Abstracts
Posters
Poster 1
Poster 2
CORONARY ARTERY CALCIFICATIONS ARE CORRELATED WITH BREAST ARTERIAL CALCIFICATIONS, BUT THEIR AETIOLOGY IS PREDOMINANTLY DIFFERENT Angela H.E.M.Maas (1). Yvonne T. van der Schouw (2), David Beijerinck (3), Jan J.M.Deurenberg (3), Willem P.Th. M.Mall (4), Yolanda van der Graaf (2). (1)Department of Cardiology, Isala kllnieken, Zwolle,(2) Julius Center for Health Sdences and Primary Care, University Medical Center Utrecht,(3) Preventicon Breast Cancer Screening Center, Utrecht,(4)Department of Radiology, University Medical Center Utrecht, The Netherlands.
THREE YEAR OPEN ACCESS ECHOCARDIOGRAPHYIN THE PARKSTAD AREA: WHAT WAS THE YIELD? LHB Baur, C. Lodewijks, T. Lenderink, F. Guldemond, 2. Nijhof, M. Hundscheid, F. Soomers. On behalf of the working group on open access echocardlography in the Parkstad Area.
Objective: Vascular calcification is considered a marker of cardiovascular risk and imaging of calcium Is increasingly used for cardiovascular (CV) screening purposes. It is not known whether calcificatlons In the breast arteries are related to coronary artery
calcifications.
Methods: We studied 499 women, aged 49-70 years, participating in a breast cancer screening program and Investigated whether arterial calciflcations In the breast (BAC) are associated with coronary arterial calcdflcatlons (CAC) after a mean foilow-up of 9 years. Baseline mammograms of all women were reviewed on the presence of BAC by two Independent reviewers. CAC was assessed by multislice computed tomography (MSCT), with 3.0 mm slices, using the Agatston score. Logistic regression analysis was performed to Investigate the independent effect of BAC and various risk factors and reproductive factors on the occurrence of CAC.
Results: aAC was present in 58 of 499 women (12%) at baseline and CAC score > 0 was present In 262 of 499 women (53%) after follow-up. Age was the most Important determinant for both BAC and CAC. In all age groups CAC was more prevalent than BAC. The presence of BAC was strongly associated with the occurrence of CAC (OR 3.2, 95% CI 1.71-6.04) and this remained significant after adjustment for age and the duration of foliow-up (OR 2.1, 95% CI 1.104.23). Most of the coronary heart disease risk factors were associated with CAC but not with BAC. The only common risk factor was parity, which was signiflcantly associated with both increased CAC (OR 2.1, 95% CI 1.26-3.50) and increased BAC (OR 5.4, 95 % CI 1.28-22.52). Breastfeeding after pregnancy was associated with BAC (OR 3.7, 95% CI 1.55-8.83) but not with CAC (OR 1.4, 95% CI 0.95-2.08).
Methods: GPs, who participated in the project were able to ask for an echocardiogram without referring the patient to a cardiologist if they suspected the patient of having heart failure or a cardiac murmur. The results of the echo-Doppler examination were returned to the general practitioner with a comment how to handle the patient. Results: Between december 2002 and January 2006, from a total group of 378 pts, 98 pts were referred with the diagnosis dyspnea, 151 pts with a cardiac murmur, 7 with peripheral edema and 49 with a combination dyspnea and a murmur. The rest of the pts had other reasons for referral and are not mentioned here. Results can be seen in table 1 and 2. Table 1: Patients suspe ted of havin heart failure In Iden Incdnc tncid.c _ Incid.n. Di LVEFs40% nnl P.1-n.ry I.pun t
Table 2: Patients suspected of having valvular heart disease 21% Aav vahnilar abnun,naltvt 37% 9%'i Sign. SOS y8% 3YO Slg1n 801 14%i 14 4% 51an Sb% 4%s SigCM 14%b Sin T1 °h% 16%
Incid-c
Iwnt
1 MD at the day of the procedure is more common in patients who will have an increase in the number of AF episodes up to 180 days after PVI. Also the rise in baseline heart rate > 25% is a predictor of no recurrences.
cfpc
Netherlands Heart Journal, Volume
14, Number 5, May 2006
Poster 24
OPTIMAL PACING SITE IN CARDIAC RESYNCHRONISATION THERAPY: EVALUATION OF MULTIPLE EPICARDIAL LEFT SIMULTANEOUS SITES WITH VENTRICULAR PACING CONTRACTILITY INDEX MEASUREMENT H. van Wessel, MSc, PF Bakker, MD,PhD, M.Meine, MD, W. Buhre MD,PhD, AE Tuinenburg, MD,PhD FHM Wittkampf, PHD, RNW Hauer, MD,PhD, LA van Herwerden, MD,PhD, P Loh, MD,PhD. Heart Lung Center Utrecht. Background: Cardiac resynchronisation therapy (CRT) is an emerging treatment for patients with advanced heart failure and left ventricular (LV) asynchrony. The LV lead is usually positioned transvenously in a posterior branch of the coronary venous system. However, anatomical obstacles, the absence of a suitable vessel or phrenic nerve stimulation can render this approach impractical. Epicardial lead positioning with video-assisted thoracic surgery (VATS) is an alternative approach and allows evaluation of stimulation at multiple sites. The aim of this study was to assess the optimal pacing site by measuring the maximal rate of LV pressure rise (dp/dt,,.,) as an index of cardiac contractility at different pacing sites. Method: Five patients underwent minimal invasive surgery using the VATS technique to insert an epicardial LV lead after a failed transvenous approach. A Radia pressure wire was inserted Into the LV for measuring the maximal rate of pressure rise in the LV (dp/dt-.) and calculating the contractility index (CI). With a roving electrode multiple sites were assessed during biventricular pacing. The epicardial electrode was fixed at the position where the best dP/dt-.X was measured. Subsequently, atrioventricular delay and W timing were optimized.
Results: In two patients the best pacing site was found mid posterior. In the three other patients the optimal sites were mid anterior, mid lateral and basal postero-lateral. Remarkably, spatial differences of only 1-2 cm could translate in relatively large differences in LV dP/dtx,,. The baseline LV dP/dt- x was 720 * 215 mmHg/s (mean±std) during intrinsic rhythm and increased up to 1190 ± 275 mmHg/s during optimal biventricular pacing. This means an increase factor of 1.7 ± 0.5. During short-term follow up, all patients clinically responded to CRT. No procedural complications occurred.
Conclusion: In CRT, epicardial lead placement using the VATS technique allows the identification of the optimal pacing site where the highest CI can be achieved. Small differences in pacing position could cause substantial differences in LV pressure rise. Subsequent optimalization of biventricular pacing parameters lead to an increase factor of 1.7 * 0.5.
13
Poster 21
CLOSURE OF A PATENT FORAMEN OVALE IS ASSOCIATED WITH A DECREASE IN PREVALENCE OF MIGRAINE: A PROSPECTIVE OBSERVATIONAL STUDY M.C. Post', J.G.L.M. Luermans', F. Temmerman2, V. Thijs3, W.J. Schonewille4, H.W.M. Plokkerl, M.J. Suttorpl, W. Budts2. Departments of Cardiology' and Neurology4, St. Antonius Hospital Nieuwegein, The Netherlands and Departments of Cardiology2 and Neurology3, University Hospital Gasthuisberg, Leuven, Belgium Purpose: A patent foramen ovale (PFO) is one of the major causes of right-to-left shunt and a relationship with migraine has been suggested. In mainly retrospective studies percutaneous PFO closure has been associated with a decrease in the prevalence of migraine. We evaluated the influence of PFO closure on the occurrence of migraine in a prospective observational study.
Methods: All 103 patients (> 16 years of age) who underwent a percutaneous PFO closure in our centres between November 2003 and December 2005 were included in the study. They received a headache questionnaire before and six months after closure. A neurologist, blinded to the patients' files, diagnosed migraine according to the International Headache Criteria. The McNemar paired chi-square test was used to describe changes in prevalence of migraine. Results: Ninety-eight patients (95%, mean age 51.3±12.1 years, 68 males) filled in the questionnaire before closure and in this group the prevalence of migraine was 27.6%, migraine without aura (MA-) 17.3%, and migraine with aura (MA+) 10.2%. The 6 months follow up was reached in 86 patients and 68 (79%, mean age 52.3±12.5 years, 49 males) of them sent back the questionnaire. The prevalence of migraine decreased from 27.9% to 8.8%/, a relative reduction of 68% (p=0.001), MA- from 17.6% to 5.9%, a relative reduction of 66% (p=0.02), and MA+ from 10.3% to 2.9%, a relative reduction of 72% (p=0.13). In one patient MA- changed into MA+ and one patient developed MA- six months after closure.
Conclusion: Percutaneous patent foramen ovale closure is related to a decrease in the prevalence of migraine in this prospective observational study. Whether PFO closure will become a new treatment in patients with migraine needs to be determined in a prospective randomized trial.
Poster 22
NONINVASIVE VISUALIZATION OF THE CARDIAC VENOUS SYSTEM IN CORONARY ARTERY DISEASE PATIENTS USING 64SLICE CT N. Van de Veire 2, J. Schuijfl, J. De Sutter2, D Devos2, A de Roos', MJ Schalijl, 3J Baxl, EE van der Wall'. 'Leiden University Medical Center and 2Ghent University (Belgium)
Purpose: Cardiac Resynchronization Therapy is an attractive treatment for highly symptomatic heart failure patients. Knowledge on the anatomy of the coronary sinus (CS) and its tributaries could help identifying potential candidates for successful left ventricular lead implantation. Study aim was to evaluate the value of 64-slice computed tomography (CT) to depict the cardiac venous anatomy in patients with coronary artery disease (CAD).
Methods: The 64-slice cardiac CT data of 50 individuals (age 59+11 years, 76% men) were evaluated. Subjects were divided in 3 groups: 15 controls (without CAD), 18 patients with significant CAD and 17 CAD patients with a history of myocardial infarction. The presence of the following CS tributaries was evaluated: posterior interventricular vein (PIV), posterior vein of the left ventricle (PVLV) and left marginal vein (LMV). Diameters of the proximal part of these veins and in-between distances were measured. Results: Anatomic variations are depicted in the Figure. The CS diameter was 11.4*3.5 mm in the anterior-posterior direction and 11.5±3.2 diameter in the superior-inferior direction. Diameters of the PIV, PVLV and LMV were 5.2*1.3, 3.8*1.1 and 3.5±1 mm respectively. Mean distance from the PIV to the PVLV was 35±21 mm and mean distance from the PVLV to LMV was 38±16 mm.
Conclusion: The anatomy of the coronary sinus and its tributaries can be evaluated with 64-slice CT. There is considerable variation in cardiac venous anatomy. Patients with a history of myocardial infarction were less likely to have a left marginal vein thus limiting optimal left ventricular lead positioning in case of CRT implantation. 100. 80.
