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Biomedical subjects

Martin J Schalij

Publications and source records attributed to Martin J Schalij.

At least 19 recordsLinked to original sources
PubMed2007

MISSION!: optimization of acute and chronic care for patients with acute myocardial infarction.

BACKGROUND: Guideline implementation programs for patients with acute myocardial infarction (AMI) enhance adherence to evidence-based medicine (EBM) and improve clinical outcome. Although undertreatment of patients with AMI is well recognized in both acute and chronic phases of care, most implementation programs focus on acute and secondary prevention strategies during the index hospitalization phase only. HYPOTHESIS: Implementation of an all-phase integrated AMI care program maximizes EBM in daily practice and improves the care for patients with AMI. AIM: The objective of this study is to assess the effects of the MISSION! program on adherence to EBM for patients with AMI by the use of performance indicators. DESIGN: The MISSION! protocol is based on the most recent American College of Cardiology/American Heart Association and European Society of Cardiology guidelines for patients with AMI. It contains a prehospital, inhospital, and outpatient clinical framework for decision making and treatment, up to 1 year after the index event. MISSION! concentrates on rapid AMI diagnosis and early reperfusion, followed by active lifestyle improvement and structured medical therapy. Because MISSION! covers both acute and chronic AMI phase, this design implies an intensive multidisciplinary collaboration among all regional health care providers. CONCLUSION: Continuum of care for patients with AMI is warranted to take full advantage of EBM in day-to-day practice. This manuscript describes the rationale, design, and preliminary results of MISSION!, an all-phase integrated AMI care program.

Acute Disease↗
PubMed2006

Persistence of functional atrioventricular accessory pathways in postseptated embryonic avian hearts: implications for morphogenesis and functional maturation of the cardiac conduction system.

BACKGROUND: During heart development, the ventricular activation sequence changes from a base-to-apex to an apex-to-base pattern. We investigated the possibility of impulse propagation through remnants of atrioventricular (AV) connections in quail hearts. METHODS AND RESULTS: In 86 hearts (group A, HH30-34, n=15; group B, HH35-44, n=65; group C, 5 to 6 months, n=6) electrodes were positioned at the left atrium, right ventricular base, left ventricular (LV) base, and LV apex. In group A, LV base activation preceded LV apex activation in the majority of cases (60%; 9 of 15), whereas hearts in group B primarily demonstrated an LV apex-to-base activation pattern (72%; 47 of 65). Interestingly, in group B, the right ventricular base (17%; 11 of 65) or LV base (8%; 5 of 65) exhibited premature activation in 25% (16 of 65) of cases, whereas in 26% (17 of 65), the right ventricular base or LV base was activated simultaneously with the LV apex. Morphological analysis confirmed functional data by showing persistent muscular AV connections in embryonic hearts. Interestingly, all myocardial AV connections stained positive for periostin, a nonmyocardial marker. Longitudinal analysis (HH35-44) demonstrated a decrease in both the number of hearts that exhibited premature base activation (P=0.015) and the number (P=0.004) and width (P=0.179) of accessory AV pathways with developmental stage in a similar time course. In the adult quail hearts, accessory myocardial AV pathways were functionally and morphologically absent. CONCLUSIONS: Thus, impulse propagation through persistent accessory AV connections remains possible at near-hatching stages (HH44) of development, which may provide a substrate for AV reentrant arrhythmias in perinatal life. Periostin positivity and absence of AV pathways in the adult heart suggest that these connections eventually lose their myocardial phenotype, which implicates ongoing AV ring isolation perinatally and postnatally.

Animals↗
PubMed2006

Baroreflex sensitivity, blood pressure buffering, and resonance: what are the links? Computer simulation of healthy subjects and heart failure patients.

