Tammo Delhaas

Asymmetric thickness of the left ventricular wall resulting from asynchronous electric activation: a study in dogs with ventricular pacing and in patients with left bundle branch block.

Various kinds of abnormal, asynchronous electric activation of the left ventricle (LV) decrease mechanical load in early versus late activated regions of the ventricular wall. Because myocardium usually adapts its mass to changes in workload, we investigated by echocardiography whether regional differences in wall thickness are present in two kinds of asynchronous electric activation of different origin and conduction pathway: epicardial ventricular pacing in dogs and left bundle branch block (LBBB) in patients. In six dogs, 3 months of epicardial LV pacing at physiologic heart rates decreased the thickness of the early activated anterior wall by 20.5 +/- 8.1% without significantly changing LV cavity area and septal thickness. In a retrospective study of 228 LBBB patients, the early activated septum was significantly thinner than the late activated posterior wall. The asymmetry most pronounced was as large as 10% in 28 patients with LBBB and paradoxic septal motion. No difference in regional wall thickness was present in 154 control patients. In conclusion, chronic asynchronous electric activation in the heart induces redistribution of cardiac mass. This redistribution occurs in hearts, which differ in impulse conduction pathway, disease, and species and is characterized by thinning of early versus late activated myocardium.

Cardiac resynchronisation therapy in paediatric and congenital heart disease: differential effects in various anatomical and functional substrates

Background: Cardiac resynchronisation therapy (CRT) is increasingly used in children in a variety of anatomical and pathophysiological conditions, but published data are scarce. Objective: To record current practice and results of CRT in paediatric and congenital heart disease. Design: Retrospective multicentre European survey. Setting: Paediatric cardiology and cardiac surgery centres. Patients: One hundred and nine patients aged 0.24–73.8 (median 16.9) years with structural congenital heart disease (n = 87), congenital atrioventricular block (n = 12) and dilated cardiomyopathy (n = 10) with systemic left (n = 69), right (n = 36) or single (n = 4) ventricular dysfunction and ventricular dyssynchrony during sinus rhythm (n = 25) or associated with pacing (n = 84). Interventions: CRT for a median period of 7.5 months (concurrent cardiac surgery in 16/109). Main outcome measures: Functional improvement and echocardiographic change in systemic ventricular function. Results: The z score of the systemic ventricular end-diastolic dimension decreased by median 1.1 (p<0.001). Ejection fraction (EF) or fractional area of change increased by a mean (SD) of 11.5 (14.3)% (p<0.001) and New York Heart Association (NYHA) class improved by median 1.0 grade (p<0.001). Non-response to CRT (18.5%) was multivariably predicted by the presence of primary dilated cardiomyopathy (p = 0.002) and poor NYHA class (p = 0.003). Presence of a systemic left ventricle was the strongest multivariable predictor of improvement in EF/fractional area of change (p<0.001). Results were independent of the number of patients treated in each contributing centre. Conclusion: Heart failure associated with ventricular pacing is the largest indication for CRT in paediatric and congenital heart disease. CRT efficacy varies widely with the underlying anatomical and pathophysiological substrate.

Pediatric Pulmonary Hypertension in the Netherlands Epidemiology and Characterization During the Period 1991 to 2005

