Cardiac magnetic resonance and electroanatomical mapping of acute and chronic atrial ablation injury: a histological validation study.

AIMS: To provide a comprehensive histopathological validation of cardiac magnetic resonance (CMR) and endocardial voltage mapping of acute and chronic atrial ablation injury. METHODS AND RESULTS: 16 pigs underwent pre-ablation T2-weighted (T2W) and late gadolinium enhancement (LGE) CMR and high-density voltage mapping of the right atrium (RA) and both were repeated after intercaval linear radiofrequency ablation. Eight pigs were sacrificed following the procedure for pathological examination. A further eight pigs were recovered for 8 weeks, before chronic CMR, repeat RA voltage mapping and pathological examination. Signal intensity (SI) thresholds from 0 to 15 SD above a reference SI were used to segment the RA in CMR images and segmentations compared with real lesion volumes. The SI thresholds that best approximated histological volumes were 2.3 SD for LGE post-ablation, 14.5 SD for T2W post-ablation and 3.3 SD for LGE chronically. T2-weighted chronically always underestimated lesion volume. Acute histology showed transmural injury with coagulative necrosis. Chronic histology showed transmural fibrous scar. The mean voltage at the centre of the ablation line was 3.3 mV pre-ablation, 0.6 mV immediately post-ablation, and 0.3 mV chronically. CONCLUSION: This study presents the first histopathological validation of CMR and endocardial voltage mapping to define acute and chronic atrial ablation injury, including SI thresholds that best match histological lesion volumes. An understanding of these thresholds may allow a more informed assessment of the underlying atrial substrate immediately after ablation and before repeat catheter ablation for atrial arrhythmias.

Multi-site left ventricular pacing as a potential treatment for patients with postero-lateral scar: insights from cardiac magnetic resonance imaging and invasive haemodynamic assessment.

AIMS: Multi-site left ventricular (LV) pacing may be superior to single-site stimulation in correcting dyssynchrony and avoiding areas of myocardial scar. We sought to characterize myocardial scar using cardiac magnetic resonance imaging (CMR). We aimed to quantify the acute haemodynamic response to single-site and multi-site LV stimulation and to relate this to the position of the LV leads in relation to myocardial scar. METHODS: Twenty patients undergoing cardiac resynchronization therapy had implantation of two LV leads. One lead (LV1) was positioned in a postero-lateral vein, the second (LV2) in a separate coronary vein. LV dP/dtmax was recorded using a pressure wire during stimulation at LV1, LV2, and both sites simultaneously (LV1 + 2). Patients were deemed acute responders if ΔLV dP/dtmax was ≥ 10%. Cardiac magnetic resonance imaging was performed to assess dyssynchrony as well as location and burden of scar. Scar anatomy was registered with fluoroscopy to assess LV lead position in relation to scar. RESULTS: LV dP/dtmax increased from 726 ± 161 mmHg/s in intrinsic rhythm to 912 ± 234 mmHg/s with LV1, 837 ± 188 mmHg/s with LV2, and 932 ± 201 mmHg/s with LV1 and LV2. Nine of 19 (47%) were acute responders with LV1 vs. 6/19 (32%) with LV2. Twelve of 19 (63%) were acute responders with simultaneous LV1 + 2. Two of three patients benefitting with multi-site pacing had the LV1 lead positioned in postero-lateral scar. CONCLUSION: Multi-site LV pacing increased acute response by 16% vs. single-site pacing. This was particularly beneficial in patients with postero-lateral scar identified on CMR.

Time-Averaged Wavefront Analysis Demonstrates Preferential Pathways of Atrial Fibrillation, Predicting Pulmonary Vein Isolation Acute Response.

