Evaluation of left atrial remodeling using cardiovascular magnetic resonance imaging in breast cancer patients treated with adjuvant trastuzumab.

OBJECTIVES: We evaluated left atrial (LA) remodeling using cardiac MRI (CMR) in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer during and after trastuzumab therapy. METHODS: In this prospective 2-center longitudinal study, 41 women with HER2-positive breast cancer received adjuvant trastuzumab for 12 months, in addition to standard chemotherapy. Serial CMRs were performed at baseline, 6, 12, and 18 months after initiation of trastuzumab. LA volumes were measured by a blinded reader. Linear mixed model was used to evaluate longitudinal changes. RESULTS: Of 41 women (mean age 52 ± 11 [SD] years; 56% received anthracycline), one patient experienced trastuzumab-induced cardiotoxicity (TIC) for which trastuzumab was interrupted for one cycle. Mean baseline left ventricular ejection fraction (LVEF) was 68.0 ± 5.9% and LA ejection fraction (LAEF) was 66.0 ± 6.6%. Compared to baseline, LAEF decreased significantly at 6 months (62.7 ± 5.7%, p = 0.027) and 12 months (62.2 ± 6.1%, p = 0.003), while indexed LA minimum volume (LAmin) significantly increased at 12 months (11.6 ± 4.9 ml/m2 vs 13.8 ± 4.5 ml/m2, p = 0.002). At 18 months, all changes from baseline were no longer significant. From baseline to 6 months, change in LAEF correlated with change in LVEF (Spearman's r = 0.41, p = 0.014). No significant interactions (all p > 0.10) were detected between time and anthracycline use for LA parameters. CONCLUSIONS: Among trastuzumab-treated patients with low incidence of TIC, we observed a small but significant decline in LAEF and increase in LAmin that persisted for the duration of therapy and recovered 6 months after therapy cessation. These findings suggest that trastuzumab has concurrent detrimental effects on atrial and ventricular remodeling. KEY POINTS: • In trastuzumab-treated breast cancer patients evaluated by cardiac MRI, left atrial ejection fraction declined and minimum volume increased during treatment and recovered to baseline after trastuzumab cessation. • Changes in left atrial ejection fraction correlated with changes in left ventricular ejection fraction in the first 6 months of trastuzumab treatment. • Trastuzumab therapy is associated with concurrent detrimental effects on left atrial and ventricular remodeling.

Right Ventricular Function at Cardiac MRI Predicts Cardiovascular Events in Patients with an Implantable Cardioverter-Defibrillator.

Background Right ventricular ejection fraction (RVEF) is an independent predictor of death and adverse cardiovascular outcomes in patients with various cardiac conditions. Purpose To investigate whether RVEF, measured with cardiac MRI, is a predictor of appropriate shock or death in implantable cardioverter-defibrillator (ICD) recipients for primary and secondary prevention of sudden cardiac death. Materials and Methods This retrospective, multicenter, observational study included patients who underwent cardiac MRI before ICD implantation between January 2007 and May 2017. Right ventricular end-diastolic and end-systolic volumes and RVEF were measured with cardiac MRI. The primary end point was a composite of all-cause mortality or appropriate ICD shock. The secondary end point was all-cause mortality. The association between RVEF and primary and secondary outcomes was evaluated by using multivariable Cox regression analysis. Potential interactions were tested between primary prevention, ischemic cause, left ventricular ejection fraction (LVEF), and RVEF. Results Among 411 patients (mean age ± standard deviation, 60 years; 315 men) during a median follow-up of 63 months, 143 (35%) patients experienced an appropriate ICD shock or died. In univariable analysis, lower RVEF was associated with greater risks for appropriate ICD shock or death and for death alone (log-rank trend test, P = .003 and .005 respectively). In multivariable Cox regression analysis adjusting for age at ICD implantation, LVEF, ICD indication (primary vs secondary), ischemic heart disease, and late gadolinium enhancement, RVEF was an independent predictor of the primary outcome (hazard ratio [HR], 1.21 per 10% lower RVEF; 95% CI: 1.04, 1.41; P = .01) and all-cause mortality (HR, 1.25 per 10% lower RVEF; 95% CI: 1.01, 1.55; P = .04). No evidence of significant interactions was found between RVEF and primary or secondary prevention (P = .49), ischemic heart disease (P = .78), and LVEF (P = .29). Conclusion Right ventricular ejection fraction measured with cardiac MRI was a predictor of appropriate implantable cardioverter-defibrillator shock or death. © RSNA, 2021 See also the editorial by Nazarian and Zghaib in this issue. An earlier incorrect version of this article appeared online. This article was corrected on August 24, 2021.

