Stress Perfusion Cardiac Magnetic Resonance vs SPECT Imaging for Detection of Coronary Artery Disease.

BACKGROUND: GadaCAD2 was 1 of 2 international, multicenter, prospective, Phase 3 clinical trials that led to U.S. Food and Drug Administration approval of gadobutrol to assess myocardial perfusion and late gadolinium enhancement (LGE) in adults with known or suspected coronary artery disease (CAD). OBJECTIVES: A prespecified secondary objective was to determine if stress perfusion cardiovascular magnetic resonance (CMR) was noninferior to single-photon emission computed tomography (SPECT) for detecting significant CAD and for excluding significant CAD. METHODS: Participants with known or suspected CAD underwent a research rest and stress perfusion CMR that was compared with a gated SPECT performed using standard clinical protocols. For CMR, adenosine or regadenoson served as vasodilators. The total dose of gadobutrol was 0.1 mmol/kg body weight. The standard of reference was a 70% stenosis defined by quantitative coronary angiography (QCA). A negative coronary computed tomography angiography could exclude CAD. Analysis was per patient. CMR, SPECT, and QCA were evaluated by independent central core lab readers blinded to clinical information. RESULTS: Participants were predominantly male (61.4% male; mean age 58.9 ± 10.2 years) and were recruited from the United States (75.0%), Australia (14.7%), Singapore (5.7%), and Canada (4.6%). The prevalence of significant CAD was 24.5% (n = 72 of 294). Stress perfusion CMR was statistically superior to gated SPECT for specificity (P = 0.002), area under the receiver operating characteristic curve (P < 0.001), accuracy (P = 0.003), positive predictive value (P < 0.001), and negative predictive value (P = 0.041). The sensitivity of CMR for a 70% QCA stenosis was noninferior and nonsuperior to gated SPECT. CONCLUSIONS: Vasodilator stress perfusion CMR, as performed with gadobutrol 0.1 mmol/kg body weight, had superior diagnostic accuracy for diagnosis and exclusion of significant CAD vs gated SPECT.

Comprehensive Cardiovascular Magnetic Resonance Tissue Characterization and Cardiotoxicity in Women With Breast Cancer.

Importance: There is a growing interest in understanding whether cardiovascular magnetic resonance (CMR) myocardial tissue characterization helps identify risk of cancer therapy-related cardiac dysfunction (CTRCD). Objective: To describe changes in CMR tissue biomarkers during breast cancer therapy and their association with CTRCD. Design, Setting, and Participants: This was a prospective, multicenter, cohort study of women with ERBB2 (formerly HER2)-positive breast cancer (stages I-III) who were scheduled to receive anthracycline and trastuzumab therapy with/without adjuvant radiotherapy and surgery. From November 7, 2013, to January 16, 2019, participants were recruited from 3 University of Toronto-affiliated hospitals. Data were analyzed from July 2021 to June 2022. Exposures: Sequential therapy with anthracyclines, trastuzumab, and radiation. Main Outcomes and Measures: CMR, high-sensitivity cardiac troponin I (hs-cTnI), and B-type natriuretic peptide (BNP) measurements were performed before anthracycline treatment, after anthracycline and before trastuzumab treatment, and at 3-month intervals during trastuzumab therapy. CMR included left ventricular (LV) volumes, LV ejection fraction (EF), myocardial strain, early gadolinium enhancement imaging to assess hyperemia (inflammation marker), native/postcontrast T1 mapping (with extracellular volume fraction [ECV]) to assess edema and/or fibrosis, T2 mapping to assess edema, and late gadolinium enhancement (LGE) to assess replacement fibrosis. CTRCD was defined using the Cardiac Review and Evaluation Committee criteria. Fixed-effects models or generalized estimating equations were used in analyses. Results: Of 136 women (mean [SD] age, 51.1 [9.2] years) recruited from 2013 to 2019, 37 (27%) developed CTRCD. Compared with baseline, tissue biomarkers of myocardial hyperemia and edema peaked after anthracycline therapy or 3 months after trastuzumab initiation as demonstrated by an increase in mean (SD) relative myocardial enhancement (baseline, 46.3% [16.8%] to peak, 56.2% [18.6%]), native T1 (1012 [26] milliseconds to 1035 [28] milliseconds), T2 (51.4 [2.2] milliseconds to 52.6 [2.2] milliseconds), and ECV (25.2% [2.4%] to 26.8% [2.7%]), with P <.001 for the entire follow-up. The observed values were mostly within the normal range, and the changes were small and recovered during follow-up. No new replacement fibrosis developed. Increase in T1, T2, and/or ECV was associated with increased ventricular volumes and BNP but not hs-cTnI level. None of the CMR tissue biomarkers were associated with changes in LVEF or myocardial strain. Change in ECV was associated with concurrent and subsequent CTRCD, but there was significant overlap between patients with and without CTRCD. Conclusions and Relevance: In women with ERBB2-positive breast cancer receiving sequential anthracycline and trastuzumab therapy, CMR tissue biomarkers suggest inflammation and edema peaking early during therapy and were associated with ventricular remodeling and BNP elevation. However, the increases in CMR biomarkers were transient, were not associated with LVEF or myocardial strain, and were not useful in identifying traditional CTRCD risk.

Statins to prevent early cardiac dysfunction in cancer patients at increased cardiotoxicity risk receiving anthracyclines.