Background— Incidence and prevalence rates for pediatric pulmonary hypertension (PH) and pulmonary arterial hypertension (PAH) are unknown. This study describes the nationwide epidemiological features of pediatric PH in the Netherlands during a 15-year period and the clinical course of pediatric PAH. Methods and Results— Two registries were used to retrospectively identify children (0–17 years) with PH. Overall, 3263 pediatric patients were identified with PH due to left heart disease (n=160; 5%), lung disease/hypoxemia (n=253; 8%), thromboembolic disease (n=5; <1%), and transient (n=2691; 82%) and progressive (n=154; 5%) PAH. Transient PAH included persistent PH of the newborn and children with congenital heart defects (CHD) and systemic-to-pulmonary shunt, in whom PAH resolved after successful shunt correction. Progressive PAH mainly included idiopathic PAH (n=36; iPAH) and PAH associated with CHD (n=111; PAH-CHD). Pulmonary arterial hypertension associated with CHD represented highly heterogeneous subgroups. Syndromes were frequently present, especially in progressive PAH (n=60; 39%). Survival for PAH-CHD varied depending on the subgroups, some showing better and others showing worse survival than for iPAH. Survival of children with Eisenmenger syndrome appeared worse than reported in adults. For iPAH and PAH-CHD, annual incidence and point prevalence averaged, respectively, 0.7 and 4.4 (iPAH) and 2.2 and 15.6 (PAH-CHD) cases per million children. Compared to studies in adults, iPAH occurred less whereas PAH-CHD occurred more frequently. Conclusions— Pediatric PH is characterized by various age-specific diagnoses, the majority of which comprise transient forms of PAH. Incidence of pediatric iPAH is lower whereas incidence of pediatric PAH-CHD is higher than reported in adults. Pediatric PAH-CHD represents a heterogeneous group with highly variable clinical courses. # Clinical Perspective {#article-title-25}Background— Incidence and prevalence rates for pediatric pulmonary hypertension (PH) and pulmonary arterial hypertension (PAH) are unknown. This study describes the nationwide epidemiological features of pediatric PH in the Netherlands during a 15-year period and the clinical course of pediatric PAH. Methods and Results— Two registries were used to retrospectively identify children (0–17 years) with PH. Overall, 3263 pediatric patients were identified with PH due to left heart disease (n=160; 5%), lung disease/hypoxemia (n=253; 8%), thromboembolic disease (n=5; <1%), and transient (n=2691; 82%) and progressive (n=154; 5%) PAH. Transient PAH included persistent PH of the newborn and children with congenital heart defects (CHD) and systemic-to-pulmonary shunt, in whom PAH resolved after successful shunt correction. Progressive PAH mainly included idiopathic PAH (n=36; iPAH) and PAH associated with CHD (n=111; PAH-CHD). Pulmonary arterial hypertension associated with CHD represented highly heterogeneous subgroups. Syndromes were frequently present, especially in progressive PAH (n=60; 39%). Survival for PAH-CHD varied depending on the subgroups, some showing better and others showing worse survival than for iPAH. Survival of children with Eisenmenger syndrome appeared worse than reported in adults. For iPAH and PAH-CHD, annual incidence and point prevalence averaged, respectively, 0.7 and 4.4 (iPAH) and 2.2 and 15.6 (PAH-CHD) cases per million children. Compared to studies in adults, iPAH occurred less whereas PAH-CHD occurred more frequently. Conclusions— Pediatric PH is characterized by various age-specific diagnoses, the majority of which comprise transient forms of PAH. Incidence of pediatric iPAH is lower whereas incidence of pediatric PAH-CHD is higher than reported in adults. Pediatric PAH-CHD represents a heterogeneous group with highly variable clinical courses.

Regional fibre stress-fibre strain area as an estimate of regional blood flow and oxygen demand in the canine heart.

1. In the present study the relation between regional left ventricular contractile work, regional myocardial blood flow and oxygen uptake was assessed during asynchronous electrical activation. 2. In analogy to the use of the pressure‐volume area for the estimation of global oxygen demand, the fibre stress‐fibre strain area, as assessed regionally, was used to estimate regional oxygen demand. The more often used relation between the pressure‐sarcomere length area and regional oxygen demand was also assessed. 3. Experiments were performed in six anaesthetized dogs with open chests. Regional differences in mechanical work were generated by asynchronous electrical activation of the myocardial wall. The ventricles were paced from the right atrium, the left ventricular free wall, the left ventricular apex or the right ventricular outflow tract. Regional fibre strain was measured at the epicardial anterior left ventricular free wall with a two‐dimensional video technique. 4. Regional fibre stress was estimated from left ventricular pressure, the ratio of left ventricular cavity volume to wall volume, and regional deformation. Total mechanical power (TMP) was calculated from the fibre stress‐fibre strain area (SSA) and the duration of the cardiac cycle (tcycle) using the equation: TMP = SSA/tcycle. Regional myocardial blood flow was measured with radioactive microspheres. Regional oxygen uptake was estimated from regional myocardial blood flow values and arteriovenous differences in oxygen content. 5. During asynchronous electrical activation, total mechanical power, pressure‐sarcomere length area, myocardial blood flow and oxygen uptake were significantly lower in early than in late activated regions (P < 0.05). 6. Within the experiments, the correlation between the pressure‐sarcomere length area and regional oxygen uptake was not significantly lower than the one between total mechanical power (TMP) and regional oxygen uptake (VO2,reg). However, variability of this relation between the experiments was less for total mechanical power. Pooling all experimental data revealed: VO2,reg = k1 TMP+k2, with k1 = 4.94 +/‐ 0.31 mol J‐1 k2 = 24.2 +/‐ 1.9 mmol m‐3 s‐1 (means +/‐ standard error of the estimate). 7. This relation is in quantitative agreement with previously reported relations between the pressure‐volume area and global oxygen demand. The results indicate that asynchronous electrical activation causes a redistribution of mechanical work and oxygen demand and that regional total mechanical power is a better and more general estimate of regional oxygen demand than the regional pressure‐sarcomere length area.