Reduced Flow in Delayed Graft Function as Assessed by IVIM Is Associated With Time to Recovery Following Kidney Transplantation.

BACKGROUND: Delayed graft function (DGF), defined as the need for dialysis in the first week after kidney transplantation, frequently complicates posttransplantation care. The most common cause of DGF is ischemia-reperfusion injury (IRI). To date, no clinical tools can accurately estimate its severity, nor the time required for recovery of kidney function. PURPOSE: To investigate if parameters related to directed flow and diffusion of water, as determined by intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI), could be used to differentiate DGF from normal graft function posttransplantation, predict time to recovery from DGF, and hence serve as a surrogate measure of IRI severity. STUDY TYPE: Prospective, cross-sectional cohort study. POPULATION: Fifty consecutive kidney transplant recipients within 3-10 days posttransplantation at our hospital. FIELD STRENGTH/SEQUENCE: 3.0T/IVIM-DWI. ASSESSMENT: The following IVIM-DWI parameters were studied: flow-fraction (f), apparent diffusion coefficient (ADC), and total-ADC (ADCT ). Mean intrarenal resistive index (R.I.) from Doppler ultrasound was also included for a comparison of IVIM-DWI with the clinical standard of care. STATISTICAL TESTS: Welch's t-test, Spearman's correlation, and linear regression. RESULTS: f was significantly reduced in DGF compared to non-DGF patients in the cortex, medulla, and whole renal parenchyma (P < 0.05). Time to recovery with respect to MRI correlated negatively with f (P < 0.05; rho = -0.52 (cortex), and -0.65 [parenchyma]), ADC (P < 0.05; rho = -0.59 [cortex], 0.59 [medulla], and -0.59 [parenchyma]) and ADCT (P < 0.05; rho = -0.54 [cortex], and -0.52 [medulla]). Whole renal parenchymal f predicted time to recovery relative to MRI (P < 0.05, adjusted r-squared = 0.36). R.I. was significantly different between the groups but did not correlate with time to recovery with respect to MRI (rho = 0.43, P = 0.096). DATA CONCLUSION: Quantification of renal flow using IVIM-DWI has the potential to serve as a surrogate measure of IRI severity to estimate the degree of and recovery from DGF. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 3.

Prognostic value of cardiovascular magnetic resonance left ventricular volumetry and geometry in patients receiving an implantable cardioverter defibrillator.

BACKGROUND: Current indications for implantable cardioverter defibrillator (ICD) implantation for sudden cardiac death prevention rely primarily on left ventricular (LV) ejection fraction (LVEF). Currently, two different contouring methods by cardiovascular magnetic resonance (CMR) are used for LVEF calculation. We evaluated the comparative prognostic value of these two methods in the ICD population, and if measures of LV geometry added predictive value. METHODS: In this retrospective, 2-center observational cohort study, patients underwent CMR prior to ICD implantation for primary or secondary prevention from January 2005 to December 2018. Two readers, blinded to all clinical and outcome data assessed CMR studies by: (a) including the LV trabeculae and papillary muscles (TPM) (trabeculated endocardial contours), and (b) excluding LV TPM (rounded endocardial contours) from the total LV mass for calculation of LVEF, LV volumes and mass. LV sphericity and sphere-volume indices were also calculated. The primary outcome was a composite of appropriate ICD shocks or death. RESULTS: Of the 372 consecutive eligible patients, 129 patients (34.7%) had appropriate ICD shock, and 65 (17.5%) died over a median duration follow-up of 61 months (IQR 38-103). LVEF was higher when including TPM versus excluding TPM (36% vs. 31%, p < 0.001). The rate of appropriate ICD shock or all-cause death was higher among patients with lower LVEF both including and excluding TPM (p for trend = 0.019 and 0.004, respectively). In multivariable models adjusting for age, primary prevention, ischemic heart disease and late gadolinium enhancement, both LVEF (HR per 10% including TPM 0.814 [95%CI 0.688-0.962] p = 0.016, vs. HR per 10% excluding TPM 0.780 [95%CI 0.639-0.951] p = 0.014) and LV mass index (HR per 10 g/m2 including TPM 1.099 [95%CI 1.027-1.175] p = 0.006; HR per 10 g/m2 excluding TPM 1.126 [95%CI 1.032-1.228] p = 0.008) had independent prognostic value. Higher LV end-systolic volumes and LV sphericity were significantly associated with increased mortality but showed no added prognostic value. CONCLUSION: Both CMR post-processing methods showed similar prognostic value and can be used for LVEF assessment. LVEF and indexed LV mass are independent predictors for appropriate ICD shocks and all-cause mortality in the ICD population.

