in 9.7% of patients. In 29% the
Medtronic Core Valve/Evolute R, in 67.7% the Edwards SAPIEN, and in 3.2% the Boston
Scientific Lotus valve was used.
The 3rd generation TriGuard device is safe with improved performance and ease of use,
100% of the cases had 3 vessel coverage and no strokes.
GENOTYPE IMPACTS SURVIVAL IN MARFAN SYNDROME
Romy Franken (AMC, Amsterdam), Groenink M. (AMC, Amsterdam), de Waard V (AMC,
Amsterdam), Feenstra HM (AMC, Amsterdam),, Scholte AJ (LUMC, Leiden), van den Berg
MP (UMCG, Groningen), Pals G (VUMC, Amsterdam), Zwinderman AH (AMC, Amsterdam),
Timmermans J (Radboud MC, Nijmegen), Mulder BJ (AMC, Amsterdam).
The aorta in Marfan syndrome (MFS) patients is variably affected. We investigated the
assumed genotype-effect on protein production as a risk factor for a severe aortic
phenotype in adult MFS patients.
We collected clinical and genetic data from all 570 adults with MFS who had been included
in the Dutch CONgenital CORvitia registry since the start in 2001. Mean age was 36.5 ±
13.5 years (51.2% male, 28.9% prior aortic surgery, 8.2% prior aortic dissection). Patients
were prospectively followed for a mean duration of 8.2 ± 3.1 years.
Men had more frequently aortic surgery at baseline (38.0 vs. 19.4%, P < 0.001) and during
follow-up (24.0 vs. 15.1%, P = 0.008) compared with women. After 10-year follow-up
cumulative survival was 93.8% and dissection-free survival was 84.2%. We found a
pathogenic FBN1 mutation in 357 patients, of whom 146 patients (40.9%) were positive for
a mutation causing haploinsufficiency (reduced fibrillin-1 protein) and 211 (59.1%) for a
mutation leading to a DN effect (abnormal fibrillin-1 protein). Corrected for age, sex, and
previous aortic complications, patients with a haploinsufficient (HI) mutation had a 2.5-fold
increased risk for cardiovascular death (hazard ratio, HR: 2.5, 95% CI: 1.0-6.1, P = 0.049),
a 2.4-fold increased risk for the combined endpoint comprising death and dissection (HR:
2.4, 95% CI: 1.4-4.2, P < 0.001) and a 1.6-fold increased risk for any aortic complication
compared with patients with a DN mutation (HR: 1.6, 95% CI 1.1-2.3, P = 0.014).
Marfan syndrome patients with an HI mutation are at increased risk for cardiovascular
death and aortic dissection compared with patients with a DN mutation.
This prospective registry will provide more insight in the clinical performance and
accelerated healing strategy of the Combo Stent, that aims to lower the risk of in-stent
restenosis, stent thrombosis and may have the potential to safely reduce the regiment of
DAPT, thereby minimizing bleeding complications in a fragile population scheduled for TAVIprocedure.
Netherlands Heart Journal, Volume 24, Supplement, April 2016
NHJ 1604 Abstracts NVVC incl omslag_proef5.indd 9
Session IV: Valvular and aortic disease (continued)
PROGNOSIS OF AORTOPATHY IN ADULTS WITH CONGENITAL HEART DISEASE
PREDICTORS AND PROGNOSIS OF THE POST PERICARDIOTOMY SYNDROME
J.M. Kuijpers (AMC, Amsterdam); D.R. Koolbergen (AMC, Amsterdam); M. Groenink (AMC,
Amsterdam); S.M. Boekholdt (AMC, Amsterdam); B.J.M. Mulder (AMC, Amsterdam); B.J.
Bouma (AMC Amsterdam)
D. van Osch (University Medical Center Utrecht, Utrecht); J.M. Dieleman (University
Medical Center Utrecht, Utrecht); J.J.H. Bunge (Erasmus Medical Center, Rotterdam); D.
van Dijk (University Medical Center Utrecht, Utrecht); P.A.F.M. Doevendans (University
Medical Center Utrecht, Utrecht); W.J.L. Suyker (University Medical Center Utrecht,
Utrecht); H.M. Nathoe (University Medical Center Utrecht, Utrecht)
Proximal aortic dilatation is frequently found in adults with bicuspid aortic valve (BAV), aortic
coarctation with/without BAV (CoA-BAV/CoA), tetralogy of Fallot (ToF) and transposition of
the great arteries (TGA). We aimed to prospectively determine the contemporary risk of
aortic dissection, and effect of aortic replacement on prognosis in these patients.
All patients with a native proximal (neo-)aorta and a main diagnosis of BAV (n=1378), CoABAV (n=617), CoA (n=849), ToF (n=1179) or TGA (n=593) were selected from the CONCOR
database. Incidence of aortic dissection (cases/person-time lived with native proximal
aorta) was calculated using Poisson regression. Survival was calculated using the KaplanMeier estimator, with time of inclusion (non-operated group) or time of aortic replacement in
follow-up (operated group) as time zero.
Post Pericardiotomy Syndrome (PPS) is associated with short-term adverse events, however
the long-term prognosis and predictors of PPS are largely unknown.
We performed a cohort study in 822 patients undergoing valve surgery. Possible predictors
of PPS were evaluated using multivariable logistic regression analysis. We also compared
the incidence of reoperation for tamponade at one year between patients with and without
PPS. Main secondary outcomes were hospital stay, mortality and quality of life.
During 28881 person-years in 4616 patients (61.4% male, median age 31.6years), 5 aortic
dissections occurred (incidence rate=1.73/10.000person-years;95%CI,0.62-3.72); CoA, 2
cases (3.99;0.66-12.31); CoA-BAV, 1 (2.36;0.13-10.40); BAV, 1 (1.66;0.09-7.32); TGA, 1
(2.27;0.13-10.00). No dissections occurred in ToF patients. Three dissections were lethal
(60%). During follow-up, 121 native proximal aortic replacements occurred (BAV,82; CoABAV,20; ToF,11; CoA,5; TGA,3), with 1 death <30days after surgery (0.83%). The Figure
shows ten-year survival after proximal aortic replacement was similar to that of unoperated
Of the 822 patients, 119 (14.5%) developed PPS. A higher Body Mass Index (BMI) (OR per
point increase: 0.93, 95% CI 0.88-0.99) and preoperative corticosteroid use (OR 0.15, 95%
CI 0.04-0.53) decreased the risk of PPS, whereas preoperative treatment for pulmonary
disease increased the risk of PPS (OR 2.86, 95% CI 1.44-5.68). The incidence of
reoperation for tamponade at one year in PPS versus no PPS was 20.2% versus 2.4% (OR
14.26, 95% CI 6.88-29.56), with all rethoracotomies taking place within the first 2 months.
One year mortality in PPS versus no PPS was 3.4% versus 5.3% (OR 0.69, 95% CI 0.232.08). Median hospital stay was 13 days (IQR 9-18) versus 11 days (IQR 8-15) (p<0.001),
respectively. Quality of life at 1 year did not differ significantly between the two groups
In contemporary practice, reflecting current guidelines for prophylactic aortic replacement,
the risk of aortic dissection in adults with predisposing CHD is low. Proximal aortic
replacement is associated with low peri-operative mortality and good long-term outcome in
Despite of a longer hospital stay and more rethoracotomies, patients with
PPS had an excellent long-term prognosis and quality of life. A higher BMI and preoperative
corticosteroid use decreased the risk of PPS, whereas treated pulmonary disease increased
the risk of PPS.