The arterial baroreflex buffers slow (<0.05 Hz) blood pressure (BP) fluctuations, mainly by controlling peripheral resistance. Baroreflex sensitivity (BRS), an important characteristic of baroreflex control, is often noninvasively assessed by relating heart rate (HR) fluctuations to BP fluctuations; more specifically, spectral BRS assessment techniques focus on the BP-to-HR transfer function around 0.1 Hz. Skepticism about the relevance of BRS to characterize baroreflex-mediated BP buffering is based on two considerations: 1) baroreflex-modulated peripheral vasomotor function is not necessarily related to baroreflex-HR transfer; and 2) although BP fluctuations around 0.1 Hz (Mayer waves) might be related to baroreflex BP buffering, they are merely a not-intended side effect of a closed-loop control system. To further investigate the relationship between BRS and baroreflex-mediated BP buffering, we set up a computer model of baroreflex BP control to simulate normal subjects and heart failure patients. Output variables for various randomly chosen combinations of feedback gains in the baroreflex arms were BP resonance, BP-buffering capacity, and BRS. Our results show that BP buffering and BP resonance are related expressions of baroreflex BP control and depend strongly on the sympathetic gain to the peripheral resistance. BRS is almost uniquely determined by the vagal baroreflex gain to the sinus node. In conclusion, BP buffering and BRS are unrelated unless coupled gains in all baroreflex limbs are assumed. Hence, the clinical benefit of a high BRS is most likely to be attributed to vagal effects on the heart instead of to effective BP buffering.

Algorithms↗
PubMed2006

Triplane tissue Doppler imaging to evaluate mechanical dyssynchrony before and after cardiac resynchronization in a patient with congenitally corrected transposition of the great arteries.

We report the case of a 13-year-old girl with congenitally corrected transposition of the great arteries. Since the implantation of a conventional pacemaker for acquired complete atrioventricular block, the patient experienced increased heart failure symptoms. Using triplane tissue Doppler imaging, significant intraventricular dyssynchrony induced by unilateral pacing and associated with diminished exercise capacity was demonstrated. A biventricular pacemaker was successfully implanted transvenously, leading to synchronous activation of the systemic ventricle and improved exercise capacity.

Adolescent↗
PubMed2006

Impact of viability and scar tissue on response to cardiac resynchronization therapy in ischaemic heart failure patients.

AIMS: At present, 20-30% of patients do not respond to cardiac resynchronization therapy (CRT). In this study, the relation between the extent of viable myocardium and scar tissue vs. response to CRT was evaluated. In addition, the presence of scar tissue in the left ventricular (LV) lead position was specifically related to response to CRT. METHODS AND RESULTS: A total of 51 consecutive patients with ischaemic heart failure and substantial LV dyssynchrony undergoing CRT were included. All patients underwent gated SPECT before CRT implantation to determine the extent of scar tissue and viable myocardium. Clinical and echocardiographic parameters were assessed at baseline and after 6 months of CRT. The results demonstrated direct relations between the response to CRT and the extent of viable myocardium and scar tissue. In addition, the 15 patients (29%) with transmural scar tissue (< 50% tracer activity) in the region of the LV pacing lead showed no improvement after 6 months of CRT. CONCLUSION: The extent of scar tissue and viable myocardium were directly related to the response to CRT. Furthermore, scar tissue in the LV pacing lead region may prohibit response to CRT. Evaluation for viability and scar tissue may be considered in the selection process for CRT.

Aged↗
PubMed2006

Relative merits of M-mode echocardiography and tissue Doppler imaging for prediction of response to cardiac resynchronization therapy in patients with heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

M-mode echocardiography (using the septal-to-posterior wall motion delay [SPWMD]) and color-coded tissue Doppler imaging (TDI; using the septal-to-lateral delay in peak systolic velocity) have been proposed for assessment of left ventricular (LV) dyssynchrony and prediction of response to cardiac resynchronization therapy (CRT). In this study, a head-to-head comparison between M-mode echocardiography and color-coded TDI was performed for assessment of LV dyssynchrony and prediction of response to CRT. Consecutive (n = 98) patients with severe heart failure (New York Heart Association class III/IV), LV ejection fraction < or =35%, and QRS duration >120 ms underwent CRT. Before pacemaker implantation, LV dyssynchrony was assessed by M-mode echocardiography (SPWMD) and color-coded TDI (septal-to-lateral delay). At baseline and 6 months after implantation, clinical and echocardiographic parameters were evaluated. SPWMD measurement was not feasible in 41% of patients due to akinesia of the septal and/or posterior walls or poor acoustic windows. Conversely, the septal-to-lateral delay could be assessed in 96% of patients. At 6-month follow-up, 75 patients (77%) were classified as responders to CRT (improvement > or =1 New York Heart Association class). The sensitivity and specificity of SPWMD were lower compared with those of septal-to-lateral delay (66% vs 90%, p <0.05; 50% vs 82%, p = NS, respectively). In conclusion, LV dyssynchrony assessment was feasible in 59% of patients with M-mode echocardiography compared with 96% (p <0.05) when color-coded TDI was used. Color-coded TDI was superior to M-mode echocardiography for prediction of response to CRT.