~~~~~~~~CAD
%
Myocardal
200
P
CS
PIV
PVLV
LMV
I
Figure: Coronary sinus and tributaries
intarcUonl
Poster 23
RECURRENCE PATTERNS OF ATRIAL FIBRILLATION IN THE FIRST MONTHS AFTER PULMONARY VEINS CRYOISOLATION Wendel Moreira, MD; Carl Timmermans,MD,PhD; Yuka Mizusawa,MD; David Perez,MD; Suzanne Philippens,RN; HJGM Crijns,MD,PhD; Luz-Maria Rodriguez,MD, PhD. Academic Hospital Maastricht, Maastricht, The Netherlands.
Background: Early recurrence of paroxysmal atrial fibrillation (PAF) post PVI (pulmonary vein isolation) is a recognized phenomenon. Our study evaluates the recurrence behavior of AF in the first months following PVI. Methods: PVI using cryoablation was performed in 60 patients from 2001 to 2005. Daily recordings with transtelephonic telemetry were obtained 30 days prior and up to 180 days after the procedure. Group A consisted of patients with no further evidence of AF. Group B consisted of patients that had a significant decrease in the number of AF episodes. Group C consisted of patients that had an increase in the AF episodes after PVI. Results: Groups A, B and C had 26, 20 and 14 patients respectively. Age, gender, duration of AF, LA size, presence of LVH, LVEF and number of PVs treated were similar in all groups. Patients in group A had an increase in mean HR pre and post procedure of 16 bpm (from 64 to 80, p=0.02). The variation in HR for groups B and C *did not achieve statistic significance. History of atrial flutter was present in 63 % of group C pts, 30 % of group A and 20% of group B. The percentage of pts taking more than one antiarrhythmic drug (MD) at the time of ablation were: Group A = 13.3%; Group B = 40 0/0, Group C = 72.7%.
Conclusions: History of atrial flutter and current use of > 1 AAD at the day of the procedure is more common in patients who will have an increase in the number of AF episodes up to 180 days after PVI. Also the rise in baseline heart rate > 25% is a predictor of no recurrences.
Poster 24
OPTIMAL PACING SITE IN CARDIAC RESYNCHRONISATION THERAPY: EVALUATION OF MULTIPLE EPICARDIAL LEFT WITH SIMULTANEOUS SITES PACING VENTRICULAR CONTRACTILITY INDEX MEASUREMENT H. van Wessel, MSc, PF Bakker, MD,PhD, M.Meine, MD, W. Buhre MD,PhD, AE Tuinenburg, MD,PhD FHM Wittkampf, PHD, RNW Hauer, MD,PhD, LA van Herwerden, MD,PhD, P Loh, MD,PhD. Heart Lung Center Utrecht.
Background: Cardiac resynchronisation therapy (CRT) is an emerging treatment for patients with advanced heart failure and left ventricular (LV) asynchrony. The LV lead is usually positioned transvenously in a posterior branch of the coronary venous system. However, anatomical obstacles, the absence of a suitable vessel or phrenic nerve stimulation can render this approach impractical. Epicardial lead positioning with video-assisted thoracic surgery (VATS) is an alternative approach and allows evaluation of stimulation at multiple sites. The aim of this study was to assess the optimal pacing site by measuring the maximal rate of LV pressure rise (dp/dtmax) as an index of cardiac contractility at different pacing sites. Method: Five patients underwent minimal invasive surgery using the VATS technique to insert an epicardial LV lead after a failed transvenous approach. A Radi® pressure wire was inserted into the LV for measuring the maximal rate of pressure rise in the LV (dp/dtmax) and calculating the contractility index (CI). With a roving electrode multiple sites were assessed during biventricular pacing. The epicardial electrode was fixed at the position where the best dP/dtmax was measured. Subsequently, atrioventricular delay and W timing were optimized.
Results: In two patients the best pacing site was found mid posterior. In the three other patients the optimal sites were mid anterior, mid lateral and basal postero-lateral. Remarkably, spatial differences of only 1-2 cm could translate in relatively large differences in LV dP/dtmx. The baseline LV dP/dtmax was 720 ± 215 mmHg/s (mean±std) during intrinsic rhythm and increased up to 1190 i 275 mmHg/s during optimal biventricular pacing. This means an increase factor of 1.7 ± 0.5. During short-term follow up, all patients clinically responded to CRT. No procedural complications occurred. Conclusion: In CRT, epicardial lead placement using the VATS technique allows the identification of the optimal pacing site where the highest CI can be achieved. Small differences in pacing position could cause substantial differences in LV pressure rise. Subsequent optimalization of biventricular pacing parameters lead to an increase factor of 1.7 ± 0.5.
Abstracts
Posters
Poster 26
Poster 25
SUSTAINED EFFECT OF AUTOLOGOUS BONE MARROW CELL TRANSPLANTATION IN NO-OPTION PATIENTS WITH CHRONIC SEVERE ANGINA PECTORIS AND MYOCARDIAL ISCHEMIA: FINAL 12 MONTHS RESULTS SLMiA Beeres, 3 Bax, P Dibbets, K Zeppenfeld, MPM Stokkel, WE Fibbe, EE van der Wall, MJ Schalli, DE Atsma Dept. of Cardiology, Leiden University Medical Center, Leiden.
Background: Cell transplantation Is proposed as a novel therapeutic option for patients with coronary artery disease. This study Investigated whether bone marrow cell injection into ischemic myocardium of patients with severe angina pectoris could safely reduce anginal symptoms, improve myocardial perfusion and increase LV function. Methods: In 25 patients (64+10 yrs, 21 male) with drug-refractory angina pectoris (CCS class III-IV) despite optimized medical therapy and without options for conventional revascularization, bone marrow was aspirated from the Iliac crest. Mononuclear cells (84*29x106) were injected Intramyocardially (using the NOGA system) in regions with stress-induced ischemia on Tc-99m tetrofosmin gated SPECT. Anginal symptoms were reassessed at 3, 6 and 12 months follow-up. At baseline, 3 and 12 months follow-up, gated SPECT imaging was performed to assess LV function and myocardial perfusion. Rewlts: Intramyocardial injection of bone marrow cells was safe: laboratory measures did not reveal infarction, echocardiography showed no pericardial effusion, and sustained ventricular tachycardias were not observed. One patient died at 7 months follow-up, presumably of intracranial haemorrhage. CCS class improved from 3.4±0.6 at baseline to 2.3±0.6 after 3 months, 2.3±0.6 after 6 months and 2.6±0.7 after 12 months (all P 75 years, diabetes and previous stroke or TIA. These factors constitute the CHADS2 score. Not included in CHADS2 are blood stasis and complex aortic plaque which, when found on transoesophageal echocardiography (TEE), represent a high stroke risk. We aimed to describe the relation between TEE and the CHADS2 score.
Purpose: Guidelines on atrial fibrillation (AF) mainly focus on prevention of thromboembolism. The EXAMINE-AF study recorded antithrombotic treatment (ATT) in patients with AF in the daily practice of Dutch general physicians (GPs), internists and cardiologists. Adherence to the present AHA/ACC/ESC guidelines was compared among these physicians.
Methods: 87 patients with NVAF underwent multiplane TEE under local anaesthesia, focusing on left atrial stasis and complex plaques.
Results: Patients were 66 * 11 years old. Hypertension, coronary artery disease, diabetes, previous stroke or TIA, LV dysfunction or congestive heart failure were prevalent in 91%, 16%, 6%, 3%, and 3%, respectively. Mean ejection fraction was 58*7%, mean left atrial size was 43*6 mm, 60% had mild to moderate mitral regurgitation. 14 patients (16%) had (combined) abnormalities on TEE: 3 (3%), 5 (6%), 1 (1%), 4 (5%) and 1 (1%) patients had spontaneous contrast, low flow velocities, complex plaques, patent oval foramen and LV thrombus, respectively. Pahients were divided into groups according to stroke risk; 1 (1.1%), 61 (70.1%), 25 (28.8)% had CHADS2 score of 0, 1 and 22. Percentages of abnormal TEEs in the CHADS2 risk groups are depicted in figure 1. Maximal flow velocities in left atrial appendage were not different between the risk groups.
Conclusion: TEE abnormalities correspond well with CHADS2 score lower than 3. Furthermore, TEE can identify low risk patients among patients with presumed high risk (CHADS2 score ?2), but who might respond well to aspirin. TEE may be used for fine-tuning of stroke risk in patients with intermediate stroke risk. TIM con,red o CHAOS2 ncore
|l wesm]
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Netherlands.
Methods: Between October 2004 and March 2005, 300 Dutch GPs, internists and cardiologists were asked to fill in questionnaires for 5, 5, and 10 (respectively) consecutive AF patients for clinical stroke risk factors (SRF) and significant bleeding risk factors (BRF). Guidelines were adhered if patients had (a) no SRF or BRF and received aspirin or no ATU, (b) .1 SRF and no BRF and received oral anticoagulation (OAC), or (c) .1 SRF and 21 BRF and received aspirin. Patients were overtreated If they had (a) no SRF but received no OAC, and (b) .1 BRF and received OAC. Patients were undertreated if they had 21 SRF and no BRF but received no OAC. Results: 86 GPs, 93 intemists and 99 cardiologist enrolled 1596 patients: 365, 351 and 880, respectively. Cardiologists patients were younger and had less hypertension and heart failure, whereas internists patients were older and had more often BRF factors. Percentages of patients who were overtreated, undertreated or correctly treated according to the guidelines are depicted in table 1. A cardiologist was indicated to be the main treating physician for AF in 82% of all patients and current ATU was initiated in 80% by a cardiologist. When selecting the physician who prescnbed current ATT, cardiologists initiated ATT more often according to the guidelines (58, 55 and 70%: p0o.001).
Conclusion: Antithrombotic treatment is mainly handled by cardiologists, and compared to GPs and internist, adhere best to the guidelines. Therefore, patients with AF should at least be seen by cardiologist once, as cardiologists seem to be more aware of the guidelines.
14% 23%
71% 11% 18%
n-161
n-99
n-1292
Undertrearnent
58% 33%
9%
55% 28% 17%
70% 11%
Overtreatment
Unde8treatment
C0
prescribing
cufent ATT Guideline followed
Purpose: The right ventricular outflow tract (RVOT) of patients with corrected tetralogy of Fallot may influence RV function, but can be corrected surgically, in contrast to the rest of the RV myocardium. Therefore, we were to quantify the RVOT in multiple directions and to analyze the relationship with RV function. Methods: We performed cardiac MR (Philips, 3T) on 44 consecutive patients with a corrected tetralogy of Fallot (mean age 27±8years, 33 male, 11 female), and included 9 age- and sex-matched controls. Patients were scanned following routine protocol for analyzing RV function. Additional transversal black blood images (figure 1A) and sagittal cine images, aligned to the RVOT (figure 1B), were obtained for calculation of RVOT diameters. Results: There is a significant difference in the AP diameter (Figure 1A) of the RVOT of patients compared to controls (34.8*10.1mm versus 25.1*3.9mm, P grade 3A) was 63 pmol/l with a sensitivity and specificity of 86 and 94 0/0 respectively. Conclusion: Present data shows that late rejection is often associated with significantly higher NT Pro-BNP levels, with a cut-of value of 63 pmol/l. Measurement of NT Pro-BNP may become a useful marker for non-invasive diagnosis of rejection, being most valuable in the exclusion of allograft rejection necessating additional therapy
Abstracts
Posters
Poster 49
Poster 50
MYOCARDIAL CONTRAST ECHOCARDIOGRAPHY FOR ASSESSMENT OF CORONARY ARTERY DISEAS: A META-ANALYSIS P.A. Diikmans, MD, M. Spreeuwenberg, C.A. Visser, MD, PhD, 0. Kamp, MD, PhD.