Figure. Adults with CHD predisposing to aortopathy: survival after proximal aortic replacement versus that
of patients with a native proximal aorta
Figure 1. Survival free of rethoracotomy for tamponade
LONG-TERM MORTALITY AND MORBIDITY IN PATIENTS AFTER PERCUTANEOUS MITRAL
J.F. Velu (Academisch Medisch Centrum, Amsterdam), B.J. Bouma (Academisch Medisch
Centrum, Amsterdam), J. Baan (Academisch Medisch Centrum, Amsterdam)
High-risk patients suffering from Mitral Regurgitation (MR) can be treated by a percutaneous
mitral valve repair with the MitraClip. Long-term mortality and morbidity after a MitraClip
treatment has not been extensively investigated yet. However, knowledge about long-term
follow-up is required to assess the sustainability of the outcome after percutaneous mitral
valve repair in order to improve clinical decision making.
The mortality of patients treated with a MitraClip was analyzed. The morbidity was quantified
with the NYHA classification and MR grade at baseline and during follow-up. A riskmodel for
mortality was developed to improve clinical decision making.
140 patients received a MitraClip in the Academic Medical Center Amsterdam (AMC), the
Netherlands. Mean age was 75 years, 54% was male and 30% had a poor LV function (<30%).
The cumulative mortality was 4% after 30 days, 20% after 1 year and 58% after 5 years. The
1-year mortality of patients with severe MR is 57%, if left untreated. At baseline, 81% of the
patients were classified in NHYA class > III/IV and 96% had MR grade ≥ 3. During follow-up,
27% were classified in NHYA class > II/IV and 36% had MR grade ≥ 3. Patients with NYHA class
IV, NT-proBNP levels >5000 ng/L, creatinine >200 µmol/L, previous valve surgery or TR grade
≥ 3 prior to MitraClip had significantly higher mortality rates in multivariate analysis.
NHJ 1604 Abstracts NVVC incl omslag_proef5.indd 10
The cumulative mortality is 58% after 5 years. The founded predictors may improve clinical
decisions making in order to optimize patient selection.
Table 1 Predictors for 5-year survival in univariate and multivariate analysis (Cox model).
Age > 80 years
NYHA class IV
Creatinine >200 µmol/L
Previous valve surgery
TR > grade 2
HR: hazard ratio; LEVEF: left ventricular ejection fraction; NYHA: New York Heart Association; TR: tricuspid
Netherlands Heart Journal, Volume 24, Supplement, April 2016
Session IV: Valvular and aortic disease (continued)
Session V: Heart failure/ Coronary artery disease
FILTER BASED CEREBRAL EMBOLIC PROTECTION WITH TRANSCATHETER AORTIC
VALVE IMPLANTATION: THE RANDOMIZED MISTRAL-C TRIAL
STRUCTURED CARDIAC RESYNCHRONISATION THERAPY PATHWAY BASED ON LEAN
SIX SIGMA METHODOLOGY; A FIRST EVALUATION OF OPERATIONAL OUTCOMES
N.M. Van Mieghem (Erasmus MC, Rotterdam); L. van Gils (Erasmus MC, Rotterdam); H.
Ahmad (Erasmus MC, Rotterdam); F. van Kesteren (AMC, Amsterdam), H.W. van der Werf
(UMC Groningen); G. Brueren (Catharina Ziekenhuis, Eindhoven); M. Storm (Erasmus MC,
Rotterdam); M. Lenzen (Erasmus MC, Rotterdam); J. Daemen (Erasmus MC, Rotterdam);
A.F.M. van den Heuvel (UMC Groningen); P. Tonino (Catharina Ziekenhuis, Eindhoven); J.
Baan (AMC, Amsterdam); P.J. Koudstaal (Erasmus MC, Rotterdam); M.E.I. Schipper
(Erasmus MC, Rotterdam); A. van der Lugt (Erasmus MC, Rotterdam); P.P.T. De Jaegere
(Erasmus MC, Rotterdam)
A.M.W. van Stipdonk (MUMC+, Maastricht), A. Rao (Liverpool heart and chest hospital,
Liverpool), R. Videbaek (Rigshospitalet, Copenhagen), Helen H Petersen (Rigshospitalet,
Copenhagen), C. Knackstedt (MUMC+, Maastricht), I. A. Colin (Medtronic, Tolochenaz),
J.M. Morgan (Southampton University Hospitals, Southampton), W. Mullens (Ziekenhuis
Oost-Limburg, Genk), K. Vernooy (MUMC+, Maastricht)J12
To determine whether use of the filter-based Sentinel Cerebral Protection System (CPS)™
during transcatheter aortic valve implantation (TAVI) can affect the early incidence of new
brain lesions as assessed by diffusion-weighted magnetic resonance imaging (DW-MRI)
and neurocognitive performance.
From January 2013 to July 2015 65 patients were randomized 1:1 to transfemoral TAVI with
or without the Sentinel CPS at four Dutch centers. Patients underwent a DW-MRI scan and
extensive neurological examination including neurocognitive testing by study blinded
neuro-radiologists and neurology specialists one day before and five to seven days after
Follow up DW-MRI and neurocognitive testing was completed in 57% and 80% respectively.
New brain lesions were found in 78% of patients with follow up MRI. Patients with Sentinel
CPS had numerically less new lesions and a smaller total lesion volume (95 mm3 (IQR 10
– 257) vs. 197 mm3 (95 – 525). Overall 27% of Sentinel CPS patients and 13% of control
patients had no new lesions. Ten or more new brain lesions were found only in the control
cohort (in 20% vs. 0% in the Sentinel CPS cohort, p=0,03). Neurocognitive deterioration
was present in 4% of patients with Sentinel CPS vs. 27% in patients without (p = 0.017).
Thrombotic and tissue derived debris was present in 87% and 100% of patients with
Sentinel CPS protection.
Filter-based embolic protection with the Sentinel CPS captures debris en route to the brain
in all patients undergoing TAVI. Its use results in less and overall smaller new brain lesions
by MRI and preserves early postoperative neurocognitive performance.
Cardiac resynchronisation therapy (CRT) reduces mortality and morbidity in specific heart
failure patients. Care for these patients is complex and puts a significant burden on health
care resources. Care pathways are increasingly used to structure complex interventions;
supporting evidence based medicine, as well as optimizing resource utilisation. Objective
of this study is to design and implement a structured care.
To design and implement a care pathway in the Maastricht University Medical Centre
(MUMC+) we used Lean Six Sigma methodology. After evaluating current, usual care (UC)
and comparing it to an expert consensus based best practice care pathway, UC processes
were mapped and caveats were identified. Then a stepwise implementation of care
pathway processes (Figure 1.) was performed with the help of standardized aides
A total of 101 patients were included in this analyses. Referral-to-treatment time was
reduced from 64 to 51 days (p=ns) and the number of pre-implantation consultations was
reduced from 1.8 to 1.6 (p=ns). Though implementation of the pathway was only 60%.
When excluding patients not treated accordingly, number of pre-implantation consultations
were further reduced to 1.4 (p=0.03). Length of in-patient stay was reduced from 2.1 to 1.2
This study shows the feasibility of the design and implementation of a structured CRT care
pathway. Preliminary results show significant improvement of organisational outcomes.