BACKGROUND AND AIMS: Anthracyclines can cause cancer therapy-related cardiac dysfunction (CTRCD). We aimed to assess whether statins prevent decline in left ventricular ejection fraction (LVEF) in anthracycline-treated patients at increased risk for CTRCD. METHODS: In this multicenter double-blinded, placebo-controlled trial, patients with cancer at increased risk of anthracycline-related CTRCD (per ASCO guidelines) were randomly assigned to atorvastatin 40 mg or placebo once-daily. Cardiovascular magnetic resonance (CMR) imaging was performed before and within 4 weeks after anthracyclines. Blood biomarkers were measured at every cycle. The primary outcome was post-anthracycline LVEF, adjusted for baseline. CTRCD was defined as a fall in LVEF by >10% to <53%. Secondary endpoints included left ventricular (LV) volumes, CTRCD, CMR tissue characterization, high sensitivity troponin I (hsTnI), and B-type natriuretic peptide (BNP). RESULTS: We randomized 112 patients (56.9 ± 13.6 years, 87 female, and 73 with breast cancer): 54 to atorvastatin and 58 to placebo. Post-anthracycline CMR was performed 22 (13-27) days from last anthracycline dose. Post-anthracycline LVEF did not differ between the atorvastatin and placebo groups (57.3 ± 5.8% and 55.9 ± 7.4%, respectively) when adjusted for baseline LVEF (P = 0.34). There were no significant between-group differences in post-anthracycline LV end-diastolic (P = 0.20) or end-systolic volume (P = 0.12), CMR myocardial edema and/or fibrosis (P = 0.06-0.47), or peak hsTnI (P ≥ 0.99) and BNP (P = 0.23). CTRCD incidence was similar (4% versus 4%, P ≥ 0.99). There was no difference in adverse events. CONCLUSIONS: In patients at increased risk of CTRCD, primary prevention with atorvastatin during anthracycline therapy did not ameliorate early LVEF decline, LV remodeling, CTRCD, change in serum cardiac biomarkers, or CMR myocardial tissue changes. TRIAL REGISTRATION: NCT03186404.

Diagnostic and Prognostic Value of Myocardial Work Indices for Identification of Cancer Therapy-Related Cardiotoxicity.

BACKGROUND: Echocardiographic global longitudinal strain (GLS) is a useful measure for detection of cancer treatment-related cardiac dysfunction (CTRCD) but is influenced by blood pressure changes. This limitation may be overcome by assessment of myocardial work (MW), which incorporates blood pressure into the calculation. OBJECTIVES: This work aims to determine whether myocardial work indices (MWIs) can help diagnose or prognosticate CTRCD. METHODS: In this prospective cohort study, 136 women undergoing anthracycline and trastuzumab treatment for HER2+ breast cancer, underwent serial echocardiograms and cardiac magnetic resonance pre- and post-anthracycline and every 3 months during trastuzumab. GLS, global work index (GWI), global constructive work (GCW), global wasted work, and global work efficiency were measured. CTRCD was defined with cardiac magnetic resonance. Generalized estimating equations quantified the association between changes in GLS and MWIs and CTRCD at the current (diagnosis) and subsequent visit (prognosis). Regression tree analysis was used to explore the combined use of GLS and MW for the diagnostic/prognostic assessment of CTRCD. RESULTS: Baseline left ventricular ejection fraction (LVEF) was 63.2 ± 4.0%. Thirty-seven (27.2%) patients developed CTRCD. An absolute change in GLS (standardized odds ratio [sOR]: 1.97 [95% CI: 1.07-3.66]; P = 0.031) and GWI (sOR: 1.73 [95% CI: 1.04-2.85]; P = 0.033) were associated with concurrent CTRCD. An absolute change in GLS (sOR: 1.79 [95% CI: 1.22-2.62]; P = 0.003), GWI (sOR: 1.67 [95% CI: 1.20-2.32]; P = 0.003), and GCW (sOR: 1.65 [95% CI: 1.17-2.34]; P = 0.005) were associated with subsequent CTRCD. Change in GWI and GCW demonstrated incremental value over GLS and clinical factors for the diagnosis of concurrent CTRCD. In a small group with a GLS change <3.3% (absolute), and a >21 mm Hg reduction in systolic blood pressure, worsening of GWI identified patients with higher probability of concurrent CTRCD (24.0% vs 5.2%). MWIs did not improve identification of subsequent CTRCD beyond knowledge of GLS change. CONCLUSIONS: GLS can be used to diagnose and prognosticate cardiac magnetic resonance (CMR) defined CTRCD, with additional value from MWIs in selected cases. (Evaluation of Myocardial Changes During Breast Adenocarcinoma Therapy to Detect Cardiotoxicity Earlier With MRI [EMBRACE-MRI]; NCT02306538).

Clinical Impact of Cardiac MRI T1 and T2 Parametric Mapping in Patients with Suspected Cardiomyopathy.

