Coronary Flow Reserve and Myocardial Resistance Reserve Changes After Transcatheter Aortic Valve Implantation in Aortic Stenosis.

Aortic valve stenosis (AS) induces an alteration in hemodynamic conditions that are responsible for coronary microvasculature impairment. Relief of AS by transcatheter aortic valve implantation (TAVI) is expected to improve the coronary artery hemodynamic. We aimed to assess the midterm effects of TAVI in coronary flow reserve (CFR) and myocardial resistance reserve (MRR) by a continuous intracoronary thermodilution technique. At-rest and hyperemic coronary flow was measured by a continuous thermodilution technique in 23 patients with AS and compared with that in 17 matched controls, and repeated 6 ± 3 months after TAVI in 11 of the patients with AS. In patients with AS, absolute coronary flow at rest was significantly greater, and absolute resistance at rest was significantly less, than in controls (p <0.01 for both), causing less CFR and MRR (1.73 ± 0.4 vs 2.85 ± 1.1, p <0.01 and 1.95 ± 0.4 vs 3.22 ± 1.4, p <0.01, respectively). TAVI implantation yielded a significant 35% increase in CFR (p >0.01) and a 39% increase in MRR (p <0.01) driven by absolute coronary flow at rest reduction (p = 0.03). In patients with AS, CFR and MRR determined by continuous thermodilution are significantly impaired. At 6-month follow-up, TAVI improves these indexes and partially relieves the pathophysiologic alterations, leading to a partial restoration of CFR and MRR.

Outcomes of cavotricuspid isthmus-dependent flutter ablation: randomized study comparing single vs. multiple catheter procedures-the SIMPLE study.

BACKGROUND: Catheter ablation is recommended as first-line therapy for patients with symptomatic typical AFl. Although the conventional multi-catheter approach is the standard of care for cavotricuspid isthmus (CTI) ablation, a single-catheter approach was recently described as a feasible alternative. The present study sought to compare safety, efficacy, and efficiency of single vs. multi-catheter approach for atrial flutter (AFl) ablation. METHODS: In this randomized multi-center study, consecutive patients referred for AFl ablation (n = 253) were enrolled and randomized to multiple vs. single-catheter approach for CTI ablation. In the single-catheter arm, PR interval (PRI) on the surface ECG was used to prove CTI block. Procedural and follow-up data were collected and compared between the two arms. RESULTS: 128 and 125 patients were assigned to the single-catheter and to the multi-catheter arms, respectively. In the single-catheter arm, procedure time was significantly shorter (37 ± 25 vs. 48 ± 27 minutes, p = 0.002) and required less fluoroscopy time (430 ± 461 vs. 712 ± 628 seconds, p < 0.001) and less radiofrequency time (428 ± 316 vs. 643 ± 519 seconds, p < 0.001), achieving a higher first-pass CTI block rate (55 (45%) vs. 37 (31%), p = 0.044), compared with the multi-catheter arm. After a median follow-up of 12 months, 11 (4%) patients experienced AFl recurrences (5 (4%) in the single-catheter arm and 6 (5%) in the multi-catheter arm, p = 0.99). No differences were found in arrhythmia-free survival between arms (log-rank = 0.71). CONCLUSIONS: The single-catheter approach for typical AFl ablation is not inferior to the conventional multiple-catheter approach, reducing procedure, fluoroscopy, and radiofrequency time.

A hybrid clinical and electrocardiographic score to predict the origin of outflow tract ventricular arrhythmias.

