Pulse arrival time variation as a non-invasive marker of acute response to cardiac resynchronization therapy.

AIMS: Successful cardiac resynchronization therapy (CRT) shortens the pre-ejection period (PEP) which is prolonged in the left bundle branch block (LBBB). In a combined animal and patient study, we investigated if changes in the pulse arrival time (PAT) could be used to measure acute changes in PEP during CRT implantation and hence be used to evaluate acute CRT response non-invasively and in real time. METHODS AND RESULTS: In six canines, a pulse transducer was attached to a lower limb and PAT was measured together with left ventricular (LV) pressure by micromanometer at baseline, after induction of LBBB and during biventricular pacing. Time-to-peak LV dP/dt (Td) was used as a surrogate for PEP. In twelve LBBB patients during implantation of CRT, LV and femoral pressures were measured at baseline and during five different pacing configurations. PAT increased from baseline (277 ± 9 ms) to LBBB (313 ± 16 ms, P < 0.05) and shortened with biventricular pacing (290 ± 16 ms, P < 0.05) in animals. There was a strong relationship between changes in PAT and Td in patients (r2 = 0.91). Two patients were classified as non-responders at 6 months follow-up. CRT decreased PAT from 320 ± 41 to 298 ± 39 ms (P < 0.05) in the responders, while PAT increased by 5 and 8 ms in the two non-responders. CONCLUSION: This proof-of-concept study indicates that PAT can be used as a simple, non-invasive method to assess the acute effects of CRT in real time with the potential to identify long-term response in patients.

An image fusion tool for echo-guided left ventricular lead placement in cardiac resynchronization therapy: Performance and workflow integration analysis.

BACKGROUND: The response rate to cardiac resynchronization therapy (CRT) may be improved if echocardiographic-derived parameters are used to guide the left ventricular (LV) lead deployment. Tools to visually integrate deformation imaging and fluoroscopy to take advantage of the combined information are lacking. METHODS: An image fusion tool for echo-guided LV lead placement in CRT was developed. A personalized average 3D cardiac model aided visualization of patient-specific LV function in fluoroscopy. A set of coronary venography-derived landmarks facilitated registration of the 3D model with fluoroscopy into a single multimodality image. The fusion was both performed and analyzed retrospectively in 30 cases. Baseline time-to-peak values from echocardiography speckle-tracking radial strain traces were color-coded onto the fused LV. LV segments with suspected scar tissue were excluded by cardiac magnetic resonance imaging. The postoperative augmented image was used to investigate: (a) registration accuracy and (b) agreement between LV pacing lead location, echo-defined target segments, and CRT response. RESULTS: Registration time (264 ± 25 seconds) and accuracy (4.3 ± 2.3 mm) were found clinically acceptable. A good agreement between pacing location and echo-suggested segments was found in 20 (out of 21) CRT responders. Perioperative integration of the proposed workflow was successfully tested in 2 patients. No additional radiation, compared with the existing workflow, was required. CONCLUSIONS: The fusion tool facilitates understanding of the spatial relationship between the coronary veins and the LV function and may help targeted LV lead delivery.

Measuring Blood Pulse Wave Velocity with Bioimpedance in Different Age Groups.

In this project, we have studied the use of electrical impedance cardiography as a possible method for measuring blood pulse wave velocity, and hence be an aid in the assessment of the degree of arteriosclerosis. Using two different four-electrode setups, we measured the timing of the systolic pulse at two locations, the upper arm and the thorax, and found that the pulse wave velocity was in general higher in older volunteers and furthermore that it was also more heart rate dependent for older subjects. We attribute this to the fact that the degree of arteriosclerosis typically increases with age and that stiffening of the arterial wall will make the arteries less able to comply with increased heart rate (and corresponding blood pressure), without leading to increased pulse wave velocity. In view of these findings, we conclude that impedance cardiography seems to be well suited and practical for pulse wave velocity measurements and possibly for the assessment of the degree of arteriosclerosis. However, further studies are needed for comparison between this approach and reference methods for pulse wave velocity and assessment of arteriosclerosis before any firm conclusions can be drawn.

Cardiac resynchronization therapy when no lateral pacing option exists: vectorcardiographic guided non-lateral left ventricular lead placement predicts acute hemodynamic response.

