Nicholas Child

Reference values for healthy human myocardium using a T1 mapping methodology: results from the International T1 Multicenter cardiovascular magnetic resonance study

BackgroundT1 mapping is a robust and highly reproducible application to quantify myocardial relaxation of longitudinal magnetisation. Available T1 mapping methods are presently site and vendor specific, with variable accuracy and precision of T1 values between the systems and sequences. We assessed the transferability of a T1 mapping method and determined the reference values of healthy human myocardium in a multicenter setting.MethodsHealthy subjects (n = 102; mean age 41 years (range 17–83), male, n = 53 (52%)), with no previous medical history, and normotensive low risk subjects (n=113) referred for clinical cardiovascular magnetic resonance (CMR) were examined. Further inclusion criteria for all were absence of regular medication and subsequently normal findings of routine CMR. All subjects underwent T1 mapping using a uniform imaging set-up (modified Look- Locker inversion recovery, MOLLI, using scheme 3(3)3(3)5)) on 1.5 Tesla (T) and 3 T Philips scanners. Native T1-maps were acquired in a single midventricular short axis slice and repeated 20 minutes following gadobutrol. Reference values were obtained for native T1 and gadolinium-based partition coefficients, λ and extracellular volume fraction (ECV) in a core lab using standardized postprocessing.ResultsIn healthy controls, mean native T1 values were 950 ± 21 msec at 1.5 T and 1052 ± 23 at 3 T. λ and ECV values were 0.44 ± 0.06 and 0.25 ± 0.04 at 1.5 T, and 0.44 ± 0.07 and 0.26 ± 0.04 at 3 T, respectively. There were no significant differences between healthy controls and low risk subjects in routine CMR parameters and T1 values. The entire cohort showed no correlation between age, gender and native T1. Cross-center comparisons of mean values showed no significant difference for any of the T1 indices at any field strength. There were considerable regional differences in segmental T1 values. λ and ECV were found to be dose dependent. There was excellent inter- and intraobserver reproducibility for measurement of native septal T1.ConclusionWe show transferability for a unifying T1 mapping methodology in a multicenter setting. We provide reference ranges for T1 values in healthy human myocardium, which can be applied across participating sites.

T1-Mapping and Outcome in Nonischemic Cardiomyopathy: All-Cause Mortality and Heart Failure

OBJECTIVES The study sought to examine prognostic relevance of T1 mapping parameters (based on a T1 mapping method) in nonischemic dilated cardiomyopathy (NIDCM) and compare them with conventional markers of adverse outcome. BACKGROUND NIDCM is a recognized cause of poor clinical outcome. NIDCM is characterized by intrinsic myocardial remodeling due to complex pathophysiological processes affecting myocardium diffusely. Lack of accurate and noninvasive characterization of diffuse myocardial disease limits recognition of early cardiomyopathy and effective clinical management in NIDCM. Cardiac magnetic resonance (CMR) supports detection of diffuse myocardial disease by T1 mapping. METHODS This is a prospective observational multicenter longitudinal study in 637 consecutive patients with dilated NIDCM (mean age 50 years [interquartile range: 37 to 76 years]; 395 males [62%]) undergoing CMR with T1 mapping and late gadolinium enhancement (LGE) at 1.5-T and 3.0-T. The primary endpoint was all-cause mortality. A composite of heart failure (HF) mortality and hospitalization was a secondary endpoint. RESULTS During a median follow-up period of 22 months (interquartile range: 19 to 25 months), we observed a total of 28 deaths (22 cardiac) and 68 composite HF events. T1 mapping indices (native T1 and extracellular volume fraction), as well as the presence and extent of LGE, were predictive of all-cause mortality and HF endpoint (p < 0.001 for all). In multivariable analyses, native T1 was the sole independent predictor of all-cause and HF composite endpoints (hazard ratio: 1.1; 95% confidence interval: 1.06 to 1.15; hazard ratio: 1.1; 95% confidence interval: 1.05 to 1.1; p < 0.001 for both), followed by the models including the extent of LGE and right ventricular ejection fraction, respectively. CONCLUSIONS Noninvasive measures of diffuse myocardial disease by T1 mapping are significantly predictive of all-cause mortality and HF events in NIDCM. We provide a basis for a novel algorithm of risk stratification in NIDCM using a complementary assessment of diffuse and regional disease by T1 mapping and LGE, respectively.

