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European Heart Journal Advance Access originally published online on June 13, 2008
European Heart Journal 2008 29(13):1608-1617; doi:10.1093/eurheartj/ehn247
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Impact of coronary revascularization and transmural extent of scar on regional left ventricular remodelling

Jonathan Chan1, Frederick Khafagi1, Alistair A. Young2, Brett R. Cowan2, Charles Thompson1 and Thomas H. Marwick1,*

1 Department of Medicine, University of Queensland, Princess Alexandra Hospital, Ipswich Road, Brisbane, Qld 4102, Australia
2 University of Auckland, Auckland, New Zealand

Received 22 February 2007; revised 14 May 2008; accepted 23 May 2008; online publish-ahead-of-print 13 June 2008.

* Corresponding author. Tel: +61 7 3240 5340, Fax: +61 7 3240 5399. Email: t.marwick{at}uq.edu.au


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 Funding
 Appendix: Calculation and...
 Acknowledgements
 References
 
Aims: Transmural extent (TME) of myocardial scar, contractile reserve, and perfusion all predict improvement in regional myocardial function after coronary revascularization. We sought their association with regional remodelling after infarction.

Methods and results: We studied 89 patients (age 62 ± 10 years) with left ventricular (LV) dysfunction, at least 1 month post infarction. Viability was identified by TME < 75% on contrast-enhanced magnetic resonance imaging (ce-MRI), augmentation at low-dose dobutamine echocardiography (DbE), or >60% uptake on delayed redistribution on TI-201 SPECT (single photon emission computed tomography). Coronary revascularization was performed in 36 patients. Regional LV end-diastolic volume (EDV) and end-systolic volume, and ejection fraction were measured with MRI at baseline and after a median follow-up of 18 months.

Of 357 segments identified with subendocardial infarction (TME 0–25%) on ce-MRI, 176 were revascularized. Subendocardial scar segments were associated with reverse regional remodeling during follow-up. Revascularization was an independent correlate of change in EDV, but TME and revascularization showed no interaction with respect to their influence on regional volumes. Contractile reserve was present on DbE in 228 segments, of which 129 were TME 0–25%; remodelling was associated with intervention in non-transmural infarcts showing viability by DbE. Viability was identified by TI-201 SPECT in 381 segments (233 with TME 0–25%), but viability by SPECT was not associated with reverse remodelling. No significant reverse remodelling occurred in segments with intermediate scar thickness (TME 26–75%) or transmural scar, independent of revascularization or viability by DbE or TI-SPECT.

Conclusion: Reverse regional remodelling is associated with subendocardial infarction, especially in the setting of contractile reserve and revascularization.

Key Words: Viable myocardium • Remodelling • Dobutamine echo • SPECT • Revascularization


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 Funding
 Appendix: Calculation and...
 Acknowledgements
 References
 
The presence of viable myocardium in patients with ischaemic cardiomyopathy and chronic left ventricular (LV) dysfunction has important implications for recovery of regional and global function after revascularization, and prognosis.1–3 Though viability is often defined in terms of functional recovery, a subgroup of patients may derive prognostic benefit from revascularization despite absence of functional recovery of myocardium. It has been postulated that the underlying mechanism of this benefit may be the avoidance of adverse LV remodelling. However, the relationship between viability and remodelling after myocardial infarction (MI) has been investigated less extensively than its effects on function.

LV volume is a major determinant of post-infarct survival,4 and post-infarct remodelling has both global and regional effects on LV volume, shape, and function.5,6 Viability identified by dobutamine stress echocardiography (DbE) has been shown to protect against global LV remodelling in both revascularized7 and medically treated patients.8,9 However, though changes in global LV volume are important prognostically, the global response is dependent not only on the improvement in infarct zone but also loss of compensatory hyperkinesis in non-infarct regions after medical treatment or revascularization. Assessment of regional volume may provide more information in relation to specific local changes in geometry and shape of the infarct region.10,11 Indeed, regional function correlates with clinical outcomes.12

Delayed contrast-enhanced cardiac magnetic resonance imaging (ce-MRI) allows the direct visualization of the transmural extent (TME) of scar at high spatial resolution. TME is inversely correlated with regional functional recovery after revascularization.13,14 In animal models, the TME of viable tissue is inversely proportional to infarct expansion and may protect from subsequent remodelling.15,16 The role of TME on remodelling in humans is less clear, particularly, in relation to the amount of residual viability if the non-transmural scar is of intermediate thickness. We, therefore, sought to examine the hypothesis that the revascularization of non-infarcted epicardial tissue (measured using ce-MRI) would reduce regional remodelling in non-transmural infarction, and that this effect would be dependent on the contractile reserve and perfusion of the residual myocardium [assessed by DbE and TI-201 SPECT (single photon emission computed tomography), respectively].