Reduced Cognitive Assessment Scores Among Individuals With Magnetic Resonance Imaging-Detected Vascular Brain Injury.

Background and Purpose- Little is known about the association between covert vascular brain injury and cognitive impairment in middle-aged populations. We investigated if scores on a cognitive screen were lower in individuals with higher cardiovascular risk, and those with covert vascular brain injury. Methods- Seven thousand five hundred forty-seven adults, aged 35 to 69 years, free of cardiovascular disease underwent a cognitive assessment using the Digital Symbol Substitution test and Montreal Cognitive Assessment, and magnetic resonance imaging (MRI) to detect covert vascular brain injury (high white matter hyperintensities, lacunar, and nonlacunar brain infarctions). Cardiovascular risk factors were quantified using the INTERHEART (A Global Study of Risk Factors for Acute Myocardial Infarction) risk score. Multivariable mixed models tested for independent determinants of reduced cognitive scores. The population attributable risk of risk factors and MRI vascular brain injury on low cognitive scores was calculated. Results- The mean age of participants was 58 (SD, 9) years; 55% were women. Montreal Cognitive Assessment and Digital Symbol Substitution test scores decreased significantly with increasing age (P<0.0001), INTERHEART risk score (P<0.0001), and among individuals with high white matter hyperintensities, nonlacunar brain infarction, and individuals with 3+ silent brain infarctions. Adjusted for age, sex, education, ethnicity covariates, Digital Symbol Substitution test was significantly lowered by 1.0 (95% CI, -1.3 to -0.7) point per 5-point cardiovascular risk score increase, 1.9 (95% CI, -3.2 to -0.6) per high white matter hyperintensities, 3.5 (95% CI, -6.4 to -0.7) per nonlacunar stroke, and 6.8 (95% CI, -11.5 to -2.2) when 3+ silent brain infarctions were present. No postsecondary education accounted for 15% (95% CI, 12-17), moderate and high levels of cardiovascular risk factors accounted for 19% (95% CI, 8-30), and MRI vascular brain injury accounted for 10% (95% CI, -3 to 22) of low test scores. Conclusions- Among a middle-aged community-dwelling population, scores on a cognitive screen were lower in individuals with higher cardiovascular risk factors or MRI vascular brain injury. Much of the population attributable risk of low cognitive scores can be attributed to lower educational attainment, higher cardiovascular risk factors, and MRI vascular brain injury.

MR imaging in the presence of ballistic debris of unknown composition: a review of the literature and practical approach.

Due to a combination of increasing indications for MR imaging, increased MRI accessibility, and extensive global armed conflict over the last few decades, an increasing number of patients now and in the future will present with retained metallic ballistic debris of unknown composition. To date, there are no guidelines on how to safely image these patients which may result in patients who would benefit from MRI not receiving it. In this article, we review the current literature pertaining to the MRI safety of retained ballistic materials and present the process we use to safely image these patients.

Left ventricular strain analysis using cardiac magnetic resonance imaging in patients undergoing in-centre nocturnal haemodialysis.