A U-shaped type II contraction pattern in patients with strict left bundle branch block predicts super-response to cardiac resynchronization therapy.

BACKGROUND New criteria to define strict left bundle branch block (LBBB) on the basis of pathophysiological principles predict response to cardiac resynchronization therapy (CRT). Heterogeneous activation and contraction patterns have been identified in patients with classical LBBB. Cardiac magnetic resonance (CMR) imaging has demonstrated that a U-shaped (type II) contraction predicts reverse remodeling post-CRT. A homogeneous spread of (type I) contraction is less predictive. OBJECTIVES The purpose of this study was to investigate contraction patterns among patients with strict LBBB and to test whether a type II contraction pattern better predicts CRT response and super-response. METHODS Thirty-seven patients with strict LBBB (QRS duration ≥140 ms for men and ≥130 ms for women with mid-QRS notching or slurring in ≥2 contiguous leads) underwent cine CMR imaging pre-CRT with an analysis of their contraction patterns by using endocardial contour tracking software. Patients were evaluated for reverse remodeling 6 months postimplantation. RESULTS Nineteen patients (51%) had a type II contraction pattern. A total of 25 patients (68%) of the cohort reverse remodeled. In the type II contraction group, all 19 patients (100%) reverse remodeled as compared with 6 patients (33%) in the type I contraction group (P < .01). Super-response was achieved in 21 patients (57%) of the total cohort: 5 patients with a type I contraction pattern (28%) and 16 patients with a type II contraction pattern (84%) (P < .01). CONCLUSION Patients with strict LBBB who are guideline indicated for CRT have heterogeneous contraction patterns derived from cine CMR. A type II contraction pattern is strongly predictive for reverse remodeling and super-response. This questions whether strict LBBB criteria alone are sufficient to reliably predict a positive response to CRT.

Effect of Mental Challenge Induced by Movie Clips on Action Potential Duration in Normal Human Subjects Independent of Heart Rate

Background—Mental stress and emotion have long been associated with ventricular arrhythmias and sudden death in animal models and humans. The effect of mental challenge on ventricular action potential duration (APD) in conscious healthy humans has not been reported. Methods and Results—Activation recovery intervals measured from unipolar electrograms as a surrogate for APD (n=19) were recorded from right and left ventricular endocardium during steady-state pacing, whilst subjects watched an emotionally charged film clip. To assess the possible modulating role of altered respiration on APD, the subjects then repeated the same breathing pattern they had during the stress, but without the movie clip. Hemodynamic parameters (mean, systolic, and diastolic blood pressure, and rate of pressure increase) and respiration rate increased during the stressful part of the film clip (P=0.001). APD decreased during the stressful parts of the film clip, for example, for global right ventricular activation recovery interval at end of film clip 193.8 ms (SD, 14) versus 198.0 ms (SD, 13) during the matched breathing control (end film left ventricle 199.8 ms [SD, 16] versus control 201.6 ms [SD, 15]; P=0.004). Respiration rate increased during the stressful part of the film clip (by 2 breaths per minute) and was well matched in the respective control period without any hemodynamic or activation recovery interval changes. Conclusions—Our results document for the first time direct recordings of the effect of a mental challenge protocol on ventricular APD in conscious humans. The effect of mental challenge on APD was not secondary to emotionally induced altered respiration or heart rate.

Prevalence of myocardial crypts in a large retrospective cohort study by cardiovascular magnetic resonance