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 Funding
 Appendix: Calculation and...
 Acknowledgements
 References
 
Patients and study design
Eighty-nine patients (age 62 ± 10 years) with LV dysfunction (at least two segments with abnormal resting wall motion on echocardiography) were studied post MI. The diagnosis of MI was based on typical ECG changes and/or ischaemic chest pain associated with elevation of cardiac enzymes. Only patients who were stable and able to return for follow-up studies were approached. Patients with significant valvular disease, previous coronary revascularization, chronic renal failure, and any contraindications to MRI or DbE were excluded.

At baseline, all patients underwent ce-MRI for assessment of TME, DbE for identification of contractile reserve, and TI-201 SPECT for identification of perfusion abnormalities. The viability studies were performed and interpreted independently at separate laboratories over a median interval of 25 days. Remodelling was assessed by measuring serial changes in global and regional LV volumes using MRI at baseline and after a median of 18 months of follow-up. During this period, 36 patients underwent clinically indicated coronary revascularization by coronary artery bypass surgery (31 patients) and percutaneous transluminal coronary angioplasty (5 patients). The remaining 53 patients were subject to conservative medical treatment at the discretion of their independent treating physician. No patient had recurrence of a clinical event between the time of the index infarction and the three viability studies, or between these and completion of follow-up.

Magnetic resonance imaging
MRI was performed using a 1.5 Tesla scanner (Siemens Sonata, Siemens, Erlangen, Germany). A TrueFISP sequence (TR 47.1 ms, TE 1.57 ms, flip angle 60°, bandwidth 930 Hz/pixel) was used to examine LV anatomy and function. Images were acquired in horizontal and vertical long-axis planes (voxel size 1.8 x 1.3 x 5 mm3), with the projections mimicking echocardiographic four- and two-chamber views, and eight to 11 short-axis views (voxel size 1.8 x 1.3 x 10 mm3). All images were acquired during breath-hold.

The same long- and short-axis images were acquired after infusion of 0.1 mmol/kg gadoversetamide (Optimark, Mallinkrodt, St Louis, MO, USA), contrast enhanced images were obtained using an inversion recovery TurboFLASH sequence (TR 85% R–R interval, TE 4.38 ms, flip angle 25°, TI 280–450 ms adjusted to null normal myocardial signal, bandwidth 130 Hz/pixel). Voxel size was adjusted to 2.1 x 1.3 x 6 mm3 for all views.

Wall motion and TME were independently assessed by a reader who was blinded to patient data and the results of other studies. Quantification of TME post contrast was performed on short-axis images using an offline analysis program (Efilm, Merge, Milwaukee, WI, USA) within 16 myocardial segments, using the apex, mitral annulus, aortic valve, and septum to ensure the same segmentation as with echocardiography.17 Segments were classified into three groups according to TME (TME: 0–25, 26–75, and >75%). Previous studies have suggested that segments with TME >50% have a 92% likelihood of failure to recover function if they are revascularized.13

Global and regional volumes were measured using off-line software (CIM 4.5, University of Auckland, New Zealand). The LV was divided into 16 regional volumes calculated from a finite element model method that had been previously validated by Young et al.18 in patients with regional wall motion abnormalities post MI. Each regional volume corresponded to the three-dimensional (3D) space between the central vertical axis of the heart (between the centre of the mitral annulus and the apex) and the endocardial borders of the corresponding 16 segments (Figure 1A), as described in Appendix. Endocardial borders were tracked by means of a system of guide points to accurately delineate the variable contours of any geometrically altered LV.18 Global LV volumes were derived from the resultant 3D model. This method enabled a variety of different LV shapes to be accurately modelled.