Figure 1. Process overview in CRT care pathway. Summarizing processes for Usual Care and Care after
implementation of the CRT care pathway.
INCREASED REFERRAL OF STABLE HEART FAILURE TO PRIMARY CARE IN THE
CONNECT HEART FAILURE PROGRAM
M Niesing-Lut (Alrijne Zorggroep, Leiderdorp); P. van Pol (Alrijne Zorggroep, Leiderdorp); J.
Eysink Smeets (Lupine praktijk, Alphen a/d Rijn), A. van Haarlem (Alrijne Zorggroep,
Leiderdorp), J. Flaman (Alrijne Zorggroep, Leiderdorp), C. Lucas (Alrijne Zorggroep,
The Connect Heart Failure Program has recently started in the Netherlands. Major goal of
this program is to optimize shared care for heart failure patients between primary and
secondary/tertiary care. One of the goals is to refer stable heart failure (HF) patients back
to primary care. The first region where the program is running is the region of Alphen a/d
Rijn, which is connected to the Alrijne Hospital where since 2000 a dedicated outpatient HF
clinic has been available.
Comparison was made between number of stable patients being referred back to primary
care before and after the connect program was started in this region. Furthermore follow-up
data of these patients after referral have been collected.
From 2000 until 2013 heart failure care responsibility was taken by primary care for 100
HF patients. In 2014 and 2015 when the new program was running, 74 patients in total
were discharged from the outpatient clinic to the general practitioner. Five because of
recovered myocardial function, 22 because of stable heart failure, 13 for end-stage heart
failure, 22 because of frailty, 12 for other reasons. Sixteen patients of this 74 deceased, 3
were re-hospitalized for recurrent heart failure. None of the remaining 55 patients have
been sent back to the HF outpatient clinic.
Application of the Connect heart failure program results in increased referral of HF patients
to primary care so far in short-term not resulting in readmissions or referral back to
secondary care. Long-term follow-up data will be collected.
Netherlands Heart Journal, Volume 24, Supplement, April 2016
NHJ 1604 Abstracts NVVC incl omslag_proef5.indd 11
Session V: Heart failure/ Coronary artery disease (continued)
QRS FRAGMENTATION IS ASSOCIATED WITH RIGHT VENTRICULAR FAILURE IN
ADULTS WITH TETRALOGY OF FALLOT
IMPROVEMENT OF LONG-TERM SURVIVAL OVER TIME IN PATIENTS WITH ACUTE
HEART FAILURE: DATA FROM THE PERIOD 1985-2008
J.P. Bokma (Academisch Medisch Centrum, Amsterdam); M.M. Winter (Academisch
Medisch Centrum, Amsterdam); K.C. de Wilde (Academisch Medisch Centrum,
Amsterdam); H.W. Vliegen (Universitair Medisch Centrum, Leiden); M. Groenink
(Academisch Medisch Centrum, Amsterdam); B.J.M. Mulder (Academisch Medisch
Centrum, Amsterdam); B.J. Bouma (Academisch Medisch Centrum, Amsterdam)
J.C. van den Berge (Erasmus MC, Rotterdam); K.M. Akkerhuis (Erasmus MC, Rotterdam);
A.A. Constantinescu (Erasmus MC, Rotterdam); J.A. Kors (Erasmus MC, Rotterdam); R.T.
van Domburg (Erasmus MC, Rotterdam); J.W. Deckers (Erasmus MC, Rotterdam)
Limited data is available to identify tetralogy of Fallot (TOF) patients at risk for right
ventricular (RV) function deterioration and subsequent heart failure. Recently,
fragmentation of QRS complexes (fQRS) was related to regional RV fibrosis and all-cause
mortality. Our objective was to determine whether fQRS was associated with RV failure.
This dual center study included all adult TOF patients with two cardiovascular magnetic
resonance (CMR) investigations from the Concor registry. Notches in the QRS complex in ≥2
contiguous leads on standard 12-lead electrocardiograms (ECG), not related to right bundle
branch block, were defined as fQRS. Extent of fQRS was classified as none, moderate (≤4
leads) or severe (≥5 leads). The change in RV ejection fraction (EF) between first and
second CMR (3.3±1.8 years later) was calculated.
A total of 175 TOF patients (age at inclusion: 33±11 years, 51% male) were included. The
extent of fQRS at inclusion was classified as none in 55% of patients, moderate in 32% and
severe in 13%. Baseline RV EF was 47±10%. The number of fQRS leads was negatively
correlated with baseline RV EF (R=-0.24, p=0.002). Average change in RV EF was
+0.4±8.8%. After correction for baseline RV EF, fQRS extent was associated with RV EF
deterioration (β=-2.2%/class, p=0.004). Furthermore, fQRS extent was associated with
increasing odds for RV EF<35% at follow-up CMR (OR:2.97/class, p=0.006).
In adult TOF patients, fQRS extent was associated with progressive RV dysfunction. These
findings may improve selection of patients for therapy to prevent heart failure.
Acute heart failure (AHF) has a poor prognosis. However, limited data is available regarding
their long-term mortality. We investigated the trends in short- and long-term mortality of AHF
patients in the period 1985 thru 2008. We also determined the influence of major prognostic
In this prospective consecutive registry, we included patients admitted for AHF at the
Intensive Coronary Care Unit of our tertiary referral hospital in the period of 1985 until 2008.
Patients were classified into four aetiology categories: ischemic cardiomyopathy, other
cardiomyopathy, valvular heart disease, and other/unknown. The time window was split up in
periods of 1985-1989, 1990-1999 and 2000-2008.
We identified 1810 patients (age 64 years, 64% male). The overall cumulative mortality at
one and ten years was respectively 32% and 73%. In the last decade, the number of patients
with a history of coronary revascularization therapy and diabetes increased significantly.
Mortality was lowest in the last decade (Figure). Compared to valvular heart disease,
ischemic cardiomyopathy was associated with a higher mortality (HR 1.22; 95% CI 1.041.30). Other parameters associated with poor outcome were advanced age (HR 1.027; 95%
CI 1.023-1.032), male sex (HR 1.27; 95% CI 1.13-1.42), previous heart failure (HR 1.57; 95%
CI 1.41-1.75), and diabetes (HR 1.19; 95% CI 1.05-1.36).
Patients admitted with AHF continue to have very high short- as well as long-term mortality.
However, their prognosis has improved in the last decade. Patients with AHF due to ischemic
cause has the worst outcome.
Figure 1: Leads V2 and V3 of an ECG in a tetralogy of Fallot patient (1A) with a wide right bundle branch
block and evident fragmentation (arrows) of the QRS complexes compared to a tetralogy of Fallot patient
(1B) with a wide right bundle branch block without fragmentation of QRS complexes.
MECHANICAL CIRCULATORY SUPPORT (MCS) IN THE NETHERLANDS: LONG TERM
RESULTS FROM THE UNIVERSITY MEDICAL CENTER UTRECHT (UMCU)
SERIAL MEASURES OF CLINICAL PARAMETERS PREDICT PROGNOSIS IN PAH-CHD
M.T.U. Schuijt (AMC, Amsterdam); I.M. Blok (AMC, Amsterdam/NHI, Utrecht); A.C.M.J. van
Riel (AMC, Amsterdam/NHI, Utrecht); A.H. Zwinderman (AMC Amsterdam); B.J.M. Mulder
(AMC, Amsterdam/NHI, Utrecht); B.J. Bouma (AMC, Amsterdam).