Aged↗
PubMed2006

Cardiac resynchronization therapy in patients with a narrow QRS complex.

OBJECTIVES: The purpose of this study was to evaluate the effects of cardiac resynchronization therapy (CRT) in heart failure patients with narrow QRS complex (<120 ms) and evidence of left ventricular (LV) dyssynchrony on tissue Doppler imaging (TDI). BACKGROUND: Cardiac resynchronization therapy is beneficial in selected heart failure patients with wide QRS complex (> or =120 ms). Patients with narrow QRS complex are currently not eligible for CRT, and the potential effects of CRT are not well studied. METHODS: Thirty-three consecutive patients with narrow QRS complex and 33 consecutive patients with wide QRS complex (control group) were prospectively included. All patients needed to have LV dyssynchrony > or =65 ms on TDI, New York Heart Association (NYHA) functional class III/IV heart failure, and LV ejection fraction < or =35%. RESULTS: Baseline characteristics, particularly LV dyssynchrony, were comparable between patients with narrow and wide QRS complex (110 +/- 8 ms vs. 175 +/- 22 ms; p = NS). No significant relationship was observed between baseline QRS duration and LV dyssynchrony (r = 0.21; p = NS). The improvement in clinical symptoms and LV reverse remodeling was comparable between patients with narrow and wide QRS complex (mean NYHA functional class reduction 0.9 +/- 0.6 vs. 1.1 +/- 0.6 [p = NS] and mean LV end-systolic volume reduction 39 +/- 34 ml vs. 44 +/- 46 ml [p = NS]). CONCLUSIONS: Cardiac resynchronization therapy appears to be beneficial in patients with narrow QRS complex and severe LV dyssynchrony on TDI, with similar improvement in symptoms and comparable LV reverse remodeling to patients with wide QRS complex. The current results need confirmation in larger patient cohorts.

Aged↗
PubMed2006

Non-invasive visualization of the cardiac venous system in coronary artery disease patients using 64-slice computed tomography.

OBJECTIVES: This study was designed to evaluate the value of 64-slice computed tomography (CT) to visualize the cardiac veins and evaluate the relation between variations in venous anatomy and history of infarction. BACKGROUND: Cardiac resynchronization therapy (CRT) is an attractive treatment for selected heart failure patients. Knowledge of venous anatomy may help in identifying candidates for successful left ventricular lead implantation. METHODS: The 64-slice CT of 100 individuals (age 61 +/- 11 years, 68% men) was studied. Subjects were divided into 3 groups: 28 control patients, 38 patients with significant coronary artery disease (CAD), and 34 patients with a history of infarction. Presence of the following coronary sinus (CS) tributaries was evaluated: posterior interventricular vein (PIV), posterior vein of the left ventricle, and left marginal vein (LMV). Vessel diameters were also measured. RESULTS: Coronary sinus and PIV were identified in all individuals. Posterior vein of the left ventricle was observed in 96% of control patients, 84% of CAD patients, and 82% of infarction patients. In patients with a history of infarction, a LMV was significantly less observed as compared with control patients and CAD patients (27% vs. 71% and 61%, respectively, p < 0.001). None of the patients with lateral infarction and only 22% of patients with anterior infarction had a LMV. Regarding quantitative data, no significant differences were observed between the groups. CONCLUSIONS: Non-invasive evaluation of cardiac veins with 64-slice CT is feasible. There is considerable variation in venous anatomy. Patients with a history of infarction were less likely to have a LMV, which may hamper optimal left ventricular lead positioning in CRT implantation.

Aged↗
PubMed2006

Outcome of implantable cardioverter defibrillators in adults with congenital heart disease: a multi-centre study.