Figure 1
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  		Figure 1 (A) Three-dimensional (3D) magnetic resonance imaging reconstruction model, showing regional volumes bound by central vertical axis and endocardial borders (left), and magnification of isolated regional volume associated with the basal lateral segment (right). (B) (a) 3D drawing of the segmental regions phantom; (b) coronal magnetic resonance (MR) section (c) sagittal MR section.

 
Validation of regional volumes
A phantom (Figure 1B) was constructed from MR compatible plastics to validate the calculation of regional volumes. The phantom geometry consisted of a hemispherical apex attached to a cylindrical mid-ventricle and base (Appendix). A plastic wedge subtending an arc of 120° was placed in the basal third of the phantom to demarcate the basal septal regions. The remaining volume was filled with water and imaged with a TrueFISP cine sequence. Regional volumes were calculated with the CIM software as described in Appendix and compared with the analytic values calculated from the phantom geometry. Intra-observer and inter-observer correlations were performed on 64 segments from six randomly selected patients within our same study population to validate reproducibility of regional volume measurements by Pearson’s correlation and Bland–Altman analysis. Intra-observer measurements were performed in a blinded fashion by the same observer 7 days apart. Inter-observer measurements were performed between two blinded independent observers, 7 days apart.

Dobutamine echocardiography
A standard dobutamine stress protocol19 was used, starting at an infusion rate of 5 µg/kg/min and increasing at 3 min intervals up to 40 µg/kg/min. Intermittent hand-grip and/or atropine (up to 2 mg i.v.) was employed if a maximum heart rate of 85% predicted maximum was not attained with dobutamine alone. Harmonic 2DE images were obtained using a commercially available machine (Vivid 7, GE Vingmed, Horten, Norway); this imaging was performed in five views and saved in digital format at baseline, low dose (5 and 10 µg/kg/min), and peak (40 µg/kg/min). Images were interpreted off-line by the consensus of two observers using a standard 16-segment model.17 Segments were considered viable with contractile reserve if they were dysfunctional at rest and had augmented function at low dose (5–10 µg/kg/min). Segments were considered scar if they were dysfunctional at rest and showed no contractile reserve with dobutamine stimulation.

Myocardial scintigraphy by TI-201 single photon emission computed tomography
A standard rest–late redistribution protocol20 was used, with initial imaging 20–30 min after injection of 150 MBq of TI-201 at rest, and redistribution images 20 h later. Sixty-four views were obtained in a semicircular orbit from the right anterior oblique to the left posterior oblique projections using a dual-head gamma camera (Optima, GE Medical Systems, Milwaukee, WI, USA) fitted with low-energy, all-purpose, parallel-hole collimators. Tomograms were reconstructed using filtered back-projection and displayed as short-axis and horizontal and vertical long-axis slices, and as quantitative polar maps. Using the same 16 segments, aligned using the apex, mitral annulus, and the junction of the posterior right ventricular wall and septum to ensure the same segmentation as with echocardiography, segmental thallium uptake was assessed visually for redistribution and was quantified as a proportion of maximum counts on the redistribution image. Data were not corrected for scatter or attenuation. Segments with a resting wall motion abnormality on 2DE were designated as viable if activity was >60% of maximum on the late image.21

Statistical analysis
The statistical package SPSS for Windows (Release 11.0 SPSS Inc., Chicago, IL, USA) was used for basic statistical analysis, with Stata (version 10, Stata Corp, College Station, TX, USA) being used for statistical models. Values were presented as mean ± SD. A P-value of <0.05 was considered statistically significant.

A series of random effects models were used to compare the regional volume and ejection fraction (EF) responses in segments categorized by TME status and evidence of viability by DbE or TI-201 SPECT, adjusting for the correlation between segments within each patient, and using Scheffe’s test to correct for type I error due to multiple testing. Data were modelled as Generalized Linear Mixed Models with the use of Stata’s GLLAMM command. Each segment of the heart was uniquely identified, and segments were nested in uniquely identified patients. These constitute the model’s random effects. Measurements of the response variables [end-systolic volume (ESV), end-diastolic volume (EDV) and ES] were taken at baseline and follow-up. The effects of visit and intervention (the fixed effects in the model) were estimated for the different scar grades. The model included: (i) a time variable, ‘visit’, representing the change in regional volumes or EF from baseline to follow-up; (ii) TME < 25%; (iii) a group variable representing the change attributable to revascularization; and (iv) an interaction between revascularization and TME < 25%. All statistical tests were two-sided; because of correlation between outcome variables (EDV, ESV, EF – average correlation 0.41), the Dubey modification of the Bonferroni correction was used.22