Background There are limited data on the incremental value of parametric mapping compared with core cardiac MRI protocols for suspected cardiomyopathy in routine clinical practice. Purpose To evaluate the impact of cardiac MRI T1 and T2 mapping in routine clinical practice with respect to diagnostic accuracy, reader diagnostic confidence, and downstream cardiac imaging utilization. Materials and Methods In this retrospective single-center study, consecutive clinical cardiac MRI scans obtained with and without T1 and T2 mapping for evaluation of suspected cardiomyopathy between January 2017 and October 2019 were evaluated. Diagnostic accuracy and reader diagnostic confidence were evaluated in a random subset. Downstream cardiac imaging utilization was analyzed in patients with a minimum of 1 year of clinical follow-up ending before January 2020. Results A total of 1876 patients (mean age, 51 years ± 17 [SD]; 1113 men) were evaluated. Of these, 751 (40%) underwent cardiac MRI with the core protocol and 1125 (60%) with the core protocol plus T1 and T2 mapping. In the mapping group, T1 and T2 were high in 280 (25%) and 47 patients (4%), respectively. In the subset evaluated for diagnostic utility (n = 450), the addition of T1 and T2 maps to the core protocol resulted in an improvement in reader diagnostic confidence in 174 patients (39%). Diagnostic sensitivity was higher with the core protocol plus mapping compared with the core protocol alone for myocarditis (89% [31 of 35 patients] vs 69% [24 of 35]; P = .008), Fabry disease (93% [13 of 14 patients] vs 50% [seven of 14]; P = .01), and amyloidosis (100% [16 of 16 patients] vs 63% [10 of 16]; P = .01). In the subset evaluated for downstream imaging utilization (n = 903), 47% of patients with mapping had at least one subsequent cardiac imaging test compared with 55% of patients without mapping (P = .01). Conclusion In patients with suspected cardiomyopathy, cardiac MRI with T1 and T2 mapping had high diagnostic utility and was associated with lower downstream cardiac imaging utilization. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Jerosch-Herold and Coelho-Filho in this issue.

A Combined Echocardiography Approach for the Diagnosis of Cancer Therapy-Related Cardiac Dysfunction in Women With Early-Stage Breast Cancer.

IMPORTANCE: Diagnosis of cancer therapy-related cardiac dysfunction (CTRCD) remains a challenge. Cardiovascular magnetic resonance (CMR) provides accurate measurement of left ventricular ejection fraction (LVEF), but access to repeated scans is limited. OBJECTIVE: To develop a diagnostic model for CTRCD using echocardiographic LVEF and strain and biomarkers, with CMR as the reference standard. DESIGN, SETTING, AND PARTICIPANTS: In this prospective cohort study, patients were recruited from University of Toronto-affiliated hospitals from November 2013 to January 2019 with all cardiac imaging performed at a single tertiary care center. Women with human epidermal growth factor receptor 2 (HER2)-positive early-stage breast cancer were included. The main exclusion criterion was contraindication to CMR. A total of 160 patients were recruited, 136 of whom completed the study. EXPOSURES: Sequential therapy with anthracyclines and trastuzumab. MAIN OUTCOMES AND MEASURES: Patients underwent echocardiography, high-sensitivity troponin I (hsTnI), B-type natriuretic peptide (BNP), and CMR studies preanthracycline and postanthracycline every 3 months during and after trastuzumab therapy. Echocardiographic measures included 2-dimensional (2-D) LVEF, 3-D LVEF, peak systolic global longitudinal strain (GLS), and global circumferential strain (GCS). LVEF CTRCD was defined using the Cardiac Review and Evaluation Committee Criteria, GLS or GCS CTRCD as a greater than 15% relative change, and abnormal hsTnI and BNP as greater than 26 pg/mL and ≥ 35 pg/mL, respectively, at any follow-up point. Combinations of echocardiographic measures and biomarkers were examined to diagnose CMR CTRCD using conditional inference tree models. RESULTS: Among 136 women (mean [SD] age, 51.1 [9.2] years), CMR-identified CTRCD occurred in 37 (27%), and among those with analyzable images, in 30 of 131 (23%) by 2-D LVEF, 27 of 124 (22%) by 3-D LVEF, 53 of 126 (42%) by GLS, 61 of 123 (50%) by GCS, 32 of 136 (24%) by BNP, and 14 of 136 (10%) by hsTnI. In isolation, 3-D LVEF had greater sensitivity and specificity than 2-D LVEF for CMR CTRCD while GLS had greater sensitivity than 2-D or 3-D LVEF. Regression tree analysis identified a sequential algorithm using 3-D LVEF, GLS, and GCS for the optimal diagnosis of CTRCD (area under the receiver operating characteristic curve, 89.3%). The probability of CTRCD when results for all 3 tests were negative was 1.0%. When 3-D LVEF was replaced by 2-D LVEF in the model, the algorithm still performed well; however, its primary value was to rule out CTRCD. Biomarkers did not improve the ability to diagnose CTRCD. CONCLUSIONS AND RELEVANCE: Using CMR CTRCD as the reference standard, these data suggest that a sequential approach combining echocardiographic 3-D LVEF with 2-D GLS and 2-D GCS may provide a timely diagnosis of CTRCD during routine CTRCD surveillance with greater accuracy than using these measures individually. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02306538.

Immune checkpoint inhibitor-related myocarditis: an illustrative case series of applying the updated Cardiovascular Magnetic Resonance Lake Louise Criteria.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have improved outcomes for many types of cancer. However, ICI therapies are associated with the development of myocarditis, an immune-mediated adverse event associated with a high mortality rate. Therefore, prompt diagnosis and early intervention are of outmost importance. There is limited data on the application of cardiovascular magnetic resonance (CMR)-based modified Lake Louise Criteria (mLLC) with the use of relaxometry techniques for the diagnosis of ICI myocarditis. CASE SUMMARY: Four cancer patients undergoing ICI treatment presented with various clinical symptoms and troponin elevation to emergency/ambulatory clinics within 10-21 days after ICI initiation. On the suspicion of possible ICI-related myocarditis all patients underwent CMR within a few days after admission. Applying mLLC including relaxometry techniques, all patients met 'non-ischaemic injury criteria', while 3/4 patients met 'oedema criteria'. In most patients, quantitative mapping revealed substantially increased T1 values, while T2 values were only mildly increased or normal. In two patients with follow-up, CMR demonstrated improvement in findings after immunosuppressive treatment. However, there was only limited agreement between the degree of high-sensitive troponin levels and T1/T2 levels. DISCUSSION: The application of mLLC with T1/T2 mapping appears useful in the CMR diagnosis of acute ICI myocarditis with non-ischaemic myocardial injury criteria being the most common finding. The sensitivity of native T1 appears higher than T2 mapping in the acute diagnosis as well as in the assessment of treatment response. As troponin elevations may persist for some time with ICI myocarditis, CMR may represent an alternate strategy to monitor treatment response.