BACKGROUND: To predict the outflow tract ventricular arrhythmias (OTVA) site of origin (SOO) before the ablation procedure has important practical implications. The present study sought to prospectively evaluate the accuracy of a clinical and electrocardiographic hybrid algorithm (HA) for the prediction of OTVAs-SOO, and at the same time to develop and to prospectively validate a new score with improved discriminatory capacity. METHODS: In this multicenter study, we prospectively enrolled consecutive patients referred for OTVA ablation (N = 202), and we divided them in a derivation sample and a validation cohort. Surface ECGs during OTVA were analyzed to compare previous published ECG-only criteria and to develop a new score. RESULTS: In the derivation sample (N = 105), the correct prediction rate of HA and ECG-only criteria ranged from 74 to 89%. R-wave amplitude in V3 was the best ECG parameter for discriminating LVOT origin in V3 precordial transition (V3PT) patients, and was incorporated to the novel weighted hybrid score (WHS). WHS correctly classified 99 (94.2%) patients, presenting 90% sensitivity and 96% specificity (AUC 0.97) in the entire population; WHS mantained a 87% sensitivity and 91% specificity (AUC 0.95) in patients with V3PT subgroup. The high discriminatory capacity was confirmed in the validation sample (N = 97): the WHS exhibited an AUC (0.93), and a WHS ≥ 2 allowed a correct prediction of LVOT origin in 87 (90.0%) cases, yielding a sensitivity of 87% and specificity of 90%; moreover, the V3PT subgroup showed an AUC of 0.92, and a punctuation ≥ 2 predicted an LVOT origin with a sensitivity of 94% and specificity of 78%. CONCLUSIONS: The novel hybrid score has proved to accurately anticipate the OTVA's origin, even in those with a V3 precordial transition. A Weighted hybrid score. B Typical examples of the use of the weighted hybrid score. C ROC analysis of WHS and previous ECG criteria for prediction of LVOT origin in the derivation cohort. D ROC analysis of WHS and previous ECG criteria for prediction of LVOT origin in the V3 precordial transition OTVA subgroup.

Joint Analysis of Morphological Parameters and In Silico Haemodynamics of the Left Atrial Appendage for Thrombogenic Risk Assessment.

Background: Atrial fibrillation (AF) is considered the most common human arrhythmia. In nonvalvular AF, around 99% of thrombi are formed in the left atrial appendage (LAA). Nevertheless, there is not a consensus in the community about the relevant factors to stratify the AF population according to thrombogenic risk. Objective: To demonstrate the need for combining left atrial morphological and haemodynamics indices to improve the thrombogenic risk assessment in nonvalvular AF patients. Methods: A cohort of 71 nonvalvular AF patients was analysed. Statistical analysis, regression models, and random forests were used to analyse the differences between morphological and haemodynamics parameters, extracted from computational simulations built on 3D rotational angiography images, between patients with and without transient ischemic attack (TIA) or cerebrovascular accident (CVA). Results: The analysis showed that models composed of both morphological and haemodynamic factors were better predictors of TIA/CVA compared with models based on either morphological or haemodynamic factors separately. Maximum ostium diameter, length of the centreline, blood flow velocity within the LAA, oscillatory shear index, and time average wall shear stress parameters were found to be key risk factors for TIA/CVA prediction. In addition, TIA/CVA patients presented more flow stagnation within the LAA. Conclusion: Thrombus formation in the LAA is the result of multiple factors. Analyses based only on morphological or haemodynamic parameters are not precise enough to predict such a phenomenon, as demonstrated in our results; a better patient stratification can be obtained by jointly analysing morphological and haemodynamic features.

Impact of a predefined pacemapping protocol use for ablation of infrequent premature ventricular complexes: A prospective, multicenter study.

BACKGROUND: Pacemapping (PM) is a useful maneuver for aiding premature ventricular complex (PVC) ablation. Its standalone clinical value is still to be defined. OBJECTIVES: The purpose of this study was to analyze the efficacy of a predefined PM protocol for low-burden PVC ablation, regardless of their site of origin (SOO) and the presence of structural heart disease. METHODS: This was a prospective, nonrandomized, multicenter study. The PM protocol was performed when <1 PVC/min was found. The "target area" was delimited by the 3 best matching points >94% correlation, and 3 radiofreqency (RF) applications were delivered. RESULTS: Of 185 patients, 105 (57%) underwent activation mapping, 60 (32%) were PM-guided, and 20 (11%) were canceled due to absence of PVCs. Baseline QRS, PVC burden, and outflow tract origin were independent predictors of PM-guided ablation. A higher proportion of right ventricular outflow tract SOO in the PM group (52% vs 40%; P = .03) was observed. Mean target area was 0.6 ± 0.9 cm2. Mean 10-ms isochronal area in local activation time (LAT)-guided procedures was higher (1.7 ± 2.3 cm2; P <.001). Mean number of PM matching points acquired was 39 ± 21 (range 6-98). Mean mapping and RF times were similar in both groups. However, significantly shorter procedural (53 ± 24 vs 61 ± 26 minutes; P = .04) as well as RF times (111 ± 51 vs 149 ± 149 seconds; P = .05) were needed in the PM group using the proposed protocol. Global clinical success reached 87% for the PM group and 90% (P = .58) the for LAT mapping group. CONCLUSION: When LAT mapping is precluded, application of a PM-guided ablation protocol directed to >94% matching correlation target area is a more efficient alternative with comparable clinical results.