Reproducibility of regional MRI volumes was validated in 64 segments from six patients by a single observer at two different points in time 7 days apart as well as by two independent observers; agreement was assessed using the method of Bland and Altman.22


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 Funding
 Appendix: Calculation and...
 Acknowledgements
 References
 
Patient characteristics
Baseline clinical characteristics in revascularized and medically treated groups are compared in Table 1. Infarct size (based on peak creatine kinase) was moderate. All patients had more than two infarct segments with significant objective evidence of LV enlargement, LV systolic dysfunction, and clinical symptoms of heart failure.


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  		Table 1 Baseline clinical and echocardiographic characteristics of patients (n = 89)

 
Change in global volumes and ejection fraction
There were no significant serial changes in global EDV (196 ± 68 vs. 193 ± 69 mL, P = 0.55), global ESV (107 ± 64 vs. 107 ± 61 mL, P = 0.92) in the medically treated group. Reverse LV remodelling in global volumes was demonstrated in the revascularized group at follow-up, including a borderline serial reduction in global EDV (198 ± 43 vs. 186 ± 46 mL, P = 0.06) and significant reduction in global ESV (104 ± 38 vs. 93 ± 38 mL, P = 0.05).

Assessment of transmural extent and other indices of viability
A total of 738 dysfunctional segments were identified by a blinded expert observer to have resting wall motion abnormalities on echo. Of these dysfunctional segments, 357 were identified as TME 0–25%, 267 as TME 26–75%, 114 as TME >75% by ce-MRI. Revascularization was performed in 36 patients, involving 176 segments with TME 0–25%, 111 with TME 26–75%, and 29 with TME >75%. TME remained stable throughout the study period on serial ce-MRI (20 ± 35 vs. 21 ± 36%, P = 0.33), consistent with the lack of further ischaemic events among the study population during the follow-up period.

Contractile reserve was present on DbE in 228 segments, of which 129 were TME 0–25%, 75 were intermediate thickness (TME 26–75%), and 24 were TME >75%. Viability was identified by TI-201 SPECT in 381 segments, of which 233 were TME 0–25%, 115 were intermediate thickness (TME 26–75%), and 33 were TME >75%.

Relationship between transmural extent and regional volumes
Table 2 shows the relationship between TME and revascularization with changes in regional volumes and function, taking into account the association of segments in each patient in a series of random effects models, and correcting for the multiple outcome parameters. Analysis of the progression of regional volumes and EF in each group without reference to revascularization status (listed in the column titled time variable) showed overall changes in EDV only in segments with subendocardial scar (TME 0–25%). Intervention had a borderline influence on the evolution of EF and none on regional volumes.


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  		Table 2 Serial changes (%) in regional end-diastolic volumes (EDV), regional left ventricular systolic volumes (ESV), and regional ejection fraction (EF) according to the presence of transmural extent (TME) by contrast-enhanced magnetic resonance imaging (ce-MRI). The time variable relates to change from baseline, regardless of study group. The ‘Intervention’ column relates to the differences in changes from baseline between the two groups

 
In order to investigate the roles of TME and revascularization on alteration of regional volumes and EF, a series of random effects models were set up, including interactions between revascularization and TME <25% (Table 3). The models contain a time variable, which dichotomizes regional volumes or EF into baseline and follow-up measurements for the purposes of estimating a visit effect. This visit effect had a marginal influence on ESV, but the evolution of ESV was not associated with TME, revascularization or the interaction term. Revascularization was associated with change in EDV, but no interaction with TME was identified. None of the explanatory variables were significant in relation to EF change.


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  		Table 3 Correlates of changes in regional volumes and ejection fraction

 
Taking into account the association of segments in each patient, the influence of viability by DbE (Table 4) had no association with the evolution of regional volumes and function in the group overall. However, there was a significant association between revascularization and reverse remodelling of ESV in the subendocardial scar group (TME <25%). Viability by SPECT was not associated with differences in the time variable, nor was an effect of intervention identified (Table 4).


