Joseph J Pagano

Saturation recovery single-shot acquisition (SASHA) for myocardial T1 mapping

To validate a new saturation recovery single‐shot acquisition (SASHA) pulse sequence for T1 mapping and to compare SASHA T1 values in heart failure patients and healthy controls.

Diffuse myocardial fibrosis by T1-mapping in children with subclinical anthracycline cardiotoxicity: relationship to exercise capacity, cumulative dose and remodeling

BackgroundThe late cardiotoxic effects of anthracycline chemotherapy influence morbidity and mortality in the growing population of childhood cancer survivors. Even with lower anthracycline doses, evidence of adverse cardiac remodeling and reduced exercise capacity exist. We aim to examine the relationship between cardiac structure, function and cardiovascular magnetic resonance (CMR) tissue characteristics with chemotherapy dose and exercise capacity in childhood cancer survivors.MethodsThirty patients (15 ± 3 years), at least 2 years following anthracycline treatment, underwent CMR, echocardiography, and cardiopulmonary exercise testing (peak VO2). CMR measured ventricular function, mass, T1 and T2 values, and myocardial extracellular volume fraction, ECV, a measure of diffuse fibrosis based on changes in myocardial T1 values pre- and post-gadolinium. Cardiac function was also assessed with conventional and speckle tracking echocardiography.ResultsPatients had normal LVEF (59 ± 7%) but peak VO2 was 17% lower than age-predicted normal values and were correlated with anthracycline dose (r = −0.49). Increased ECV correlated with decreased mass/volume ratio (r = −0.64), decreased LV wall thickness/height ratio (r = −0.72), lower peak VO2(r = −0.52), and higher cumulative dose (r = 0.40). Echocardiographic measures of systolic and diastolic function were reduced compared to normal values (p < 0.01), but had no relation to ECV, peak VO2 or cumulative dose.ConclusionsMyocardial T1 and ECV were found to be early tissue markers of ventricular remodeling that may represent diffuse fibrosis in children with normal ejection fraction post anthracycline therapy, and are related to cumulative dose, exercise capacity and myocardial wall thinning.

Multidisciplinary Approach to Novel Therapies in Cardio-Oncology Research (MANTICORE 101–Breast): A Randomized Trial for the Prevention of Trastuzumab-Associated Cardiotoxicity

Purpose The primary toxicity of trastuzumab therapy for human epidermal growth factor receptor 2-overexpressing (HER2-positive) breast cancer is dose-independent cardiac dysfunction. Angiotensin-converting enzyme inhibitors and β-blockers are recommended first-line agents for heart failure. We hypothesized that angiotensin-converting enzyme inhibitors and β-blockers could prevent trastuzumab-related cardiotoxicity. Patients and Methods In this double-blinded, placebo-controlled trial, patients with HER2-positive early breast cancer were randomly assigned to receive treatment with perindopril, bisoprolol, or placebo (1:1:1) for the duration of trastuzumab adjuvant therapy. Patients underwent cardiac magnetic resonance imaging at baseline and post-cycle 17 for the determination of left ventricular volumes and left ventricular ejection fraction (LVEF). Cardiotoxicity was evaluated as the change in indexed left ventricular end diastolic volume and LVEF. Results Thirty-three patients received perindopril, 31 received bisoprolol, and 30 received placebo. Baseline demographic, cancer, and cardiovascular profiles were similar between groups. Study drugs were well tolerated with no serious adverse events. After 17 cycles of trastuzumab, indexed left ventricular end diastolic volume increased in patients treated with perindopril (+7 ± 14 mL/m2), bisoprolol (+8 mL ± 9 mL/m2), and placebo (+4 ± 11 mL/m2; P = .36). In secondary analyses, trastuzumab-mediated decline in LVEF was attenuated in bisoprolol-treated patients (-1 ± 5%) relative to the perindopril (-3 ± 4%) and placebo (-5 ± 5%) groups ( P = .001). Perindopril and bisoprolol use were independent predictors of maintained LVEF on multivariable analysis. Conclusion Perindopril and bisoprolol were well tolerated in patients with HER2-positive early breast cancer who received trastuzumab and protected against cancer therapy-related declines in LVEF; however, trastuzumab-mediated left ventricular remodeling-the primary outcome-was not prevented by these pharmacotherapies.

T2-dependent errors in MOLLI T1 values: simulations, phantoms, and in-vivo studies

Background Diffuse myocardial fibrosis occurs in various cardiomyopathies and can be indirectly assessed with blood and myocardial T1 mapping at baseline and after gadolinium administration. The widely used MOdified Look-Locker Inversion-recovery (MOLLI) [1] sequence is known to underestimate myocardial T1 at higher heart rates, but its dependence on T2 has not been explored. We investigate MOLLI’s T1 accuracy in phantoms and confirm with simulations and in-vivo studies. T1 values are further compared with a saturation-recovery T1 mapping sequence [2].

Improved precision in SASHA T1 mapping with a variable flip angle readout

Background The SAturation-recovery single-SHot Acquisition (SASHA) T1 mapping sequence has excellent accuracy independent of T1, T2, heart rate, and flip angle [1], which are known dependencies of the more commonly used MOdified Look-Locker Inversion-recovery (MOLLI) sequence. However, SASHA has a greater T1 variability (poorer precision) compared to MOLLI. A two-parameter fit, with assumed ideal saturation, has been shown to improve precision compared to the standard three-parameter fit used for SASHA, but at the expense of introducing systematic errors [2]. We propose that a variable flip angle (VFA) readout will reduce these systematic errors and thereby allow the improved precision of a two-parameter fit while maintaining the accuracy of the three-parameter fit.