AIM: Intensified haemodialysis is associated with regression of left ventricular (LV) mass. Compared to LV ejection fraction, LV strain allows more direct assessment of LV function. We sought to assess the impact of in-centre nocturnal haemodialysis (INHD) on global LV strain (radial, circumferential, and longitudinal) and torsion by cardiac MRI (CMR). METHODS: In this prospective, two-centre cohort study, 37 participants on conventional haemodialysis (CHD, 3-4 h/session for three sessions/week) converted to INHD (7-8 h/session for three sessions/week) and 30 participants continued CHD. Participants underwent CMR using a standardized protocol and had biomarker measurements at baseline and 52 weeks. RESULTS: Among the 55 participants (mean age 55; 40% women) with complete CMR data, those who converted to INHD had a significant improvement in their global circumferential strain (GCS, P = 0.025), while those continuing CHD did not have any significant changes in LV strain. When the two groups were compared, there was significant improvement in torsion. LV strains were significantly correlated with each other, but not with troponin I, C-reactive protein, or brain natriuretic protein (NT-proBNP), except for global longitudinal strain (GLS) with troponin I (P = 0.001) and NT-proBNP (P = 0.038). CONCLUSION: Conversion to INHD was associated with significant improvement in GCS over one year of study, although comparisons with the CHD group were not significant. There was also a significant decrease in torsion in the INHD group compared with CHD. Improvement in LV regional function would support the notion that INHD has favourable effects on both LV structure and function.

Association between conversion to in-center nocturnal hemodialysis and right ventricular remodeling.

Background: In-center nocturnal hemodialysis (INHD) is associated with favorable left ventricular (LV) remodeling. Although right ventricular (RV) structure and function carry prognostic significance, the impact of dialysis intensification on RV is unknown. Our objectives were to evaluate changes in RV mass index (MI), end-diastolic volume index (EDVI), end-systolic volume index (ESVI) and ejection fraction (EF) after conversion to INHD and their relationship with LV remodeling. Methods: Of 67 conventional hemodialysis (CHD, 4 h/session, three times/week) patients, 30 continued on CHD and 37 converted to INHD (7-8 h/session, three times/week). Cardiac magnetic resonance imaging was performed at baseline and 1 year using a standardized protocol; an experienced and blinded reader performed RV measurements. Results: At 1 year there were significant reductions in RVMI {-2.1 g/m2 [95% confidence interval (CI) -3.8 to - 0.4], P = 0.017}, RVEDVI [-9.5 mL/m2 (95% CI - 16.3 to - 2.6), P = 0.008] and RVESVI [-6.2 mL/m2 (95% CI - 10.9 to - 1.6), P = 0.011] in the INHD group; no significant changes were observed in the CHD group. Between-group comparisons showed significantly greater reduction of RVESVI [-7.9 mL/m2 (95% CI - 14.9 to - 0.9), P = 0.03] in the INHD group, a nonsignificant trend toward greater reduction in RVEDVI and no significant difference in RVMI and RVEF changes. There was significant correlation between LV and RV in terms of changes in mass index (MI) (r = 0.46), EDVI (r = 0.73), ESVI (r = 0.7) and EF (r = 0.38) over 1 year (all P < 0.01). Conclusions: Conversion to INHD was associated with a significant reduction of RVESVI. Temporal changes in RV mass, volume and function paralleled those of LV. Our findings support the need for larger, longer-term studies to confirm favorable RV remodeling and determine its impact on clinical outcomes.

Longitudinal assessment of right ventricular structure and function by cardiovascular magnetic resonance in breast cancer patients treated with trastuzumab: a prospective observational study.