Aims: A difficult cardiac resynchronization therapy (CRT) implantation scenario emerges when no lateral pacing option exists. The aim of this study was to explore the effect of biventricular pacing (BIVP) on vectorcardiographic parameters in patients with a non-lateral left ventricular (LV) lead position. We hypothesized that perimeter and area reduction for both the QRS complex and T-wave would predict acute CRT response. Methods and results: Twenty-six patients (14 ischaemic) with a mean age of 63 ± 10 years and standard CRT indication underwent device implantation with continuous LV pressure registration. The LV lead was placed in either an anterior or apical position. Biventricular pacing was performed at a rate 10% above intrinsic rhythm with acute CRT response defined as LV ΔdP/dtmax >10%. Using this criterion 12 patients were identified as acute CRT responders (responders: 16.7 ± 4.8% vs. non-responders: 1.9 ± 5.3%, P < 0.001). Vectorcardiographic assessment of the QRS complex and T-wave were performed at baseline and under BIVP. Based on the observed changes in three-dimensional area and perimeter, ΔQRS-area (responders: -46.7 ± 39.6% vs. non-responders: 1.1 ± 50.9%, P = 0.006) was considered as the preferred parameter. Receiver operating characteristic curve analysis identified -40% as the optimal cut-off value (sensitivity 67% and specificity 93%) for prediction of acute CRT response (AUC = 0.81, P < 0.01). A significant correlation was observed between LV ΔdP/dtmax and ΔQRS-area (R2 = 0.37, P = 0.001). Conclusion: ΔQRS-area is correlated to LV ΔdP/dtmax and predicts acute CRT response in patients with a non-lateral LV lead position. Assessment of ΔQRS-area might be a useful tool for patient specific LV lead placement when no lateral pacing option exists.

[Cardiovascular risk assessment for the use of ADHD drugs in children]. / Kardiovaskulær risikovurdering ved bruk av AD/HD-medikamenter hos barn.

BACKGROUND: Drug therapy for ADHD (Attention Deficit Hyperactivity Disorder) has generally been regarded as safe. ECG screening of healthy children and adolescents before initiating this type of treatment appears to be usual in Norway, despite recommendations that ECGs should only be undertaken in individuals who are at risk. The purpose of this article is to clarify relevant guidelines for cardiovascular risk assessment for the use of ADHD drugs in children and adolescents, as well as to propose practical recommendations. METHOD: The article is based on a literature search in PubMed completed on 1 October 2013, and on the author's own clinical experience and discretionary assessments. RESULTS: The use of CNS stimulants and atomoxetine is associated with a slight rise in blood pressure and pulse rate, as well as small changes in QT interval. A small percentage of patients (5-10%) experience a clinically significant rise in blood pressure and pulse rate. Sudden death does not appear to occur more frequently in children and adolescents taking ADHD drugs in therapeutic doses than in children and adolescents who do not use such drugs. There is little knowledge available on the long-term effects of ADHD drugs on the cardiovascular system of otherwise healthy individuals, or on the risk related to the use of ADHD drugs in children and adolescents with cardiac disease. The drugs are thought to increase the risk of sudden cardiac death in some arrhythmia syndromes. INTERPRETATION: Our assessment is that caution should be exercised in the use of ADHD drugs in children with potentially dangerous cardiac arrhythmias. We recommend clinical examination and a thorough medical history review in order to identify individuals at risk before initiating drug therapy, and also suggest that it is not necessary for healthy children to be given an ECG examination before introducing ADHD drugs. In children with known cardiac disease, arrhythmia or risk factors for cardiac disease, ADHD treatment should be undertaken in consultation with a medical specialist with competence in pediatric cardiology.

Cardiac resynchronization by repositioning of a ventricular epicardial lead in a patient with hypoplastic left heart syndrome.

Patients with congenital heart disease and univentricular circulation are vulnerable to ventricular dysfunction. In the context of atrioventricular conduction defects, a ventricular pacemaker may be placed, possibly introducing dyssynchronous wall motion and deterioration of ventricular pump function. We describe such a case in which repositioning of the ventricular lead restored synchronicity.

Regional Left Ventricular Fiber Stress Analysis for Cardiac Resynchronization Therapy Response.