Clinical, Echocardiographic, and Biomarker Associations With Impaired Cardiorespiratory Fitness Early After HER2-Targeted Breast Cancer Therapy.

BACKGROUND: Cardiorespiratory fitness (CRF) is reduced in cancer survivors and predicts cardiovascular disease (CVD)-related and all-cause mortality. However, routine measurement of CRF is not always feasible. OBJECTIVES: The purpose of this study was to identify clinical, cardiac biomarker, and imaging measures associated with reduced peak oxygen consumption (VO2peak) (measure of CRF) early post-breast cancer therapy to help inform CVD risk. METHODS: Consecutive women with early-stage HER2+ breast cancer receiving anthracyclines and trastuzumab were recruited prospectively. Within 6 ± 2 weeks of trastuzumab completion, we collected clinical information, systolic/diastolic echocardiographic measures, high-sensitivity troponin I, B-type natriuretic peptide, and VO2peak using a cycle ergometer. Regression models were used to examine the association between VO2peak and clinical, imaging, and cardiac biomarkers individually and in combination. RESULTS: Among 147 patients (age 52.2 ± 9.3 years), the mean VO2peak was 19.1 ± 5.0 mL O2·kg-1·min-1 (84.2% ± 18.7% of predicted); 44% had a VO2peak below threshold for functional independence (<18 mL O2·kg-1·min-1). In multivariable analysis, absolute global longitudinal strain (GLS) (ß = 0.58; P = 0.007), age per 10 years (ß: -1.61; P = 0.001), and E/e' (measure of diastolic filling pressures) (ß = -0.45; P = 0.038) were associated with VO2peak. GLS added incremental value in explaining the variability in VO2peak. The combination of age ≥50 years, E/e' ≥7.8, and GLS <18% identified a high probability (85.7%) of compromised functional independence, whereas age <50 years, E/e' <7.8, and GLS ≥18% identified a low probability (0%). High-sensitivity troponin I and B-type natriuretic peptide were not associated with VO2peak. CONCLUSIONS: Readily available clinical measures were associated with VO2peak early post-breast cancer therapy. A combination of these parameters had good discrimination to identify patients with compromised functional independence and potentially increased future CVD risk.

Serial Cardiovascular Magnetic Resonance Strain Measurements to Identify Cardiotoxicity in Breast Cancer: Comparison With Echocardiography.

OBJECTIVES: This study sought to compare the prognostic value of cardiovascular magnetic resonance (CMR) and 2-dimensional echocardiography (2DE) derived left ventricular (LV) strain, volumes, and ejection fraction for cancer therapy-related cardiac dysfunction (CTRCD) in women with early stage breast cancer. BACKGROUND: There are limited comparative data on the association of CMR and 2DE derived strain, volumes, and LVEF with CTRCD. METHODS: A total of 125 prospectively recruited women with HER2+ early stage breast cancer receiving sequential anthracycline/trastuzumab underwent 5 serial CMR and 6 of 2DE studies before and during treatment. CMR LV volumes, left ventricular ejection fraction tagged-CMR, and feature-tracking (FT) derived global systolic longitudinal (GLS) and global circumferential strain (GCS) and 2DE-based LV volumes, function, GLS, and GCS were measured. CTRCD was defined by the cardiac review and evaluation committee criteria. RESULTS: Twenty-eight percent of patients developed CTRCD by CMR and 22% by 2DE. A 15% relative reduction in 2DE-GLS increased the CTRCD odds by 133% at subsequent follow-up, compared with 47%/50% by tagged-CMR GLS/GCS and 87% by FT-GCS. CMR and 2DE-LVEF and indexed left ventricular end-systolic volume (LVESVi) were also associated with subsequent CTRCD. The prognostic threshold change in CMR-left ventricular ejection fraction and FT strain for subsequent CTRCD was similar to the known minimum-detectable difference for these measures, whereas for tagged-CMR strain it was lower than the minimum-detectable difference; for 2DE, only the prognostic threshold for GLS was greater than the minimum-detectable difference. Of all strain methods, 2DE-GLS provided the highest increase in discriminatory value over baseline clinical risk factors for subsequent CTRCD. The combination of 2DE-left ventricular ejection fraction or LVESVi and strain provided greater increase in the area under the curve for subsequent CTRCD over clinical risk factors than CMR left ventricular ejection fraction or LVESVi and strain (18% to 22% vs. 9% to 14%). CONCLUSIONS: In women with HER2+ early stage breast cancer, changes in CMR and 2DE strain, left ventricular ejection fraction, and LVESVi were prognostic for subsequent CTRCD. When LVEF can be measured precisely by CMR, FT strain may function as an additional confirmatory prognostic measure, but with 2DE, GLS is the optimal prognostic measure. (Evaluation of Myocardial Changes During BReast Adenocarcinoma Therapy to Detect Cardiotoxicity Earlier With MRI [EMBRACE-MRI]; NCT02306538).