Electrical activation during atrial fibrillation (AF) appears chaotic and disorganised, which impedes characterisation of the underlying substrate and treatment planning. While globally chaotic, there may be local preferential activation pathways that represent potential ablation targets. This study aimed to identify preferential activation pathways during AF and predict the acute ablation response when these are targeted by pulmonary vein isolation (PVI). In patients with persistent AF (n = 14), simultaneous biatrial contact mapping with basket catheters was performed pre-ablation and following each ablation strategy (PVI, roof, and mitral lines). Unipolar wavefront activation directions were averaged over 10 s to identify preferential activation pathways. Clinical cases were classified as responders or non-responders to PVI during the procedure. Clinical data were augmented with a virtual cohort of 100 models. In AF pre-ablation, pathways originated from the pulmonary vein (PV) antra in PVI responders (7/7) but not in PVI non-responders (6/6). We proposed a novel index that measured activation waves from the PV antra into the atrial body. This index was significantly higher in PVI responders than non-responders (clinical: 16.3 vs. 3.7%, p = 0.04; simulated: 21.1 vs. 14.1%, p = 0.02). Overall, this novel technique and proof of concept study demonstrated that preferential activation pathways exist during AF. Targeting patient-specific activation pathways that flowed from the PV antra to the left atrial body using PVI resulted in AF termination during the procedure. These PV activation flow pathways may correspond to the presence of drivers in the PV regions.

Unraveling the Underlying Arrhythmia Mechanism in Persistent Atrial Fibrillation: Results From the STARLIGHT Study.

BACKGROUND: The mechanisms that initiate and sustain persistent atrial fibrillation are not well characterized. Ablation results remain significantly worse than in paroxysmal atrial fibrillation in which the mechanism is better understood and subsequent targeted therapy has been developed. The aim of this study was to characterize and quantify patterns of activation during atrial fibrillation using contact mapping. METHODS: Patients with persistent atrial fibrillation (n=14; mean age, 61±8 years; ejection fraction, 59±10%) underwent simultaneous biatrial contact mapping with 64 electrode catheters. The atrial electrograms were transformed into phase, and subsequent spatiotemporal mapping was performed to identify phase singularities (PSs). RESULTS: PSs were located in both atria, but we observed more PSs in the left atrium compared with the right atrium (779±302, 552±235; P=0.015). Although some PSs of duration sufficient to complete >1 rotation were detected, the maximum PS duration was only 1150 ms, and the vast majority (97%) of PSs persisted for too short a period to complete a full rotation. Although in selected patients there was evidence of PS local clustering, overall, PSs were distributed globally throughout both chambers with no clear anatomic predisposition. In a subset of patients (n=7), analysis was repeated using an alternative established atrial PS mapping technique, which confirmed our initial findings. CONCLUSIONS: No sustained rotors or localized drivers were detected, and instead, the mechanism of arrhythmia maintenance was consistent with the multiple wavelet hypothesis, with passive activation of short-lived rotational activity. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01765075.

Development, Preclinical Validation, and Clinical Translation of a Cardiac Magnetic Resonance - Electrophysiology System With Active Catheter Tracking for Ablation of Cardiac Arrhythmia.

OBJECTIVES: This study sought to develop an actively tracked cardiac magnetic resonance-guided electrophysiology (CMR-EP) system and perform first-in-human clinical ablation procedures. BACKGROUND: CMR-EP offers high-resolution anatomy, arrhythmia substrate, and ablation lesion visualization in the absence of ionizing radiation. Implementation of active tracking, where catheter position is continuously transmitted in a manner analogous to electroanatomic mapping (EAM), is crucial for CMR-EP to take the step from theoretical technology to practical clinical tool. METHODS: The setup integrated a clinical 1.5-T scanner, an EP recording and ablation system, and a real-time image guidance platform with components undergoing ex vivo validation. The full system was assessed using a preclinical study (5 pigs), including mapping and ablation with histological validation. For the clinical study, 10 human subjects with typical atrial flutter (age 62 ± 15 years) underwent MR-guided cavotricuspid isthmus (CTI) ablation. RESULTS: The components of the CMR-EP system were safe (magnetically induced torque, radiofrequency heating) and effective in the CMR environment (location precision). Targeted radiofrequency ablation was performed in all animals and 9 (90%) humans. Seven patients had CTI ablation completed using CMR guidance alone; 2 patients required completion under fluoroscopy, with 2 late flutter recurrences. Acute and chronic CMR imaging demonstrated efficacious lesion formation, verified with histology in animals. Anatomic shape of the CTI was an independent predictor of procedural success. CONCLUSIONS: CMR-EP using active catheter tracking is safe and feasible. The CMR-EP setup provides an effective workflow and has the potential to change the way in which ablation procedures may be performed.