Three-Wall Segment (TriSeg) Model Describing Mechanics and Hemodynamics of Ventricular Interaction

A mathematical model (TriSeg model) of ventricular mechanics incorporating mechanical interaction of the left and right ventricular free walls and the interventricular septum is presented. Global left and right ventricular pump mechanics were related to representative myofiber mechanics in the three ventricular walls, satisfying the principle of conservation of energy. The walls were mechanically coupled satisfying tensile force equilibrium in the junction. Wall sizes and masses were rendered by adaptation to normalize mechanical myofiber load to physiological standard levels. The TriSeg model was implemented in the previously published lumped closed-loop CircAdapt model of heart and circulation. Simulation results of cardiac mechanics and hemodynamics during normal ventricular loading, acute pulmonary hypertension, and chronic pulmonary hypertension (including load adaptation) agreed with clinical data as obtained in healthy volunteers and pulmonary hypertension patients. In chronic pulmonary hypertension, the model predicted right ventricular free wall hypertrophy, increased systolic pulmonary flow acceleration, and increased right ventricular isovolumic contraction and relaxation times. Furthermore, septal curvature decreased linearly with its transmural pressure difference. In conclusion, the TriSeg model enables realistic simulation of ventricular mechanics including interaction between left and right ventricular pump mechanics, dynamics of septal geometry, and myofiber mechanics in the three ventricular walls.

Mapping Displacement and Deformation of the Heart With Local Sine-Wave Modeling

The new SinMod method extracts motion from magnetic resonance imaging (MRI)-tagged (MRIT) image sequences. Image intensity in the environment of each pixel is modeled as a moving sine wavefront. Displacement is estimated at subpixel accuracy. Performance is compared with the harmonic-phase analysis (HARP) method, which is currently the most common method used to detect motion in MRIT images. SinMod can handle line tags, as well as speckle patterns. In artificial images (tag distance six pixels), SinMod detects displacements accurately (error < pixels). Effects of noise are suppressed effectively. Sharp transitions in motion at the boundary of an object are smeared out over a width of 0.6 tag distance. For MRIT images of the heart, SinMod appears less sensitive to artifacts, especially later in the cardiac cycle when image quality deteriorates. For each pixel, the quality of the sine-wave model in describing local image intensity is quantified objectively. If local quality is low, artifacts are avoided by averaging motion over a larger environment. Summarizing, SinMod is just as fast as HARP, but it performs better with respect to accuracy of displacement detection, noise reduction, and avoidance of artifacts.

The left ventricular apex is the optimal site for pediatric pacing: correlation with animal experience.

Pacing at the commonly used right ventricular (RV) apex results in impaired ventricular performance. Previous animal studies indicated that the left ventricular (LV) apex is a superior pacing site. The purpose of this study was to investigate in dogs whether this good performance is associated with a more synchronous electrical activation pattern of the LV and whether the LV apex is also a good pacing site in children. In 11 healthy dogs and 8 children undergoing cardiac surgery, dual chamber pacing was performed at the RV apex, LV apex and LV lateral free wall (LVFW). In dogs, a basket electrode was inserted into the LV to assess pattern and timing of LV endocardial activation. In the children, hemodynamic measurements were performed immediately after recovery from cardiopulmonary bypass. In dogs, LV apex pacing resulted in synchronous activation around the LV circumference whereas RV apex and LVFW pacing resulted in asynchrony of activation between the septum and LVFW. In both canine and childrens hearts most hemodynamic variables remained at sinus rhythm level during LV apex pacing, but LVdPdtmax, stroke work (dogs), and pulse pressure (children) were reduced as compared with sinus rhythm during RV apex and LVFW pacing. LV apex pacing results in synchronous activation of the LV and is, in adult dogs and in children, associated with superior hemodynamic performance. (PACE 2004; 27 [Pt. II]:837–843)

Left Ventricular Septal and Left Ventricular Apical Pacing Chronically Maintain Cardiac Contractile Coordination, Pump Function and Efficiency