BACKGROUND: There are limited data on the effects of trastuzumab on the right ventricle (RV). Therefore, we sought to evaluate the temporal changes in right ventricular (RV) structure and function as measured by cardiovascular magnetic resonance (CMR), and their relationship with left ventricular (LV) structure and function in breast cancer patients treated with trastuzumab. METHODS: Prospective, longitudinal, observational study involving 41 women with HER2+ breast cancer who underwent serial CMR at baseline, 6, 12, and 18 months after initiation of trastuzumab. A single blinded observer measured RV parameters on de-identified CMRs in a random order. Linear mixed models were used to investigate temporal changes in RV parameters. RESULTS: Of the 41 women (age 52 ± 11 years), only one patient experienced trastuzumab-induced cardiotoxicity. Compared to baseline, there were small but significant increases in the RV end-diastolic volume at 6 months (p = 0.002) and RV end-systolic volume at 6 and 12 months (p < 0.001 for both), but not at 18 months (p = 0.82 and 0.13 respectively). RV ejection fraction (RVEF), when compared to baseline (58.3%, 95% CI 57.1-59.5%), showed corresponding decreases at 6 months (53.9%, 95% CI 52.5-55.4%, p < 0.001) and 12 months (55%, 95% CI 53.8-56.2%, p < 0.001) that recovered at 18 months (56.6%, 95% CI 55.1-58.0%, p = 0.08). Although the temporal pattern of changes in LVEF and RVEF were similar, there was no significant correlation between RVEF and LVEF at baseline (r = 0.29, p = 0.07) or between their changes at 6 months (r = 0.24, p = 0.17). CONCLUSION: In patients receiving trastuzumab without overt cardiotoxicity, there is a subtle but significant deleterious effect on RV structure and function that recover at 18 months, which can be detected by CMR. Furthermore, monitoring of LVEF alone may not be sufficient in detecting early RV injury. These novel findings provide further support for CMR in monitoring early cardiotoxicity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01022086 . Date of registration: November 27, 2009.

Effect of a Biopsy Center on Adequacy Rates of Thyroid Nodule Fine-Needle Aspiration.

OBJECTIVE: The purpose of this study was to investigate the effect of a biopsy center-a dedicated space with a dedicated ultrasound machine and technologist, staffed daily by a radiologist responsible for performing ultrasound-guided procedures only-on the rate of non-diagnostic or unsatisfactory thyroid fine-needle aspiration (FNA). MATERIALS AND METHODS: Three radiologists performed FNA on 1200 nodules in 998 patients between September 2010 and November 2015. We compared rates of nondiagnostic or unsatisfactory FNA before and after implementation of a biopsy center in September 2014 as part of a quality improvement initiative. Before the establishment of our biopsy center, ultrasound-guided procedures were scheduled between diagnostic studies in the main ultrasound department and were performed by a radiologist responsible for both. Multivariate logistic regression analysis was performed to assess the effect of the biopsy center on the odds of obtaining an adequate sample. RESULTS: Rates of nondiagnostic or unsatisfactory FNA decreased significantly from 15.1% to 8.5% (p < 0.001) after implementation of the biopsy center. The odds of obtaining an adequate sample were higher in the biopsy center (odds ratio, 2.07; 95% CI, 1.43-3.01), even after adjusting for patient age, nodule size, the radiologist performing the procedure, and time over the study period. CONCLUSION: The implementation of a biopsy center was associated with significantly lower rates of nondiagnostic or unsatisfactory thyroid FNA, suggesting target rates of 10% or lower are achievable with quality improvement measures.

The role of thrombectomy and diffusion-weighted imaging with MRI in post-transplant renal vein thrombosis: a case report.

BACKGROUND: Surgical thrombectomy in the context of acute renal vein thrombosis (RVT) post-transplantation has had limited success, with considerable variation in the surgical techniques used. Unfortunately, it is usually followed by allograft nephrectomy within a few days if rapid allograft recovery does not ensue. We report a case of acute RVT in which nephrectomy was not performed despite a prolonged requirement for dialysis post-thrombectomy, but with recovery of renal function 2 weeks later. We also report the findings of serial MRI with diffusion-weighted imaging (DW-MRI) throughout the patient's recovery, which provided novel insights into allograft microvascular perfusion changes post-thrombectomy. CASE PRESENTATION: A 65-year old patient underwent living-unrelated kidney transplantation complicated by acute RVT. Surgical thrombectomy and irrigation led to a delayed, but significant, recovery of renal function. Serial non-contrast DW-MRI scanning was used to non-invasively assess microvascular renal blood flow post-operatively. Unlike standard Doppler ultrasonography, DW-MRI documented reduced microvascular perfusion initially, with gradual but incomplete recovery that mirrored the partial improvement in renal function. CONCLUSIONS: Our findings suggest that surgical thrombectomy may be more effective than previously described if followed by careful patient observation. Moreover, diffusion-weighted MRI appears to provide important insights into the pathophysiology of delayed graft function and deserves further investigation.