AIMS: To investigate outcome and complications of implantable cardioverter defibrillators (ICDs) in adults with congenital heart disease (CHD) and to identify predictors of (in-) appropriate shocks. METHODS AND RESULTS: Sixty-four CHD patients >/= 18 years at first ICD implantation [63% tetralogy of Fallot (TOF) and age at implantation 37 +/- 13 years] were identified using the Dutch adult CHD registry and a Belgian tertiary care centre database. Median follow-up duration was 3.7 years. Early complications included pocket haematoma (n = 3), lead failure (n = 2), and pneumothorax (n = 2). Late complications occurred in 11 (17%) patients, including lead failure (n = 6) and and electrical storm (n = 3). Overall, 30 device-related re-interventions were performed in 20 patients (31%), including four premature generator changes and seven lead replacements. Half of the patients received one or more shocks, and 46 shocks in 15 patients (23%) were classified as appropriate. One hundred and sixty shocks in 26 patients (41%) were classified as inappropriate. No predictors of (in-)appropriate shocks were identified, except TOF being associated with less appropriate shocks than patients with other CHD (HR 0.29, P = 0.02). CONCLUSION: The ICD provided effective therapy in a quarter of adults with CHD with low complication rates. The incidence of inappropriate shocks, however, appeared to be excessive and warrants further attention.

Adult↗
PubMed2006

Right ventricular pacing can induce ventricular dyssynchrony in patients with atrial fibrillation after atrioventricular node ablation.

OBJECTIVES: This study was designed to assess the effects of long-term right ventricular (RV) pacing on left ventricular (LV) dyssynchrony, LV function, and heart failure symptoms. BACKGROUND: Atrioventricular (AV) node ablation and subsequent long-term RV pacing is a well-established treatment option in patients with atrial fibrillation (AF). METHODS: In 55 patients with drug-refractory AF, AV node ablation and implantation of a pacemaker was performed. At baseline and after a mean of 3.8 +/- 1.7 years, LV dyssynchrony (by M-mode echocardiography and tissue Doppler imaging), LV function, and volumes and functional status were assessed. RESULTS: After long-term RV pacing, 27 patients (49%) had developed LV dyssynchrony. Concomitantly, these patients worsened in heart failure symptoms (New York Heart Association functional class increased from 1.8 +/- 0.6 to 2.2 +/- 0.7, p < 0.05), with a decrease in LV ejection fraction (from 48 +/- 7% to 43 +/- 7%, p < 0.05) and an increase in LV end-diastolic volume (from 116 +/- 39 ml to 130 +/- 52 ml, p < 0.05). Conversely, patients without LV dyssynchrony did not deteriorate in heart failure symptoms, LV function, or LV volumes. CONCLUSIONS: Long-term RV pacing can induce LV dyssynchrony in almost 50% of patients treated with AV node ablation for chronic AF. The development of LV dyssynchrony was associated with deterioration in heart failure symptoms, systolic LV function, and LV dilatation.

Atrial Fibrillation↗
PubMed2006

Epicardial cells of human adults can undergo an epithelial-to-mesenchymal transition and obtain characteristics of smooth muscle cells in vitro.

Myocardial and coronary development are both critically dependent on epicardial cells. During cardiomorphogenesis, a subset of epicardial cells undergoes an epithelial-to-mesenchymal transition (EMT) and invades the myocardium to differentiate into various cell types, including coronary smooth muscle cells and perivascular and cardiac interstitial fibroblasts. Our current knowledge of epicardial EMT and the ensuing epicardium-derived cells (EPDCs) comes primarily from studies of chick and mouse embryonic development. Due to the absence of an in vitro culture system, very little is known about human EPDCs. Here, we report for the first time the establishment of cultures of primary epicardial cells from human adults and describe their immunophenotype, transcriptome, transducibility, and differentiation potential in vitro. Changes in morphology and beta-catenin staining pattern indicated that human epicardial cells spontaneously undergo EMT early during ex vivo culture. The surface antigen profile of the cells after EMT closely resembles that of subepithelial fibroblasts; however, only EPDCs express the cardiac marker genes GATA4 and cardiac troponin T. After infection with an adenovirus vector encoding the transcription factor myocardin or after treatment with transforming growth factor-beta1 or bone morphogenetic protein-2, EPDCs obtain characteristics of smooth muscle cells. Moreover, EPDCs can undergo osteogenesis but fail to form adipocytes or endothelial cells in vitro. Cultured epicardial cells from human adults recapitulate at least part of the differentiation potential of their embryonic counterparts and represent an excellent model system to explore the biological properties and therapeutic potential of these cells.

