Philip J. Kilner

Contemporary predictors of death and sustained ventricular tachycardia in patients with repaired tetralogy of Fallot enrolled in the INDICATOR cohort

Objective Patients with repaired tetralogy of Fallot (TOF) experience increased rates of mortality and morbidity in adulthood. This study was designed to identify risk factors for death and ventricular tachycardia (VT) in a large contemporary cohort of patients with repaired TOF. Methods Subjects with repaired TOF from four large congenital heart centres in the USA, Canada and Europe were enrolled. Clinical, ECG, exercise, cardiac magnetic resonance (CMR) and outcome data were analysed. Results Of the 873 patients (median age 24.4u2005years), 32 (3.7%) reached the primary outcome (28 deaths, 4 sustained VT; median age at outcome 38u2005years; median time from CMR to outcome 1.9u2005years). Cox proportional-hazards regression identified RV mass-to-volume ratio ≥0.3u2005g/mL (HR, 5.04; 95% CI 2.3 to 11.0; p<0.001), LV EF z score<−2.0 (HR, 3.34; 95% CI 1.59 to 7.01; p=0.001), and history of atrial tachyarrhythmia (HR, 3.65; 95% CI 1.75 to 7.62; p=0.001) as outcome predictors. RV dysfunction was predictive of the outcome similar to LV dysfunction. In subgroup analysis of 315 subjects with echocardiographic assessment of RV systolic pressure, higher pressure (HR 1.39; 95% CI 1.19 to 1.62; p<0.001) was associated with death and sustained VT independent of RV hypertrophy and LV dysfunction. Conclusions RV hypertrophy, ventricular dysfunction and atrial tachyarrhythmias are predictive of death and sustained VT in adults with repaired TOF. These findings may inform risk stratification and the design of future therapeutic trials.

4D flow cardiovascular magnetic resonance consensus statement

Pulsatile blood flow through the cavities of the heart and great vessels is time-varying and multidirectional. Access to all regions, phases and directions of cardiovascular flows has formerly been limited. Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) has enabled more comprehensive access to such flows, with typical spatial resolution of 1.5×1.5×1.5 – 3×3×3 mm3, typical temporal resolution of 30–40xa0ms, and acquisition times in the order of 5 to 25xa0min. This consensus paper is the work of physicists, physicians and biomedical engineers, active in the development and implementation of 4D Flow CMR, who have repeatedly met to share experience and ideas. The paper aims to assist understanding of acquisition and analysis methods, and their potential clinical applications with a focus on the heart and greater vessels. We describe that 4D Flow CMR can be clinically advantageous because placement of a single acquisition volume is straightforward and enables flow through any plane across it to be calculated retrospectively and with good accuracy. We also specify research and development goals that have yet to be satisfactorily achieved. Derived flow parameters, generally needing further development or validation for clinical use, include measurements of wall shear stress, pressure difference, turbulent kinetic energy, and intracardiac flow components. The dependence of measurement accuracy on acquisition parameters is considered, as are the uses of different visualization strategies for appropriate representation of time-varying multidirectional flow fields. Finally, we offer suggestions for more consistent, user-friendly implementation of 4D Flow CMR acquisition and data handling with a view to multicenter studies and more widespread adoption of the approach in routine clinical investigations.

Principles of cardiovascular magnetic resonance feature tracking and echocardiographic speckle tracking for informed clinical use

Tissue tracking technology of routinely acquired cardiovascular magnetic resonance (CMR) cine acquisitions has increased the apparent ease and availability of non-invasive assessments of myocardial deformation in clinical research and practice. Its widespread availability thanks to the fact that this technology can in principle be applied on images that are part of every CMR or echocardiographic protocol. However, the two modalities are based on very different methods of image acquisition and reconstruction, each with their respective strengths and limitations. The image tracking methods applied are not necessarily directly comparable between the modalities, or with those based on dedicated CMR acquisitions for strain measurement such as tagging or displacement encoding. Here we describe the principles underlying the image tracking methods for CMR and echocardiography, and the translation of the resulting tracking estimates into parameters suited to describe myocardial mechanics. Technical limitations are presented with the objective of suggesting potential solutions that may allow informed and appropriate use in clinical applications.