Cardiac resynchronization therapy (CRT) is an effective treatment for a subgroup of heart failure (HF) patients, but more than 30% of those selected do not improve after CRT implantation. Imperfect pre-procedural criteria for patient selection and optimization are the main causes of the high non-response rate. In this study, we evaluated a novel measure for assessing CRT response. We used a computational modeling framework to calculate the regional stress of the left ventricular wall of seven CRT patients and seven healthy controls. The standard deviation of regional wall stress at the time of mitral valve closure (SD_MVC) was used to quantify dyssynchrony and compared between patients and controls and among the patients. The results show that SD_MVC is significantly lower in controls than patients and correlates with long-term response in patients, based on end-diastolic volume reduction. In contrast to our initial hypothesis, patients with lower SD_MVC respond better to therapy. The patient with the highest SD_MVC was the only non-responder in the patient cohort. The distribution of fiber stress at the beginning of the isovolumetric phase seems to correlate with the degree of response and the use of this measurement could potentially improve selection criteria for CRT implantation. Further studies with a larger cohort of patients are needed to validate these results.

Myocardial longitudinal peak systolic acceleration (pSac): relationship to ejection phase, pressure, and contractility.

Acceleration has been measured both noninvasively and invasively, during both isovolumic contraction and early ejection and has been shown to reflect contractility, especially through correlation with dP/dt(max) . In this study timing and amplitude of mitral valve annulus acceleration assessed by tissue Doppler were measured and related to diastolic and systolic events. Invasive load independent measures of contractility, based on pressure-volume relationships, were derived, and pacing was done to modulate and control heart rate. Peak systolic acceleration (pSac) of the mitral valve annulus was shown to occur slightly later but timely related to dP/dt(max) (P < 0.05), while peak preejection acceleration (pPac) was related to diastolic events. During inotropy and preload modulation dP/dt(max) was found to be the strongest determinant of pSac (ß= 0.9 ± 0.1; P < 0.001 and ß= 1.3 ± 0.4; P < 0.001, respectively, log-transformed variables). PSac increased with pacing at a higher rate (ß= 0.1 ± 0.0 cm/sec(2), P = 0.03). Furthermore, pSac indexed to end-diastolic volume (EDV) was linearly correlated to load independent contractility parameters (E(max), R = 0.7; ESPVR, R = 0.7; and PRSW, R = 0.5), and proved stable toward changes in preload and afterload. The relation between dP/dt(max)/EDV and pSac/EDV was stable throughout the study. In conclusion we found that peak systolic longitudinal acceleration (pSac) of the mitral valve annulus during aortic valve opening is strongly associated with dP/dt(max). Indexed to EDV, pSac may represent a load independent noninvasive contractility parameter. We consider pSac a candidate marker of long-axis contractility which should be viewed upon as the long-axis contribution to dP/dt(max).

Paroxysmal Tachycardia Diagnosed by ECG247 Smart Heart Sensor in a Previously Healthy Child.

Supraventricular tachycardia (SVT) is the most common symptomatic heart rhythm disorder in children and adolescents. ECG recordings of the heart rhythm during episodes is necessary for the diagnosis and for the selection of treatment. However, conventional long-term ECG recording systems may miss the diagnosis due to the disease's intermittent nature. Novel adhesive patch ECG monitors, like ECG247 Smart Heart Sensor, may represent new important diagnostic tools in children and adolescents with symptoms of heart rhythm disorders. We report a case of tachyarrhythmia in a previously healthy 12-year-old child.

Determinants of the time-to-peak left ventricular dP/dt (Td) and QRS duration with different fusion strategies in cardiac resynchronization therapy.