ONGOING FUNCTIONAL INTEGRATION OF TRANSPLANTED HUMAN MESENCHYNAL STEM CELLS IN AN ELECTRICAL SYNCYTIUM OF CARDIOMYOCYTES DURING LONG-TERM INCUBATION D. A.PTJnappSI, A. van der Laarse, J. van Tuyn, A. A. F. de Vnes, E. E. van der Wall, M. J. Schali;, D. E. Atsma. Dept. of Cardiology, Leiden University Medical Center.
Purpose: Several studies demonstrated that the value of MCE for detection of significant coronary artery disease (CAD) is comparable to that of SPECT and dobutamine stress echocardiography (DSE). We provided a meta-analysis to compare the pooled sensitivity and specificity of MCE for detection of CAD with alternative stress tests such as SPECT/DSE.
Methods: We provided a meta-analysis on 8 studies that assessed patient-based sensitivity and specificity of MCE and SPECT/DSE for detection of significant CAD, using coronary angiography as gold standard. RevMan 4.2 of the Cochrane Collaboration group was used to calculate variance weighted pooled difference of proportions for the differences in sensitivity and specificity between MCE and SPECT/DSE. Results: The pooled estimates of the sensitivity and specificity of MCE were 85% [CI:81.5-88,5] and 74% [CI:67.7-80.3], respectively (figure). The pooled estimates of the sensitivity and specificity of the SPECT/DSE were 71% [CI: 0.66-0.76] and 71% [CI: 0.64-0.78], respectively. The pooled estimates of the differences in sensitivity and specificity were 0.14 (Cl: 0.04-0.14] and 0.03 [Cl: -0.14-0.21], respectively, indicating a higher sensitivity for MCE than for the SPECT/DSE. No difference was found for the specificity.
Conclusion: MCE is a dinically feasible tool for assessment of stable CAD, which is not inferior to SPECT/DSE, and has potential value in routine clinical care. Cse.n p ae= Of in5Wmnotemot cTW sebf e5m*V
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Background: Cardiac cell therapy using certain cell types carries the risk of ventricular arrhythmias, associated with electrical isolation of transplanted cells from host myocardium. Therefore, we assessed whether bone-marrow derived human adult mesenchymal stem cells (hMSCs) are able to electrically integrate in an electrical syncytium of cardiomyocytes (CMCs) for longer periods. Furthermore, we studied the role of connexin43 (Cx43) in this process using RNA interference (RNAi) technique and immunohistochemistry.
Methods: Neonatal rat CMCs were cultured in multi electrode mapping array (MEA, Multichannel Systems, Germany) culture dishes. After 2 days, a central a-cellular channel was made, dividing the spontaneously and synchronously beating monolayer in two asynchronously beating CMC fields. hMSCs were transfected by adeno-viral constructs knocking down connexin43 (hMSCs-Cx431) or Firefly luciferase (pLuc) (hMSCspLucl) as control. Efhciency of knock down was assessed by westero blot analysis. Then, 5x10E4 hMSCs-Cx431 or hMSCs-pLucJ were applied in the channel. Electrical conduction velocity (CV) across the channel with hMSCs was measured for up to 14 days and compared with CV across CMCs. Immunostaining of Cx43 was performed at day 1, 7, and 14 of coculture. Results: In the control group, hMSCs-pLucl (n-8) restored electrical conduction between two CMCs fields within 24 h, which sustained for at least 14 days. CV across hMSCs-pLucJ was constant during the first 7 days (1.4*0.3 cm/s), but increased significantly to 3.5*0.5 cm/s at day 14 (p70% decrease in Cx43 in expression hMSCs-Cx431 compared to hMSCs-pLucJ. Conclusions: Transplanted bone-marrow derived human adult mesenchymal stem cells (hMSCs) are electrically coupled with host cardiomyocytes (CMCs) in a connexin43-dependent process. During 14 days in co-culture, ongoing electrical integration of the transplanted hMSCs occurs in the syncytium of CMCs. This is reflected by a steadily rising electrical conduction velocity across hMSCs, accompanied by increased Cx43 expression.
Poster 51
Poster 52
CONSTRTICTIVE PERICARDITIS: EARY AND LATE OUTCOME A. Broeren, B.J. Bouma, IJ. Kloek, R.B.A. van den Brink Academic Medical Centre, Amsterdam.
MEASUREMENT OF BAROREFLEX SENSITIVM IN HEART FAILURE PATIENTS WITH FREQUENT EPISODES OF NON-SINUS RHYTHM Van de Vooren H, Gademan MG], Swenne CA, Schalij MI, Van der Wall EE. Cardiology Dept, Leiden University Medical Center.
Purpose: Patients with constrictive pericarditis (CP) are thought to be cured by pericardiectomy. Because of the low incidence of cp only limited data on outcome is available. Therefore, we determined the short- and long-term survival of pericardiectomy. Methods: All patients who underwent pericardiectomy for constrictive pericarditis at the Academic Medical Center (AMC) between 1985 and 2004 were reviewed. Baseline characteristics and operative data were reviewed retrospectively. Follow up was done with a questionnaire send to the general practitioner and by reviewing the hospital records.
Results: A total of 34 patients were identified (85% male, age 57 ± 16 years, mean symptom duration 11 ± 12 months). Heart failure was present in 82% of the patients. Most patients who developed CP had a history of cardiac surgery or no identifiable cause could be found. A concomitant procedure was performed in 9% of the cases. Perioperative mortality was 12% (4/34), all due to heart failure. The follow up was 100% complete and lasted almost 4 years. The oneand five-year survival was 89% and 60%. Age was the only an independent predictor of late mortality. Late mortality was due to a cardiac cause in 62% of the cases. At the end of follow up 87% (14/16) of the patients were in NYHA class I or II.
Conclusions: Cardiac surgery is an important cause of constrictive pericarditis. The operative mortality of pericardiectomy is considerably and long-term survival is limited, but the functional outcome of survivors is good.
Purpose: Noninvasive baroreflex sensitivity (BRS) has prognostic value in chronic heart failure (CHF). During BRS measurement, ECG and blood pressure is recorded during several minutes. For BRS computation a data segment with uninterrupted sinus rhythm is needed. As CHF patients have frequent arrhythmias, the longest usable data-segment is often less than a minute. The resulting BRS is then highly unreliable. We addressed this problem by defining and testing a procedure for the composition of a reliable session BRS from multiple unreliable single-segment BRS values.
Methods: We selected 9 episodes of > 7 minutes uninterrupted sinus rhythm from our CHF (NYHA-class II&III) database and computed the episode BRSs and confidence intervals (CIs). Then, the episodes were cut into 2, 4 or 8 equal-length segments in which BRSs and CIs were computed. Finally, composite BRS and CI values for the whole episodes were computed from the multiple segment BRS and CI values by the best linear unbiased estimator (BLUE) method. Results: As expected the short data segments yielded very unreliable results. However, the BRS and CI values composed from the multiple unreliable data segments remained within 4% and 8°u, respectively, from the complete episode values: averaged BRS * CI [ms/mmHg] values were 4.68 ± 1.17 (episode), 4.76 i1.19 (composed from 2 segments), 4.52 + 1.16 (composed from 4 segments) and 4.62 ± 1.26 (composed from 8 segments).
Conclusions: BRS computation in patients which fragmented episodes of sinus rhythm can reliably been done by composing a session BRS from multiple segment BRS values by the BLUE method. Our solution makes noninvasive BRS measurement feasible in the clinic.
20
Netherlands Heart Journal, Volume 14, Number 5, May 2006
|
Poster 49 MYOCARDIAL CONTRAST ECHOCARDIOGRAPHY FOR ASSESSMENT OF CORONARY ARTERY DISEAS: A META-ANALYSIS P.A. Dilkmans, MD, M. Spreeuwenberg, C.A. Visser, MD, PhD, O. Kamp, MD, PhD.
Purpos: Several studies demonstrated that the value of MCE for detection of significant coronary artery disease (CAD) is comparable to that of SPECT and dobutamine stress echocardiography (DSE). We provided a meta-analysis to compare the pooled sensitivity and specificity of MCE for detection of CAD with alternative stress tests such as SPECT/DSE.
Methods: We provided a meta-analysis on 8 studies that assessed patient-based sensitivity and specificity of MCE and SPECT/DSE for detection of significant CAD, using coronary angiography as gold standard. RevMan 4.2 of the Cochrane Collaboration group was used to calculate variance weighted pooled difference of proportions for the differences in sensitivity and specificity between MCE and SPECT/DSE.
Results: The pooled estimates of the sensitivity and specificity of MCE were 85% [CI:81.5-88,5] and 74% [CI:67.7-80.3], respectively (figure). The pooled estimates of the sensitivity and specificity of the SPECT/DSE were 71% [CI: 0.66-0.76] and 71% [CI: 0.64-0.78], respectively. The pooled estimates of the differences in sensitivity and specificity were 0.14 [CI: 0.04-0.14] and 0.03 [CI: -0.14-0.21], respectively, indicating a higher sensitivity for MCE than for the SPECT/DSE. No difference was found for the specificity.
Conclusion: MCE is a dinically feasible tool for assessment of stable CAD, which is not inferior to SPECT/DSE, and has potential value in routine clinical care. v. = eVfw* 001 «~tva 4a,y mm WeT M
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Poster 50
ONGOING FUNCTIONAL INTEGRATION OF TRANSPLANTED HUMAN MESENCHYMAL STEM CELLS IN AN ELECTRICAL SYNCYTIUM OF CARDIOMYOCYTES DURING LONG-TERM INCUBATION D. A. Pijnaooels A. van der Laarse, I. van Tuyn, A. A. F. de Vries, E. E. van der Wall, M. J. Schalij, D. E. Atsma. Dept. of Cardiology, Leiden University Medical Center. Background: Cardiac cell therapy using certain cell types carries the risk of ventricular arrhythmias, associated with electrical isolation of transplanted cells from host myocardium. Therefore, we assessed whether bone-marrow derived human adult mesenchymal stem cells (hMSCs) are able to electrically integrate in an electrical syncytium of cardiomyocytes (CMCs) for longer periods. Furthermore, we studied the role of connexin43 (Cx43) in this process using RNA interference (RNAi) technique and immunohistochemistry.