Cardiac magnetic resonance for asymptomatic patients with type 2 diabetes and cardiovascular high risk (CATCH): a pilot study.

BACKGROUND: Stress cardiovascular magnetic resonance (CMR) to screen for silent myocardial ischaemia in asymptomatic high risk patients with type 2 diabetes mellitus (DM) has never been performed, and its effectiveness is unknown. Our aim was to determine the feasibility of a screening programme using stress CMR by obtaining preliminary data on the prevalence of silent ischaemia caused by obstructive coronary artery disease (CAD) and quantify myocardial perfusion in asymptomatic high risk patients with type 2 diabetes. METHODS: In this prospective cohort study, we recruited 63 asymptomatic DM patients (mean age 66 years ± 4.4 years; 77.8% male); with Framingham risk score ≥ 20% from 3 sites from June 2017 to August 2018. Normal volunteers were recruited to determine normal global myocardial perfusion reserve index (MPRI). Adenosine stress CMR and global MPRI was performed and measured in all subjects. Positive stress CMR cases were referred for catheter coronary angiography (CCA) with/without fractional flow reserve (FFR) measurements. Positive CCA was defined as an FFR ≤ 0.8 or coronary narrowing ≥ 70%. Patients were followed up for major adverse cardiovascular events. Prevalence is presented as patient numbers and percentage. Mann-Whitney U test was used to compare global MPRI between patients and normal volunteers. RESULTS: 13 patients had positive stress CMR with positive CCA (20.6% of patient population), while 9 patients with positive stress CMR examinations had a negative CCA. 5 patients (7.9%) had infarcts detected of which 2 patients had no stress perfusion defects. 12 patients had coronary artery stents inserted, whilst 1 patient declined stent placement. DM patients had lower global MPRI than normal volunteers (n = 7) (1.43 ± 0.27 vs 1.83 ± 0.31 respectively; p < 0.01). After a median follow-up of 653 days, there was no death, heart failure, acute coronary syndrome hospitalisation or stroke. CONCLUSION: 20.6% of asymptomatic DM patients (with Framingham risk ≥ 20%) had silent obstructive CAD. Furthermore, asymptomatic patients have reduced global MPRI than normal volunteers. TRIAL REGISTRATION: ClinicalTrials.gov Registration Number: NCT03263728 on 28th August 2017; https://clinicaltrials.gov/ct2/show/NCT03263728.

Diagnostic Performance of Abnormal Nulling on Cardiac Magnetic Resonance Imaging Look Locker Inversion Time Sequence in Differentiating Cardiac Amyloidosis Types.

PURPOSE: To evaluate the diagnostic utility of the Look Locker inversion time (TI) sequence on cardiac magnetic resonance imaging in patients with suspected cardiac amyloidosis and to evaluate whether there are differences in the nulling pattern between amyloid types. MATERIALS AND METHODS: A total of 144 patients with suspected cardiac amyloidosis who had undergone cardiac magnetic resonance imaging were included in this retrospective study. Sixty-four had cardiac amyloidosis (62.1±9.2 y, 70.3% male, 68.8% had light chain amyloid [AL], 18.8% had familial transthyretin amyloid caused by mutant genes [ATTRm], and 12.5% had wild-type transthyretin amyloid [ATTRwt]) and 80 did not have cardiac amyloidosis (61.3±13.3 y, 58.8% male). Time to myocardial and blood pool nulling on the Look Locker TI sequence was classified as normal if blood pool nulled before myocardium or abnormal if blood pool nulling was coincident with or after myocardial nulling. RESULTS: The nulling pattern was abnormal in 26 patients with cardiac amyloidosis compared with none of the patients without cardiac amyloidosis (40.6% vs. 0.0%, P<0.0001). Abnormal nulling had 40.6% sensitivity and 100% specificity for cardiac amyloidosis (area under the receiver operating characteristic curve: 0.703, 95% confidence interval: 0.642-0.764). All patients with cardiac amyloidosis with an abnormal nulling pattern demonstrated late gadolinium enhancement. Among patients with cardiac amyloidosis, there was no significant difference in abnormal nulling between AL, ATTRm, and ATTRwt amyloid types (31.8%, 58.3%, 62.5%, respectively, P=0.10). CONCLUSIONS: An abnormal nulling pattern on the Look Locker TI sequence is highly specific for cardiac amyloidosis when present. However, abnormal nulling is a late finding with low sensitivity and does not differentiate between amyloid types.

Variability in echocardiography and MRI for detection of cancer therapy cardiotoxicity.