Adenoviridae↗
PubMed2006

Progressive increase in conduction velocity across human mesenchymal stem cells is mediated by enhanced electrical coupling.

OBJECTIVE: The purpose of the study was to investigate the development of electrical transmission across human adult bone marrow-derived mesenchymal stem cells (hMSCs) during long-term co-incubation with cardiomyocytes (CMCs). METHODS: Neonatal rat CMCs were cultured in multi-electrode array dishes. A conduction block was induced by creating a central acellular channel, yielding two asynchronously beating CMC fields. Enhanced green fluorescent protein (eGFP)-labeled hMSCs from ischemic heart disease patients (n=8), eGFP-labeled hMSCs having RNA interference-mediated connexin43 (Cx43) knockdown (n=6), 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine (Dil)-labeled CMCs (n=6), or no cells (n=9) were seeded in the channel. Assessment of conduction velocity (CV), Cx expression and localization, gap junctional coupling, and intracellular electrical recordings were performed for up to 14 days. RESULTS: Resynchronization of the two CMC fields occurred within 24 h after seeding of hMSCs. CV across hMSCs increased from 1.4+/-0.4 cm/s at day 7 to 3.5+/-0.1 cm/s (p<0.05) at day 14. CV across seeded CMCs was 16.8+/-0.2 cm/s throughout this period. No resynchronization occurred in the absence of seeded cells. Knockdown of Cx43 in hMSCs abolished conduction across the channel completely. Time-dependent increase of CV across hMSCs was associated with increased Cx43 mRNA and protein expression resulting in increased gap junctional coupling. Intracellular recordings in coupled hMSCs showed increased conducted action potential (AP) amplitude, lower resting membrane potential, and decreased duration of conducted AP (p<0.05, day 14 versus day 1). CONCLUSIONS: CV across hMSCs increases progressively after 7 days of co-incubation with CMCs, most likely via improved electrotonic interaction. This is associated with increased Cx43 expression, increased functional gap junctional coupling, and enhanced intercellular electrical coupling between hMSCs and CMCs.

Action Potentials↗
PubMed2006

Benefit of combined resynchronization and defibrillator therapy in heart failure patients with and without ventricular arrhythmias.

OBJECTIVES: We attempted to assess the efficacy of combined cardiac resynchronization therapy-implantable cardioverter-defibrillator (CRT-ICD) in heart failure patients with and without ventricular arrhythmias. BACKGROUND: Because CRT and ICDs both lower all-cause mortality in patients with advanced heart failure, combination of both therapies in a single device is challenging. METHODS: A total of 191 consecutive patients with advanced heart failure, left ventricular ejection fraction <35%, and a QRS duration >120 ms received CRT-ICD. Seventy-one patients had a history of ventricular arrhythmias (secondary prevention); 120 patients did not have prior ventricular arrhythmias (primary prevention). During follow-up, ICD therapy rate, clinical improvement after 6 months, and mortality rate were evaluated. RESULTS: During follow-up (18 +/- 4 months), primary prevention patients experienced less appropriate ICD therapies than secondary prevention patients (21% vs. 35%, p < 0.05). Multivariate analysis revealed, however, no predictors of ICD therapy. Furthermore, a similar, significant, improvement in clinical parameters was observed at 6 months in both groups. Also, the mortality rate in the primary prevention group was lower than in the secondary prevention group (3% vs. 18%, p < 0.05). CONCLUSIONS: As 21% of the primary prevention patients and 35% of the secondary prevention patients experienced appropriate ICD therapy within 2 years after implant, and no predictors of ICD therapy could be identified, implantation of a CRT-ICD device should be considered in all patients eligible for CRT.

Aged↗