In vivo cardiovascular magnetic resonance diffusion tensor imaging shows evidence of abnormal myocardial laminar orientations and mobility in hypertrophic cardiomyopathy

BackgroundCardiac diffusion tensor imaging (cDTI) measures the magnitudes and directions of intramyocardial water diffusion. Assuming the cross-myocyte components to be constrained by the laminar microstructures of myocardium, we hypothesized that cDTI at two cardiac phases might identify any abnormalities of laminar orientation and mobility in hypertrophic cardiomyopathy (HCM).MethodsWe performed cDTI in vivo at 3 Tesla at end-systole and late diastole in 11 healthy controls and 11 patients with HCM, as well as late gadolinium enhancement (LGE) for detection of regional fibrosis.ResultsVoxel-wise analysis of diffusion tensors relative to left ventricular coordinates showed expected transmural changes of myocardial helix-angle, with no significant differences between phases or between HCM and control groups. In controls, the angle of the second eigenvector of diffusion (E2A) relative to the local wall tangent plane was larger in systole than diastole, in accord with previously reported changes of laminar orientation. HCM hearts showed higher than normal global E2A in systole (63.9° vs 56.4° controls, p =0.026) and markedly raised E2A in diastole (46.8° vs 24.0° controls, p < 0.001). In hypertrophic regions, E2A retained a high, systole-like angulation even in diastole, independent of LGE, while regions of normal wall thickness did not (LGE present 57.8°, p =0.0028, LGE absent 54.8°, p =0.0022 vs normal thickness 38.1°).ConclusionsIn healthy controls, the angles of cross-myocyte components of diffusion were consistent with previously reported transmural orientations of laminar microstructures and their changes with contraction. In HCM, especially in hypertrophic regions, they were consistent with hypercontraction in systole and failure of relaxation in diastole. Further investigation of this finding is required as previously postulated effects of strain might be a confounding factor.

Assessment of Myocardial Microstructural Dynamics by In Vivo Diffusion Tensor Cardiac Magnetic Resonance.

BACKGROUNDnCardiomyocytes are organized in microstructures termed sheetlets that reorientate during left ventricular thickening. Diffusion tensor cardiac magnetic resonance (DT-CMR) may enable noninvasive interrogation of inxa0vivo cardiac microstructural dynamics. Dilated cardiomyopathy (DCM) is a condition of abnormal myocardium withxa0unknown sheetlet function.nnnOBJECTIVESnThis study sought to validate inxa0vivo DT-CMR measures of cardiac microstructure against histology, characterize microstructural dynamics during left ventricular wall thickening, and apply the technique in hypertrophic cardiomyopathy (HCM) and DCM.nnnMETHODSnInxa0vivo DT-CMR was acquired throughout the cardiac cycle in healthy swine, followed by in situ andxa0exxa0vivoxa0DT-CMR, then validated against histology. Inxa0vivo DT-CMR was performed in 19 control subjects, 19 DCM, and 13xa0HCMxa0patients.nnnRESULTSnIn swine, a DT-CMR index of sheetlet reorientation (E2A) changed substantially (E2A mobility ∼46°). E2A changes correlated with wall thickness changes (inxa0vivo r2xa0= 0.75; in situ r2xa0= 0.89), were consistently observed under all experimental conditions, and accorded closely with histological analyses in both relaxed and contracted states. The potential contribution of cyclical strain effects to inxa0vivo E2A was ∼17%. In healthy human control subjects, E2A increased from diastole (18°) to systole (65°; pxa0< 0.001; E2A mobilityxa0= 45°). HCM patients showed significantly greater E2A in diastole than control subjects did (48°; pxa0< 0.001) with impaired E2A mobility (23°; pxa0< 0.001). In DCM, E2A was similar to control subjects in diastole, butxa0systolic values were markedly lower (40°; pxa0< 0.001) with impaired E2A mobility (20°; pxa0< 0.001).nnnCONCLUSIONSnMyocardial microstructure dynamics can be characterized by inxa0vivo DT-CMR. Sheetlet function was abnormal in DCM with altered systolic conformation and reduced mobility, contrasting with HCM, which showed reducedxa0mobility with altered diastolic conformation. These novel insights significantly improve understanding of contractile dysfunction at a level of noninvasive interrogation not previously available in humans.