Methods: Neonatal rat CMCs were cultured in multi electrode mapping array (MEA, Multichannel Systems, Germany) culture dishes. After 2 days, a central a-cellular channel was made, dividing the spontaneously and synchronously beating monolayer in two asynchronously beating CMC fields. hMSCs were transfected by adeno-viral constructs knocking down connexin43 (hMSCs-Cx431) or Firefly luciferase (pLuc) (hMSCspLucl) as control. Efficiency of knock down was assessed by western blot analysis. Then, 5x10E4 hMSCs-Cx431 or hMSCs-pLucJ were applied in the channel. Electrical conduction velocity (CV) across the channel with hMSCs was measured for up to 14 days and compared with CV across CMCs. Immunostaining of Cx43 was performed at day 1, 7, and 14 of coculture.
Results: In the control group, hMSCs-pLucl (n=8) restored electrical conduction between two CMCs fields within 24 h, which sustained for at least 14 days. CV across hMSCs-pLuc1 was constant during the first 7 days (1.4*0.3 cm/s), but increased significantly to 3.5*0.5 cm/s at day 14 (p70% decrease in Cx43 in to hMSCs-Cx434 expression compared hMSCs-pLuc4. derived human bone-marrow Conclusions: Transplanted adult mesenchymal stem cells (hMSCs) are electrically coupled with host cardiomyocytes (CMCs) in a connexin43-dependent process. During 14 days in co-culture, ongoing electrical integration of the transplanted hMSCs occurs in the syncytium of CMCs. This is reflected by a steadily rising electrical conduction velocity across hMSCs, accompanied by increased Cx43 expression.
Poster 51
CONSTRTICTIVE PERICARDITIS: EARY AND LATE OUTCOME A. Broeren, B.J. Bouma, J.J. Kloek, R.B.A. van den Brink Academic Medical Centre, Amsterdam. Purpose: Patients with constrictive pericarditis (CP) are thought to be cured by pericardiectomy. Because of the low incidence of cp only limited data on outcome is available. Therefore, we determined the short- and long-term survival of pericardiectomy.
Methods: All patients who underwent pericardiectomy for constrictive pericarditis at the Academic Medical Center (AMC) between 1985 and 2004 were reviewed. Baseline characteristics and operative data were reviewed retrospectively. Follow up was done with a questionnaire send to the general practitioner and by reviewing the hospital records.
Results: A total of 34 patients were identified (85% male, age 57 i 16 years, mean symptom duration 11 i 12 months). Heart failure was present in 82% of the patients. Most patients who developed CP had a history of cardiac surgery or no identifiable cause could be found. A concomitant procedure was performned in 90/O of the cases. Perioperative mortality was 12% (4/34), all due to heart failure. The follow up was 100% complete and lasted almost 4 years. The oneand five-year survival was 890/o and 60%. Age was the only an independent predictor of late mortality. Late mortality was due to a cardiac cause in 62% of the cases. At the end of follow up 87% (14/16) of the patients were in NYHA class I or II.
Conclusions: Cardiac surgery is an important cause of constrictive pericarditis. The operative mortality of pericardiectomy is considerably and long-term survival is limited, but the functional outcome of survivors is good.
Poster 52
MEASUREMENT OF BAROREFLEX SENSITIVITY IN HEART FAILURE PATIENTS WITH FREQUENT EPISODES OF NON-SINUS RHYTHM Van de Vooren H, Gademan MG], Swenne CA, Schalij MJ, Van der Wall EE. Cardiology Dept, Leiden University Medical Center. Purpose: Noninvasive baroreflex sensitivity (BRS) has prognostic value in chronic heart failure (CHF). During BRS measurement, ECG and blood pressure is recorded during several minutes. For BRS computation a data segment with uninterrupted sinus rhythm is needed. As CHF patients have frequent arrhythmias, the longest usable data-segment is often less than a minute. The resulting BRS is then highly unreliable. We addressed this problem by defining and testing a procedure for the composition of a reliable session BRS from multiple unreliable single-segment BRS values.
Methods: We selected 9 episodes of > 7 minutes uninterrupted sinus rhythm from our CHF (NYHA-class II&III) database and computed the episode BRSs and confidence intervals (CIs). Then, the episodes were cut into 2, 4 or 8 equal-length segments in which BRSs and CIs were computed. Finally, composite BRS and CI values for the whole episodes were computed from the multiple segment BRS and CI values by the best linear unbiased estimator (BLUE) method. Results: As expected the short data segments yielded very unreliable results. However, the BRS and CI values composed from the multiple unreliable data segments remained within 4% and 8%, respectively, from the complete episode values: averaged BRS i CI [ms/mmHg] values were 4.68 ± 1.17 (episode), 4.76 i 1.19 (composed from 2 segments), 4.52 i 1.16 (composed from 4 segments) and 4.62 i 1.26 (composed from 8 segments).
Conclusions: BRS computation in patients which fragmented episodes of sinus rhythm can reliably been done by composing a session BRS from multiple segment BRS values by the BLUE method. Our solution makes noninvasive BRS measurement feasible in the clinic.
Abstracts
Posters
Poster 53
Poster 54
ARRHYTHMIAS IN PRESSURE OVERLOADED MICE ARE ASSOCIATED WITH STRUCTURAL EUT NOT WITH CONTRACTILE REMODELING MBLulaksil", MA Engelen', M Stein", AT Jansen', NAM Mutsaers', MA Vos', ]MT de Bakker' HVM van Rijen'. (1) IaN; (2) Medical Physiology, Heart Lung Center Utrecht, UMC Utrecht; (3) Cardiology, Heart Lung Center Utrecht, UMC Utrecht.
ANEMIA IN CHRONIC HEART FAILURE IS INDEPENDENTLY ASSOCIATED WITH AN IMPAIRED HEMODYNAMIC STATUS, FLUID RETENTION AND BLUNTED EPO PRODUCTION BD. Westenbrink, TD]. Smilde, E. Lipsic, AA. Voors, HL. Hillege, G]. Navis, WH. Van Gilst, DI. Van Veldhuisen Groningen, University Medical Center Groningen, Netherlands.
Background: Structural and electrical remodeling of the heart during progression of congestive heart failure is characterized by high susceptibility to ventricular arrhythmias. We have used a mouse model of pressure overload (transverse aortic constriction, TAC) to study the relationship between cardiac remodeling and occurrence of arrhythmias.
Methods: 26 Wild-type mice were subjected to either pressure overload (n=14) or sham operation (n=12). Mice were biweekly monitored by Doppler echocardiography and electrocardiography to follow temporal evolution of contractile, structural and electrical remodeling. After 16 weeks epicardial ventricular activation mapping was performed on Langendorff perfused hearts. Conduction velocity longitudinal (CVlong) and transverse (CVtrans) to myocardial fiber orientation was measured. Effective Refractory Period (ERP) and susceptibility to arrhythmias was determined by programmed stimulation. Subsequently, hearts were processed for Cx43 immunohistology, Western blotting (WB), qPCR and Sirius Red staining (fibrosis). All data are shown as mean*SEM. Results: Fractional shortening (FS) was preserved in sham mice (46.1*1.0%), but gradually decreased in TAC mice to 37.6*2.4% at 16 weeks (p 70 jaar; situaties waarbij een verhoogde plasmaspiege kan optreden, gelijktijdig gebruik van fibraten. Bij deze patinten wordt klinische controle aanbevolen. Patienten 4 onverklaarbare spierpijn, spierzwakte of spierkramp, met name als deze gepaard gaan et malaise of koorts, dienen te worden 4 11aagd onmiddellijk te me4den. De behandeling dient te worden gestaakt wanneer de CK-spiegels dukielijk ziin verhoogd (> 5 x ULN) of als de spiersymptomen emstig zijn en dagelijks ongemak veroorzaken. De combinatie van CRESTOR met gemfibrozil wordt niet geadviseerd. De 40 mg dosering is gecontrarndkieerd bij gelijktiid4g gebruik van fibraten. CRESTOR d1ent niet te worden gebruikt bij pat4enten met een acute, emstige aandoening mogelijk wijzend op myopathie of waarbij een predispositie bestaat voor het ontwikkelen van nierfalen als gevolg van rhabdomyolyse. Voorzkchtigheid is geboden bij pati,enten met overmatig alcohol gebruik en/of een leverziekte in de anamnese. Het wordt aanbevolen leverfunctietesten uit te voeren voor en 3 maanden na het starten van de behandeling mnet CRESTOR. Wanneer de concentratie van de srumtransaminases > 3 x ULN is, dient CRESTOR te worden gestaakt of de dosering te worden ve11aagd. Bij Azbtische pati4nten laten farmacokinetische studies een toegenomen blootstelling zien in vergelijking met Kaukasi#rs. Interacties: Geneesmkideleninteracties ten gevolge van cytochroom P450 gemedieerd metabolisme worden niet verwacht Bij patienten die gelijktijdig vitamine K antagonisten gebruiken is wen14li1k het de 1NR acequaat te volgen bi1 starten of staken van behandeling met CRESTOR en bij aanpassing van de doseGing. Gemfibrozil vephk1en het risico van myopathie indien gelijktiidig gegeven en doseringen van n14otinezuur) fenofibraat, andere fibraten lip4den-ve0agende met HMG-CoA reductase remmers, mogelijk omdat zij wanneer zij alleen worden gegeven myopathie- kunnen veroorzaken. De 40 mg dosering is gecontrarnckceerd bij gebruik van een fibraat Deze patienten dienen te starten 1met de mg do1ring. Geli/ktf1dig gebruik van van met een gemfibrozil of erythromycine leidde tot een verandering van de C_ en AUC van CRESTOR. Men dkent rekening te houden s111ging de AUC van ethinylestradiol en norgestrel bij gelijktUjdig gebruik van CRESTOR en een oraal anticonceptivum en mogelijk bij hormoonsubstitutfethera pie. Gelij ktfjdkg toedkenen van een antacida-suspensie met CRESTOR lekide tot een afna me van de plasmaconcentratie van CRESTOR. Dit effect werd verminderd wanneer het antacidum 2 uur na CRE5TOR werd toegediend. CRE5TOR is gecontraindkceerd bij gelijktfjdig gebruik van cyclosporine. Er worden geen klinische relevante interacties verwacht met dkgoxine. Bilwerkingen: Bijwerkingen zijn over het algemeen mild en van voorbijgaande aard. Gemeld zijn: Vaak (1: 10-1:1 00) hoofdpijn, duizeligheid, obstfpatie, misseliikheid, buikpiin, spierpijn, gevoel van zwakte. Soms (1:100-1:1000) prurifs, huiduitslag en urticaria. Zelden (1:1000-1:10.000) myopathie, rhabdomyolyse, overgevoeligheidsreact4es inclusief ang14,-dem. Post marke1ng ervaring: zelden (1:1000-1:10.000) toegenomen levertransaminasen, (
Posters
Poster 1
Poster 2
CORONARY ARTERY CALCIFICATIONS ARE CORRELATED WITH BREAST ARTERIAL CALCIFICATIONS, BUT THEIR AETIOLOGY IS PREDOMINANTLY DIFFERENT Angela H.E.M.Maas (1). Yvonne T. van der Schouw (2), David Beijerinck (3), Jan J.M.Deurenberg (3), Willem P.Th. M.Mall (4), Yolanda van der Graaf (2). (1)Department of Cardiology, Isala kllnieken, Zwolle,(2) Julius Center for Health Sdences and Primary Care, University Medical Center Utrecht,(3) Preventicon Breast Cancer Screening Center, Utrecht,(4)Department of Radiology, University Medical Center Utrecht, The Netherlands.