Predictors of inappropriate shock in Brugada syndrome patients with a subcutaneous implantable cardiac defibrillator.

BACKGROUND: Subcutaneous implantable cardioverter defibrillators (S-ICDs) avoid complications secondary to transvenous leads, but inappropriate shocks (ISs) are frequent. Furthermore, IS data from patients with Brugada syndrome (BrS) with an S-ICD are scarce. OBJECTIVE: We aimed to establish the frequency and predictors of IS in this population. METHODS: We analyzed the clinical and electrocardiographic characteristics, automated screening test data, device programming, and IS occurrence in adult patients with BrS with an S-ICD. RESULTS: Thirty-nine patients were enrolled (69% male, mean age at diagnosis 46 ± 13 years, mean age at implantation 48 ± 13 years). During a mean follow-up of 26 ± 21 months, 18% patients experienced IS. Patients with IS were younger at the time of diagnosis (36 ± 8 vs. 48 ± 13 years, p = .018) and S-ICD implantation (38 ± 9 vs. 50 ± 23 years, p = .019) and presented with spontaneous type 1 Brugada electrocardiogram pattern more frequently at diagnosis or during follow-up (71% vs. 25%, p = .018). During automated screening tests, patients with IS showed lower QRS voltage in the primary vector in the supine position (0.58 ± 0.26 vs. 1.10 ± 0.35 mV, p = .011) and lower defibrillator automated screening score in the primary vector in the supine (123 ± 165 vs. 554 ± 390 mV, p = .005) and standing (162 ± 179 vs. 486 ± 388 mV, p = .038) positions. Age at diagnosis was the only independent predictor of IS (hazard ratio = 0.873, 95% confidence interval: 0.767-0.992, p = .037). CONCLUSION: IS was a frequent complication in patients with BrS with an S-ICD. Younger age was independently associated with IS. A more thorough screening process might help prevent IS in this population.

MANual vs. automatIC local activation time annotation for guiding Premature Ventricular Complex ablation procedures (MANIaC-PVC study).

AIMS: To assess potential benefits of a local activation time (LAT) automatic acquisition protocol using wavefront annotation plus an ECG pattern matching algorithm [automatic (AUT)-arm] during premature ventricular complex (PVC) ablation procedures. METHODS AND RESULTS: Prospective, randomized, controlled, and international multicentre study (NCT03340922). One hundred consecutive patients with indication for PVC ablation were enrolled and randomized to AUT (n = 50) or manual (MAN, n = 50) annotation protocols using the CARTO3 navigation system. The primary endpoint was mapping success. Clinical success was defined as a PVC-burden reduction of ≥80% in the 24-h Holter within 6 months after the procedure. Mean age was 56 ± 14 years, 54% men. The mean baseline PVC burden was 25 ± 13%, and mean left ventricular ejection fraction (LVEF) 55 ± 11%. Baseline characteristics were similar between the groups. The most frequent PVC-site of origin were right ventricular outflow tract (41%), LV (25%), and left ventricular outflow tract (17%), without differences between groups. Radiofrequency (RF) time and number of RF applications were similar for both groups. Mapping and procedure times were significantly shorter in the AUT-arm (25.5 ± 14.3 vs. 32.8 ± 12.6 min, P = 0.009; and 54.8 ± 24.8 vs. 67.4 ± 25.2, P = 0.014, respectively), while more mapping points were acquired [136 (94-222) AUT vs. 79 (52-111) MAN; P < 0.001]. Mapping and clinical success were similar in both groups. There were no procedure-related complications. CONCLUSION: The use of a complete automatic protocol for LAT annotation during PVC ablation procedures allows to achieve similar clinical endpoints with higher procedural efficiency when compared with conventional, manual annotation carried out by expert operators.

Premature ventricular complex site of origin and ablation outcomes in patients with prior myocardial infarction.

