Saturation-pulse prepared heart-rate independent inversion-recovery (SAPPHIRE) biventricular T1 mapping: inter-field strength, head-to-head comparison of diastolic, systolic and dark-blood measurements.

BACKGROUND: To assess the feasibility of biventricular SAPPHIRE T1 mapping in vivo across field strengths using diastolic, systolic and dark-blood (DB) approaches. METHODS: 10 healthy volunteers underwent same-day non-contrast cardiovascular magnetic resonance at 1.5 Tesla (T) and 3 T. Left and right ventricular (LV, RV) T1 mapping was performed in the basal, mid and apical short axis using 4-variants of SAPPHIRE: diastolic, systolic, 0th and 2nd order motion-sensitized DB and conventional modified Look-Locker inversion recovery (MOLLI). RESULTS: LV global myocardial T1 times (1.5 T then 3 T results) were significantly longer by diastolic SAPPHIRE (1283 ± 11|1600 ± 17 ms) than any of the other SAPPHIRE variants: systolic (1239 ± 9|1595 ± 13 ms), 0th order DB (1241 ± 10|1596 ± 12) and 2nd order DB (1251 ± 11|1560 ± 20 ms, all p < 0.05). In the mid septum MOLLI and diastolic SAPPHIRE exhibited significant T1 signal contamination (longer T1) at the blood-myocardial interface not seen with the other 3 SAPPHIRE variants (all p < 0.025). Additionally, systolic, 0th order and 2nd order DB SAPPHIRE showed narrower dispersion of myocardial T1 times across the mid septum when compared to diastolic SAPPHIRE (interquartile ranges respectively: 25 ms, 71 ms, 73 ms vs 143 ms, all p < 0.05). RV T1 mapping was achievable using systolic, 0th and 2nd order DB SAPPHIRE but not with MOLLI or diastolic SAPPHIRE. All 4 SAPPHIRE variants showed excellent re-read reproducibility (intraclass correlation coefficients 0.953 to 0.996). CONCLUSION: These small-scale preliminary healthy volunteer data suggest that DB SAPPHIRE has the potential to reduce partial volume effects at the blood-myocardial interface, and that systolic SAPPHIRE could be a feasible solution for right ventricular T1 mapping. Further work is needed to understand the robustness of these sequences and their potential clinical utility.

Use of rapid cardiac magnetic resonance imaging to guide chelation therapy in patients with transfusion-dependent thalassaemia in India: UMIMI study.

AIMS: To explore the impact of incorporating a faster cardiac magnetic resonance (CMR) imaging protocol in a low-middle-income country (LMIC) and using the result to guide chelation in transfusion-dependent patients. METHODS AND RESULTS: A prospective UK-India collaborative cohort study was conducted in two cities in India. Two visits 13 months apart included clinical assessment and chelation therapy recommendations based on rapid CMR results. Participants were recruited by the local patient advocate charity, who organized the patient medical camps. The average scanning time was 11.3 ± 2.5 min at the baseline and 9.8 ± 2.4 min (P < 0.001) at follow-up. The baseline visit was attended by 103 patients (mean age 25 years) and 83% attended the second assessment. At baseline, 29% had a cardiac T2* < 20 ms, which represents significant iron loading, and 12% had left ventricular ejection fraction <60%, the accepted lower limit in this population. Only 3% were free of liver iron (T2* ≥ 17 ms). At 13 months, more patients were taking intensified dual chelation therapy (43% vs. 55%, P = 0.002). In those with cardiac siderosis (baseline T2* < 20 ms), there was an improvement in T2*-10.9 ± 5.9 to 13.5 ± 8.7 ms, P = 0.005-and fewer were classified as having clinically important cardiac iron loading (T2* < 20 ms, 24% vs. 16%, P < 0.001). This is the first illustration in an LMIC that incorporating CMR results into patient management plans can improve cardiac iron loading. CONCLUSION: For thalassaemia patients in an LMIC, a simplified CMR protocol linked to therapeutic recommendation via the patient camp model led to enhanced chelation therapy and a reduction in cardiac iron in 1 year.

Randomised, double-blind, placebo-controlled clinical trial investigating the effects of inorganic nitrate in hypertension-induced target organ damage: protocol of the NITRATE-TOD study in the UK.