THREE YEAR OPEN ACCESS ECHOCARDIOGRAPHYIN THE PARKSTAD AREA: WHAT WAS THE YIELD? LHB Baur, C. Lodewijks, T. Lenderink, F. Guldemond, 2. Nijhof, M. Hundscheid, F. Soomers. On behalf of the working group on open access echocardlography in the Parkstad Area.
Objective: Vascular calcification is considered a marker of cardiovascular risk and imaging of calcium Is increasingly used for cardiovascular (CV) screening purposes. It is not known whether calcificatlons In the breast arteries are related to coronary artery
calcifications.
Methods: We studied 499 women, aged 49-70 years, participating in a breast cancer screening program and Investigated whether arterial calciflcations In the breast (BAC) are associated with coronary arterial calcdflcatlons (CAC) after a mean foilow-up of 9 years. Baseline mammograms of all women were reviewed on the presence of BAC by two Independent reviewers. CAC was assessed by multislice computed tomography (MSCT), with 3.0 mm slices, using the Agatston score. Logistic regression analysis was performed to Investigate the independent effect of BAC and various risk factors and reproductive factors on the occurrence of CAC.
Results: aAC was present in 58 of 499 women (12%) at baseline and CAC score > 0 was present In 262 of 499 women (53%) after follow-up. Age was the most Important determinant for both BAC and CAC. In all age groups CAC was more prevalent than BAC. The presence of BAC was strongly associated with the occurrence of CAC (OR 3.2, 95% CI 1.71-6.04) and this remained significant after adjustment for age and the duration of foliow-up (OR 2.1, 95% CI 1.104.23). Most of the coronary heart disease risk factors were associated with CAC but not with BAC. The only common risk factor was parity, which was signiflcantly associated with both increased CAC (OR 2.1, 95% CI 1.26-3.50) and increased BAC (OR 5.4, 95 % CI 1.28-22.52). Breastfeeding after pregnancy was associated with BAC (OR 3.7, 95% CI 1.55-8.83) but not with CAC (OR 1.4, 95% CI 0.95-2.08).
Methods: GPs, who participated in the project were able to ask for an echocardiogram without referring the patient to a cardiologist if they suspected the patient of having heart failure or a cardiac murmur. The results of the echo-Doppler examination were returned to the general practitioner with a comment how to handle the patient. Results: Between december 2002 and January 2006, from a total group of 378 pts, 98 pts were referred with the diagnosis dyspnea, 151 pts with a cardiac murmur, 7 with peripheral edema and 49 with a combination dyspnea and a murmur. The rest of the pts had other reasons for referral and are not mentioned here. Results can be seen in table 1 and 2. Table 1: Patients suspe ted of havin heart failure In Iden Incdnc tncid.c _ Incid.n. Di LVEFs40% nnl P.1-n.ry I.pun t
Table 2: Patients suspected of having valvular heart disease 21% Aav vahnilar abnun,naltvt 37% 9%'i Sign. SOS y8% 3YO Slg1n 801 14%i 14 4% 51an Sb% 4%s SigCM 14%b Sin T1 °h% 16%
Incid-c
Iwnt
1 MD at the day of the procedure is more common in patients who will have an increase in the number of AF episodes up to 180 days after PVI. Also the rise in baseline heart rate > 25% is a predictor of no recurrences.
cfpc
Netherlands Heart Journal, Volume
14, Number 5, May 2006
Poster 24
OPTIMAL PACING SITE IN CARDIAC RESYNCHRONISATION THERAPY: EVALUATION OF MULTIPLE EPICARDIAL LEFT SIMULTANEOUS SITES WITH VENTRICULAR PACING CONTRACTILITY INDEX MEASUREMENT H. van Wessel, MSc, PF Bakker, MD,PhD, M.Meine, MD, W. Buhre MD,PhD, AE Tuinenburg, MD,PhD FHM Wittkampf, PHD, RNW Hauer, MD,PhD, LA van Herwerden, MD,PhD, P Loh, MD,PhD. Heart Lung Center Utrecht. Background: Cardiac resynchronisation therapy (CRT) is an emerging treatment for patients with advanced heart failure and left ventricular (LV) asynchrony. The LV lead is usually positioned transvenously in a posterior branch of the coronary venous system. However, anatomical obstacles, the absence of a suitable vessel or phrenic nerve stimulation can render this approach impractical. Epicardial lead positioning with video-assisted thoracic surgery (VATS) is an alternative approach and allows evaluation of stimulation at multiple sites. The aim of this study was to assess the optimal pacing site by measuring the maximal rate of LV pressure rise (dp/dt,,.,) as an index of cardiac contractility at different pacing sites. Method: Five patients underwent minimal invasive surgery using the VATS technique to insert an epicardial LV lead after a failed transvenous approach. A Radia pressure wire was inserted Into the LV for measuring the maximal rate of pressure rise in the LV (dp/dt-.) and calculating the contractility index (CI). With a roving electrode multiple sites were assessed during biventricular pacing. The epicardial electrode was fixed at the position where the best dP/dt-.X was measured. Subsequently, atrioventricular delay and W timing were optimized.
Results: In two patients the best pacing site was found mid posterior. In the three other patients the optimal sites were mid anterior, mid lateral and basal postero-lateral. Remarkably, spatial differences of only 1-2 cm could translate in relatively large differences in LV dP/dtx,,. The baseline LV dP/dt- x was 720 * 215 mmHg/s (mean±std) during intrinsic rhythm and increased up to 1190 ± 275 mmHg/s during optimal biventricular pacing. This means an increase factor of 1.7 ± 0.5. During short-term follow up, all patients clinically responded to CRT. No procedural complications occurred.
Conclusion: In CRT, epicardial lead placement using the VATS technique allows the identification of the optimal pacing site where the highest CI can be achieved. Small differences in pacing position could cause substantial differences in LV pressure rise. Subsequent optimalization of biventricular pacing parameters lead to an increase factor of 1.7 * 0.5.
13
Poster 21
CLOSURE OF A PATENT FORAMEN OVALE IS ASSOCIATED WITH A DECREASE IN PREVALENCE OF MIGRAINE: A PROSPECTIVE OBSERVATIONAL STUDY M.C. Post', J.G.L.M. Luermans', F. Temmerman2, V. Thijs3, W.J. Schonewille4, H.W.M. Plokkerl, M.J. Suttorpl, W. Budts2. Departments of Cardiology' and Neurology4, St. Antonius Hospital Nieuwegein, The Netherlands and Departments of Cardiology2 and Neurology3, University Hospital Gasthuisberg, Leuven, Belgium Purpose: A patent foramen ovale (PFO) is one of the major causes of right-to-left shunt and a relationship with migraine has been suggested. In mainly retrospective studies percutaneous PFO closure has been associated with a decrease in the prevalence of migraine. We evaluated the influence of PFO closure on the occurrence of migraine in a prospective observational study.
Methods: All 103 patients (> 16 years of age) who underwent a percutaneous PFO closure in our centres between November 2003 and December 2005 were included in the study. They received a headache questionnaire before and six months after closure. A neurologist, blinded to the patients' files, diagnosed migraine according to the International Headache Criteria. The McNemar paired chi-square test was used to describe changes in prevalence of migraine. Results: Ninety-eight patients (95%, mean age 51.3±12.1 years, 68 males) filled in the questionnaire before closure and in this group the prevalence of migraine was 27.6%, migraine without aura (MA-) 17.3%, and migraine with aura (MA+) 10.2%. The 6 months follow up was reached in 86 patients and 68 (79%, mean age 52.3±12.5 years, 49 males) of them sent back the questionnaire. The prevalence of migraine decreased from 27.9% to 8.8%/, a relative reduction of 68% (p=0.001), MA- from 17.6% to 5.9%, a relative reduction of 66% (p=0.02), and MA+ from 10.3% to 2.9%, a relative reduction of 72% (p=0.13). In one patient MA- changed into MA+ and one patient developed MA- six months after closure.
Conclusion: Percutaneous patent foramen ovale closure is related to a decrease in the prevalence of migraine in this prospective observational study. Whether PFO closure will become a new treatment in patients with migraine needs to be determined in a prospective randomized trial.
Poster 22
NONINVASIVE VISUALIZATION OF THE CARDIAC VENOUS SYSTEM IN CORONARY ARTERY DISEASE PATIENTS USING 64SLICE CT N. Van de Veire 2, J. Schuijfl, J. De Sutter2, D Devos2, A de Roos', MJ Schalijl, 3J Baxl, EE van der Wall'. 'Leiden University Medical Center and 2Ghent University (Belgium)
Purpose: Cardiac Resynchronization Therapy is an attractive treatment for highly symptomatic heart failure patients. Knowledge on the anatomy of the coronary sinus (CS) and its tributaries could help identifying potential candidates for successful left ventricular lead implantation. Study aim was to evaluate the value of 64-slice computed tomography (CT) to depict the cardiac venous anatomy in patients with coronary artery disease (CAD).
Methods: The 64-slice cardiac CT data of 50 individuals (age 59+11 years, 76% men) were evaluated. Subjects were divided in 3 groups: 15 controls (without CAD), 18 patients with significant CAD and 17 CAD patients with a history of myocardial infarction. The presence of the following CS tributaries was evaluated: posterior interventricular vein (PIV), posterior vein of the left ventricle (PVLV) and left marginal vein (LMV). Diameters of the proximal part of these veins and in-between distances were measured. Results: Anatomic variations are depicted in the Figure. The CS diameter was 11.4*3.5 mm in the anterior-posterior direction and 11.5±3.2 diameter in the superior-inferior direction. Diameters of the PIV, PVLV and LMV were 5.2*1.3, 3.8*1.1 and 3.5±1 mm respectively. Mean distance from the PIV to the PVLV was 35±21 mm and mean distance from the PVLV to LMV was 38±16 mm.
Conclusion: The anatomy of the coronary sinus and its tributaries can be evaluated with 64-slice CT. There is considerable variation in cardiac venous anatomy. Patients with a history of myocardial infarction were less likely to have a left marginal vein thus limiting optimal left ventricular lead positioning in case of CRT implantation. 100. 80.