BACKGROUND: Frequent premature ventricular complexes (PVCs) are common after a myocardial infarction (MI), but data on PVC ablation in this population are limited. OBJECTIVE: The purpose of this study was to analyze data on PVC ablation in post-MI patients. METHODS: Three hundred thirty-two patients with frequent PVCs and left ventricular (LV) dysfunction were prospectively studied. Data from 67 patients (20%; age 63 ± 10 years; 65 men [93%]) with previous MI were compared with the remaining 265 patients. RESULTS: PVCs in post-MI patients originate predominantly from the LV (92% LV vs 6% right ventricle [RV]; P <.001). The most frequent sites of origin (SOO) were MI scar in 23 patients (34%) and left ventricular outflow tract (LVOT) in 22 patients (33%). A papillary muscle origin was more frequent in post-MI patients (16% vs 4%; P = .001), whereas an RV outflow tract origin was less frequent (1% vs 33%; P <.001) compared to patients without MI. In post-MI patients, PVC burden decreased from 29% ± 12% at baseline to 4.6% ± 7% (P <.001); left ventricular ejection fraction (LVEF) improved from 33.6% ± 8% to 42% ± 10% (P <.001); and New York Heart Association functional class improved from 2.1 ± 0.7 to 1.4 ± 0.5 points (P <.001) at 12 months. Compared with the remaining 265 patients, there were no differences in acute ablation success (85% vs 85%; P = .45), complication rate (6% vs 6%; P = .41), or absolute improvement in LVEF (8.8 ± 10 vs 9.9 ± 11 absolute points; P = .38). CONCLUSION: PVC ablation significantly improves cardiac function and functional status in post-MI patients. PVCs predominantly originate from MI scar and LVOT. A papillary muscle SOO was found to be strongly associated with previous MI.

Contrast FFR plus intracoronary injection of nitro-glycerine accurately predicts FFR for coronary stenosis functional assessment.

BACKGROUND: Fractional flow reserve (FFR) is the "gold standard" for assessing the physiological significance of coronary disease. In the last decade, several alternative adenosine-free indexes have been proposed in order to facilitate the dissemination of the functional evaluation of coronary stenosis. Our aim was to investigate whether radiographic contrast plus intracoronary nitroglycerin (cFFR-NTG) can predict functional assessment of coronary stenosis offering superior diagnostic agreement with FFR compared to non-hyperemic indexes and contrast mediated FFR (cFFR). METHODS: Three hundred twenty-nine lesions evaluated with pressure wire in 266 patients were prospectively included in this multicenter study. RESULTS: The ROC curves for cFFR-NTG using an FFR≤0.80 showed a higher accuracy in predicting FFR (AUC=0.97) than resting Pd/Pa (AUC=0.90, P<0.01) and cFFR (AUC=0.93.5, P<0.01). A significant (P<0.01) strong correlation was found between FFR and the four analyzed indexes: Pd/Pa (r=0.78); iFR/RFR (r=0.73); cFFR(r=0.89) and cFFR-NTG (r=0.93). cFFR-NTG showed the closest agreement at Bland-Altman analysis. The cFFR-NTG cut off value >0.84 showed the highest negative predictive value (88%), specificity (91%), sensitivity (94%) and accuracy (92%) of the studied indexes. CONCLUSIONS: Submaximal hyperemic adenosine-free indexes are an efficient alternative to adenosine for the physiological assessment of epicardial coronary disease. The most accurate index in predicting the functional significance of coronary stenosis using FFR as reference was cFFR-NTG.

Continuous Thermodilution Method to Assess Coronary Flow Reserve.