Percutaneous pulmonary valve implantation in humans: results in 59 consecutive patients.

BACKGROUND: Right ventricular outflow tract (RVOT) reconstruction with valved conduits in infancy and childhood leads to reintervention for pulmonary regurgitation and stenosis in later life. METHODS AND RESULTS: Patients with pulmonary regurgitation with or without stenosis after repair of congenital heart disease had percutaneous pulmonary valve implantation (PPVI). Mortality, hemodynamic improvement, freedom from explantation, and subjective and objective changes in exercise tolerance were end points. PPVI was performed successfully in 58 patients, 32 male, with a median age of 16 years and median weight of 56 kg. The majority had a variant of tetralogy of Fallot (n=36), or transposition of the great arteries, ventricular septal defect with pulmonary stenosis (n=8). The right ventricular (RV) pressure (64.4+/-17.2 to 50.4+/-14 mm Hg, P<0.001), RVOT gradient (33+/-24.6 to 19.5+/-15.3, P<0.001), and pulmonary regurgitation (PR) (grade 2 of greater before, none greater than grade 2 after, P<0.001) decreased significantly after PPVI. MRI showed significant reduction in PR fraction (21+/-13% versus 3+/-4%, P<0.001) and in RV end-diastolic volume (EDV) (94+/-28 versus 82+/-24 mL.beat(-1).m(-2), P<0.001) and a significant increase in left ventricular EDV (64+/-12 versus 71+/-13 mL.beat(-1).m(-2), P=0.005) and effective RV stroke volume (37+/-7 versus 42+/-9 mL.beat(-1).m(-2), P=0.006) in 28 patients (age 19+/-8 years). A further 16 subjects, on metabolic exercise testing, showed significant improvement in VO2max (26+/-7 versus 29+/-6 mL.kg(-1).min(-1), P<0.001). There was no mortality. CONCLUSIONS: PPVI is feasible at low risk, with quantifiable improvement in MRI-defined ventricular parameters and pulmonary regurgitation, and results in subjective and objective improvement in exercise capacity.

Novel method of quantifying pulmonary vascular resistance by use of simultaneous invasive pressure monitoring and phase-contrast magnetic resonance flow.

BACKGROUND: Pulmonary vascular resistance (PVR) quantification is important in the treatment of children with pulmonary hypertension. The Fick principle, used to quantify pulmonary artery flow, may be a flawed technique. We describe a novel method of PVR quantification by the use of magnetic resonance (MR) flow data and invasive pressure measurements. METHODS AND RESULTS: In 24 patients with either suspected pulmonary hypertension or congenital heart disease requiring preoperative assessment, PVR was calculated by the use of simultaneously acquired MR flow and invasive pressure measurements (condition 1). In 19 of the 24 patients, PVR was also calculated at 20 ppm nitric oxide +30% (condition 2) and at 20 ppm nitric oxide +100% oxygen (condition 3), with the use of the MR method. This method proved safe and feasible in all patients. In 15 of 19 patients, PVR calculated by Fick flow was compared with the MR method. At condition 1, Bland-Altman analysis revealed a bias of 2.3% (MR > Fick) and limits of agreement of 50.2% to -45.5%. At condition 2, there was poorer agreement (bias was 28%, and the limits of agreement were 151.3% to 95.2%). At condition 3, there was very poor agreement (bias was 54.2%, and the limits of agreement were 174.4% to -66.0%). CONCLUSIONS: We have demonstrated the feasibility of using simultaneous invasive pressure measurements and MR flow data to measure PVR in humans.

Repeat left atrial catheter ablation: cardiac magnetic resonance prediction of endocardial voltage and gaps in ablation lesion sets.