Adult patients with pulmonary arterial hypertension due to congenital heart disease (PAHCHD) suffer from a high mortality. This underlines the importance of adequate risk
stratification to guide treatment decisions. Several cross-sectional clinical variables have
been associated with mortality, but nowadays longer follow-up is available. Therefore we
investigated the prognostic relevance of serial measurements in patients with PAH-CHD.
In this prospective observational cohort study, we included consecutive adult patients with
PAH-CHD between 2005 and 2015. Control visits on the outpatient clinic were standardised,
including WHO functional class (WHO-FC), six-minute walk distance (6-MWD) and NT-proBNP. All patients were treated with bosentan following the first visit. We evaluated prognosis
of PAH-CHD patients who met the following criteria: first time worsening to WHO-FC 4, a
6-MWD decrease of 25 meters and an NT-pro-BNP increase of 200 ng/L during follow-up.
Sixty-six patients with PAH-CHD were included (mean age 44 years, 33% male, 33% Down,
71% Eisenmenger). During a mean follow-up of 5.5 years (SD 3.2), 21 patients died (32%).
In our risk stratification model during follow-up (Figure 1), worsening to WHO-FC 4 occurred
in 10 patients, a 6-MWD decrease of 25 meters in 47 patients and an NT-pro-BNP increase
of 200 ng/L in 33 patients. The time from onset of these criteria until 25% of patients died,
differed between WHO-FC (0.08 yrs), 6-MWD (4.5 yrs) and NT-pro-BNP (2.1 yrs).
Serial measurements of WHO-FC, 6-MWD and NT-pro-BNP during semi-annual control visits,
each have specific implications for the prognosis.
Figure 1. Prognosis of PAH-CHD patients based on serial measures of clinical status
NHJ 1604 Abstracts NVVC incl omslag_proef5.indd 12
S.E.A. Felix (UMC Utrecht, Utrecht); F.Z. Ramjankhan (UMC Utrecht, Utrecht); F.de Heer
(UMC Utrecht, Utrecht); M.P. Buijsrogge (UMC Utrecht, Utrecht); W.J.L. Suyker (UMC
Utrecht, Utrecht); N. Hulstein (UMC Utrecht, Utrecht); C. Klöpping (UMC Utrecht, Utrecht);
J.H. Kirkels (UMC Utrecht, Utrecht); P.A. Doevendans (UMC Utrecht, Utrecht); N. de Jonge
(UMC Utrecht, Utrecht).
MCS improves survival and quality of life in selected patients with end-stage heart failure,
refractory to medical therapy. Currently, Heartmate II (HM-II)®, Heartmate 3 (St.Jude
Medical) and HVAD® (HeartWare) are most widely used MCS devices. In the Netherlands,
the waiting list for heart transplantation increases as a result of shortage of donor hearts.
Consequently, experience is built on longer term support, of which our single center results
Data of all patients who received MCS between March 2006 and January 2016 were
prospectively collected in a database. It includes baseline clinical characteristics as well as
complications defined according to INTERMACS. Data were extracted to SAS for statistical
In the UMCU 203 patients received MCS (160 HM-II, 2 HM 3 and 41 HVAD). Heart
transplantation was performed in 67 patients and in 7 patients MCS was explanted.
Actuarial survival at 5 years is 68%. Death was most often caused by neurological
complications and sepsis. Gastro-intestinal bleeding and intracerebral complications
(hemorrhage and stroke) both occurred 0.15 times per patient year. Twenty-seven
replacements were performed, most often due to pump thrombosis or driveline problems.
5-year survival in MCS patients is 68%. It is a promising therapy that might be a good alternative
for heart transplantation in selected patients. However, further optimization of therapy by
technical improvements, as well as management of long term complications is required.
Figure 1. Kaplan Meier survival curve
Netherlands Heart Journal, Volume 24, Supplement, April 2016
Session V: Heart failure/ Coronary artery disease
Session VI: General Cardiology
PROGNOSTIC VALUE OF N-TERMINAL PRO-B-TYPE NATRIURETIC PEPTIDE IN ADULTS
WITH CONGENITAL HEART DISEASE
BNP CONCENTRATIONS AFTER PROLONGED MODERATE-INTENSITY EXERCISE IN
INDIVIDUALS WITH CARDIOVASCULAR DISEASE AND RISK FACTORS
V.J.M. Baggen (Erasmus MC, Rotterdam); A.E. van den Bosch (Erasmus MC, Rotterdam);
J.A. Eindhoven (Erasmus MC, Rotterdam); J.A.A.E. Cuypers (Erasmus MC, Rotterdam); M.
Witsenburg (Erasmus MC, Rotterdam); M. de Waart (Erasmus MC, Rotterdam); E. Boersma
(Erasmus MC, Rotterdam); J.W. Roos-Hesselink (Erasmus MC, Rotterdam).
V.L. Aengevaeren (Radboudumc, Nijmegen); M.T.E. Hopman (Radboudumc, Nijmegen); MJ
de Boer (Radboudumc, Nijmegen); D.H.J. Thijssen (Radboudumc, Nijmegen; LJMU,
Liverpool); T.M.H. Eijsvogels (Radboudumc, Nijmegen; LJMU, Liverpool)
N-terminal pro-B-type natriuretic peptide (NT-proBNP) is related to echocardiographic
measurements and exercise capacity in adults with congenital heart disease (CHD). Followup data are yet very limited in this patient group. This study aims to investigate the
association between NT-proBNP and adverse outcomes in adults with CHD.
In this prospective cohort study, consecutive stable adults with CHD who visited the
outpatient clinic between April 2011 and April 2013 underwent NT-proBNP level
measurement and extensive echocardiography. Multivariable Cox proportional hazards
regression was performed to identify associations with clinical outcome events,
independently of age, sex and systemic ventricular function.
We included 602 patients (median age 32 [IQR 25-41] years, 58% male, 90% NYHA class
I): congenital aortic stenosis (n=138), aortic coarctation (n=112), arterial switch operation
(n=24), tetralogy of Fallot (n=179), Mustard operation (n=65), congenitally corrected
transposition of the great arteries (n=21), Fontan (n=36) or other (n=27). Patients were
followed-up during a median of 3.5 [IQR 3.0-3.8] years. In multivariable analysis, a two-fold
increase in NT-proBNP was independently related to an increased risk of death (n=12, HR
2.68 [95%CI 1.54-4.67], p=0.001), hospitalization for cardiac reasons (n=125, HR 1.74
[95%CI 1.52-2.00], p<0.001), heart failure (n=46, HR 2.23 [95%CI 1.75-2.85], p<0.001),
arrhythmia (n=90, HR 1.52 [95%CI 1.30-1.77], p<0.001) and re-intervention (n=89, HR
1.68 [95%CI 1.44-1.96], p<0.001).
NT-proBNP measured on a single random moment in the clinical course of adults with CHD
is strongly associated with adverse outcomes, independently of age, sex and systemic
Figure 1 Kaplan-Meier curves demonstrating the heart failure-free survival (A) and event-free survival (B)
according to quartiles of NT-proBNP. Per two-fold increase in NT-proBNP the risk of death or heart failure
(n=50, HR 2.18 [95%CI 1.73-2.74], p<0.001) and any adverse event (n=165, HR 1.55 [95%CI 1.38-1.75],
p<0.001) significantly increased.