Cardiac magnetic resonance markers of progressive RV dilation and dysfunction after tetralogy of Fallot repair

Objective Patients with repaired tetralogy of Fallot (TOF) are followed serially by cardiac magnetic resonance (CMR) for surveillance of RV dilation and dysfunction. We sought to define the prevalence of progressive RV disease and the optimal time interval between CMR evaluations. Methods Candidates were selected from a multicentre TOF registry and were included if ≥2 CMR studies performed ≥6u2005months apart were available without interval cardiovascular interventions. Patients with ‘disease progression’ (defined as increase in RV end-diastolic volume index (RVEDVi) ≥30u2005mL/m2, decrease in RVEF ≥10% or decrease in LVEF ≥10%) were compared with those with ‘disease non-progression’ (defined as RVEDVi increase ≤5u2005mL/m2, RVEF decrease ≤3% and LVEF decrease ≤3%). Results A total of 849 CMR studies in 339 patients (median age at first CMR 23.6u2005years) were analysed. Over a median interval of 2.2u2005years between CMR pairs, RVEDVi increased 4±18u2005mL/m2 (p<0.001), RV end-systolic volume index increased 3±13u2005mL/m2 (p<0.001), RVEF decreased 1%±6% (p=0.02) and LVEF decreased 1%±6% (p=0.001). Disease progression was observed in 15% (n=76) and non-progression in 26% (n=133). There were no significant differences between those with and without progression in baseline demographic, anatomic, ECG, exercise or baseline CMR characteristics. The optimal time interval between CMR studies for detection of progression was a 3-year interval (63% sensitivity, 65% specificity, area under the receiver operating characteristic curve 0.65). Conclusions Although progressive RV dilation and decline in biventricular systolic function occur at a slow pace in the majority of adults with repaired TOF, 15% of patients experience rapid disease progression. The results of this study support the practice of serial CMR examinations to identify progressive disease at a time interval of up to 3u2005years.

Systemic Right Ventricular Fibrosis Detected by Cardiovascular Magnetic Resonance Is Associated With Clinical Outcome, Mainly New-Onset Atrial Arrhythmia, in Patients After Atrial Redirection Surgery for Transposition of the Great Arteries

Background—We hypothesized that fibrosis detected by late gadolinium enhancement (LGE) cardiovascular magnetic resonance predicts outcomes in patients with transposition of the great arteries post atrial redirection surgery. These patients have a systemic right ventricle (RV) and are at risk of arrhythmia, premature RV failure, and sudden death. Methods and Results—Fifty-five patients (aged 27±7 years) underwent LGE cardiovascular magnetic resonance and were followed for a median 7.8 (interquartile range, 3.8–9.6) years in a prospective single-center cohort study. RV LGE was present in 31 (56%) patients. The prespecified composite clinical end point comprised new-onset sustained tachyarrhythmia (atrial/ventricular) or decompensated heart failure admission/transplantation/death. Univariate predictors of the composite end point (n=22 patients; 19 atrial/2 ventricular tachyarrhythmia, 1 death) included RV LGE presence and extent, RV volumes/mass/ejection fraction, right atrial area, peak VO2, and age at repair. In bivariate analysis, RV LGE presence was independently associated with the composite end point (hazard ratio, 4.95 [95% confidence interval, 1.60–15.28]; P=0.005), and only percent predicted peak VO2 remained significantly associated with cardiac events after controlling for RV LGE (hazard ratio, 0.80 [95% confidence interval, 0.68–0.95]; P=0.009/5%). In 8 of 9 patients with >1 event, atrial tachyarrhythmia, itself a known risk factor for mortality, occurred first. There was agreement between location and extent of RV LGE at in vivo cardiovascular magnetic resonance and histologically documented focal RV fibrosis in an explanted heart. There was RV LGE progression in a different case restudied for clinical indications. Conclusions—Systemic RV LGE is strongly associated with adverse clinical outcome especially arrhythmia in transposition of the great arteries, thus LGE cardiovascular magnetic resonance should be incorporated in risk stratification of these patients.