BACKGROUND: Studies have reported an inverse relationship between late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) signal intensity and left atrial (LA) endocardial voltage after LA ablation. However, there is controversy regarding the reproducibility of atrial LGE CMR and its ability to identify gaps in ablation lesions. Using systematic and objective techniques, this study examines the correlation between atrial CMR and endocardial voltage. METHODS AND RESULTS: Twenty patients who had previous ablation for atrial fibrillation and represented with paroxysmal atrial fibrillation or atrial tachycardia underwent preablation LGE CMR. During the ablation procedure, high-density point-by-point Carto voltage maps were acquired. Three-dimensional CMR reconstructions were registered with the Carto anatomies to allow comparison of voltage and LGE signal intensity. Signal intensities around the left and right pulmonary vein antra and along the LA roof and mitral lines on the CMR-segmented LA shells were extracted to examine differences between electrically isolated and reconnected lesions. There were a total of 6767 data points across the 20 patients. Only 119 (1.8%) of the points were ≤ 0.05 mV. There was only a weak inverse correlation between either unipolar (r = -0.18) or bipolar (r = -0.17) voltage and LGE CMR signal intensities with low voltage occurring across a large range of signal intensities. Signal intensities were not statistically different for electrically isolated and reconnected lesions. CONCLUSIONS: This study demonstrates that there is only a weak point-by-point relationship between LGE CMR and endocardial voltage in patients undergoing repeat LA ablation. Using an objective method of assessing gaps in ablation lesions, LGE CMR is unable to reliably predict sites of electrical conduction.

Prenatal diagnosis by echocardiogram and outcome of absent pulmonary valve syndrome.

We reported echocardiographic findings and outcomes of fetuses with absent pulmonary valve syndrome diagnosed during fetal life. Cases were identified from a prospectively acquired computerized database of 18,308 pregnancies referred to a fetal cardiology center between January 1988 and July 2000. Twenty fetuses were identified with a median gestation of 23 weeks (range 18 to 36) at presentation. In 18 cases (90%), there was an associated ventricular septal defect. Eighteen cases (90%) had branch pulmonary artery diameters above the normal range. In four cases (20%), an arterial duct was present. A chromosome 22q11 deletion was identified in 2 of 9 cases (22%) in which this deletion was sought. There were 6 terminations of pregnancy (30%), 3 intrauterine deaths (15%), 5 neonatal deaths (25%), 3 infant deaths (15%), and 3 patients who did not die (15%). Ten of the 11 "liveborn" infants required early ventilation. The outcome of absent pulmonary valve syndrome diagnosed prenatally appears poor. The high morbidity and mortality is due to both cardiac disease and associated bronchomalacia.

A comprehensive cardiac motion estimation framework using both untagged and 3-D tagged MR images based on nonrigid registration.

In this paper, we present a novel technique based on nonrigid image registration for myocardial motion estimation using both untagged and 3-D tagged MR images. The novel aspect of our technique is its simultaneous usage of complementary information from both untagged and 3-D tagged MR images. To estimate the motion within the myocardium, we register a sequence of tagged and untagged MR images during the cardiac cycle to a set of reference tagged and untagged MR images at end-diastole. The similarity measure is spatially weighted to maximize the utility of information from both images. In addition, the proposed approach integrates a valve plane tracker and adaptive incompressibility into the framework. We have evaluated the proposed approach on 12 subjects. Our results show a clear improvement in terms of accuracy compared to approaches that use either 3-D tagged or untagged MR image information alone. The relative error compared to manually tracked landmarks is less than 15% throughout the cardiac cycle. Finally, we demonstrate the automatic analysis of cardiac function from the myocardial deformation fields.

A registration-based propagation framework for automatic whole heart segmentation of cardiac MRI.

Magnetic resonance (MR) imaging has become a routine modality for the determination of patient cardiac morphology. The extraction of this information can be important for the development of new clinical applications as well as the planning and guidance of cardiac interventional procedures. To avoid inter- and intra-observer variability of manual delineation, it is highly desirable to develop an automatic technique for whole heart segmentation of cardiac magnetic resonance images. However, automating this process is complicated by the limited quality of acquired images and large shape variation of the heart between subjects. In this paper, we propose a fully automatic whole heart segmentation framework based on two new image registration algorithms: the locally affine registration method (LARM) and the free-form deformations with adaptive control point status (ACPS FFDs). LARM provides the correspondence of anatomical substructures such as the four chambers and great vessels of the heart, while the registration using ACPS FFDs refines the local details using a constrained optimization scheme. We validated our proposed segmentation framework on 37 cardiac MR volumes on the end-diastolic phase, displaying a wide diversity of morphology and pathology, and achieved a mean accuracy of 2.14 +/- 0.63 mm (rms surface distance) and a maximal error of 4.31 mm.