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  		Table 4 Serial changes (%) in regional end diastolic volumes (EDV), regional left ventricular systolic volumes (ESV), and regional ejection fraction (EF) according to the presence of viability by (A) dobutamine echocardiography (DbE) and (B) TI-201 at different levels of transmural extent (TME) by contrast-enhanced magnetic resonance imaging (ce-MRI)

 
Validation of regional magnetic resonance imaging volumes
Regional volumes of the segmental volume phantom were calculated using the CIM software as described in Appendix. The true values for the regional volumes were 16.0 mL for the six basal regions, 16.5 mL for the six mid-ventricular regions, and 6.1 mL for the four apical regions. The corresponding values calculated from the MR images were 15.6 ± 0.3 mL (range 15.1–16.0 mL) for the basal regions, 15.9 ± 0.6 mL (range 15.0–16.5 mL) for the mid-ventricular regions and 6.8 ± 0.1 mL (6.6–6.9 mL) for the apical regions, giving an average error of –0.2 mL (range –1.5–0.8 mL). The total true volume was 219.6 mL, compared with 216.1 mL calculated from the model.

There was significant agreement by a single observer at two different points in time 7 days apart (95% limits of agreement by Bland–Altman analysis were –7.6 to 7.6 mL for EDV and –5.0 to 5.4 mL for ESV) and by two independent observers (95% limits of agreement –10.9 to 11.5 mL for EDV, and –9.8 to 10.2 mL for ESV).


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
Funding
 Appendix: Calculation and...
 Acknowledgements
 References
 
The results of this follow-up study indicate that subendocardial scar segments are most likely to demonstrate reverse regional remodelling during follow-up and that revascularization is an independent correlate of change in EDV (but without an interaction with TME). Remodelling was associated with intervention in non-transmural infarction showing evidence of viability by DbE, but evidence of viability by SPECT was not associated with reverse remodelling.

Global and regional left ventricular remodelling
The accurate measurement of LV volume in the post-infarct ventricle is difficult in the absence of 3D techniques, and MRI has the advantage of overcoming the geometric assumptions of angiography and 2D echocardiography.23,24 This is particularly important when sequential measurements are made within individual patients, and MRI has been proven to be accurate and highly reproducible in the serial assessment of LV volumes.25–28 Interestingly, regional remodelling was not associated with significant change in regional EF. The stability of this parameter likely reflects myocardial compensatory mechanisms whereby both regional ESV and EDV change proportionately during the remodelling process.

The assessment of remodelling using global LV volumes and function may be influenced by compensatory alterations of non-infarcted regions, which may explain why our results showed lack of overall global remodelling in the medical group. In contrast, regional changes truly reflect the direct impact of regional scar and viability. The process of regional remodelling post MI has been previously investigated by Eaton et al.10 who showed disproportionate regional dilatation of transmural infarcts. The impact of scar thickness on global remodelling was also reported by Bello et al.5 In that study of 45 patients with severe LV dysfunction post MI (EF 26 ± 11%) undergoing optimized medical therapy with beta blockers, the amount of dysfunctional but viable myocardium on ce-MRI was an independent negative predictor of global EDV and ESV changes at 6 months. Other studies have demonstrated a direct relationship between regional volume changes and regional wall stress29 as well as clinical outcomes.6,12 The development of a 3D LV model from finite element methods18 has permitted reproducible assessment of regional volumes, and allowed us to study the association of viability with regional remodelling.

Implications of transmural extent of scar
The use of ce-MRI has enabled the direct visualization of non-viable tissue, quantified as the TME of scar, and residual viable tissue, which is non-enhanced and often resides in the epicardial rim of the infarct zone.30 Delayed hyper-enhancement with gadolinium has been shown to correlate well with myocardial necrosis on histopathology,31 and inversely associated with viability as defined by positron emission tomography.14 The use of regional analysis permits an appreciation of the interaction between TME and the nature of the residual myocardium.