OBJECTIVES: To compare variability of echocardiographic and cardiovascular magnetic resonance (CMR) measured left ventricular (LV) function parameters and their relationship to cancer therapeutics-related cardiac dysfunction (CTRCD). METHODS: We prospectively recruited 60 participants (age: 49.8±11.6 years), 30 women with human epidermal growth factor receptor 2-positive breast cancer (15 with CTRCD and 15 without CTRCD) and 30 healthy volunteers. Patients were treated with anthracyclines and trastuzumab. Participants underwent three serial CMR (1.5T) and echocardiography studies at ~3-month intervals. Cine-CMR for LV ejection fraction (LVEF), myocardial tagging for global longitudinal strain (GLS) and global circumferential strain (GCS), two-dimensional (2D) echocardiography for strain and LVEF and three-dimensional (3D) echocardiography for LVEF measurements were obtained. Temporal, interobserver and intraobserver variability were calculated as the coefficient of variation and as the SE of the measurement (SEM). Minimal detected difference (MDD) was defined as 2xSEM. RESULTS: Patients with CTRCD demonstrated larger mean temporal changes in all parameters compared with those without: 2D-LVEF: 4.6% versus 2.8%; 3D-LVEF: 5.2% vs 2.3%; CMR-LVEF: 6.6% versus 2.7%; 2D-GLS: 1.9% versus 0.7%, 2D-GCS: 2.5% versus 2.2%; CMR-GCS: 2.7% versus 1.6%; and CMR-GLS: 2.1% versus 1.4%, with overlap in 95% CI for 2D-LVEF, 2D-GCS, CMR-GLS and CMR-GCS. The respective mean temporal variability/MDD in healthy volunteers were 3.3%/6.5%, 1.8%/3.7%, 2.2%/4.4%, 0.8%/1.5%, 1.9%/3.7%, 1.8%/3.6% and 1.4%/2.8%. Although the mean temporal variability in healthy volunteers was lower than the mean temporal changes in CTRCD, at the individual level, 2D-GLS, 3D-LVEF and CMR-LVEF had the least overlap. 2D-GLS and CMR-LVEF had the lowest interobserver/intraobserver variabilities. CONCLUSION: Temporal changes in 3D-LVEF, 2D-GLS and CMR LVEF in patients with CTRCD had the least overlap with the variability in healthy volunteers; however, 2D-GLS appears to be the most suitable for clinical application in individual patients.

Cardiovascular Magnetic Resonance Imaging: Identifying the Effects of Cancer Therapy.

The era of modern oncology incorporates an ever-evolving personalized approach to hematological malignancies and solid tumors. As a result, patient survival rates have, in part, substantially improved, depending on the specific type of underlying malignancy. However, systemic therapies may come along with potential cardiotoxic effects resulting in heart failure with increased morbidity and mortality. Ultimately, patients may survive their malignancy but die as a result of cancer treatment. Cardiovascular magnetic resonance imaging has long been in use for the assessment of function and tissue characteristics in patients with various nonischemic cardiac diseases. Besides an introductory overview on the general definition of cardiotoxicity including potential underlying mechanisms, this review provides insight into the application of various cardiovascular magnetic resonance imaging techniques in the setting of cancer therapy-related cardiac and vascular toxicity. Early identification of cardiotoxic effects may allow for on-time therapy adjustment and/or cardioprotective measures to avoid subsequent long-term heart failure with increased mortality.

Can Quantitative CMR Tissue Characterization Adequately Identify Cardiotoxicity During Chemotherapy?: Impact of Temporal and Observer Variability.

OBJECTIVES: The purpose of this study was to investigate the effect of the temporal and observer variability of cardiac magnetic resonance (CMR)-measured native T1, T2, and extracellular volume fraction (ECV) and serum biomarkers for the detection of cancer-therapeutics-related cardiac dysfunction (CTRCD). BACKGROUND: Biomarkers and serial quantitative CMR tissue characterization may help identify early myocardial changes of CTRCD, but these parameters require both accuracy and reliability. METHODS: A total of 50 participants (age 48.9 ± 12.1 years) underwent 3 CMR studies (1.5-T) and biomarker measurements (high-sensitivity troponin-I and B-type natriuretic peptide) at 3-month intervals: 20 with HER2-positive breast cancer (10 with and 10 without CTRCD), and 30 prospectively recruited healthy participants. T1 and T2 maps were obtained at 3 left ventricular short-axis locations. Temporal and observer variability were calculated as the coefficient of variation and as the standard error of the measurement (SEM) using repeated measures and 2-way analysis of variance. Minimal detected difference was defined as 2 × SEM. RESULTS: Compared with the patients without CTRCD, those with CTRCD had larger temporal change in native T1 (27.2 ms [95% confidence interval (CI): 20.8 to 39.3 ms] vs. 12.4 ms [95% CI: 9.5 to 17.9 ms]), T2 (2.0 ms [95% CI: 1.5 to 2.9 ms] vs. 1.0 ms [95% CI: 0.74 to 1.4 ms]), and ECV (2.1% [95% CI: 1.5% to 3.1%] vs. 1.0% [95% CI: 0.8% to 1.5%]). However, the temporal changes in biomarkers overlapped. The minimal detected difference for T1 (29 ms), T2 (3.0 ms), and ECV (2.2%) in healthy participants approached the mean temporal changes in patients with CTRCD. For individual patients with CTRCD, there was overlap in the temporal changes of all 3 parameters, and the variability in healthy participants with the least overlap for native T1. The interobserver/intraobserver variabilities for the CMR parameters were low (coefficient of variation 0.5% to 4.3%). CONCLUSIONS: The temporal changes in both biomarkers and tissue characterization measures in individual patients overlap with the temporal variability in healthy participants and approach the minimal detectable temporal differences. While the accuracy of the parameters awaits further study, the temporal variability of these methods may pose challenges to routine clinical application in individual patients receiving cancer therapy.

Loss of base-to-apex circumferential strain gradient assessed by cardiovascular magnetic resonance in Fabry disease: relationship to T1 mapping, late gadolinium enhancement and hypertrophy.