Optimal diffusion weighting for in vivo cardiac diffusion tensor imaging

To investigate the influence of the diffusion weighting on in vivo cardiac diffusion tensor imaging (cDTI) and obtain optimal parameters.

Prevalence of Inferobasal Myocardial Crypts Among Patients Referred for Cardiovascular Magnetic Resonance

Background—Crypts or clefts in the left ventricular inferobasal myocardium have been detected by cardiovascular magnetic resonance (CMR), but the extent to which they represent prephenotypic markers of hypertrophic cardiomyopathy (HCM) or incidental structural variants remains controversial. Methods and Results—We examined retrospectively the routine vertical long-axis cines in 686 consecutive patients (48±20 years, 55% men) referred for CMR. Crypts were identified in 46 (6.7%), 17 being among patients (8.7% of 196) with otherwise normal CMR findings and without a known family history of HCM. Higher percentages were found in patients with HCM (16%), myocarditis (15%), and hypertension (14%) but without reaching statistical significance (P=0.12). Only 1 (5%) of 20 phenotype -negative HCM family members had a visible crypt. Relative to those without, patients with crypts had lower indexed left ventricular end-systolic volumes (P=0.042) and higher indexed left and right ventricular stroke volumes (P=0.007 and P=0.015) and ejection fractions (P=0.003 and P=0.021). Crypts tended to narrow in systole, varying slightly in size, shape- and number, without obvious group-related features. Conclusions—Single or paired inferobasal myocardial crypts were an occasional and by no means rare finding among patients referred for CMR without a pretest suspicion of HCM. This, together with similar previous findings in a cohort of healthy volunteers, supports their being regarded, in such individuals, as incidental variants of local myocardial structure, unlikely to require further investigation. However, a larger registry-type study may be justified to investigate the clinical implications of multiple crypts, especially if associated with HCM family history.

Prevalence and prognostic implication of restenosis or dilatation at the aortic coarctation repair site assessed by cardiovascular MRI in adult patients late after coarctation repair

BACKGROUNDnCardiovascular magnetic resonance (CMR) is ideal for assessing patients with repaired aortic coarctation (CoA). Little is known on the relation between long-term complications of CoA repair as assessed by CMR and clinical outcome. We examined the prevalence of restenosis and dilatation at the repair site and the long-term outcome in patients with repaired CoA.nnnMETHODS AND RESULTSnCMR imaging and clinical data for adult CoA patients (247 patients aged 33.0 ± 12.8 years, 60% male), were analyzed. The diameter of the aorta at the repair site was measured on CMR and its ratio to the aortic diameter at the diaphragm (repair site-diaphragm ratio, RDR) was calculated. Restenosis (RDR≤70%) was present in 31% of patients (and significant in 9% [RDR<50%]), and dilatation (RDR>150%) in 13.0%. A discrete aneurysm at the repair site was observed in 9%. Restenosis was more likely after resection and end-end anastomosis, whereas dilatation after patch repair. Systemic hypertension was present in 69% of patients. Of the hypertensive patients, blood pressure (133 ± 20/73 ± 10 mm Hg) was well controlled in 93% with antihypertensive therapy. Mortality rate over a median length of 5.9 years was low (0.69% per year, 95% CI: 0.33-1.26), but significantly higher than age-matched healthy controls (standardised mortality ratio 2.86, CI 1.43-5.72, p<0.001).nnnCONCLUSIONnRestenosis or dilatation at the CoA repair site as assessed by CMR is not uncommon. Medium term survival remains good, however, albeit lower than in the general population. Life-long follow-up and optimal blood pressure control are likely to secure a good longer term outlook in these patients.