Coronary flow reserve (CFR) is a well-validated flow-based physiological parameter that has shown value in clinical risk stratification. CFR can be invasively assessed, classically by Doppler and, more recently, by thermodilution with saline boluses (CFRthermo-bolus). Alternatively, continuous thermodilution is a novel operator-independent, highly-reproducible technique to invasively quantify maximum absolute coronary flow (AF). This study aimed to assess the feasibility of this method to quantify resting AF and to determine CFR (CFRThermo-infusion) as compared with CFRthermo-bolus. Sixty-two consecutive patients with suspicion of coronary disease and absence of significant epicardial lesions were prospectively investigated. AF at maximal hyperemia (20 mL/min) and at lower infusion rates (6-8-10-12 mL/min) were systematically measured using a dedicated catheter and a temperature/pressure guidewire. The absence of baseline Pd/Pa decrease at 6 (0.15 ± 0.2%), 8 (0.17 ± 0.18%) and 10 mL/min (0.2 ± 0.12%) demonstrated absence of hyperemia at ≤10 mL/min (all p = NS). However, at 12 mL/min hyperemia was confirmed by a significant decrease in Pd/Pa (1.3 ± 1.5%, p <0.01) and increase in AF from 10 mL/min to 12 mL/min (31.4 ± 28.1 mL, p <0.05). All curve tracings at 10 mL/min (129/129, 100%) were adequate versus only (7/15, 53%) and (15/18, 17%) at 6 mL/min, and 8 mL/min, respectively, and this infusion-rate was considered to determine resting-AF. CFRThermo-infusion was determined as the ratio of hyperemic-AF (20 mL/min) by resting-AF (10 mL/min). Mean CFRThermo-infusion was 2.56 ± 0.9 and CFRthermo-bolus 2.49 ± 1. Both parameters showed a good correlation (r = 0.76; p <0.001) and intraclass agreement (ICC = 0.76; p <0.001).The continuous thermodilution method enables to quantify resting-AF providing a novel clinical tool to determine CRF. CFRThermo-infusion shows a good correlation with CFRthermo-bolus..

In silico Optimization of Left Atrial Appendage Occluder Implantation Using Interactive and Modeling Tools.

According to clinical studies, around one third of patients with atrial fibrillation (AF) will suffer a stroke during their lifetime. Between 70 and 90% of these strokes are caused by thrombus formed in the left atrial appendage. In patients with contraindications to oral anticoagulants, a left atrial appendage occluder (LAAO) is often implanted to prevent blood flow entering in the LAA. A limited range of LAAO devices is available, with different designs and sizes. Together with the heterogeneity of LAA morphology, these factors make LAAO success dependent on clinician's experience. A sub-optimal LAAO implantation can generate thrombi outside the device, eventually leading to stroke if not treated. The aim of this study was to develop clinician-friendly tools based on biophysical models to optimize LAAO device therapies. A web-based 3D interactive virtual implantation platform, so-called VIDAA, was created to select the most appropriate LAAO configurations (type of device, size, landing zone) for a given patient-specific LAA morphology. An initial LAAO configuration is proposed in VIDAA, automatically computed from LAA shape features (centreline, diameters). The most promising LAAO settings and LAA geometries were exported from VIDAA to build volumetric meshes and run Computational Fluid Dynamics (CFD) simulations to assess blood flow patterns after implantation. Risk of thrombus formation was estimated from the simulated hemodynamics with an index combining information from blood flow velocity and complexity. The combination of the VIDAA platform with in silico indices allowed to identify the LAAO configurations associated to a lower risk of thrombus formation; device positioning was key to the creation of regions with turbulent flows after implantation. Our results demonstrate the potential for optimizing LAAO therapy settings during pre-implant planning based on modeling tools and contribute to reduce the risk of thrombus formation after treatment.

Sensitivity analysis of geometrical parameters to study haemodynamics and thrombus formation in the left atrial appendage.

The left atrial appendage (LAA) is a complex and heterogeneous protruding structure of the left atrium (LA). In atrial fibrillation patients, it is the location where 90% of the thrombi are formed. However, the role of the LAA in thrombus formation is not fully known yet. The main goal of this work is to perform a sensitivity analysis to identify the most relevant LA and LAA morphological parameters in atrial blood flow dynamics. Simulations were run on synthetic ellipsoidal left atria models where different parameters were individually studied: pulmonary veins and mitral valve dimensions; LAA shape; and LA volume. Our computational analysis confirmed the relation between large LAA ostia, low blood flow velocities and thrombus formation. Additionally, we found that pulmonary vein configuration exerted a critical influence on LAA blood flow patterns. These findings contribute to a better understanding of the LAA and to support clinical decisions for atrial fibrillation patients.