~~~~~~~~CAD
%
Myocardal
200
P
CS
PIV
PVLV
LMV
I
Figure: Coronary sinus and tributaries
intarcUonl
Poster 23
RECURRENCE PATTERNS OF ATRIAL FIBRILLATION IN THE FIRST MONTHS AFTER PULMONARY VEINS CRYOISOLATION Wendel Moreira, MD; Carl Timmermans,MD,PhD; Yuka Mizusawa,MD; David Perez,MD; Suzanne Philippens,RN; HJGM Crijns,MD,PhD; Luz-Maria Rodriguez,MD, PhD. Academic Hospital Maastricht, Maastricht, The Netherlands.
Background: Early recurrence of paroxysmal atrial fibrillation (PAF) post PVI (pulmonary vein isolation) is a recognized phenomenon. Our study evaluates the recurrence behavior of AF in the first months following PVI. Methods: PVI using cryoablation was performed in 60 patients from 2001 to 2005. Daily recordings with transtelephonic telemetry were obtained 30 days prior and up to 180 days after the procedure. Group A consisted of patients with no further evidence of AF. Group B consisted of patients that had a significant decrease in the number of AF episodes. Group C consisted of patients that had an increase in the AF episodes after PVI. Results: Groups A, B and C had 26, 20 and 14 patients respectively. Age, gender, duration of AF, LA size, presence of LVH, LVEF and number of PVs treated were similar in all groups. Patients in group A had an increase in mean HR pre and post procedure of 16 bpm (from 64 to 80, p=0.02). The variation in HR for groups B and C *did not achieve statistic significance. History of atrial flutter was present in 63 % of group C pts, 30 % of group A and 20% of group B. The percentage of pts taking more than one antiarrhythmic drug (MD) at the time of ablation were: Group A = 13.3%; Group B = 40 0/0, Group C = 72.7%.
Conclusions: History of atrial flutter and current use of > 1 AAD at the day of the procedure is more common in patients who will have an increase in the number of AF episodes up to 180 days after PVI. Also the rise in baseline heart rate > 25% is a predictor of no recurrences.
Poster 24
OPTIMAL PACING SITE IN CARDIAC RESYNCHRONISATION THERAPY: EVALUATION OF MULTIPLE EPICARDIAL LEFT WITH SIMULTANEOUS SITES PACING VENTRICULAR CONTRACTILITY INDEX MEASUREMENT H. van Wessel, MSc, PF Bakker, MD,PhD, M.Meine, MD, W. Buhre MD,PhD, AE Tuinenburg, MD,PhD FHM Wittkampf, PHD, RNW Hauer, MD,PhD, LA van Herwerden, MD,PhD, P Loh, MD,PhD. Heart Lung Center Utrecht.
Background: Cardiac resynchronisation therapy (CRT) is an emerging treatment for patients with advanced heart failure and left ventricular (LV) asynchrony. The LV lead is usually positioned transvenously in a posterior branch of the coronary venous system. However, anatomical obstacles, the absence of a suitable vessel or phrenic nerve stimulation can render this approach impractical. Epicardial lead positioning with video-assisted thoracic surgery (VATS) is an alternative approach and allows evaluation of stimulation at multiple sites. The aim of this study was to assess the optimal pacing site by measuring the maximal rate of LV pressure rise (dp/dtmax) as an index of cardiac contractility at different pacing sites. Method: Five patients underwent minimal invasive surgery using the VATS technique to insert an epicardial LV lead after a failed transvenous approach. A Radi® pressure wire was inserted into the LV for measuring the maximal rate of pressure rise in the LV (dp/dtmax) and calculating the contractility index (CI). With a roving electrode multiple sites were assessed during biventricular pacing. The epicardial electrode was fixed at the position where the best dP/dtmax was measured. Subsequently, atrioventricular delay and W timing were optimized.
Results: In two patients the best pacing site was found mid posterior. In the three other patients the optimal sites were mid anterior, mid lateral and basal postero-lateral. Remarkably, spatial differences of only 1-2 cm could translate in relatively large differences in LV dP/dtmx. The baseline LV dP/dtmax was 720 ± 215 mmHg/s (mean±std) during intrinsic rhythm and increased up to 1190 i 275 mmHg/s during optimal biventricular pacing. This means an increase factor of 1.7 ± 0.5. During short-term follow up, all patients clinically responded to CRT. No procedural complications occurred. Conclusion: In CRT, epicardial lead placement using the VATS technique allows the identification of the optimal pacing site where the highest CI can be achieved. Small differences in pacing position could cause substantial differences in LV pressure rise. Subsequent optimalization of biventricular pacing parameters lead to an increase factor of 1.7 ± 0.5.
Abstracts
Posters
Poster 26
Poster 25
SUSTAINED EFFECT OF AUTOLOGOUS BONE MARROW CELL TRANSPLANTATION IN NO-OPTION PATIENTS WITH CHRONIC SEVERE ANGINA PECTORIS AND MYOCARDIAL ISCHEMIA: FINAL 12 MONTHS RESULTS SLMiA Beeres, 3 Bax, P Dibbets, K Zeppenfeld, MPM Stokkel, WE Fibbe, EE van der Wall, MJ Schalli, DE Atsma Dept. of Cardiology, Leiden University Medical Center, Leiden.
Background: Cell transplantation Is proposed as a novel therapeutic option for patients with coronary artery disease. This study Investigated whether bone marrow cell injection into ischemic myocardium of patients with severe angina pectoris could safely reduce anginal symptoms, improve myocardial perfusion and increase LV function. Methods: In 25 patients (64+10 yrs, 21 male) with drug-refractory angina pectoris (CCS class III-IV) despite optimized medical therapy and without options for conventional revascularization, bone marrow was aspirated from the Iliac crest. Mononuclear cells (84*29x106) were injected Intramyocardially (using the NOGA system) in regions with stress-induced ischemia on Tc-99m tetrofosmin gated SPECT. Anginal symptoms were reassessed at 3, 6 and 12 months follow-up. At baseline, 3 and 12 months follow-up, gated SPECT imaging was performed to assess LV function and myocardial perfusion. Rewlts: Intramyocardial injection of bone marrow cells was safe: laboratory measures did not reveal infarction, echocardiography showed no pericardial effusion, and sustained ventricular tachycardias were not observed. One patient died at 7 months follow-up, presumably of intracranial haemorrhage. CCS class improved from 3.4±0.6 at baseline to 2.3±0.6 after 3 months, 2.3±0.6 after 6 months and 2.6±0.7 after 12 months (all P 75 years, diabetes and previous stroke or TIA. These factors constitute the CHADS2 score. Not included in CHADS2 are blood stasis and complex aortic plaque which, when found on transoesophageal echocardiography (TEE), represent a high stroke risk. We aimed to describe the relation between TEE and the CHADS2 score.
Purpose: Guidelines on atrial fibrillation (AF) mainly focus on prevention of thromboembolism. The EXAMINE-AF study recorded antithrombotic treatment (ATT) in patients with AF in the daily practice of Dutch general physicians (GPs), internists and cardiologists. Adherence to the present AHA/ACC/ESC guidelines was compared among these physicians.
Methods: 87 patients with NVAF underwent multiplane TEE under local anaesthesia, focusing on left atrial stasis and complex plaques.
Results: Patients were 66 * 11 years old. Hypertension, coronary artery disease, diabetes, previous stroke or TIA, LV dysfunction or congestive heart failure were prevalent in 91%, 16%, 6%, 3%, and 3%, respectively. Mean ejection fraction was 58*7%, mean left atrial size was 43*6 mm, 60% had mild to moderate mitral regurgitation. 14 patients (16%) had (combined) abnormalities on TEE: 3 (3%), 5 (6%), 1 (1%), 4 (5%) and 1 (1%) patients had spontaneous contrast, low flow velocities, complex plaques, patent oval foramen and LV thrombus, respectively. Pahients were divided into groups according to stroke risk; 1 (1.1%), 61 (70.1%), 25 (28.8)% had CHADS2 score of 0, 1 and 22. Percentages of abnormal TEEs in the CHADS2 risk groups are depicted in figure 1. Maximal flow velocities in left atrial appendage were not different between the risk groups.
Conclusion: TEE abnormalities correspond well with CHADS2 score lower than 3. Furthermore, TEE can identify low risk patients among patients with presumed high risk (CHADS2 score ?2), but who might respond well to aspirin. TEE may be used for fine-tuning of stroke risk in patients with intermediate stroke risk. TIM con,red o CHAOS2 ncore
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Methods: Between October 2004 and March 2005, 300 Dutch GPs, internists and cardiologists were asked to fill in questionnaires for 5, 5, and 10 (respectively) consecutive AF patients for clinical stroke risk factors (SRF) and significant bleeding risk factors (BRF). Guidelines were adhered if patients had (a) no SRF or BRF and received aspirin or no ATU, (b) .1 SRF and no BRF and received oral anticoagulation (OAC), or (c) .1 SRF and 21 BRF and received aspirin. Patients were overtreated If they had (a) no SRF but received no OAC, and (b) .1 BRF and received OAC. Patients were undertreated if they had 21 SRF and no BRF but received no OAC. Results: 86 GPs, 93 intemists and 99 cardiologist enrolled 1596 patients: 365, 351 and 880, respectively. Cardiologists patients were younger and had less hypertension and heart failure, whereas internists patients were older and had more often BRF factors. Percentages of patients who were overtreated, undertreated or correctly treated according to the guidelines are depicted in table 1. A cardiologist was indicated to be the main treating physician for AF in 82% of all patients and current ATU was initiated in 80% by a cardiologist. When selecting the physician who prescnbed current ATT, cardiologists initiated ATT more often according to the guidelines (58, 55 and 70%: p0o.001).
Conclusion: Antithrombotic treatment is mainly handled by cardiologists, and compared to GPs and internist, adhere best to the guidelines. Therefore, patients with AF should at least be seen by cardiologist once, as cardiologists seem to be more aware of the guidelines.
14% 23%
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Purpose: The right ventricular outflow tract (RVOT) of patients with corrected tetralogy of Fallot may influence RV function, but can be corrected surgically, in contrast to the rest of the RV myocardium. Therefore, we were to quantify the RVOT in multiple directions and to analyze the relationship with RV function. Methods: We performed cardiac MR (Philips, 3T) on 44 consecutive patients with a corrected tetralogy of Fallot (mean age 27±8years, 33 male, 11 female), and included 9 age- and sex-matched controls. Patients were scanned following routine protocol for analyzing RV function. Additional transversal black blood images (figure 1A) and sagittal cine images, aligned to the RVOT (figure 1B), were obtained for calculation of RVOT diameters. Results: There is a significant difference in the AP diameter (Figure 1A) of the RVOT of patients compared to controls (34.8*10.1mm versus 25.1*3.9mm, P grade 3A) was 63 pmol/l with a sensitivity and specificity of 86 and 94 0/0 respectively. Conclusion: Present data shows that late rejection is often associated with significantly higher NT Pro-BNP levels, with a cut-of value of 63 pmol/l. Measurement of NT Pro-BNP may become a useful marker for non-invasive diagnosis of rejection, being most valuable in the exclusion of allograft rejection necessating additional therapy
Abstracts
Posters
Poster 49
Poster 50
MYOCARDIAL CONTRAST ECHOCARDIOGRAPHY FOR ASSESSMENT OF CORONARY ARTERY DISEAS: A META-ANALYSIS P.A. Diikmans, MD, M. Spreeuwenberg, C.A. Visser, MD, PhD, 0. Kamp, MD, PhD.