Just as subendocardial scar is usually associated with functional recovery after revascularization,13 the results of this study confirm that small non-transmural scars (TME < 25%) are most likely to demonstrate reverse remodelling – this process is associated with contractile reserve and revascularization. Although it has previously been suggested that the presence of subepicardial viable tissue is protective against subsequent LV remodeling,32 and scars of intermediate severity are sometimes associated with functional recovery after revascularization,13 this group did not show reverse remodelling in this study, irrespective of revascularization or other evidence of viability (contractile reserve or perfusion). Transmural scars can be considered as non-viable, as they showed worsening of regional remodelling in both treatment groups. Previous studies of non-viable segments using other imaging modalities (e.g. thallium perfusion imaging, positron emission tomography, and DbE) have also shown adverse clinical outcomes irrespective of treatment strategy.1

Association of standard viability tests with remodelling
There is a low likelihood of functional recovery post revascularization in segments without contractile reserve.33 Studies using DbE have shown that contractile reserve is protective against global remodelling.8,9 Our findings build on this observation, demonstrating that contractile reserve is not associated with reverse remodelling apart from the presence of subsendocardial infarcts (TME < 25%). Apart from artefactual causes of discrepancies between ce-MRI and other techniques such as mal-alignment between the images, this finding may reflect disturbances in the micro-architecture of the myocardium that compromises the contractile response, in the absence of scarring. This pattern may explain why some segments showing viability by metabolic imaging lack a contractile reserve response and demonstrate late functional recovery after revascularization.34

Non-transmural infarcts (TME 26–75%) demonstrate reverse regional remodelling after revascularization even in the presence of a fixed perfusion defect by SPECT. This may reflect the limited spatial resolution of SPECT, which may limit the appreciation of localized or non-transmural infarction. In a study by Wagner et al.,35 ce-MRI was able to detect 92% of histologically confirmed subendocardial infarcts but a significant proportion was missed by SPECT, which could only detect 28% of these subendocardial infarcts.

Study limitations
Not all patients in this study had undergone coronary angiography at baseline, as this test is usually a prelude to revascularization in our practice, and not all patients were considered eligible for revascularization. Nonetheless, patency of the infarct related artery is a potential determinant of post-infarct remodelling,36 and the implications of functional testing might be different if patients are stratified according to vessel patency.

Patients in this study were recruited at least 1 month after infarction, in order to permit resolution of oedema, which may compromise the reliability of TME measurements, and were followed for >1 year. Infarct resorption and expansion is a dynamic process, so the timing of recruitment after infarction may have an impact on remodelling – some of this process may have occurred by 6 months after the infarction. Although our follow-up would have identified most of this process and confirmed stability of TME, longer-term studies are needed to evaluate whether protection from regional remodelling by viable tissue can translate into better clinical outcomes with increased survival and reduction of adverse clinical events.

The segmental analysis was important for understanding the change in segmental response without the influence of loss of hyperkinesis in normal myocardium. A nested analysis is necessary in order to correct for the fact that segments within the same patient are not independent. However, the use of a generalized linear mixed model with a random intercept assumes that all correlations between each pair of segments are the same. This assumption may be untrue but it is difficult to plan a model, which accounts for all the possible influences (adjacent and remote infarction, hypertrophy, and ischaemia are but few features which would influence these findings).

Finally, some selection issues may be pertinent. The study was observational rather than a clinical trial, so despite the lack of difference documented in Table 1, there may be other differences between these groups. Frail and immobile patients may have been disinclined to return for sequential follow-up. More importantly, many patients being assessed for viability have more severe LV dysfunction than the study population, so that care should be taken in generalizing these results to patients with ischaemic cardiomyopathy.

Clinical implications
The results of this study further confirm the importance of myocardial scar and viability to the LV response after infarction. Our results show that non-transmural scars may be associated with post-infarct remodelling, which is associated with revascularization in the presence of contractile reserve. Previous studies have also shown that remodelling can be attenuated by maximizing medical therapy with subsequent translation into better outcomes.5,37,38 This will be particularly applicable to those patients who are unsuitable for revascularization (e.g. multiple comorbidities, high operative risks, advanced age) and ce-MRI may identify such patients with non-transmural scars as candidates for more aggressive medical therapy.


   Funding
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Funding
Appendix: Calculation and...
 Acknowledgements
 References
 
This study was supported in part by a project grant (210217) from the National Health and Medical Research Council of Australia.