Background: Cardiac resynchronization therapy (CRT) is helpful in selected patients; however, responder rates rarely exceed 70%. Optimization of CRT may therefore benefit a large number of patients. Time-to-peak dP/dt (Td) is a novel marker of myocardial synergy that reflects the degree of myocardial dyssynchrony with the potential to guide and optimize treatment with CRT. Optimal electrical activation is a prerequisite for CRT to be effective. Electrical activation can be altered by changing the electrical wave-front fusion resulting from pacing to optimize resynchronization. We designed this study to understand the acute effects of different electrical wave-front fusion strategies and LV pre-/postexcitation on Td and QRS duration (QRSd). A better understanding of measuring and optimizing resynchronization can help improve the benefits of CRT. Methods: Td and QRSd were measured in 19 patients undergoing a CRT implantation. Two biventricular pacing groups were compared: pacing the left ventricle (LV) with fusion with intrinsic right ventricular activation (FUSION group) and pacing the LV and right ventricle (RV) at short atrioventricular delay (STANDARD group) to avoid fusion with intrinsic RV activation. A quadripolar LV lead enabled pacing from widely separated electrodes; distal (DIST), proximal (PROX) and both electrodes combined (multipoint pacing, MPP). The LV was stimulated relative in time to RV activation (either RV pace-onset or QRS-onset), with the LV stimulated prior to (PRE), simultaneous with (SIM) or after (POST) RV activation. In addition, we analyzed the interactions of the two groups (FUSION/STANDARD) with three different electrode configurations (DIST, PROX, MPP), each paced with three different degrees of LV pre-/postexcitation (PRE, SIM, POST) in a statistical model. Results: We found that FUSION provided shorter Td and QRSd than STANDARD, MPP provided shorter Td and QRSd than DIST and PROX, and SIM provided both the shortest QRSd and Td compared to PRE and POST. The interaction analysis revealed that pacing MPP with fusion with intrinsic RV activation simultaneous with the onset of the QRS complex (MPP*FUSION*SIM) shortened QRSd and Td the most compared to all other modes and configurations. The difference in QRSd and Td from their respective references were significantly correlated (ß = 1, R = 0.9, p < 0.01). Conclusion: Pacing modes and electrode configurations designed to optimize electrical wave-front fusion (intrinsic RV activation, LV multipoint pacing and simultaneous RV and LV activation) shorten QRSd and Td the most. As demonstrated in this study, electrical and mechanical measures of resynchronization are highly correlated. Therefore, Td can potentially serve as a marker for CRT optimization.

Tracking Early Systolic Motion for Assessing Acute Response to Cardiac Resynchronization Therapy in Real Time.

An abnormal systolic motion is frequently observed in patients with left bundle branch block (LBBB), and it has been proposed as a predictor of response to cardiac resynchronization therapy (CRT). Our goal was to investigate if this motion can be monitored with miniaturized sensors feasible for clinical use to identify response to CRT in real time. Motion sensors were attached to the septum and the left ventricular (LV) lateral wall of eighteen anesthetized dogs. Recordings were performed during baseline, after induction of LBBB, and during biventricular pacing. The abnormal contraction pattern in LBBB was quantified by the septal flash index (SFI) equal to the early systolic shortening of the LV septal-to-lateral wall diameter divided by the maximum shortening achieved during ejection. In baseline, with normal electrical activation, there was limited early-systolic shortening and SFI was low (9 ± 8%). After induction of LBBB, this shortening and the SFI significantly increased (88 ± 34%, p < 0.001). Subsequently, CRT reduced it approximately back to baseline values (13 ± 13%, p < 0.001 vs. LBBB). The study showed the feasibility of using miniaturized sensors for continuous monitoring of the abnormal systolic motion of the LV in LBBB and how such sensors can be used to assess response to pacing in real time to guide CRT implantation.

Automatic Detection of Aortic Valve Events Using Deep Neural Networks on Cardiac Signals From Epicardially Placed Accelerometer.

BACKGROUND: Miniaturized accelerometers incorporated in pacing leads attached to the myocardium, are used to monitor cardiac function. For this purpose functional indices must be extracted from the acceleration signal. A method that automatically detects the time of aortic valve opening (AVO) and aortic valve closure (AVC) will be helpful for such extraction. We tested if deep learning can be used to detect these valve events from epicardially attached accelerometers, using high fidelity pressure measurements to establish ground truth for these valve events. METHOD: A deep neural network consisting of a CNN, an RNN, and a multi-head attention module was trained and tested on 130 recordings from 19 canines and 159 recordings from 27 porcines covering different interventions. Due to limited data, nested cross-validation was used to assess the accuracy of the method. RESULT: The correct detection rates were 98.9% and 97.1% for AVO and AVC in canines and 98.2% and 96.7% in porcines when defining a correct detection as a prediction closer than 40 ms to the ground truth. The incorrect detection rates were 0.7% and 2.3% for AVO and AVC in canines and 1.1% and 2.3% in porcines. The mean absolute error between correct detections and their ground truth was 8.4 ms and 7.2 ms for AVO and AVC in canines, and 8.9 ms and 10.1 ms in porcines. CONCLUSION: Deep neural networks can be used on signals from epicardially attached accelerometers for robust and accurate detection of the opening and closing of the aortic valve.

Determinants of LV dP/dtmax and QRS duration with different fusion strategies in cardiac resynchronisation therapy.