Integración de la imagen mecánica, estructural y eléctrica para entender la respuesta a la terapia de resincronización cardiaca / Integration of Mechanical, Structural and Electrical Imaging to Understand Response to Cardiac Resynchronization Therapy

Introducción y objetivos: Debido a la controversia existente al determinar si la terapia de resincronización cardiaca corrige asincronía eléctrica o mecánica, el objetivo del estudio es determinar si hay correlación entre las secuencias eléctricas y mecánicas y si la cicatriz miocárdica tiene un impacto relevante. Métodos Se estudió a 6 pacientes con función ventricular izquierda normal y 12 pacientes con disfunción del ventrículo izquierdo y bloqueo de rama izquierda tratados con terapia de resincronización cardiaca. Se realizaron ecografías tridimensionales en tiempo real y cartografías electroanatómicas de todos los pacientes, antes y después de dicha terapia, así como una resonancia magnética para evaluar la cicatriz miocárdica. Se posprocesaron las imágenes, se definieron secuencias de activación mecánica y eléctrica y se determinaron diferencias temporales entre el primer y el último segmento del ventrículo izquierdo. Se consideró respuesta a la terapia una reducción del volumen telesistólico del ventrículo izquierdo ≥ 15% a los 12 meses. Resultados: Se encontró buena correlación entre tiempos eléctricos y mecánicos en pacientes con función ventricular normal (r2 = 0,88; p = 0,005), pero no en aquellos con disfunción (r2 = 0,02; p = no significativa). Después de optimizar el dispositivo, se modificaron y mejoraron los tiempos y las secuencias, excepto los de aquellos con cicatriz miocárdica. Conclusiones: A pesar de la estrecha relación electromecánica en ventrículos normales, no hay una correlación significativa en los pacientes con disfunción ventricular. Aunque la terapia mejora esta correlación, los cambios en la activación eléctrica no pueden producir cambios similares en la mecánica del ventrículo izquierdo, sobre todo en función del sustrato miocárdico subyacente (AU)

Introduction and objectives There is extensive controversy exists on whether cardiac resynchronization therapy corrects electrical or mechanical asynchrony. The aim of this study was to determine if there is a correlation between electrical and mechanical sequences and if myocardial scar has any relevant impact. Methods Six patients with normal left ventricular function and 12 patients with left ventricular dysfunction and left bundle branch block, treated with cardiac resynchronization therapy, were studied. Real-time three-dimensional echocardiography and electroanatomical mapping were performed in all patients and, where applicable, before and after therapy. Magnetic resonance was performed for evaluation of myocardial scar. Images were postprocessed and mechanical and electrical activation sequences were defined and time differences between the first and last ventricular segment to be activated were determined. Response to therapy was defined as a reduction in left ventricular end-systolic volume 15% after 12 months of follow-up. Results: Good correlation between electrical and mechanical timings was found in patients with normal left ventricular function (r2=0.88; P= .005) but not in those with left ventricular dysfunction (r2=0.02; P=not significant). After therapy, both timings and sequences were modified and improved, except in those with myocardial scar. Conclusions: Despite a close electromechanical relationship in normal left ventricular function, there is no significant correlation in patients with dysfunction. Although resynchronization therapy improves this correlation, the changes in electrical activation may not yield similar changes in left ventricular mechanics particularly depending on the underlying myocardial substrate (AU)

Integration of mechanical, structural and electrical imaging to understand response to cardiac resynchronization therapy.

INTRODUCTION AND OBJECTIVES: There is extensive controversy exists on whether cardiac resynchronization therapy corrects electrical or mechanical asynchrony. The aim of this study was to determine if there is a correlation between electrical and mechanical sequences and if myocardial scar has any relevant impact. METHODS: Six patients with normal left ventricular function and 12 patients with left ventricular dysfunction and left bundle branch block, treated with cardiac resynchronization therapy, were studied. Real-time three-dimensional echocardiography and electroanatomical mapping were performed in all patients and, where applicable, before and after therapy. Magnetic resonance was performed for evaluation of myocardial scar. Images were postprocessed and mechanical and electrical activation sequences were defined and time differences between the first and last ventricular segment to be activated were determined. Response to therapy was defined as a reduction in left ventricular end-systolic volume ≥ 15% after 12 months of follow-up. RESULTS: Good correlation between electrical and mechanical timings was found in patients with normal left ventricular function (r(2) = 0.88; P = .005) but not in those with left ventricular dysfunction (r(2) = 0.02; P = not significant). After therapy, both timings and sequences were modified and improved, except in those with myocardial scar. CONCLUSIONS: Despite a close electromechanical relationship in normal left ventricular function, there is no significant correlation in patients with dysfunction. Although resynchronization therapy improves this correlation, the changes in electrical activation may not yield similar changes in left ventricular mechanics particularly depending on the underlying myocardial substrate.