An adaptive and predictive respiratory motion model for image-guided interventions: theory and first clinical application.

This paper describes a predictive and adaptive single parameter motion model for updating roadmaps to correct for respiratory motion in image-guided interventions. The model can adapt its motion estimates to respond to changes in breathing pattern, such as deep or fast breathing, which normally would result in a decrease in the accuracy of the motion estimates. The adaptation is made possible by interpolating between the motion estimates of multiple submodels, each of which describes the motion of the target organ during cycles of different amplitudes. We describe a predictive technique which can predict the amplitude of a breathing cycle before it has finished. The predicted amplitude is used to interpolate between the motion estimates of the submodels to tune the adaptive model to the current breathing pattern. The proposed technique is validated on affine motion models formed from cardiac magnetic resonance imaging (MRI) datasets acquired from seven volunteers and one patient. The amplitude prediction technique showed errors of 1.9-6.5 mm. The combined predictive and adaptive technique showed 3-D motion prediction errors of 1.0-2.8 mm, which represents an improvement in modelling performance of up to 40% over a standard nonadaptive single parameter motion model. We also applied the combined technique in a clinical setting to test the feasibility of using it for respiratory motion correction of roadmaps in image-guided cardiac catheterisations. In this clinical case we show that 2-D registration errors due to respiratory motion are reduced from 7.7 to 2.8 mm using the proposed technique.

Interactive MR imaging and tracking of catheters with multiple tuned fiducial markers.

PURPOSE: The lack of magnetic resonance (MR) safe catheters and guide wires remains an important obstacle to widespread clinical use of MR-guided endovascular procedures. The authors looked at the feasibility of using multiple tuned fiducial markers (TFM) and novel imaging sequences to track catheters reliably under MR and to evaluate the safety of such markers in terms of heating. MATERIALS AND METHODS: The visualization and tracking of a catheter with six quadrature tuned fiducial coils was carried out in a special designed in-vitro setup within a 1.5-T MR imager simulating an MR-guided endovascular intervention. The fiducial markers were also tested for heating. RESULTS: The excellent signal contrast between the fiducial and the background when using novel interleaved real time and interactive sequences allowed for rapid and reliable identification of the fiducial markers and therefore the catheter. No significant heating of the marker was noted. CONCLUSIONS: The authors have shown that catheters with multiple tuned fiducial markers are superior to passive catheter designs in terms of visualization and do not carry the risk of heating that is commonly associated with active catheters.

Spontaneous improvement of severe right ventricular dysfunction in the setting of hypoplasia of the left heart.

Right ventricular dysfunction is known to occur after the first stage of the Norwood sequence for treatment of patients with hypoplasia of the left heart. In a subset of patients, such ventricular dysfunction occurs without a specific anatomical cause. We describe two such cases with severe right ventricular dysfunction. In both cases, magnetic resonance imaging was used accurately to measure ventricular function and assess the arterial trunks. In both cases, cardiac transplantation was considered, but right ventricular function improved without invasive management. Transient right ventricular dysfunction in these cases may be due to the reduced ability of the right ventricle to adapt to the systemic vasculature. The improvement in ventricular function in these two cases may be due to delayed adaptation.

Inter-breath-hold registration for the production of high resolution cardiac MR volumes.

High resolution MRI images of the beating heart permit observation of detailed anatomical features and enable quantification of small changes in metrics of cardiac function. To obtain approximately isotropic sampling with an adequate spatial and temporal resolution, these images need to be acquired in multiple breath-holds. They are, therefore, often affected by through-plane discontinuities due to inconsistent breath-hold positions. This paper presents a method to correct for these discontinuities by performing breath-hold-by-breath-hold registration of high resolution 3D data to radial long axis images. The corrected images appear free of discontinuities, and it was found that they could be delineated more reproducibly than uncorrected images. This reduces the sample size required to detect systematic changes in blood pool volume by 57% at end systole and 78% at end diastole.