ONGOING FUNCTIONAL INTEGRATION OF TRANSPLANTED HUMAN MESENCHYNAL STEM CELLS IN AN ELECTRICAL SYNCYTIUM OF CARDIOMYOCYTES DURING LONG-TERM INCUBATION D. A.PTJnappSI, A. van der Laarse, J. van Tuyn, A. A. F. de Vnes, E. E. van der Wall, M. J. Schali;, D. E. Atsma. Dept. of Cardiology, Leiden University Medical Center.
Purpose: Several studies demonstrated that the value of MCE for detection of significant coronary artery disease (CAD) is comparable to that of SPECT and dobutamine stress echocardiography (DSE). We provided a meta-analysis to compare the pooled sensitivity and specificity of MCE for detection of CAD with alternative stress tests such as SPECT/DSE.
Methods: We provided a meta-analysis on 8 studies that assessed patient-based sensitivity and specificity of MCE and SPECT/DSE for detection of significant CAD, using coronary angiography as gold standard. RevMan 4.2 of the Cochrane Collaboration group was used to calculate variance weighted pooled difference of proportions for the differences in sensitivity and specificity between MCE and SPECT/DSE. Results: The pooled estimates of the sensitivity and specificity of MCE were 85% [CI:81.5-88,5] and 74% [CI:67.7-80.3], respectively (figure). The pooled estimates of the sensitivity and specificity of the SPECT/DSE were 71% [CI: 0.66-0.76] and 71% [CI: 0.64-0.78], respectively. The pooled estimates of the differences in sensitivity and specificity were 0.14 (Cl: 0.04-0.14] and 0.03 [Cl: -0.14-0.21], respectively, indicating a higher sensitivity for MCE than for the SPECT/DSE. No difference was found for the specificity.
Conclusion: MCE is a dinically feasible tool for assessment of stable CAD, which is not inferior to SPECT/DSE, and has potential value in routine clinical care. Cse.n p ae= Of in5Wmnotemot cTW sebf e5m*V
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Background: Cardiac cell therapy using certain cell types carries the risk of ventricular arrhythmias, associated with electrical isolation of transplanted cells from host myocardium. Therefore, we assessed whether bone-marrow derived human adult mesenchymal stem cells (hMSCs) are able to electrically integrate in an electrical syncytium of cardiomyocytes (CMCs) for longer periods. Furthermore, we studied the role of connexin43 (Cx43) in this process using RNA interference (RNAi) technique and immunohistochemistry.
Methods: Neonatal rat CMCs were cultured in multi electrode mapping array (MEA, Multichannel Systems, Germany) culture dishes. After 2 days, a central a-cellular channel was made, dividing the spontaneously and synchronously beating monolayer in two asynchronously beating CMC fields. hMSCs were transfected by adeno-viral constructs knocking down connexin43 (hMSCs-Cx431) or Firefly luciferase (pLuc) (hMSCspLucl) as control. Efhciency of knock down was assessed by westero blot analysis. Then, 5x10E4 hMSCs-Cx431 or hMSCs-pLucJ were applied in the channel. Electrical conduction velocity (CV) across the channel with hMSCs was measured for up to 14 days and compared with CV across CMCs. Immunostaining of Cx43 was performed at day 1, 7, and 14 of coculture. Results: In the control group, hMSCs-pLucl (n-8) restored electrical conduction between two CMCs fields within 24 h, which sustained for at least 14 days. CV across hMSCs-pLucJ was constant during the first 7 days (1.4*0.3 cm/s), but increased significantly to 3.5*0.5 cm/s at day 14 (p70% decrease in Cx43 in expression hMSCs-Cx431 compared to hMSCs-pLucJ. Conclusions: Transplanted bone-marrow derived human adult mesenchymal stem cells (hMSCs) are electrically coupled with host cardiomyocytes (CMCs) in a connexin43-dependent process. During 14 days in co-culture, ongoing electrical integration of the transplanted hMSCs occurs in the syncytium of CMCs. This is reflected by a steadily rising electrical conduction velocity across hMSCs, accompanied by increased Cx43 expression.
Poster 51
Poster 52
CONSTRTICTIVE PERICARDITIS: EARY AND LATE OUTCOME A. Broeren, B.J. Bouma, IJ. Kloek, R.B.A. van den Brink Academic Medical Centre, Amsterdam.
MEASUREMENT OF BAROREFLEX SENSITIVM IN HEART FAILURE PATIENTS WITH FREQUENT EPISODES OF NON-SINUS RHYTHM Van de Vooren H, Gademan MG], Swenne CA, Schalij MI, Van der Wall EE. Cardiology Dept, Leiden University Medical Center.
Purpose: Patients with constrictive pericarditis (CP) are thought to be cured by pericardiectomy. Because of the low incidence of cp only limited data on outcome is available. Therefore, we determined the short- and long-term survival of pericardiectomy. Methods: All patients who underwent pericardiectomy for constrictive pericarditis at the Academic Medical Center (AMC) between 1985 and 2004 were reviewed. Baseline characteristics and operative data were reviewed retrospectively. Follow up was done with a questionnaire send to the general practitioner and by reviewing the hospital records.
Results: A total of 34 patients were identified (85% male, age 57 ± 16 years, mean symptom duration 11 ± 12 months). Heart failure was present in 82% of the patients. Most patients who developed CP had a history of cardiac surgery or no identifiable cause could be found. A concomitant procedure was performed in 9% of the cases. Perioperative mortality was 12% (4/34), all due to heart failure. The follow up was 100% complete and lasted almost 4 years. The oneand five-year survival was 89% and 60%. Age was the only an independent predictor of late mortality. Late mortality was due to a cardiac cause in 62% of the cases. At the end of follow up 87% (14/16) of the patients were in NYHA class I or II.
Conclusions: Cardiac surgery is an important cause of constrictive pericarditis. The operative mortality of pericardiectomy is considerably and long-term survival is limited, but the functional outcome of survivors is good.
Purpose: Noninvasive baroreflex sensitivity (BRS) has prognostic value in chronic heart failure (CHF). During BRS measurement, ECG and blood pressure is recorded during several minutes. For BRS computation a data segment with uninterrupted sinus rhythm is needed. As CHF patients have frequent arrhythmias, the longest usable data-segment is often less than a minute. The resulting BRS is then highly unreliable. We addressed this problem by defining and testing a procedure for the composition of a reliable session BRS from multiple unreliable single-segment BRS values.
Methods: We selected 9 episodes of > 7 minutes uninterrupted sinus rhythm from our CHF (NYHA-class II&III) database and computed the episode BRSs and confidence intervals (CIs). Then, the episodes were cut into 2, 4 or 8 equal-length segments in which BRSs and CIs were computed. Finally, composite BRS and CI values for the whole episodes were computed from the multiple segment BRS and CI values by the best linear unbiased estimator (BLUE) method. Results: As expected the short data segments yielded very unreliable results. However, the BRS and CI values composed from the multiple unreliable data segments remained within 4% and 8°u, respectively, from the complete episode values: averaged BRS * CI [ms/mmHg] values were 4.68 ± 1.17 (episode), 4.76 i1.19 (composed from 2 segments), 4.52 + 1.16 (composed from 4 segments) and 4.62 ± 1.26 (composed from 8 segments).
Conclusions: BRS computation in patients which fragmented episodes of sinus rhythm can reliably been done by composing a session BRS from multiple segment BRS values by the BLUE method. Our solution makes noninvasive BRS measurement feasible in the clinic.
20
Netherlands Heart Journal, Volume 14, Number 5, May 2006
|
Poster 49 MYOCARDIAL CONTRAST ECHOCARDIOGRAPHY FOR ASSESSMENT OF CORONARY ARTERY DISEAS: A META-ANALYSIS P.A. Dilkmans, MD, M. Spreeuwenberg, C.A. Visser, MD, PhD, O. Kamp, MD, PhD.
Purpos: Several studies demonstrated that the value of MCE for detection of significant coronary artery disease (CAD) is comparable to that of SPECT and dobutamine stress echocardiography (DSE). We provided a meta-analysis to compare the pooled sensitivity and specificity of MCE for detection of CAD with alternative stress tests such as SPECT/DSE.
Methods: We provided a meta-analysis on 8 studies that assessed patient-based sensitivity and specificity of MCE and SPECT/DSE for detection of significant CAD, using coronary angiography as gold standard. RevMan 4.2 of the Cochrane Collaboration group was used to calculate variance weighted pooled difference of proportions for the differences in sensitivity and specificity between MCE and SPECT/DSE.
Results: The pooled estimates of the sensitivity and specificity of MCE were 85% [CI:81.5-88,5] and 74% [CI:67.7-80.3], respectively (figure). The pooled estimates of the sensitivity and specificity of the SPECT/DSE were 71% [CI: 0.66-0.76] and 71% [CI: 0.64-0.78], respectively. The pooled estimates of the differences in sensitivity and specificity were 0.14 [CI: 0.04-0.14] and 0.03 [CI: -0.14-0.21], respectively, indicating a higher sensitivity for MCE than for the SPECT/DSE. No difference was found for the specificity.
Conclusion: MCE is a dinically feasible tool for assessment of stable CAD, which is not inferior to SPECT/DSE, and has potential value in routine clinical care. v. = eVfw* 001 «~tva 4a,y mm WeT M
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Poster 50
ONGOING FUNCTIONAL INTEGRATION OF TRANSPLANTED HUMAN MESENCHYMAL STEM CELLS IN AN ELECTRICAL SYNCYTIUM OF CARDIOMYOCYTES DURING LONG-TERM INCUBATION D. A. Pijnaooels A. van der Laarse, I. van Tuyn, A. A. F. de Vries, E. E. van der Wall, M. J. Schalij, D. E. Atsma. Dept. of Cardiology, Leiden University Medical Center. Background: Cardiac cell therapy using certain cell types carries the risk of ventricular arrhythmias, associated with electrical isolation of transplanted cells from host myocardium. Therefore, we assessed whether bone-marrow derived human adult mesenchymal stem cells (hMSCs) are able to electrically integrate in an electrical syncytium of cardiomyocytes (CMCs) for longer periods. Furthermore, we studied the role of connexin43 (Cx43) in this process using RNA interference (RNAi) technique and immunohistochemistry.