Degree of diffuse fibrosis measured by MRI correlates with LV remodelling in childhood cancer survivors after anthracycline chemotherapy

The effectiveness of anthracycline chemotherapy is limited by dose dependant cardiotoxicity. Current protocols reduce the cumulative dose, however subclinical myocardial damage may still manifest years after cessation of therapy. The most serious side effect is dilated cardiomyopathy with pathological changes of fibrosis. The potential presence of fibrosis in this remodelling is unknown.

Quantification of circumferential, longitudinal, and radial global fractional shortening using steady-state free precession cines: a comparison with tissue-tracking strain and application in Fabry disease.

Conventional calculation of myocardial strain requires tissue‐tracking. A surrogate for strain called global fractional shortening (GFS) is proposed based on changes in dimensions of endocardial and epicardial surfaces without tissue‐tracking.

Reduced Right Ventricular Native Myocardial T1 in Anderson-Fabry Disease: Comparison to Pulmonary Hypertension and Healthy Controls

Aims Anderson-Fabry disease (AFD) is characterized by progressive multiorgan accumulation of intracellular sphingolipids due to α-galactosidase A enzyme deficiency, resulting in progressive ventricular hypertrophy, heart failure, arrhythmias, and death. Decreased native (non-contrast) left ventricular (LV) T1 (longitudinal relaxation time) with MRI discriminates AFD from healthy controls or other presentations of concentric hypertrophy, but the right ventricle (RV) has not been studied. The aims of the current study were to evaluate native RV T1 values in AFD, with a goal of better understanding the pathophysiology of RV involvement. Methods and Results Native T1 values were measured in the inferior RV wall (RVI), interventricular septum (IVS), and inferior LV (LVI) in patients with AFD, patients with pulmonary hypertension, who provided an alternative RV pathological process for comparison, and healthy controls. A minimum wall thickness of 4 mm was selected to minimize partial volume errors in tissue T1 analysis. T1 analysis was performed in 6 subjects with AFD, 6 subjects with PH, and 21 controls. Native T1 values were shorter (adjusted p<0.05 for all comparisons), independent of location, in subjects with AFD (RVI-T1 = 1096±49 ms, IVS-T1 = 1053±41 ms, LVI-T1 = 1072±44 ms) compared to both PH (RVI-T1 = 1239±41 ms, IVS-T1 = 1280±123 ms, LVI-T1 = 1274±57 ms) and HC (IVS-T1 = 1180±60 ms, LVI-T1 = 1183±45 ms). RVI measurements were not possible in controls due to insufficient wall thickness. Conclusion Native T1 values appear similarly reduced in the left and right ventricles of individuals with AFD and RV wall thickening, suggesting a common pathology. In contrast, individuals with PH and thickened RVs showed increased native T1 values in both ventricles, suggestive of fibrosis.

Normal left-atrial structure and function despite concentric left-ventricular remodelling in a cohort of patients with Anderson-Fabry disease.

AIMS Anderson-Fabry Disease (AFD) is an important cause of cardiomyopathy characterized by concentric left-ventricular hypertrophy (LVH). We evaluated the extent of left-atrial (LA) structural and functional remodelling in this group of patients given that LA remodelling is a marker of adverse outcomes in the presence of LVH. METHODS AND RESULTS Clinical profiles were obtained and cardiac MRI was performed in cohorts of patients with AFD (n = 31), healthy controls (n = 23), and a positive control cohort with known concentric remodelling and LVH (CR/H, n = 21). Of patients with AFD, 58% were on enzyme-replacement therapy (ERT), 84% were on renin-angiotensin system antagonism, and 65% were on statins. Despite a similar increase in LV mass index in the AFD when compared with the CR/H cohort, mean LA volumes for the AFD group were similar to those seen in the healthy control group. Following from this, we observed that the percentage contribution to LV stroke volume due to elastic/passive and active LA emptying was similar in the AFD and healthy control groups, while passive emptying was significantly lower in the CR/H group. The consequences of LVH in the AFD cohort were manifested in atrioventricular uncoupling, whereby the extent of elastic/passive and active LA emptying was not a function of the extent of longitudinal movement of the mitral annular plane, as it was in healthy control subjects. CONCLUSION Left-atrial structure and function were relatively normal in our cohort of patients with AFD, who were also judiciously treated with a contemporary strategy that includes renin-angiotensin system antagonism, statins, and ERT.

Aging and gender effects in native T1 and extracellular volume fraction assessment using SASHA

Background Reference values for T1 mapping-derived extracellular volume fraction (ECV) in healthy individuals are not currently well established. Histological measurements in autopsy studies have shown decreasing ECV with healthy aging in men, however recent non-invasive measurements of ECV using different T1 mapping techniques are inconsistent with respect to the effect of aging and gender, with a relatively wide range of values depending on the method. The goal of the current study was to characterize native T1 and ECV as a function of age in healthy individuals (no cardiovascular risk factors or medication) with the SAturation-recovery single-SHot Acquisition (SASHA) method (Magn Reson Med. 2014 Jun; 71(6):2082-95), providing comparison to existing literature. Methods Well characterized healthy individuals from the Alberta HEART study (BMC Cardiovasc Disord. 2014 Jul 25;14:91) underwent CMR on a Siemens 1.5T system (Sonata, Avanto) with T1 measurements using the SASHA pulse sequence. Imaging was performed on a mid-ventricular short-axis slice at baseline (pre-contrast) and ~15 minutes after intravenous administration of 0.15 mmol/kg gadobutrol. ECV was measured in the ventricular septum, calculated as (1-hct)*(Myocardium ΔR1)/ (Blood ΔR1), where ΔR1 is 1/T1 post 1/T1 pre, and hct was the most recent hematocrit.