Measurement of total pulmonary arterial compliance using invasive pressure monitoring and MR flow quantification during MR-guided cardiac catheterization.

Pulmonary hypertensive disease is assessed by quantification of pulmonary vascular resistance. Pulmonary total arterial compliance is also an indicator of pulmonary hypertensive disease. However, because of difficulties in measuring compliance, it is rarely used. We describe a method of measuring pulmonary arterial compliance utilizing magnetic resonance (MR) flow data and invasive pressure measurements. Seventeen patients with suspected pulmonary hypertension or congenital heart disease requiring preoperative assessment underwent MR-guided cardiac catheterization. Invasive manometry was used to measure pulmonary arterial pressure, and phase-contrast MR was used to measure flow at baseline and at 20 ppm nitric oxide (NO). Total arterial compliance was calculated using the pulse pressure method (parameter optimization of the 2-element windkessel model) and the ratio of stroke volume to pulse pressure. There was good agreement between the two estimates of compliance (r = 0.98, P < 0.001). However, there was a systematic bias between the ratio of stroke volume to pulse pressure and the pulse pressure method (bias = 61%, upper level of agreement = 84%, lower level of agreement = 38%). In response to 20 ppm NO, there was a statistically significant fall in resistance, systolic pressure, and pulse pressure. In seven patients, total arterial compliance increased >10% in response to 20 ppm NO. As a population, the increase did not reach statistical significance. There was an inverse relation between compliance and resistance (r = 0.89, P < 0.001) and between compliance and mean pulmonary arterial pressure (r = 0.72, P < 0.001). We have demonstrated the feasibility of quantifying total arterial compliance using an MR method.

Three-dimensional magnetic resonance imaging of congenital cardiac anomalies.

We describe a new method of three-dimensional magnetic resonance imaging of the heart that has been used to produce high quality diagnostic images in 274 patients with congenital cardiac disease, ranging in age from 1 day to 66 years. Using a steady state free precession gradient echo technique and parallel imaging, rapid acquisition of the entire cardiac volume is possible during 8 to 15 sequential breath-holds, each lasting between 8 and 15 s. We obtained high-resolution images, with a resolution of 1 mm3, at between 3 and 10 phases of the cardiac cycle. While images of diagnostic quality were obtained in all cases, in 52 patients there was some degradation due to various factors. Children under 8 years were ventilated, and ventilation was suspended for the breath-holds. For patients breathing spontaneously a novel respiratory navigator technique was developed, using a navigator echo placed over the right hemidiaphragm. This was used successfully in 20 patients, and reduced the misalignment of images obtained during different breath-holds. Images were analysed using multi-planar reformatting and volume rendering. Image processing took approximately five minutes for each study. End-diastolic images were processed for all patients. Systolic images were also processed in selected cases. Further improvements in parallel imaging should reduce imaging times further, so that it is possible to obtain the full volume image in a single breath-hold. This will enable imaging of complex anatomy to be obtained using a standard imaging protocol that does not require the operator to understand the cardiac malformation, making the magnetic resonance imaging of congenital cardiac disease faster and more effective.

Visualization and tracking of an inflatable balloon catheter using SSFP in a flow phantom and in the heart and great vessels of patients.

Passive catheter tracking involves direct interaction between the device and its surroundings, creating a local signal loss or enhancement of the image. Using only standard balloon catheters filled with CO(2) and imaged with a steady-state free precession sequence, it was possible to visualize and passively track catheters in a flow phantom and in the heart and great vessels of 20 patients without any additional image processing. The phantom work demonstrated that it was advantageous to sacrifice spatial resolution in order to increase temporal resolution. Frame rates greater than 10/sec were necessary for ease of catheter manipulation. Although only the tip of the catheter was visualized, this technique proved to be effective in patients undergoing cardiac catheterization.