Methods: Neonatal rat CMCs were cultured in multi electrode mapping array (MEA, Multichannel Systems, Germany) culture dishes. After 2 days, a central a-cellular channel was made, dividing the spontaneously and synchronously beating monolayer in two asynchronously beating CMC fields. hMSCs were transfected by adeno-viral constructs knocking down connexin43 (hMSCs-Cx431) or Firefly luciferase (pLuc) (hMSCspLucl) as control. Efficiency of knock down was assessed by western blot analysis. Then, 5x10E4 hMSCs-Cx431 or hMSCs-pLucJ were applied in the channel. Electrical conduction velocity (CV) across the channel with hMSCs was measured for up to 14 days and compared with CV across CMCs. Immunostaining of Cx43 was performed at day 1, 7, and 14 of coculture.
Results: In the control group, hMSCs-pLucl (n=8) restored electrical conduction between two CMCs fields within 24 h, which sustained for at least 14 days. CV across hMSCs-pLuc1 was constant during the first 7 days (1.4*0.3 cm/s), but increased significantly to 3.5*0.5 cm/s at day 14 (p70% decrease in Cx43 in to hMSCs-Cx434 expression compared hMSCs-pLuc4. derived human bone-marrow Conclusions: Transplanted adult mesenchymal stem cells (hMSCs) are electrically coupled with host cardiomyocytes (CMCs) in a connexin43-dependent process. During 14 days in co-culture, ongoing electrical integration of the transplanted hMSCs occurs in the syncytium of CMCs. This is reflected by a steadily rising electrical conduction velocity across hMSCs, accompanied by increased Cx43 expression.
Poster 51
CONSTRTICTIVE PERICARDITIS: EARY AND LATE OUTCOME A. Broeren, B.J. Bouma, J.J. Kloek, R.B.A. van den Brink Academic Medical Centre, Amsterdam. Purpose: Patients with constrictive pericarditis (CP) are thought to be cured by pericardiectomy. Because of the low incidence of cp only limited data on outcome is available. Therefore, we determined the short- and long-term survival of pericardiectomy.
Methods: All patients who underwent pericardiectomy for constrictive pericarditis at the Academic Medical Center (AMC) between 1985 and 2004 were reviewed. Baseline characteristics and operative data were reviewed retrospectively. Follow up was done with a questionnaire send to the general practitioner and by reviewing the hospital records.
Results: A total of 34 patients were identified (85% male, age 57 i 16 years, mean symptom duration 11 i 12 months). Heart failure was present in 82% of the patients. Most patients who developed CP had a history of cardiac surgery or no identifiable cause could be found. A concomitant procedure was performned in 90/O of the cases. Perioperative mortality was 12% (4/34), all due to heart failure. The follow up was 100% complete and lasted almost 4 years. The oneand five-year survival was 890/o and 60%. Age was the only an independent predictor of late mortality. Late mortality was due to a cardiac cause in 62% of the cases. At the end of follow up 87% (14/16) of the patients were in NYHA class I or II.
Conclusions: Cardiac surgery is an important cause of constrictive pericarditis. The operative mortality of pericardiectomy is considerably and long-term survival is limited, but the functional outcome of survivors is good.
Poster 52
MEASUREMENT OF BAROREFLEX SENSITIVITY IN HEART FAILURE PATIENTS WITH FREQUENT EPISODES OF NON-SINUS RHYTHM Van de Vooren H, Gademan MG], Swenne CA, Schalij MJ, Van der Wall EE. Cardiology Dept, Leiden University Medical Center. Purpose: Noninvasive baroreflex sensitivity (BRS) has prognostic value in chronic heart failure (CHF). During BRS measurement, ECG and blood pressure is recorded during several minutes. For BRS computation a data segment with uninterrupted sinus rhythm is needed. As CHF patients have frequent arrhythmias, the longest usable data-segment is often less than a minute. The resulting BRS is then highly unreliable. We addressed this problem by defining and testing a procedure for the composition of a reliable session BRS from multiple unreliable single-segment BRS values.
Methods: We selected 9 episodes of > 7 minutes uninterrupted sinus rhythm from our CHF (NYHA-class II&III) database and computed the episode BRSs and confidence intervals (CIs). Then, the episodes were cut into 2, 4 or 8 equal-length segments in which BRSs and CIs were computed. Finally, composite BRS and CI values for the whole episodes were computed from the multiple segment BRS and CI values by the best linear unbiased estimator (BLUE) method. Results: As expected the short data segments yielded very unreliable results. However, the BRS and CI values composed from the multiple unreliable data segments remained within 4% and 8%, respectively, from the complete episode values: averaged BRS i CI [ms/mmHg] values were 4.68 ± 1.17 (episode), 4.76 i 1.19 (composed from 2 segments), 4.52 i 1.16 (composed from 4 segments) and 4.62 i 1.26 (composed from 8 segments).
Conclusions: BRS computation in patients which fragmented episodes of sinus rhythm can reliably been done by composing a session BRS from multiple segment BRS values by the BLUE method. Our solution makes noninvasive BRS measurement feasible in the clinic.
Abstracts
Posters
Poster 53
Poster 54
ARRHYTHMIAS IN PRESSURE OVERLOADED MICE ARE ASSOCIATED WITH STRUCTURAL EUT NOT WITH CONTRACTILE REMODELING MBLulaksil", MA Engelen', M Stein", AT Jansen', NAM Mutsaers', MA Vos', ]MT de Bakker' HVM van Rijen'. (1) IaN; (2) Medical Physiology, Heart Lung Center Utrecht, UMC Utrecht; (3) Cardiology, Heart Lung Center Utrecht, UMC Utrecht.
ANEMIA IN CHRONIC HEART FAILURE IS INDEPENDENTLY ASSOCIATED WITH AN IMPAIRED HEMODYNAMIC STATUS, FLUID RETENTION AND BLUNTED EPO PRODUCTION BD. Westenbrink, TD]. Smilde, E. Lipsic, AA. Voors, HL. Hillege, G]. Navis, WH. Van Gilst, DI. Van Veldhuisen Groningen, University Medical Center Groningen, Netherlands.
Background: Structural and electrical remodeling of the heart during progression of congestive heart failure is characterized by high susceptibility to ventricular arrhythmias. We have used a mouse model of pressure overload (transverse aortic constriction, TAC) to study the relationship between cardiac remodeling and occurrence of arrhythmias.
Methods: 26 Wild-type mice were subjected to either pressure overload (n=14) or sham operation (n=12). Mice were biweekly monitored by Doppler echocardiography and electrocardiography to follow temporal evolution of contractile, structural and electrical remodeling. After 16 weeks epicardial ventricular activation mapping was performed on Langendorff perfused hearts. Conduction velocity longitudinal (CVlong) and transverse (CVtrans) to myocardial fiber orientation was measured. Effective Refractory Period (ERP) and susceptibility to arrhythmias was determined by programmed stimulation. Subsequently, hearts were processed for Cx43 immunohistology, Western blotting (WB), qPCR and Sirius Red staining (fibrosis). All data are shown as mean*SEM. Results: Fractional shortening (FS) was preserved in sham mice (46.1*1.0%), but gradually decreased in TAC mice to 37.6*2.4% at 16 weeks (p 70 jaar; situaties waarbij een verhoogde plasmaspiege kan optreden, gelijktijdig gebruik van fibraten. Bij deze patinten wordt klinische controle aanbevolen. Patienten 4 onverklaarbare spierpijn, spierzwakte of spierkramp, met name als deze gepaard gaan et malaise of koorts, dienen te worden 4 11aagd onmiddellijk te me4den. De behandeling dient te worden gestaakt wanneer de CK-spiegels dukielijk ziin verhoogd (> 5 x ULN) of als de spiersymptomen emstig zijn en dagelijks ongemak veroorzaken. De combinatie van CRESTOR met gemfibrozil wordt niet geadviseerd. De 40 mg dosering is gecontrarndkieerd bij gelijktiid4g gebruik van fibraten. CRESTOR d1ent niet te worden gebruikt bij pat4enten met een acute, emstige aandoening mogelijk wijzend op myopathie of waarbij een predispositie bestaat voor het ontwikkelen van nierfalen als gevolg van rhabdomyolyse. Voorzkchtigheid is geboden bij pati,enten met overmatig alcohol gebruik en/of een leverziekte in de anamnese. Het wordt aanbevolen leverfunctietesten uit te voeren voor en 3 maanden na het starten van de behandeling mnet CRESTOR. Wanneer de concentratie van de srumtransaminases > 3 x ULN is, dient CRESTOR te worden gestaakt of de dosering te worden ve11aagd. Bij Azbtische pati4nten laten farmacokinetische studies een toegenomen blootstelling zien in vergelijking met Kaukasi#rs. Interacties: Geneesmkideleninteracties ten gevolge van cytochroom P450 gemedieerd metabolisme worden niet verwacht Bij patienten die gelijktijdig vitamine K antagonisten gebruiken is wen14li1k het de 1NR acequaat te volgen bi1 starten of staken van behandeling met CRESTOR en bij aanpassing van de doseGing. Gemfibrozil vephk1en het risico van myopathie indien gelijktiidig gegeven en doseringen van n14otinezuur) fenofibraat, andere fibraten lip4den-ve0agende met HMG-CoA reductase remmers, mogelijk omdat zij wanneer zij alleen worden gegeven myopathie- kunnen veroorzaken. De 40 mg dosering is gecontrarnckceerd bij gebruik van een fibraat Deze patienten dienen te starten 1met de mg do1ring. Geli/ktf1dig gebruik van van met een gemfibrozil of erythromycine leidde tot een verandering van de C_ en AUC van CRESTOR. Men dkent rekening te houden s111ging de AUC van ethinylestradiol en norgestrel bij gelijktUjdig gebruik van CRESTOR en een oraal anticonceptivum en mogelijk bij hormoonsubstitutfethera pie. Gelij ktfjdkg toedkenen van een antacida-suspensie met CRESTOR lekide tot een afna me van de plasmaconcentratie van CRESTOR. Dit effect werd verminderd wanneer het antacidum 2 uur na CRE5TOR werd toegediend. CRE5TOR is gecontraindkceerd bij gelijktfjdig gebruik van cyclosporine. Er worden geen klinische relevante interacties verwacht met dkgoxine. Bilwerkingen: Bijwerkingen zijn over het algemeen mild en van voorbijgaande aard. Gemeld zijn: Vaak (1: 10-1:1 00) hoofdpijn, duizeligheid, obstfpatie, misseliikheid, buikpiin, spierpijn, gevoel van zwakte. Soms (1:100-1:1000) prurifs, huiduitslag en urticaria. Zelden (1:1000-1:10.000) myopathie, rhabdomyolyse, overgevoeligheidsreact4es inclusief ang14,-dem. Post marke1ng ervaring: zelden (1:1000-1:10.000) toegenomen levertransaminasen, (