BACKGROUND: Cardiac involvement is common and is the leading cause of mortality in Fabry disease (FD). We explored the association between cardiovascular magnetic resonance (CMR) myocardial strain, T1 mapping, late gadolinium enhancement (LGE) and left ventricular hypertrophy (LVH) in patients with FD. METHODS: In this prospective study, 38 FD patients (45.0 ± 14.5 years, 37% male) and 8 healthy controls (40.1 ± 13.7 years, 63% male) underwent 3 T CMR including cine balanced steady-state free precession (bSSFP), LGE and modified Look-Locker Inversion recovery (MOLLI) T1 mapping. Global longitudinal (GLS) and circumferential (GCS) strain and base-to-apex longitudinal strain (LS) and circumferential strain (CS) gradients were derived from cine bSSFP images using feature tracking analysis. RESULTS: Among FD patients, 8 had LVH (FD LVH+, 21%) and 17 had LGE (FD LGE+, 45%). Nineteen FD patients (50%) had neither LVH nor LGE (FD LVH- LGE-). None of the healthy controls had LVH or LGE. FD patients and healthy controls did not differ significantly with respect to GLS (- 15.3 ± 3.5% vs. - 16.3 ± 1.5%, p = 0.45), GCS (- 19.4 ± 3.0% vs. -19.5 ± 2.9%, p = 0.84) or base-to-apex LS gradient (7.5 ± 3.8% vs. 9.3 ± 3.5%, p = 0.24). FD patients had significantly lower base-to-apex CS gradient (2.1 ± 3.7% vs. 6.5 ± 2.2%, p = 0.002) and native T1 (1170.2 ± 37.5 ms vs. 1239.0 ± 18.0 ms, p < 0.001). Base-to-apex CS gradient differentiated FD LVH- LGE- patients from healthy controls (OR 0.42, 95% CI: 0.20 to 0.86, p = 0.019), even after controlling for native T1 (OR 0.24, 95% CI: 0.06 to 0.99, p = 0.049). In a nested logistic regression model with native T1, model fit was significantly improved by the addition of base-to-apex CS gradient (χ2(df = 1) = 11.04, p < 0.001). Intra- and inter-observer agreement were moderate to good for myocardial strain parameters: GLS (ICC 0.849 and 0.774, respectively), GCS (ICC 0.831 and 0.833, respectively), and base-to-apex CS gradient (ICC 0.737 and 0.613, respectively). CONCLUSIONS: CMR reproducibly identifies myocardial strain abnormalities in FD. Loss of base-to-apex CS gradient may be an early marker of cardiac involvement in FD, with independent and incremental value beyond native T1.

Giant right atrial aneurysm.

Only a handful of congenital aneurysms of the right atrium have been reported in the literature. They are most commonly found in the third decade of life, and the differential diagnosis depends on the patient's age profile. They are associated with 5% risk of sudden cardiac death. Once diagnosed, they should be surgically removed even in the absence of symptoms.

Patterns of CMR measured longitudinal strain and its association with late gadolinium enhancement in patients with cardiac amyloidosis and its mimics.

BACKGROUND: Regional variability of longitudinal strain (LS) has been previously described with echocardiography in patients with cardiac amyloidosis (CA), however, the reason for this variability is not completely evident. We sought to describe regional patterns in LS using feature-tracking software applied to cardiovascular magnetic resonance (CMR) cine images in patients with CA, hypertrophic cardiomyopathy (HCM), and Anderson-Fabry's disease (AFD) and to relate these patterns to the distribution of late gadolinium enhancement (LGE). METHODS: Patients with CA (n = 45) were compared to LV mass indexed matched patients with HCM (n = 19) and AFD (n = 19). Peak systolic LS measurements were obtained using Velocity Vector Imaging (VVI) software on CMR cine images. A relative regional LS ratio (RRSR) was calculated as the ratio of the average of the apical segmental LS divided by the sum of the average basal and mid-ventricular segmental LS. LGE was quantified for the basal, mid, and apical segments using a threshold of 5SD above remote myocardium. A regional LGE ratio was calculated similar to RRSR. RESULTS: Patients with CA had significantly had worse global LS (-15.7 ± 4.6%) than those with HCM (-18.0 ± 4.6%, p = 0.046) and AFD (-21.9 ± 5.1%, p < 0.001). The RRSR was higher in patients with CA (1.00 ± 0.31) than in AFD (0.79 ± 0.24; p = 0.018) but not HCM (0.84 ± 0.32; p = 0.114). In CA, a regional difference in LGE burden was noted, with lower LGE in the apex (31.5 ± 19.1%) compared to the mid (38.2 ± 19.0%) and basal (53.7 ± 22.7%; p < 0.001 for both) segments. The regional LGE ratio was not significantly different between patients with CA (0.33 ± 0.15) and AFD (0.47 ± 0.58; p = 0.14) but lower compared to those with HCM (0.72 ± 0.43; p < 0.0001). LGE percentage showed a significant impact on LS (p < 0.0001), with a 0.9% decrease in absolute LS for every 10% increase in LGE percentage. CONCLUSION: The presence of marked "relative apical sparing" of LS along with a significant reduction in global LS seen in patients with CA on CMR cine analysis may provide an additional tool to differentiate CA from other cause of LVH. The concomitant presence of a base to apex gradient in quantitative LGE burden suggests that the regional strain gradient may be at least partially explained by the burden of amyloid deposition and fibrosis.

Effects of slice orientation on reproducibility of sequential assessment of right ventricular volumes and ejection fraction: short-axis vs transverse SSFP cine cardiovascular magnetic resonance.