   Appendix: Calculation and validation of regional volumes
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Funding
 Appendix: Calculation and...
Acknowledgements
 References
 
Mathematical model
A 3D mathematical model of the LV geometry was constructed using previously described methods.18 Briefly, fiducial markers were placed by the user on the hinge points of the mitral valve leaflets in each frame of the long-axis slices, the centre of the LV cavity in the most apical and basal short-axis slices, and the anterior and posterior junctions of the right ventricle free wall with the interventricular septum in the short-axis slices. These fiducial markers were used to define a 3D patient specific ‘cardiac’ coordinate system, with the x-axis aligned with the central axis of the LV pointing towards the apex, the y-axis oriented towards the centroid of the right ventricular points and the z-axis oriented posteriorly. A 3D plane was fitted to the locations of the mitral valve points to define a base plane for the LV; volumes were calculated up to but not through this plane. The cardiac coordinate system was used to construct a prolate spheroidal coordinate system as follows:



Formula 247M1

(A1)

where {lambda} is a radial coordinate ({lambda}{approx} 1 at the epicardium), {theta} is a circumferential angular coordinate ({theta} = 0 at the centroid of the RV), and µ is a longitudinal angular coordinate (at the apex µa = 0 and at the base µb {approx} 120°, where µb is a function of {theta} due to the 3D tilt of the base plane).

A Finite Element model of the LV was constructed with 16 elements, each with bicubic Hermite interpolation and C1 continuity. The model geometric parameters were defined in the prolate spheroidal coordinate system, and the {lambda} field was interactively fitted as a function of µ and {theta} to the image data by least squares optimization.18

Calculation of regional volumes
The model was divided into apex, mid-ventricle and basal segments by equal angular increments in µ, from µ = 0 at the apex to µb({theta}) at the base. At the base, the average locations of the anterior and posterior RV insertion points were used to demarcate the extent of the LV septum in {theta}, which was divided into equal portions for the posterior and anterior septal segments. The remaining LV wall was divided into four equal angular segments for the posterior, posterior lateral, anterior laterial, and anterior basal segments. The same procedure was used to define the six segments of the mid-ventricle level. The apex level was divided into four equal angular segments for the septal, posterior, lateral, and anterior apex segments. For each segment, the regional volume was calculated by numerical integration of the volume encompassed by the endocardial surface between the µ and {theta} boundaries of the region, and the central (x) axis of the model.

Validation studies
Custom-made MR-compatible perspex phantom was constructed to validate the calculation of regional volumes. Figure 1A shows a schematic of the phantom, which comprised an apical bowl of approximately hemispherical shape (maximum diameter 60 mm, depth 28 mm) attached to a cylinder of internal radius 30 mm and length 60 mm. A wedge subtending 120° was glued to the basal third of the phantom to demarcate the basal septal regions, and thus define the angular extent of all other regions (Figure 1A). The remaining volume was filled with water and imaged with a TrueFISP cine pulse sequence (5 mm slice thickness, TR 32.7 ms, TE 1.25 ms, flip angle 72°, 340 mm field of view) in nine short-axis (10 mm spacing) and six long-axis (60° angular spacing) slices. Guide point modelling was used to estimate global and regional volumes. Mitral valve points were placed at the top of the cylinder, central axis LV points were placed at the centres of the most basal and most apical slices, and RV points were placed on either side of the 120° wedge to demarcate the septal regions. From these fiducial markers, and the fitted endocardial surface geometry, the volumes of all regions could be calculated as said above. The analytic regional volumes calculated from the known phantom geometry were 16.0, 16.5, and 6.1 mL for each of the basal, mid-ventricle, and apical segments, respectively. Note that due to the non-linear nature of the prolate spheroidal coordinate system, the basal and mid-ventricular regions are not necessarily the same volume.


   Acknowledgements
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Funding
 Appendix: Calculation and...
 Acknowledgements
References
 
We gratefully acknowledge the contributions of Drs Lizelle Hanekom and Leanne Du at Princess Alexandra Hospital for their help with patient recruitment and imaging, as well as Drs Stephen Rose and Mark Strudwick and the staff of the Centre for MRI at University of Queensland. Dr Robert Kirton from University of Auckland constructed the MR phantom.

Conflict of interest: the authors have no conflicts of interest.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Funding
 Appendix: Calculation and...
 Acknowledgements
 References
 

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    The above article uses a new reference style being piloted by the EHJ that shall soon be used for all articles.

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