BACKGROUND: We designed this study to assess the acute effects of different fusion strategies and left ventricular (LV) pre-excitation/post-excitation on LV dP/dtmax and QRS duration (QRSd). METHODS: We measured LV dP/dtmax and QRSd in 19 patients having cardiac resynchronisation therapy (CRT). Two groups of biventricular pacing were compared: pacing the left ventricle (LV) with FUSION with intrinsic right ventricle (RV) activation (FUSION), and pacing the LV and RV with NO FUSION with intrinsic RV activation. In the NO FUSION group, the RV was paced before the expected QRS onset. A quadripolar LV lead enabled distal, proximal and multipoint pacing (MPP). The LV was stimulated relative in time to either RV pace or QRS-onset in four pre-excitation/post-excitation classes (PCs). We analysed the interactions of two groups (FUSION/NO FUSION) with three different electrode configurations, each paced with four different degrees of LV pre-excitation (PC1-4) in a statistical model. RESULTS: LV dP/dtmax was higher with NO FUSION than with FUSION (769±46 mm Hg/s vs 746±46 mm Hg/s, p<0.01), while there was no difference in QRSd (NO FUSION 156±2 ms and FUSION 155±2 ms). LV dP/dtmax and QRSd increased with LV pre-excitation compared with pacing timed to QRS/RV pace-onset regardless of electrode configuration. Overall, pacing LV close to QRS-onset (FUSION) with MPP shortened QRSd the most, while LV dP/dtmax increased the most with LV pre-excitation. CONCLUSION: We show how a beneficial change in QRSd dissociates from the haemodynamic change in LV dP/dtmax with different biventricular pacing strategies. In this study, LV pre-excitation was the main determinant of LV dP/dtmax, while QRSd shortens with optimal resynchronisation.

Optimal pacing sites in cardiac resynchronization by left ventricular activation front analysis.

Cardiac resynchronization therapy (CRT) can substantially improve dyssynchronous heart failure and reduce mortality. However, about one-third of patients who are implanted, derive no measurable benefit from CRT. Non-response may partly be due to suboptimal activation of the left ventricle (LV) caused by electrophysiological heterogeneities. The goal of this study is to investigate the performance of a newly developed method used to analyze electrical wavefront propagation in a heart model including myocardial scar and compare this to clinical benchmark studies. We used computational models to measure the maximum activation front (MAF) in the LV during different pacing scenarios. Different heart geometries and scars were created based on cardiac MR images of three patients. The right ventricle (RV) was paced from the apex and the LV was paced from 12 different sites, single site, dual-site and triple site. Our results showed that for single LV site pacing, the pacing site with the largest MAF corresponded with the latest activated regions of the LV demonstrated during RV pacing, which also agrees with previous markers used for predicting optimal single-site pacing location. We then demonstrated the utility of MAF in predicting optimal electrode placements in more complex scenarios including scar and multi-site LV pacing. This study demonstrates the potential value of computational simulations in understanding and planning CRT.

Shortening of time-to-peak left ventricular pressure rise (Td) in cardiac resynchronization therapy.

AIMS: We tested the hypothesis that shortening of time-to-peak left ventricular pressure rise (Td) reflect resynchronization in an animal model and that Td measured in patients will be helpful to identify long-term volumetric responders [end-systolic volume (ESV) decrease >15%] in cardiac resynchronization therapy (CRT). METHODS: Td was analysed in an animal study (n = 12) of left bundle-branch block (LBBB) with extensive instrumentation to detect left ventricular myocardial deformation, electrical activation, and pressures during pacing. The sum of electrical delays from the onset of pacing to four intracardiac electrodes formed a synchronicity index (SI). Pacing was performed at baseline, with LBBB, right and left ventricular pacing and finally with biventricular pacing (BIVP). We then studied Td at baseline and with BIVP in a clinical observational study in 45 patients during the implantation of CRT and followed up for up to 88 months. RESULTS: We found a strong relationship between Td and SI in the animals (R = 0.84, P < 0.01). Td and SI increased from narrow QRS at baseline (Td = 95 ± 2 ms, SI = 141 ± 8 ms) to LBBB (Td = 125 ± 2 ms, SI = 247 ± 9 ms, P < 0.01), and shortened with biventricular pacing (BIVP) (Td = 113 ± 2 ms and SI = 192 ± 7 ms, P < 0.01). Prolongation of Td was associated with more wasted deformation during the preejection period (R = 0.77, P < 0.01). Six patients increased ESV by 2.5 ± 18%, while 37 responders (85%) had a mean ESV decrease of 40 ± 15% after more than 6 months of follow-up. Responders presented with a higher Td at baseline than non-responders (163 ± 26 ms vs. 121 ± 19 ms, P < 0.01). Td decreased to 156 ± 16 ms (P = 0.02) with CRT in responders, while in non-responders, Td increased to 148 ± 21 ms (P < 0.01). A decrease in Td with BIVP to values similar or below what was found at baseline accurately identified responders to therapy (AUC 0.98, P < 0.01). Td at baseline and change in Td from baseline was linear related to the decrease in ESV at follow-up. All-cause mortality was high among six non-responders (n = 4), while no patients died in the responder group during follow-up. CONCLUSIONS: Prolongation of Td is associated with cardiac dyssynchrony and more wasted deformation during the preejection period. Shortening of a prolonged Td with CRT in patients accurately identifies volumetric responders to CRT with incremental value on top of current guidelines and practices. Thus, Td carries the potential to become a biomarker to predict long-term volumetric response in CRT candidates.