Myocardial motion and deformation patterns in an experimental swine model of acute LBBB/CRT and chronic infarct.

In cardiac resynchronization therapy (CRT), specific changes in motion/deformation happen with left-bundle-branch-block (LBBB) and following treatment. However, they remain sub-optimally studied. We propose a two-fold improvement of their characterization. This includes controlling them through an experimental model and using more suitable quantification techniques. We used a swine model of acute LBBB and CRT with/without chronic infarct (pure-LBBB: N = 11; LBBB + left-anterior-descending infarct: N = 11). Myocardial displacement, velocity and strain were extracted from short-axis echocardiographic sequences using 2D speckle-tracking. The data was transformed to a single spatiotemporal system of coordinates to perform subject comparisons and quantify pattern changes at similar locations and instants. Pure-LBBB animals showed a specific intra-ventricular dyssynchrony pattern with LBBB (11/11 animals), and the recovery towards a normal pattern with CRT (10/11 animals). Pattern variability was low within the pure-LBBB population, as quantified by our method. This was not correctly assessed by more conventional measurements. Infarct presence affected the pattern distribution and CRT efficiency (improvements in 6/11 animals). Pattern changes correlated with global cardiac function (global circumferential strain) changes in all the animals (corrected: (pLBBBvsBaseline) < 0.001, (pCRTvsBaseline) = NS; non-corrected: (pLBBBvsBaseline) = NS, (pCRTvsBaseline) = 0.028). Our LBBB/CRT experimental model allowed controlling specific factors responsible for changes in mechanical dyssynchrony and therapy. We illustrated the importance of our quantification method to study these changes and their variability. Our findings confirm the importance of myocardial viability and of specific LBBB-related mechanical dyssynchrony patterns.

Development of a swine model of left bundle branch block for experimental studies of cardiac resynchronization therapy.

Animal models that mimic human electrical and mechanical dyssynchrony often associated with chronic heart failure would provide an essential tool to investigate factors influencing response to cardiac resynchronization therapy. A standardized closed-chest porcine model of left bundle branch block (LBBB) was developed using 16 pigs. Radiofrequency applications were performed to induce LBBB, which was confirmed by QRS widening, a surface electrocardiogram pattern concordant with LBBB, and a prolonged activation time from endocardial. Echocardiography confirmed abnormal motion of the septum, which was not present at the baseline echocardiogram. High susceptibility of pigs to ventricular fibrillation during the endocardial ablation was overcome by applying high-rate pacing during radiofrequency applications. This is the first study to devise a closed-chest porcine model of LBBB that closely reproduces abnormalities found in patients with electrical and mechanical cardiac dyssynchrony, and provides a useful tool to investigate the basic mechanisms underlying cardiac resynchronization therapy benefits in heart failure.

Three-dimensional architecture of scar and conducting channels based on high resolution ce-CMR: insights for ventricular tachycardia ablation.

BACKGROUND: Conducting channels are the target for ventricular tachycardia (VT) ablation. Conducting channels could be identified with contrast enhanced-cardiac magnetic resonance (ce-CMR) as border zone (BZ) corridors. A 3-dimensional (3D) reconstruction of the ce-CMR could allow visualization of the 3D structure of these BZ channels. METHODS AND RESULTS: We included 21 patients with healed myocardial infarction and VT. A 3D high-resolution 3T ce-CMR was performed before CARTO-guided VT ablation. The left ventricular wall was segmented and characterized using a pixel signal intensity algorithm at 5 layers (endocardium, 25%, 50%, 75%, epicardium). A 3D color-coded shell map was obtained for each layer to depict the scar core and BZ distribution. The presence/characteristics of BZ channels were registered for each layer. Scar area decreased progressively from endocardium to epicardium (scar area/left ventricular area: 34.0±17.4% at endocardium, 24.1±14.7% at 25%, 16.3±12.1% at 50%, 13.1±10.4 at 75%, 12.1±9.3% at epicardium; P<0.01). Forty-five BZ channels (2.1±1.0 per patient, 23.7±12.0 mm length, mean minimum width 2.5±1.5 mm) were identified, 85% between the endocardium and 50% shell and 76% present in ≥1 layer. The ce-CMR-defined BZ channels identified 74% of the critical isthmus of clinical VTs and 50% of all the conducting channels identified in electroanatomic maps. CONCLUSIONS: Scar area in patients with healed myocardial infarction decreases from the endocardium to the epicardium. BZ channels, more commonly seen in the endocardium, display a 3D structure within the myocardial wall that can be depicted with ce-CMR. The use of ce-CMR-derived maps to guide VT ablation warrants further investigation.