Pancreas volume measurement in patients with Type 2 diabetes using magnetic resonance imaging-based planimetry.

BACKGROUND/OBJECTIVES: To compare pancreas volume (PV) measurement using MRI-based planimetry in patients with Type 2 diabetes mellitus (DM) to PV in normoglycemic individuals. METHODS: Our institutional review board granted approval of this retrospective study with waiver of informed consent. We searched 2296 consecutive abdominal MRI studies performed at our hospital on patients with no pancreas pathology between September 1, 2010 and February 28, 2013, for those who also had a fasting plasma glucose and/or hemoglobin A1C within six months of the MRI examination. For those patients who met biochemical criteria for DM, we used medication and clinical records to confirm that 32 of these patients had Type 2 DM. The pancreas contours of 32 Type 2 diabetics and 50 normoglycemic individuals were then traced on non-gadolinium T1-weighted 3D fat suppressed gradient echo images by a radiologist trained in abdominal MRI to calculate PV. PV index (PVI) was calculated as PV/weight to adjust PV for each patient's weight. PVs and PVIs in both cohorts were compared using t-tests and regression models correcting for weight, age and gender. RESULTS: Patients with Type 2 DM had significantly lower PVs than normoglycemic individuals (72.7 ± 20.7 cm(3) versus 89.6 ± 22.7 cm(3), p < 0.001), and significantly lower PVIs (1.0 ± 0.3 cm(3)/kg versus 1.3 ± 0.3 cm(3)/kg, p < 0.001). Using regression models, we found that given the same age, weight and gender, the PV in a patient with Type 2 DM was 17.9 mL (20%) lower compared to a normoglycemic individual (p < 0.001). CONCLUSION: PV is reduced in Type 2 DM compared to normoglycemic individuals and can be measured using MRI without contrast injection.

Improvement of ischemic cholangiopathy in three patients with hereditary hemorrhagic telangiectasia following treatment with bevacizumab.

The ischemic biliary phenotype of hereditary hemorrhagic telangiectasia (HHT) is rare but distinct, with progressive biliary tree ischemia usually resulting in an irreversible secondary sclerosing cholangiopathy. When clinically severe, liver transplant is often indicated. We report three patients with marked HHT associated biliary disease, in whom prolonged anti-vascular endothelial growth factor therapy (bevacizumab) notably reversed imaging evidence of biliary disease and clinically obviated need for liver transplantation during the first year of follow-up.

Prognostic Value of Different Thresholds for Myocardial Scar Quantification on Cardiac MRI Late Gadolinium Enhancement Images in Patients Receiving Implantable Cardioverter Defibrillators.

Purpose: To compare the predictive value of different myocardial scar quantification thresholds using cardiac MRI for appropriate implantable cardioverter defibrillator (ICD) shock and mortality. Materials and Methods: In this retrospective, two-center observational cohort study, patients with ischemic or nonischemic cardiomyopathy underwent cardiac MRI prior to ICD implantation. Late gadolinium enhancement (LGE) was first determined visually and then quantified by blinded cardiac MRI readers using different SDs above the mean signal of normal myocardium, full-width half-maximum, and manual thresholding. The intermediate signal "gray zone" was calculated as the differences between different SDs. Results: Among 374 consecutive eligible patients (mean age, 61 years ± 13 [SD]; mean left ventricular ejection fraction, 32% ± 14; secondary prevention, 62.7%), those with LGE had a higher rate of appropriate ICD shock or death than those without (37.5% vs 26.6%, log-rank P = .04) over a median follow-up of 61 months. In multivariable analysis, none of the thresholds for quantifying scar was a significant predictor of mortality or appropriate ICD shock, while the extent of gray zone was an independent predictor (adjusted hazard ratio per 1 g = 1.025; 95% CI: 1.008, 1.043; P = .005) regardless of the presence or absence of ischemic heart disease (P interaction = .57). Model discrimination was highest for the model incorporating the gray zone (between 2 SD and 4 SD). Conclusion: Presence of LGE was associated with a higher rate of appropriate ICD shock or death. Although none of the scar quantification techniques predicted outcomes, the gray zone both in infarct and nonischemic scar was an independent predictor and may refine risk stratification.Keywords: MRI, Scar Quantification, Implantable Cardioverter Defibrillator, Sudden Cardiac Death Supplemental material is available for this article. © RSNA, 2023.