Ejection time-corrected systolic velocity improves accuracy in the evaluation of myocardial dysfunction: a study in piglets.

This study aimed to assess the effect of correcting for the impact of heart rate (HR) or ejection time (ET) on myocardial velocities in the long axis in piglets undergoing hypoxia. The ability to eject a higher volume at a fixed ET is a characteristic of contractility in the heart. Systolic velocity of the atrioventricular annulus displacement is directly related to volume changes of the ventricle. Both ET and systolic velocity may be measured in a single heartbeat. In 29 neonatal pigs, systolic velocity and ET were measured with tissue Doppler techniques in the mitral valve annulus, the tricuspid valve annulus, and the septum. All ejection time corrected velocities (S((ET)), mean ± SEM, cm/s) decreased significantly during hypoxia (S(mva(ET)) 15.5 ± 0.2 to 13.2 ± 0.3 (p < 0.001), S(septal(ET)) 9.9 ± 0.1 to 7.8 ± 0.2 (p < 0.001), S(tva(ET)) 12.1 ± 0.2 to 9.8 ± 0.3 (p < 0.001)). The magnitude of change from baseline to hypoxia was greater for ejection time corrected systolic velocities than for RR-interval corrected velocities (mean ± SEM, cm/s); ΔS(mva(ET)) 2.3 ± 2.0 vs. ΔS(mva(RR)) 1.6 ± 1.1 (p = 0.02), ΔS(septal(ET)) 2.1 ± 1.0 vs. ΔS(septal(RR)) 1.6 ± 1.0 (p < 0.01), ΔS(tva(ET)) 2.3 ± 1.1 vs. ΔS(tva(RR)) 1.8 ± 1.3 (p = 0.04). The receiver operator characteristic (ROC) showed superior performance of S((ET)) compared with uncorrected velocities. The decrease in S((ET)) during hypoxia was not influenced by important hemodynamic determinants. ET-corrected systolic velocity improves accuracy and decreases variability in the evaluation of systolic longitudinal function and contractility during global hypoxia in neonatal pigs compared with systolic velocity alone. It is robust toward hemodynamic changes. This novel method has the potential of becoming a useful tool in clinical practice.

Multisite pacing and myocardial scars: a computational study.

Cardiac resynchronization therapy (CRT) is a frequently effective treatment modality for dyssynchronous heart failure, however, 30% of patients do not respond, usually due to suboptimal activation of the left ventricle (LV). Multisite pacing (MSP) may increase the response rate, but its effect in the presence of myocardial scars is not fully understood. We use a computational model to study the outcome of MSP in an LV with scars in two different locations and of two different sizes. The LV was stimulated from anterior, posterior and lateral locations individually and in pairs, while a septal stimulation site represented right ventricular (RV) pacing. Intraventricular pressures were measured, and outcomes evaluated in terms of maximum LV pressure gradient (dP/dtmax)- change compared to isolated RV pacing. The best result obtained using various LV pacing locations included a combination of sites remote from scars and the septum. The highest dP/dtmax increase was achieved, regardless of scar size, using MSP with one pacing site located on the LV free wall opposite to the scar and one site opposite to the septum. These in silico modelling results suggest that making placement of pacing electrodes dependent on location of scarring, may alter acute haemodynamics and that such modelling may contribute to future CRT optimization.