MARKED GENDER DIFFERENCES IN THE PREDICTIVE VALUE OF THE HEART SCORE
FOR MAJOR ADVERSE CARDIAC EVENTS IN PATIENTS PRESENTING TO THE
EMERGENCY DEPARTMENT WITH ACUTE CHEST PAIN
I.E.M. Bank (UMC Utrecht); V.C. de Hoog (UMC Utrecht); D.P.V. de Kleijn (UMC Utrecht &
NUS, Singapore); G.P. Pasterkamp (UMC Utrecht); H.M. den Ruijter (UMC Utrecht); P.A.F.
Doevendans (UMC Utrecht); T.X. Wildbergh (Meander MC, Amersfoort); A. Mosterd
(Meander MC, Amersfoort); L. Timmers (UMC Utrecht)
BNP concentrations are known to increase in athletes performing prolonged exercise, but
whether this also occurs in less-trained individuals with cardiovascular diseases (CVD) or
risk factors (CVRF) performing prolonged exercise is unknown.
Therefore, we aimed to determine BNP concentrations in rest and after four consecutive
days of 30-50 km/day walking exercise in participants with CVD, CVR and healthy controls.
Furthermore, we aimed to identify predictors of the exercise-induced increase in BNP.
Serum BNP concentrations were measured in 203 participants (60±1 yrs) of the Nijmegen
Marches before (baseline) and immediately after each walking day. We selected age,
gender, height, weight, BMI, CVD, CVRF, exercise duration, distance, intensity, walking
speed and baseline BNP as potential predictors for ΔBNP and post-exercise BNP.
Participants walked 484±6 min/day at 65±1% of their maximum heart rate (Table 1).
Baseline BNP levels were higher for CVD participants compared to CVRF participants and
controls. BNP increased from 19.5±2.1 to 23.4±2.7 pg/ml post-exercise (p = 0.002), whilst
no cumulative effect was observed across days (p=0.22). Comparing the 3 groups, postexercise BNP concentrations were elevated in CVD participants (p = 0.003), but not in CVRF
participants (p=0.06) or controls (p=0.15). Predictors for ΔBNP (R2=0.15) and post-exercise
BNP (R2=0.77) were baseline BNP, history of CVD and age.
Moderate-intensity walking exercise increases BNP concentrations in subjects with CVD,
but not in subjects with CVRF or healthy controls. 77% of post-exercise BNP and 15% of
ΔBNP concentrations could be predicted using baseline BNP, history of CVD and age.
57 (91) *†
32 (71) †
Walking distance, km
Walking duration, min
Walking speed, km/h
Baseline BNP, pg/mL
BNP post-ex day 1, pg/mL
BNP post-ex day 2, pg/mL
BNP post-ex day 3, pg/mL
BNP post-ex day 4, pg/mL
HR/max HR, %
Data are presented as mean±SEM; BNP data were ln-transformed for analyses.
CVD = cardiovascular disease, BMI = body mass index, ex = exercise, HR = heart rate
= significantly different from CVRF group, †= significant different from controls
The HEART score is a simple and effective tool to exclude short-term major adverse cardiac
events (MACE) in patients presenting to the emergency department (ED) with acute chest
pain. As it is suggested that diagnosing ischemic heart disease is more difficult in women
than men, we evaluated the performance of the HEART score in men vs. women.
The HEART score was assessed retrospectively in 1927 patients presenting with acute chest
pain to the ED (MINERVA cohort, n=1093 men and n= 834 women), assigning them to a low,
intermediate, or high risk category. Primary outcome was the occurrence of MACE, defined
as myocardial infarction, coronary revascularization or all-cause death, within 6 weeks.
Compared to women, men were less frequently assigned to the low risk category (34.2% vs
40.4%, p=0.006, HEART score 0-3), and more frequently assigned to the high risk category
(8.0% vs 3.8%, p<0.001, HEART score 7-10). The incidence of MACE was two times higher in
men than in women (10.0 vs 20.6%, p<0.001). Within each HEART risk category, the MACE
incidence was significantly higher in men as compared to women. (Figure 1) The c-statistic
for the HEART score was similar across sexes. However, the negative predictive value of a low
HEART score (proposed policy: early discharge) was 93.6% in men vs. 97.9% in women
The HEART score is less accurate and less efficient in ruling out MACE (without additional
testing) in men than women who present to the ED with acute chest pain.
Figure 1. Incidence of MACE in men and women within the HEART score risk groups
Netherlands Heart Journal, Volume 24, Supplement, April 2016
NHJ 1604 Abstracts NVVC incl omslag_proef5.indd 13
Session VI: General Cardiology (continued)
VALIDATION OF THE PSYCHOSOCIAL SCREENING INSTRUMENT OF THE EUROPEAN
SOCIETY OF CARDIOLOGY
E. van Montfort (Tilburg University, Tilburg); J. Denollet (Tilburg University, Tilburg); J.
Widdershoven (Elisabeth-TweeSteden ziekenhuis, Tilburg); N. Kupper (Tilburg University,
Examining the validity of the European Society of Cardiology’s’ psychosocial screening
508 (sub-)acute (67%) or elective (33%) percutaneous coronary intervention (PCI) patients
administered the 15-item ESC screening interview and established self-report
questionnaires for reputable psychosocial risk markers, i.e. depression (PHQ-9), anxiety
(GAD-7) and Type D personality (DS14) during or close after hospital admission (n=353366; 63±10 years; 79% male).
Factor Analysis identified five components: emotional distress, work stress, hostility, social
resources and social stress. Chi-square tests revealed high true negative rates for anxiety
(95%) and depression (92%), indicating consistent absence of anxiety and depression on
both screener and questionnaire. True positive scores were lower, indicating that
respectively 43% and 70% of patients scoring above the clinical threshold for anxiety and
depression were identified by the screener. For negative affectivity and social inhibition true
negative rates were 76% and 72%. From participants reporting negative affectivity, the
screener identified 74%. For social inhibition, this was 48%. Screening results were hardly
affected by PCI indication (elective vs. (sub-)acute).
The ESC screener is helpful as an early stage detector of emotional distress in both elective
and (sub-) acute PCI patients. It can be used in the clinic to make a first subdivision of
cardiac patients who may need psychosocial help and patients who do not need additional
psychosocial care. Lower true positive scores indicate that more in-depth diagnostic
assessment is needed as a second step. Future research is necessary for further validation
of the other psychosocial screening components.
Table 1. Rotated component matrix for ESC screener components
I.M. van Hagen (Erasmus MC, Rotterdam); M.R. Johnson (Imperial College School of
Medicine, Chelsea and Westminster Hospital, London, UK); R. Hall (Norwich Medical
School, University of East Anglia, Norwich, UK); J.W. Roos-Hesselink (Erasmus MC,
Maternal cardiovascular disease is known to be associated with increased risks of obstetric
and fetal adverse events. During preconception counselling it is important to recognize
women at highest risk. We aimed to validate the modified WHO classification and also
studied the underlying diagnoses and clinical parameters for prediction of separate events.
ROPAC is a worldwide ongoing prospective registry that has enrolled 2966 pregnancies
from January 2008 up to April 2014. The majority (2742 women) had a pre-pregnancy
diagnosis of structural heart disease and were included in this analysis.