Potential clinical impact of cardiovascular magnetic resonance assessment of ejection fraction on eligibility for cardioverter defibrillator implantation.

BACKGROUND: For the primary prevention of sudden cardiac death, guidelines provide left ventricular ejection fraction (EF) criteria for implantable cardioverter defibrillator (ICD) placement without specifying the technique by which it should be measured. We sought to investigate the potential impact of performing cardiovascular magnetic resonance (CMR) for EF on ICD eligibility. METHODS: The study population consisted of patients being considered for ICD implantation who were referred for EF assessment by CMR. Patients who underwent CMR within 30 days of echocardiography were included. Echocardiographic EF was determined by Simpson's biplane method and CMR EF was measured by Simpson's summation of discs method. RESULTS: Fifty-two patients (age 62±15 years, 81% male) had a mean EF of 38 ± 14% by echocardiography and 35 ± 14% by CMR. CMR had greater reproducibility than echocardiography for both intra-observer (ICC, 0.98 vs 0.94) and inter-observer comparisons (ICC 0.99 vs 0.93). The limits of agreement comparing CMR and echocardiographic EF were - 16 to +10 percentage points. CMR resulted in 11 of 52 (21%) and 5 of 52 (10%) of patients being reclassified regarding ICD eligibility at the EF thresholds of 35 and 30% respectively. Among patients with an echocardiographic EF of between 25 and 40%, 9 of 22 (41%) were reclassified by CMR at either the 35 or 30% threshold. Echocardiography identified only 1 of the 6 patients with left ventricular thrombus noted incidentally on CMR. CONCLUSIONS: CMR resulted in 21% of patients being reclassified regarding ICD eligibility when strict EF criteria were used. In addition, CMR detected unexpected left ventricular thrombus in almost 10% of patients. Our findings suggest that the use of CMR for EF assessment may have a substantial impact on management in patients being considered for ICD implantation.

Magnetic Resonance Elastography-derived Stiffness Predicts Renal Function Loss and Is Associated With Microvascular Inflammation in Kidney Transplant Recipients.

Background: Organ stiffening can be caused by inflammation and fibrosis, processes that are common causes of transplant kidney dysfunction. Magnetic resonance elastography (MRE) is a contrast-free, noninvasive imaging modality that measures kidney stiffness. The objective of this study was to assess the ability of MRE to serve as a prognostic factor for renal outcomes. Methods: Patients were recruited from the St Michael's Hospital Kidney Transplant Clinic. Relevant baseline demographic, clinical, and Banff histologic information, along with follow-up estimated glomerular filtration rate (eGFR) data, were recorded. Two-dimensional gradient-echo MRE imaging was performed to obtain kidney "stiffness" maps. Binary logistic regression analyses were performed to examine for relationships between stiffness and microvascular inflammation score. Linear mixed-effects modeling was used to assess the relationship between stiffness and eGFR change over time controlling for other baseline variables. A G2-likelihood ratio Chi-squared test was performed to compare between the baseline models with and without "stiffness." Results: Sixty-eight transplant kidneys were scanned in 66 patients (mean age 56 ± 12 y, 24 females), with 38 allografts undergoing a contemporaneous biopsy. Mean transplant vintage was 7.0 ± 6.8 y. In biopsied allografts, MRE-derived allograft stiffness was associated only with microvascular inflammation (Banff g + ptc score, Spearman ρ = 0.43, P = 0.01), but no other histologic parameters. Stiffness was negatively associated with eGFR change over time (Stiffness × Time interaction ß = -0.80, P < 0.0001), a finding that remained significant even when adjusted for biopsy status and baseline variables (Stiffness × Time interaction ß = -0.46, P = 0.04). Conversely, the clinical models including "stiffness" showed significantly better fit (P = 0.04) compared with the baseline clinical models without "stiffness." Conclusions: MRE-derived renal stiffness provides important prognostic information regarding renal function loss for patients with allograft dysfunction, over and above what is provided by current clinical variables.