BackgroundMyocardial crypts are discrete clefts or fissures in otherwise compacted myocardium of the left ventricle (LV). Recent reports suggest a higher prevalence of crypts in patients with hypertrophic cardiomyopathy (HCM) and also within small samples of genotype positive but phenotype negative relatives. The presence of a crypt has been suggested to be a predictor of gene carrier status. However, the prevalence and clinical significance of crypts in the general population is unclear. We aimed to determine the prevalence of myocardial crypts in a large cohort of subjects using clinical cardiovascular magnetic resonance (CMR).MethodsConsecutive subjects referred for clinical CMR during a 12-month period (n = 1020, age 52.6 ± 17, males: 61%) were included. Crypts were defined as >50% invagination into normal myocardium and their overall prevalence, location and shape was investigated and compared between different patient groups.ResultsThe overall prevalence of crypts was 64/1020 (6.3%). In a predefined ‘normal’ control group the prevalence was lower (11/306, 3.6%, p = 0.031), but were equally prevalent in ischemic heart disease (12/236, 5.1%, p = n/s) and the combined non-ischemic cardiomyopathy (NICM) groups (24/373; 6.4%, p = n/s). Within the NICM group, crypts were significantly more common in HCM (9/76, 11.7%, p = 0.04) and hypertensive CM subjects (3/11, 27%, p = 0.03). In patients referred for CMR for family screening of inherited forms of CM, crypts were significantly more prevalent (10/41, 23%, p < 0.001), including a smaller group with a first degree relative with HCM (3/9, 33%, p = 0.01).ConclusionMyocardial crypts are relatively common in the normal population, and increasingly common in HCM and hypertensive cardiomyopathy. Crypts are also more frequently seen in normal phenotype subjects referred because of a family history of an inherited cardiomyopathy and HCM specifically. It is uncertain what the significance of crypts are in this group, and because of variability in the imaging protocols used and their relative frequency within the normal population, should not be used to clinically stratify these patients. Prospective studies are required to confirm the clinical significance of myocardial crypts, as their significance remains unclear.

T1 values by conservative septal postprocessing approach are superior in relating to the interstitial myocardial fibrosis: findings from patients with severe aortic stenosis

Background Accumulation of diffuse interstitial myocardial fibrosis in severe aortic stenosis relates to left ventricular (LV) functional impairment and determines the postoperative outcome in these patients. T1 mapping has been proposed for non-invasive quantification of diffuse interstitial fibrosis. We examined associations between T1 values and collagen volume fraction from endomyocardial biopsies from patients with severe aortic stenosis. We compared whether these relationships differ with respect to the post-processing approach.

Comparison of MOLLI, shMOLLLI, and SASHA in discrimination between health and disease and relationship with histologically derived collagen volume fraction

Aims To determine the bioequivalence of several T1 mapping sequences in myocardial characterization of diffuse myocardial fibrosis. Methods and results We performed an intra-individual sequence comparison of three types of T1 mapping sequences [MOdified Look-Locker Inversion recovery (MOLLI), Shortened MOdified Look-Locker Inversion recovery ((sh)MOLLI), and SAturation recovery single-SHot Acquisition (SASHA)]. We employed two model diseases of diffuse interstitial fibrosis [patients with non-ischaemic dilated cardiomyopathy (NIDCM), n = 32] and aortic stenosis [(AS), n = 25)]. Twenty-six healthy individuals served as controls. Relationship with collagen volume fraction (CVF) was assessed using endomyocardial biopsies (EMB) intraoperatively in 12 AS patients. T2 mapping (GraSE) was also performed. Myocardial native T1 with MOLLI and shMOLLI showed, firstly, an excellent discriminatory accuracy between health and disease [area under the curves (P-value): 0.94 (0.88-0.99); 0.87 (0.79-0.94); 0.61 (0.49-0.72)], secondly, relationship between histological CVF [native T1 MOLLI vs. shMOLLI vs. SASHA: r = 0.582 (P = 0.027), r = 0.524 (P = 0.046), r = 0.443 (P = 0.150)], and thirdly, with native T2 [r = 0.628(P < 0.001), r = 0.459 (P = 0.003), r = 0.211 (P = 0.083)]. The respective relationships for extracellular volume fraction with CVF [r = 0.489 (P = 0.044), r = 0.417 (0.071), r = 0.353 (P = 0.287)] were significant for MOLLI, but not other sequences. In AS patients, native T2 was significantly higher compared to controls, and associated with levels of C-reactive protein and troponin. Conclusion T1 mapping sequences differ in their bioequivalence for discrimination between health and disease as well as associations with diffuse myocardial fibrosis.