Mean age was 28.2±5.5 years, 45% were nulliparous and 66.6% came from developed
countries. Diagnoses included congenital heart disease (CHD 58.2%), valvular heart
disease (31.4%), cardiomyopathy (5.9%), ischemic heart disease (0.6%), aortopathy (3.7%)
and pulmonary hypertension (0.3%). Obstetric events occurred in 8.4% of women.
Offspring events occurred in 23.7% of pregnancies. The modified WHO classification had a
poor performance for obstetric events (c-statistic=0.596) and offspring events
(c-statistic=0.561). Multivariable analysis of separate endpoints were performed to provide
more insights (Figure 1). Aortic valve disease was associated with pre-eclamptic toxaemia.
CHD was associated with spontaneous preterm birth. Complex CHD was associated with
In our study the modified WHO classification was a poor predictor of obstetric and offspring
events. Maternal complex CHD was independently associated with fetal growth restriction,
while in aortic valve disease there was a higher rate of pre-eclamptic toxaemia.
Pathophysiological mechanisms of these associations are to be elucidated.
Figure 1 Multivariable analysis: predictors of obstetric outcome
Hostility: other people
Hostility: other things
Social: living alone
Social: highest education
Work: control demands
Work: reward vs. effort
PREDICTORS OF OBSTETRIC AND OFFSPRING COMPLICATIONS IN WOMEN WITH
HEART DISEASE: DATA FROM THE REGISTRY OF PREGNANCY AND CARDIAC
RETROSPECTIVE ANALYZE OF CARDIOVASCULAR DISEASES IN A WOMEN
OUTPATIENT CLINIC IN OLVG WEST
C.A.M. Sijtsema (OLVG West, Amsterdam); B. Torensma (OLVG West, Amsterdam) J.M.
Schroeder-Tanka (OLVG West, Amsterdam)
Cardiovascular diseases are the number one cause of death for women. In previous years
women were underrepresented in many cardiovascular clinical trials. However recent
studies show gender- differences in clinic presentation, pathophysiology, risk factors and
diagnostics of cardiovascular diseases. In the Netherlands cardiological outpatient clinics
are developed especially for women. The aim of this study was to sketch a profile of the
women who visited the women outpatient clinic in OLVG West.
This study concerned a retrospective analysis of 123 pre and post-menopausal patients
between 45-65 years old with or without cardiovascular diseases. The study included
patients with possible cardiovascular complaints and/or cardiovascular risk factors. Data
was obtained through electronic patients files and a questionnaire filled in by the patients.
Results showed that 42,5% of the women suffered cardiovascular diseases. The complaint
‘chest pain’ was the most common complaint (66,7%), followed by ‘dyspnoe d’effort’
(58,5%) and ‘palpitations’ (50,4%). Four complaints was the most common (33,3%). There
was a significant deviation of SBP (>140mmHg), abnormal ECG results and a history of
cardiac diseases in women with cardiovascular disease. Regression analysis showed an
increased risk of cardiovascular diseases by continue SBP (OR1,033) and a history of
cardiac diseases (OR 5,631).
This study showed similar to higher rates of diagnoses, compared with previous studies,
suggesting that the women output clinic has been effective and representative. In the
future, well conducted studies with significance variables are required to improve the
prevention and the clinical management of cardiovascular diseases in women.
NHJ 1604 Abstracts NVVC incl omslag_proef5.indd 14
Netherlands Heart Journal, Volume 24, Supplement, April 2016
Session VI: General Cardiology (continued)
THE BENEFICIAL EFFECT OF BOSENTAN AND MACITENTAN IN CONGENITAL HEART
DISEASE PATIENTS: ARE THE OUTCOMES COMPARABLE?
I.M. Blok (AMC, Amsterdam/NHI, Utrecht); A.C.M.J. van Riel (AMC, Amsterdam/NHI,
Utrecht); A.P.J. van Dijk (Radboud UMC, Nijmegen); B.J.M. Mulder (AMC, Amsterdam/NHI,
Utrecht); B.J. Bouma (AMC, Amsterdam).
Macitentan, a novel endothelin receptor antagonist and successor of the widely applied
bosentan, improves WHO functional class (WHO-FC) and six-minute walk distance (6-MWD)
of patients with pulmonary arterial hypertension due to congenital heart disease (PAHCHD). The initial treatment effect of macitentan in therapy naïve PAH-CHD patients has
never been compared to that of bosentan.
Consecutive new PAH-therapy naïve PAH-CHD patients were started on macitentan 10 mg
once daily. This cohort was compared to our historical cohort of therapy naïve patients
starting bosentan between 2005-2013. All patients underwent standardized follow-up
including determination of WHO-FC, NT-pro-BNP and 6-MWD. Change in variables between
baseline and six months follow-up was compared between bosentan and macitentan
starters with chi square statistics, and Mann-Whitney U test.
Six PAH-CHD patients (mean age 37 years, 33% male, 17% Down syndrome, 100%
Eisenmenger syndrome) started macitentan. They were matched with a historical cohort of
12 PAH-CHD patients who started bosentan, based on age, sex, Down syndrome, baseline
NT-pro-BNP, WHO-FC, and 6-MWD. After six months of therapy in both cohorts, patients on
macitentan showed larger benefits in 6-MWD (+24 vs. +1, p=0.031) and similar benefit on
WHO-FC (17 vs. 25% improvement, p=0.622). The improvement of NT-pro-BNP seemed
better in the macitentan cohort, although non-significant (-27 vs. +34, p=0.151), however,
more patients on macitentan improved their NT-pro-BNP levels (83% vs. 25%, p=0.019).
Our historical cohort study shows larger treatment effect of macitentan compared to
bosentan in therapy naïve PAH-CHD patients during the first six months.
MOBILE HEALTH IN PATIENTS WITH CONGENITAL HEART DISEASE
M.J. Schuuring (Haga, the Hague); B.J. Bouma (AMC, Amsterdam); D.R. Koolbergen (AMC,
Amsterdam); A.P.C.M. Backx (AMC, Amsterdam); D. Robbers – Visser (AMC, Amsterdam);
J. Vriend (Haga, the Hague); M. Groenink (AMC, Amsterdam); S.M. Boekholdt (AMC,
Amsterdam); R. de Winter (AMC, Amsterdam); B.J. Mulder (AMC, Amsterdam)
Many adults with congenital heart disease (CHD) are affected by unpredictable arrhythmias
and heart failure, putting them at risk of premature death. Mobile devices are an
opportunity to monitor them. Currently, there are nearly 100,000 mobile health applications
(‘apps’) available. However, none of these smartphone applications are adopted in clinical
cardiology. There is a lack on data which patients are willing to use mobile health and which
parameters to monitor.
A survey on outpatient clinic in adults with CHD. Patients with mental retardation are
Preliminary data shows that 86% owned a smartphone (mean age 36 ± 14 years old, 64%
male, predominantly NYHA II). Whereas currently a small minority (17%) of patients with
CHD uses a smartphone health application, a majority (75%) of patients indicates that he
or she wants to use a smartphone health application, see Figure 1. Furthermore, the
majority of patients with CHD wants to receive health information on their smartphone and
are willing to fill in questionnaires regarding vitals, life style and symptoms. More
importantly, the majority wants to receive advice from their treating cardiologist in case of
aberrant parameters and progression of symptoms, want to receive stimulating (lifestyle)
messages and want to receive medication reminders.
The majority of patients with CHD are willing to use mobile health. Results from an extended
patient population with a more detailed characterization (severity of defect, corrected
analysis on gender / NYHA class, etc) are available soon.