Noncompaction cardiomyopathy is associated with mechanical dyssynchrony: a potential underlying mechanism for favorable response to cardiac resynchronization therapy.

BACKGROUND: The aim of this study was to assess the presence of evidence of ventricular mechanical dyssynchrony in patients with isolated left ventricular noncompaction cardiomyopathy (IVNC) and the potential usefulness of cardiac resynchronization therapy (CRT) in those patients. METHODS AND RESULTS: We studied 25 patients consecutively diagnosed with IVNC and a control group of 50 patients with dilated cardiomyopathy of different etiologies. Mechanical dyssynchrony was assessed by echocardiography by the presence of a septal flash, the time from peak septal to posterior wall displacement, and the time from septal to lateral wall peak systolic velocity. Among the patients with IVNC, 9 received CRT and were followed at 12 months. Overall, dyssynchrony parameters were significantly more frequent in IVNC, regardless of QRS duration. All 9 IVNC patients treated with CRT showed a septal flash, and a favorable response was observed in 8/9 patients (89%) regardless of QRS width. CONCLUSIONS: The presence of mechanical dyssynchrony, amenable to correction with CRT, is common in patients with IVNC, independently from QRS width. This might be related to altered electrical endocardial activation associated with abnormal myocardium and could be the justification for the high response rate to CRT observed in these patients.

Atlas-based quantification of myocardial motion abnormalities: added-value for understanding the effect of cardiac resynchronization therapy.

Statistical atlases may help improving the analysis of cardiac wall-motion abnormalities. This study aims at demonstrating the clinical value of such a method to better understand the effect of cardiac resynchronization therapy (CRT). We compared an atlas of normal septal motion built using apical four-chamber two-dimensional echocardiographic sequences from healthy volunteers with 88 patients undergoing CRT at baseline and at 12 months follow-up. Abnormal motion was quantified locally using a p value based on a statistical distance to normality. Reduction ≥15% in left ventricle end-systolic volume defined CRT response. Responders showed significantly higher reduction of abnormalities (p ≤ 0.001). Non-responders conserved abnormal septal motion at the end of the isovolumic contraction (IVC). A specific inward-outward motion of the septum during IVC predominated in responders and was corrected at follow-up. The method is of interest to characterize patterns of mechanical dyssynchrony and to study the link between their evolution and CRT response.

Use of myocardial scar characterization to predict ventricular arrhythmia in cardiac resynchronization therapy.

AIMS: There is insufficient evidence to implant a combined cardiac resynchronization therapy (CRT) device with defibrillation capabilities (CRT-D) in all CRT candidates. The aim of the study was to assess myocardial scar size and its heterogeneity as predictors of sudden cardiac death (SCD) in CRT candidates. METHODS AND RESULTS: A cohort of 78 consecutive patients with dilated cardiomyopathy and class I indication for CRT-D were prospectively enrolled. Before CRT-D implantation, a contrast-enhanced cardiac magnetic resonance (ce-CMR) was performed. The core and border zone (BZ) of the myocardial scar were characterized and quantified with a customized post-processing software. The first appropriate implantable cardioverter defibrillator (ICD) therapy was considered as a surrogate of SCD. During a mean follow-up of 25 months (25-75th percentiles, 15-34), appropriate ICD therapy occurred in 11.5% of patients. In a multivariate Cox proportional hazards regression model for clinical and ce-CMR variables, the scar mass percentage [hazards ratio (HR) per 1% increase 1.1 (1.06-1.15), P < 0.01], the BZ mass [HR per 1 g increase 1.06 (1.04-1.09), P < 0.01], and the BZ percentage of the scar [HR per 1% increase 1.06 (1.02-1.11), P < 0.01], were the only independent predictors of appropriate ICD therapy. Receiver-operating characteristic curve analysis showed that a scar mass <16% and a BZ < 9.5 g had a negative predictive value of 100%. CONCLUSIONS: The presence, size, and heterogeneity of myocardial scar independently predict appropriate ICD therapies in CRT candidates. The ce-CMR-based scar analysis might help identify a subgroup of patients at relatively low risk of SCD.