INTRODUCTION: Arterial stiffness and left ventricular (LV) hypertrophy are the key markers of hypertensive target organ damage (TOD) associated with increased cardiovascular morbidity and mortality. We have previously shown that dietary inorganic nitrate supplementation lowers blood pressure (BP) in hypertension, however, whether this approach might also improve markers of hypertensive TOD is unknown. In this study, we will investigate whether daily dietary inorganic nitrate administration reduces LV mass and improves measures of arterial stiffness. METHODS AND DESIGN: NITRATE-TOD is a double-blind, randomised, single-centre, placebo-controlled phase II trial aiming to enrol 160 patients with suboptimal BP control on one or more antihypertensives. Patients will be randomised to receive 4 months once daily dose of either nitrate-rich beetroot juice or nitrate-deplete beetroot juice (placebo). The primary outcomes are reduction in LV mass and reduction in pulse wave velocity (PWV) and central BP.The study has a power of 95% for detecting a 9 g LV mass change by cardiovascular MRI (~6% change for a mildly hypertrophied heart of 150 g). For PWV, we have a power of >95% for detecting a 0.6 m/s absolute change. For central systolic BP, we have a>90% power to detect a 5.8 mm Hg difference in central systolic BP.Secondary end points include change in ultrasound flow-mediated dilation, change in plasma nitrate and nitrite concentration and change in BP. ETHICS AND DISSEMINATION: The study was approved by the London-City and East Research Ethics Committee (10/H0703/98). Trial results will be published according to the Consolidated Standards of Reporting Trials statement and will be presented at conferences and reported in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03088514.

Extracellular Volume Associates With Outcomes More Strongly Than Native or Post-Contrast Myocardial T1.

OBJECTIVES: Because risk stratification data represents a key domain of biomarker validation, we compared associations between outcomes and various cardiovascular magnetic resonance (CMR) metrics quantifying myocardial fibrosis (MF) in noninfarcted myocardium: extracellular volume fraction (ECV), native T1, post-contrast T1, and partition coefficient. BACKGROUND: MF associates with vulnerability to adverse events (e.g., mortality and hospitalization for heart failure [HHF]), but investigators still debate its optimal measurement; most histological validation data show strongest ECV correlations with MF. METHODS: We enrolled 1,714 consecutive patients without amyloidosis or hypertrophic cardiomyopathy from a single CMR referral center serving an integrated healthcare network. We measured T1 (MOdified Look-Locker Inversion recovery [MOLLI]) in nonenhanced myocardium, averaged from 2 short-axis slices (basal and mid) before and 15 to 20 min after a gadolinium contrast bolus. We compared chi-square test values from CMR MF measures in univariable and multivariable Cox regression models. We assessed "dose-response" relationships in Kaplan-Meier curves using log-rank statistics for quartile strata. We also computed net reclassification improvement (NRI) and integrated discrimination improvement (IDI for Cox models with ECV vs. native T1). RESULTS: Over a median of 5.6 years, 374 events occurred after CMR (162 HHF events and 279 deaths, 67 with both). ECV yielded the best separation of Kaplan-Meier curves and the highest log-rank statistics. In univariable and multivariable models, ECV associated most strongly with outcomes, demonstrating the highest chi-square test values. Native T1 or post-contrast T1 did not associate with outcomes in the multivariable model. ECV provided added prognostic value to models with native T1, for example, in multivariable models IDI = 0.0037 (95% confidence interval [CI]: 0.0009 to 0.0071), p = 0.02; NRI = 0.151 (95% CI: 0.022 to 0.292), p = 0.04. CONCLUSIONS: Analogous to histological previously published validation data, ECV myocardial fibrosis measures exhibited more robust associations with outcomes than other surrogate CMR MF measures. Superior risk stratification by ECV supports claims that ECV optimally measures MF in noninfarcted myocardium.

Role of T1 mapping as a complementary tool to T2* for non-invasive cardiac iron overload assessment.

BACKGROUND: Iron overload-related heart failure is the principal cause of death in transfusion dependent patients, including those with Thalassemia Major. Linking cardiac siderosis measured by T2* to therapy improves outcomes. T1 mapping can also measure iron; preliminary data suggests it may have higher sensitivity for iron, particularly for early overload (the conventional cut-point for no iron by T2* is 20ms, but this is believed insensitive). We compared T1 mapping to T2* in cardiac iron overload. METHODS: In a prospectively large single centre study of 138 Thalassemia Major patients and 32 healthy controls, we compared T1 mapping to dark blood and bright blood T2* acquired at 1.5T. Linear regression analysis was used to assess the association of T2* and T1. A "moving window" approach was taken to understand the strength of the association at different levels of iron overload. RESULTS: The relationship between T2* (here dark blood) and T1 is described by a log-log linear regression, which can be split in three different slopes: 1) T2* low, <20ms, r2 = 0.92; 2) T2* = 20-30ms, r2 = 0.48; 3) T2*>30ms, weak relationship. All subjects with T2*<20ms had low T1; among those with T2*>20ms, 38% had low T1 with most of the subjects in the T2* range 20-30ms having a low T1. CONCLUSIONS: In established cardiac iron overload, T1 and T2* are concordant. However, in the 20-30ms T2* range, T1 mapping appears to detect iron. These data support previous suggestions that T1 detects missed iron in 1 out of 3 subjects with normal T2*, and that T1 mapping is complementary to T2*. The clinical significance of a low T1 with normal T2* should be further investigated.