Table 1. Historical comparison of clinical outcome during 6 months therapy with bosentan and macitentan
WITHDRAWAL OF ANTIHYPERTENSIVE MEDICATION INCREASES BLOOD PRESSURE
IN ONLY 50% OF PATIENTS
Martine M.A. Beeftink (UMC Utrecht), Margreet F. Sanders (UMC Utrecht), Michiel Voskuil
(UMC Utrecht), Pieter Doevendans (UMC Utrecht), Michiel Bots (UMC Utrecht), Wilko
Spiering (UMC Utrecht)
SECUNDUM ATRIAL SEPTAL DEFECTS AND ASTHMA-LIKE DYSPNOEA: THE IMPACT
OF TRANSCATHETER CLOSURE
M. Nassif (AMC, Amsterdam); C.B.B.C.M. Heuschen (AMC, Amsterdam); H. Lu (AMC,
Amsterdam); B.J. Bouma (AMC, Amsterdam); R.P. van Steenwijk (AMC, Amsterdam); P.J.
Sterk (AMC, Amsterdam); B.J.M. Mulder (AMC, Amsterdam); R.J. de Winter (AMC,
Patients with atrial septal defects (ASD) are often misdiagnosed as asthma patients and
receive erroneous bronchodilator treatment accordingly. In order to characterize
their symptoms of dyspnoea to explain this clinical observation, we investigated the
prevalence of asthma-like symptoms in patients with secundum ASD who then underwent
successful percutaneous closure.
A total of 80 ASD patients (74% female, mean age 46.7±16.8 years, median follow-up 3.0
[2.0-5.0] years) retrospectively completed dyspnoea questionnaires determining
the presence and extent of cough, wheezing, chest tightness, effort dyspnoea and
bronchodilator use on a 7-point scale (0=none, 6=maximum) before and after ASD closure.
The Mini Asthma Quality of Life (Mini-AQLQ) and Asthma Control Questionnaire with
bronchodilator use (ACQ6) were administered.
A total of 48 (60%) patients reported cough, 27 (34%) wheezing, 26 (33%) chest
tightness and 62 (78%) effort dyspnoea. Symptom resolution or reduction was found in 64
(80%) patients after ASD closure. Asthma symptom scores decreased significantly on MiniAQLQ and ACQ6 (both P<0.001). The number of patients using bronchodilators decreased
from 16 (20%) to 8 (10%) patients after ASD closure (P=0.039) with less frequent use of
We observed unanticipated reductions in blood pressure after withdrawal of
antihypertensive medication. To quantify this observation, we performed a structured
analysis to investigate blood pressure changes after withdrawal of antihypertensive
We reviewed the medical records of the patients who were evaluated for hypertension at
the UMC Utrecht between 2010 and 2015. Lifestyle parameter, laboratory results and
prescribed antihypertensive medication were collected for all patients who had a 24-hour
blood pressure measurement (ABPM) performed at referral (with medication), as well as
after withdrawal of antihypertensive medication.
We included 163 patients with a mean age of 56.3 years (SD 13), a median of 3
antihypertensive drugs with a mean daily defined dose of 5.1 (SD 2.9).
Eighty-seven patients (53,4%) demonstrated an increase of at least 5 mmHg after
withdrawal of medication, whereas blood pressure remained stable (i.e. less than 5 mmHg
change) in 40 patients (24,5%) and blood pressure decreased more than 5 mmHg in 36
patients (22,1%). The amount of withdrawn medication was highest in the group that
experienced a decrease in blood pressure (-3.8 DDD when BP decreased, -4.3 DDD for
stable BP and -5.2 when BP increased, p = 0.02). We also found a significant difference in
24-hour urinary sodium excretion (116 mmol/24hrs when BP decreased, 151 mmol/24hrs
for stable BP and 155 mmol/24hrs when BP increased, p= 0.003).
Withdrawal of antihypertensive medication fails to increase blood pressure in almost 50%
of patients. The causes for this remarkable observation remain to be elucidated, but may
include decreased sodium intake and poor medication adherence.
Figure 1. Change in Systolic 24-hour blood pressure after withdrawal of antihypertensive medication.
A high prevalence of asthma-like symptoms and bronchodilator use is present in ASD
patients, higher than would be expected based on the amount of patients with bronchial
asthma in this study population. The presence of an ASD should be considered in the
differential diagnosis of patients with asthma-like symptoms, after which significant
symptom relief can be achieved by ASD closure.
Netherlands Heart Journal, Volume 24, Supplement, April 2016
NHJ 1604 Abstracts NVVC incl omslag_proef5.indd 15
VERKORTE PRODUCTINFORMATIE ATOZET® Voor de volledige en meest recente productinformatie verwijzen wij naar de goedgekeurde SPC op www.cbg-meb.nl NAAM
VAN HET GENEESMIDDEL: ATOZET 10 mg/10 mg, 10 mg/20 mg en 10 mg/40 mg FARMACEUTISCHE VORM: Filmomhulde tablet KWALITATIEVE EN KWANTITATIEVE
SAMENSTELLING: Per filmomhulde tablet 10 mg ezetimibe en 10, 20 of 40 mg atorvastatine. FARMACOTHERAPEUTISCHE GROEP EN WERKINGSMECHANISME:
HMG-CoA-reductaseremmers in combinatie met andere antilipemica. Ezetimibe remt intestinale absorptie van cholesterol en atorvastatine is een selectieve,
competitieve HMG-CoA-reductaseremmer. THERAPEUTISCHE INDICATIES: Aanvullende therapie naast dieet bij volwassenen met primaire (heterozygote familiaire
(HeFH) en niet-familiaire) hypercholesterolemie of gemengde hyperlipidemie waar een combinatieproduct aangewezen is; bij patiënten onvoldoende onder controle
met statine alleen of die al met een statine en ezetimibe worden behandeld; aanvullende therapie naast dieet bij volwassenen met homozygote familiare
hypercholesterolemie (HoFH). CONTRA-INDICATIES Overgevoeligheid voor de ingrediënten; zwangerschap en borstvoeding; bij vruchtbare vrouwen die geen adequate
anticonceptiemaatregelen treffen; actieve leverziekte of onverklaarde persisterende verhogingen van serumtransaminasen (>3xULN) BELANGRIJKSTE
WAARSCHUWINGEN EN VOORZORGEN BIJ GEBRUIK: Myopathie en rabdomyolyse zijn postmarketing gemeld, meestal bij statines i.c.m. ezetimibe, zeer zelden bij
ezetimibe monotherapie of i.c.m. andere middelen met verhoogd risico op rabdomyolyse. HMG-CoA-reductaseremmers incl. atorvastatine hebben invloed op
skeletspieren en veroorzaken soms myalgie, myositis en myopathie, soms als (mogelijk levensbedreigende) rabdomyolyse (creatinekinase (CK) >10xULN),
myoglobinemie en myoglobinurie, mogelijk leidend tot nierfalen en levensbedreigend). Vóór behandeling voorzichtigheid betrachten bij predisponerende factoren voor
rabdomyolyse. Meet het CK vóór start behandeling bij nierfunctiestoornis, hypothyreoïdie, eigen/familiaire voorgeschiedenis van erfelijke spieraandoeningen,
voorgeschiedenis van spiertoxiciteit met statine/fibraat, voorgeschiedenis van leverziekte en/of overmatig alcoholgebruik, leeftijd >70 jaar met factoren voor
rabdomyolyse, bij risico op toename plasmaconcentraties (interacties, speciale populaties incl. genetische subpopulaties). In dit geval overweeg de voordelen/risico’s van
behandeling en klinische controle wordt aanbevolen. Stel behandeling niet in als CK bij baseline-meting significant is verhoogd (>5xULN). CK mag niet worden gemeten
na zware lichamelijke inspanning of andere plausibele oorzaak van CK-verhoging, wegens interpretatieproblemen. Als het CK bij baseline >5xULN, meet binnen
5-7 dagen opnieuw om resultaten te bevestigen. Tijdens behandeling: Verzoek patiënten spierpijn, -kramp of -zwakte direct te melden, vooral indien gepaard met
malaise of koorts. Meet het CK als deze symptomen optreden tijdens behandeling met ATOZET. Staak behandeling als deze waarden >5xULN). Als spiersymptomen
ernstig zijn met dagelijks ongemak, zelfs als CK verhoogd is ≤5xULN, overweeg behandeling te staken . Als symptomen verdwijnen en CK normaliseert, overweeg
herstart van ATOZET of start van andere statines in de laagste dosis, met zorgvuldige controle. Staak behandeling met ATOZET indien CK klinisch significant is verhoogd
(>10xULN), of bij (vermoeden van) rabdomyolyse. Zeer zelden is immuungemedieerde necrotiserende myopathie gemeld tijdens of na statinebehandeling, incl.