Background—Conventional right ventricular (RV) apex pacing can lead to adverse clinical outcome associated with asynchronous activation and reduced left ventricular (LV) pump function. We investigated to what extent alternate RV (septum) and LV (septum, apex) pacing sites improve LV electric activation, mechanics, hemodynamic performance, and efficiency over 4 months of pacing. Methods and Results—After AV nodal ablation, mongrel dogs were randomized to receive 16 weeks of VDD pacing at the RV apex, RV septum, LV apex, or LV septum (transventricular septal approach). Electric activation maps (combined epicardial contact and endocardial noncontact) showed that RV apical and RV septal pacing induced significantly greater electric desynchronization than LV apical and LV septal pacing. RV apex and RV septal pacing also significantly increased mechanical dyssynchrony, discoordination (MRI tagging) and blood flow redistribution (microspheres) and reduced LV contractility, relaxation, and myocardial efficiency (stroke work/myocardial oxygen consumption). In contrast, LV apical and LV septal pacing did not significantly alter these parameters as compared with the values during intrinsic conduction. At 16 weeks, acute intrasubject comparison showed that single-site LV apical and LV septal pacing generally resulted in similar or better contractility, relaxation, and efficiency as compared with acute biventricular pacing. Conclusions—Acute and chronic LV apical and LV septal pacing maintain regional cardiac mechanics, contractility, relaxation, and efficiency near native levels, whereas RV apical or RV septal pacing diminish these variables. Acute LV apical and LV septal pacing tend to maintain or improve contractility and efficiency compared with biventricular pacing.

Septal Deformation Patterns Delineate Mechanical Dyssynchrony and Regional Differences in Contractility: Analysis of Patient Data Using a Computer Model

Background— Response to cardiac resynchronization therapy depends both on dyssynchrony and (regional) contractility. We hypothesized that septal deformation can be used to infer integrated information on dyssynchrony and regional contractility, and thereby predict cardiac resynchronization therapy response. Methods and Results— In 132 cardiac resynchronization therapy candidates with left bundle branch block (LBBB)-like electrocardiogram morphology (left ventricular ejection fraction 19±6%; QRS width 170±23 ms), longitudinal septal strain was assessed by speckle tracking echocardiography. To investigate the effects of dyssynchronous activation and differences in septal and left ventricular free wall contractility on septal deformation pattern, we used the CircAdapt computer model of the human heart and circulation. In the patients, 3 characteristic septal deformation patterns were identified: LBBB-1=double-peaked systolic shortening (n=28); LBBB-2=early systolic shortening followed by prominent systolic stretching (n=34); and LBBB-3=pseudonormal shortening with less pronounced late systolic stretch (n=70). LBBB-3 revealed more scar (2 [2–5] segments) compared with LBBB-1 and LBBB-2 (both 0 [0–1], P<0.05). In the model, imposing a time difference of activation between septum and left ventricular free wall resulted in pattern LBBB-1. This transformed into pattern LBBB-2 by additionally simulating septal hypocontractility, and into pattern LBBB-3 by imposing additional left ventricular free wall or global left ventricular hypocontractility. Improvement of left ventricular ejection fraction and reduction of left ventricular volumes after cardiac resynchronization therapy were most pronounced in LBBB-1 and worst in LBBB-3 patients. Conclusions— A double-peaked systolic septal deformation pattern is characteristic for LBBB and results from intraventricular dyssynchrony. Abnormal contractility modifies this pattern. A computer model can be helpful in understanding septal deformation and predicting cardiac resynchronization therapy response.

Clinical Characterization of Pediatric Pulmonary Hypertension: Complex Presentation and Diagnosis

OBJECTIVES To describe the clinical presentation of pediatric pulmonary arterial hypertension (PAH) and the intricacies of how to classify pediatric PAH according to the Venice classification. STUDY DESIGN Children (n = 63) seen at a national referral center for pediatric PAH underwent a diagnostic work-up for diagnosis of pulmonary hypertension (PH) and associated conditions and for assessment of the explanatory role of associated conditions for the PH. Subsequently, PH was classified. RESULTS In 18 patients (29%), no associated conditions were identified; they were classified as having idiopathic PAH. In 45 patients (71%), > or = 1 associated conditions were detected: congenital heart defects (CHD, n = 40), connective tissue disease (CTD, n = 2), disorders of respiratory system and/or hypoxemia (RSH, n = 17), and chronic thromboembolic disease (CTE, n = 1). Patients were classified according to the condition judged to be primarily explanatory for the PH. In 11 of 45 patients with associated conditions, the PH was not sufficiently explained by these conditions; these patients were classified as having idiopathic-like PAH. In 17 of 40 cases of CHD and 9 of 17 cases of RSH, these conditions were not sufficiently explanatory for the PH. Syndromal abnormalities were frequent (43%). Ultimately, classification revealed idiopathic (-like) PAH (n = 29; 46%), PAH-CHD (n = 23; 37%), PAH-CTD (n = 2; 3%), PH-RSH (n = 8; 12%), and CTE-PH (n = 1; 2%). CONCLUSION Pediatric PH frequently presents with associated conditions and syndromal abnormalities. However, detailed evaluation of this complex presentation reveals that associated conditions are not always explanatory for the PH.