Age-gender normal values of native and post-contrast myocardial T1 relaxation times (lambda) on 1.5T and 3T using MOLLI: a multicenter, single vendor cardiovascular magnetic resonance study

Age-gender normal values of native and postcontrast myocardial T1 relaxation times (lambda) on 1.5T and 3T using MOLLI: a multicenter, single vendor cardiovascular magnetic resonance study Darius Dabir, Nicholas Child, Ashwin Kalra, Islam Z Mahmoud, Toby Rogers, Rolf Gebker, Ananth Kidambi, Sven Plein, Andrew Jabbour, David M Higgins, Bernhard Schnackenburg, Tobias Schaeffter, Eike Nagel, Valentina Puntmann

Cardiac magnetic resonance feature tracking in Kawasaki disease convalescence

Objective: The objective of this study was to determine whether left ventricular (LV) myocardial deformation indices can detect subclinical abnormalities in Kawasaki disease convalescence. We hypothesized that subclinical myocardial abnormalities due to inflammation represent an early manifestation of the disease that persists in convalescence. Background: Myocardial inflammation has been described as a global finding in the acute phase of Kawasaki disease. Despite normal systolic function by routine functional measurements, reduced longitudinal strain and strain rate have been detected by echocardiography in the acute phase. Methods and Results: Peak systolic LV myocardial longitudinal, radial, and circumferential strain and strain rate were examined in 29 Kawasaki disease convalescent patients (15 males; mean [standard deviation] age: 11 [6.6] years; median interval from disease onset: 5.8 [5.4] years) and 10 healthy volunteers (5 males; mean age: 14 [3.8] years) with the use of cardiac magnetic resonance (CMR) feature tracking. Routine indices of LV systolic function were normal in both groups. Comparisons were made between normal controls and (i) the entire Kawasaki disease group, (ii) Kawasaki disease subgroup divided by coronary artery involvement. Average longitudinal and circumferential strain at all levels was lower in patients compared to normal controls. In subgroup analysis, both Kawasaki disease patients with and without a history of coronary involvement had similar longitudinal and circumferential strain at all levels and lower when compared to controls. There were lower circumferential and longitudinal values in Kawasaki disease patients with persisting coronary artery lesions when compared to those with regressed ones. Conclusion: In this CMR study in Kawasaki disease convalescent patients with preserved routine functional indices, we detected lower circumferential and longitudinal strain values compared to normal controls, irrespective of the coronary artery status.

Coupling of ventricular action potential duration and local strain patterns during reverse remodeling in responders and nonresponders to cardiac resynchronization therapy.

BACKGROUND The high risk of ventricular arrhythmias in patients with heart failure remains despite the benefit of cardiac resynchronization therapy (CRT). An electromechanical interaction between regional myocardial strain patterns and the electrophysiological substrate is thought to be important. OBJECTIVE We investigated the in vivo relation between left ventricular activation recovery interval (ARI), as a surrogate measure of action potential duration (APD), and local myocardial strain patterns in responders and nonresponders to CRT. METHODS ARIs were recorded from the left ventricular epicardium in 20 patients with CRT 6 weeks and 6 months post implantation. Two-dimensional speckle tracking echocardiography was performed at the same time to assess myocardial strains. Patients with ≥15% reduction in end-systolic volume at 6 months were classified as responders. RESULTS ARI decreased in responders (263 ± 46 ms vs 246 ± 47 ms, P < .01) and increased in nonresponders (235 ± 23 ms vs 261 ± 20 ms; P < .01). Time-to-peak radial, circumferential, and longitudinal strains increased in responders (41 ± 27, 35 ± 25, 56 ± 37 ms; P < .01) and decreased in nonresponders (-58 ± 26, -47 ± 26, -64 ± 27 ms; P < .01). There was a nonlinear correlation between changes in time-to-peak strain and ARIs (Spearman correlation coefficient r ≥ 0.70; P < .01). Baseline QRS duration >145 ms and QRS duration shortening with biventricular pacing were associated with ARI shortening following CRT. CONCLUSION Changes in ventricular wall mechanics predict local APD lengthening or shortening during CRT. Nonresponders have a worsening of myocardial strain and local APD. Baseline QRS duration >145 ms and QRS duration shortening with biventricular pacing identified patients who exhibited improvement in APD.