atorvastatine (klinisch gekarakteriseerd door proximale spierzwakte en een verhoogd serumcreatinekinase, aanhoudend na staken van de statine). Atorvastatine
verhoogt het rabdomyolyserisico bij gelijktijdig gebruik van geneesmiddelen die atorvastatineconcentraties kunnen verhogen, zoals krachtige CYP3A4-remmers of
transporteiwitremmers (bijv. ciclosporine, telitromycine, claritromycine, delavirdine, stiripentol, keto/vori/itra/posaconazol en hiv-proteaseremmers). Het
myopathierisico kan verhoogd worden door fibrinezuurderivaten (incl. gemfibrozil), boceprevir, erytromycine, niacine, telaprevir, of de combinatie van tipranavir met
ritonavir. Alternatieve behandelingen moeten (zonder interactie) worden overwogen. Indien gelijktijdig gebruik van ATOZET nodig is, moeten de voordelen en risico’s
zorgvuldig worden afgewogen. Bij geneesmiddelen die plasmaconcentraties atorvastatine verhogen, wordt een lagere maximum dosis ATOZET aanbevolen. Overweeg
bij krachtige CYP3A4-remmers tevens een lagere aanvangsdosis en geschikte klinische controle is aanbevolen. Gelijktijdig gebruik met fusidinezuur wordt niet
aanbevolen; overweeg tijdelijk staken van ATOZET tijdens gebruik van fusidinezuur. In gecontroleerde onderzoeken naar co-administratie van ezetimibe met
atorvastatine, zijn opeenvolgende verhogingen van transaminasen (≥3x ULN) waargenomen. Leverfunctiecontrole wordt aanbevolen vóór start van behandeling en
regelmatig daarna, en ook bij ontwikkeling van tekenen van leverbeschadiging. Als serumtransaminasespiegels stijgen, moeten controles worden uitgevoerd totdat
afwijkingen zijn verdwenen; bij aanhoudende stijging tot 3xULN wordt dosisverlaging/staken van ATOZET aanbevolen. ATOZET met voorzichtigheid toepassen bij
patiënten die aanzienlijke hoeveelheden alcohol consumeren en/of leverziektehistorie hebben. Vanwege het onbekende effect van verhoogde blootstelling aan
ezetimibe bij een matige of ernstige leverinsufficiëntie, wordt ATOZET hierbij niet aanbevolen. De veiligheid en werkzaamheid van ezetimibe met fibraten zijn niet
vastgesteld; gelijktijdige toediening wordt niet aanbevolen. Betracht voorzichtigheid bij co-administratie van ATOZET met ciclosporine; controleer
ciclosporineconcentraties. Controleer INR bij gebruik van warfarine, andere coumarine-anticoagulantia of fluindion. In een post-hoc-analyse van subtypes van beroerte
zonder coronaire hartziekte maar met recent doorgemaakte beroerte of TIA was er een hogere incidentie van hersenbloedingen bij patiënten die waren gestart met 80
mg atorvastatine vergeleken met placebo. Een verhoogd risico werd vooral gezien bij patiënten die eerder een hemorragische beroerte of lacunair infarct hadden gehad.
Bij eerder doorgemaakte hemorragische beroerte of lacunair infarct is risico-batenbalans van 80 mg atorvastatine onduidelijk, en moet het potentiële risico op
hersenbloeding worden afgewogen alvorens de behandeling te beginnen. Uitzonderlijke gevallen van interstitiële longziekte zijn gemeld bij sommige statines, vooral
bij langdurige behandeling (kenmerken zijn o.a. dyspneu, niet-productieve hoest en afname algehele gezondheid (vermoeidheid, gewichtsverlies, koorts)). Bij
vermoeden van interstitiële longziekte moet de statine worden gestaakt. Er zijn aanwijzingen dat statines bloedglucose verhogen en bij sommige patiënten met hoog
risico op toekomstige diabetes een mate van hyperglykemie kunnen veroorzaken, die formele diabeteszorg vereist. Dit risico weegt minder zwaar dan verlaging van het
vasculaire risico en moet geen reden zijn om de statine te stoppen. Controleer patiënten met dit risico (nuchter glucose 5,6 tot 6,9 mmol/l, BMI > 30 kg/m2, verhoogde
triglyceriden, hypertensie) klinisch en biochemisch volgens de landelijke richtlijnen. ATOZET bevat lactose. Zie SPC voor interacties. BIJWERKINGEN: Vaak: diarree,
myalgie. Soms: griep, depressie, slapeloosheid, slaapstoornis, duizeligheid, dysgeusie, hoofdpijn, paresthesie, sinus-bradycardie, opvlieger, dyspneu, abdominaal
ongemak, abdominale distensie, buikpijn, pijn in de onderbuik, pijn in de bovenbuik, constipatie, dyspepsie, flatulentie, frequente darmbewegingen, gastritis,
misselijkheid, maagongemak, acne, urticaria, artralgie, rugpijn, spiervermoeidheid, spierspasmen, spierzwakte, pijn in extremiteit, asthenie, vermoeidheid, malaise,
oedeem, abnormale leverfunctietest, verhoogd ALAT en/of ASAT, verhoogde alkalische fosfatase, gamma-glutamyltransferase of leverenzymen, verhoogd CK in bloed,
gewichtstoename. Zie SPC voor postmarketing gemelde bijwerkingen. REGISTRATIEHOUDER: Merck Sharp & Dohme Ltd., Hertford Road, Hoddesdon, Hertfordshire,
EN11 9BU, UK. LOKALE VERTEGENWOORDIGER: MSD BV, Waarderweg 39, 2031 BN Haarlem, 0800 9999 000, [email protected] REGISTRATIENUMMER(S):
RVG 114373/4/5 VERGOEDING: Volledig vergoed. AFLEVERSTATUS: UR. DATUM SPC: Oktober 2014.
ATOZET SPC 85x110 Neth. Heart journal.indd 1
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