BACKGROUND: Test-retest reproducibility is of utmost importance in follow-up of right ventricular (RV) volumes and function; optimal slice orientation though is not yet known. We compared test-retest reproducibility and intra-/inter-observer variability of right ventricular (RV) volumes and function assessed with short-axis and transverse cardiovascular magnetic resonance (CMR). METHODS: Eighteen volunteers underwent cine CMR for RV assessment obtaining ventricular coverage in short-axis and transverse slice orientation. Additional 2D phase contrast flow imaging of the main pulmonary artery (MPA) was performed. After complete repositioning repeat acquisitions were performed. Data sets were contoured by two blinded observers. Statistical analysis included Student's t-test, Bland-Altman plots, intra-class correlation coefficient (ICC) and 2-way ANOVA, SEM and minimal detectable difference calculations. RESULTS: Heart rates (65.0 ± 7.4 vs. 67.6 ± 9.9 bpm; P = 0.1) and MPA flow (89.8 ± 16.6 vs. 87.2 ± 14.9 mL; P = 0.1) did not differ between imaging sessions. EDV and ESV demonstrated an inter-study bias of 0.4 %[-9.5 %,10.3 %] and 2.1 %[-12.3 %,16.4 %] for short-axis and 1.1 %[-7.3 %,9.4 %] and 0.8 %[-16.0 %,17.6 %] for transverse orientation, respectively. There was no significant interaction between imaging orientation and interstudy reproducibility (p = 0.395-0.824), intra-observer variability (p = 0.726-0.862) or inter-observer variability (p = 0.447-0.706) by 2-way ANOVA. Inter-observer agreement by ICC was greater for short axis versus transverse orientation for all parameters (0.769-0.986 vs. 0.625-0.983, respectively). Minimal detectable differences for short axis and transverse orientations were 10.1 mL/11.5 mL for EDV, 8.3 mL/8.4 mL for ESV and 4.1 % vs. 4.7 % for EF, respectively. CONCLUSION: Short-axis and transverse orientation both provide reliable and reproducible measures for follow-up of RV volumes and global function. Therefore, additional transverse SSFP cine CMR may not necessarily be required if performed for the sole purpose of quantitative volumetric RV assessment.

Randomized controlled trial of relaxation music to reduce heart rate in patients undergoing cardiac CT.

OBJECTIVES: To evaluate the heart rate lowering effect of relaxation music in patients undergoing coronary CT angiography (CCTA), pulmonary vein CT (PVCT) and coronary calcium score CT (CCS). METHODS: Patients were randomised to a control group (i.e. standard of care protocol) or to a relaxation music group (ie. standard of care protocol with music). The groups were compared for heart rate, radiation dose, image quality and dose of IV metoprolol. Both groups completed State-Trait Anxiety Inventory anxiety questionnaires to assess patient experience. RESULTS: One hundred and ninety-seven patients were recruited (61.9 % males); mean age 56y (19-86 y); 127 CCTA, 17 PVCT, 53 CCS. No significant difference in heart rate, radiation dose, image quality, metoprolol dose and anxiety scores. 86 % of patients enjoyed the music. 90 % of patients in the music group expressed a strong preference to have music for future examinations. The patient cohort demonstrated low anxiety levels prior to CT. CONCLUSION: Relaxation music in CCTA, PVCT and CCS does not reduce heart rate or IV metoprolol use. Patients showed low levels of anxiety indicating that anxiolytics may not have a significant role in lowering heart rate. Music can be used in cardiac CT to improve patient experience. KEY POINTS: • Relaxation music does not reduce heart rate in cardiac CT • Relaxation music does not reduce beta-blocker use in cardiac CT • Relaxation music has no effect on cardiac CT image quality • Low levels of anxiety are present in patients prior to cardiac CT • Patients enjoyed the relaxation music and this results in improved patient experience.

Magnetic resonance assessment of pulmonary (QP) to systemic (QS) flows using 4D phase-contrast imaging: pilot study comparison with standard through-plane 2D phase-contrast imaging.

RATIONALE AND OBJECTIVES: To investigate four-dimensional (4D) phase-contrast (PC) magnetic resonance (MR) in the evaluation of intracardiac shunts by simultaneous assessment of pulmonary (QP) and systemic (QS) flows in a pilot study and to compare results to through-plane two-dimensional (2D) PC MR. MATERIALS AND METHODS: Institutional review board approval and written informed consent were obtained. Nineteen patients with suspected intracardiac shunts underwent cardiac MR at 1.5T. Assessments of QP and QS were performed using free-breathing retrospectively gated 2D PC gradient recalled echo (GRE; 1.6 × 1.6 × 5 mm(3)) imaging with one-dimensional through-plane velocity encoding gradient (venc = 150 cm/s) in consecutive measurements for the main pulmonary artery (MPA) and ascending aorta (AA), respectively. A prospectively triggered 4D PC GRE technique (2.4 × 1.8 × 3 mm(3)) with three orthogonal venc directions was also used with volume coverage of both MPA and AA. RESULTS: QP and QS assessed by 4D PC correlated with 2D PC acquisitions (r = 0.92 and r = 0.67 respectively; P < .0001 for both) but demonstrated significant underestimation of individual flow volumes (-21.9 ± 12.2 mL; P < .0001 and -10.7 ± 13.1 mL; P = .0023, respectively). Calculated QP:QS ratios demonstrated high correlation (r = 0.78; P < .0001) and no significant differences between 4D PC and 2D PC acquisitions (-0.09 ± 0.24, P = .14). Image acquisition times for 2D PC assessment of QP and QS were 2.98 ± 0.52 and 2.84 ± 0.50 minutes, respectively (P = .038), whereas time to acquire 4D PC images was significantly longer, 18.75 ± 4.58 minutes (P < .001). CONCLUSIONS: Four-dimensional PC MR imaging allows for accurate assessment of QP:QS ratios in the evaluation of intracardiac shunts while absolute flow volumes demonstrate offsets. Further refinement of the technique with improvement in acquisition times may be required before widespread clinical implementation.