Relationship Between Left Ventricular Strain Assessment by Cardiac Magnetic Resonance Imaging and Response to Cardiac Resynchronization Therapy.

Although cardiac resynchronization therapy (CRT) is an established treatment for heart failure with reduced ejection fraction, 30 to 50% patients are non-responders. In this retrospective single-centre study, 19 patients underwent cardiac MRI pre-CRT, and global left ventricular (LV) strain and late gadolinium enhancement (LGE) were measured by a blinded reader. LV reverse remodeling was independently assessed using transthoracic echocardiogram before and after CRT implant. Both LV strain and extent of LGE correlated significantly with measures of reverse LV remodeling (reduction in LV volume and improvement in LV ejection fraction). These findings suggest that CMR derived strain analysis and scar evaluation may be useful preimplant predictors of response to CRT. Larger prospective multi-center studies are needed to confirm these findings and to further evaluate the role of CMR strain imaging in guiding CRT treatment decisions.

NUAK1 promotes organ fibrosis via YAP and TGF-ß/SMAD signaling.

Fibrosis is a central pathway that drives progression of multiple chronic diseases, yet few safe and effective clinical antifibrotic therapies exist. In most fibrotic disorders, transforming growth factor-ß (TGF-ß)-driven scarring is an important pathologic feature and a key contributor to disease progression. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are two closely related transcription cofactors that are important for coordinating fibrogenesis after organ injury, but how they are activated in response to tissue injury has, so far, remained unclear. Here, we describe NUAK family kinase 1 (NUAK1) as a TGF-ß-inducible profibrotic kinase that is up-regulated in multiple fibrotic organs in mice and humans. Mechanistically, we show that TGF-ß induces a rapid increase in NUAK1 in fibroblasts. NUAK1, in turn, can promote profibrotic YAP and TGF-ß/SMAD signaling, ultimately leading to organ scarring. Moreover, activated YAP and TAZ can induce further NUAK1 expression, creating a profibrotic positive feedback loop that enables persistent fibrosis. Using mouse models of kidney, lung, and liver fibrosis, we demonstrate that this fibrogenic signaling loop can be interrupted via fibroblast-specific loss of NUAK1 expression, leading to marked attenuation of fibrosis. Pharmacologic NUAK1 inhibition also reduced scarring, either when initiated immediately after injury or when initiated after fibrosis was already established. Together, our data suggest that NUAK1 plays a critical, previously unrecognized role in fibrogenesis and represents an attractive target for strategies that aim to slow fibrotic disease progression.

The Increase in Paraoxonase 1 Is Associated With Decrease in Left Ventricular Volume in Kidney Transplant Recipients.

Background: Patients on dialysis have impaired cardiac function, in part due to increased fluid volume and ventricular stress. Restored kidney function through transplantation reduces left ventricular volume in both systole and diastole. We previously reported that the decrease in NT-proB-type natriuretic peptide (NT-proBNP) was associated with a decrease in adiponectin. Paraoxonase 1 (PON1) has been inversely associated with cardiovascular outcomes. We now report the association of changes in PON1 with changes in left ventricular volume and left ventricular mass after kidney transplantation. Design: Patients on dialysis were assessed at baseline and 12 months after kidney transplantation (n = 38). A comparison group of patients on dialysis who were not expected to receive a transplant in the next 24 months were studied (n = 43) to determine if the change of PON1 with kidney transplantation achieved a significance greater than that due to biologic variation. Left ventricular volume and mass were determined by cardiac magnetic resonance imaging. PON1 was measured by arylesterase activity and by mass. Results: PON1 mass and activity were not different between the groups at baseline. Both PON1 mass and activity were increased post-kidney transplantation (p < 0.0001 for change). The change in PON1 mass (p = 0.0062) and PON1 arylesterase activity (p = 0.0254) were inversely correlated with the change in NT-proBNP for patients receiving a kidney transplant. However, only the change in the PON1 mass, and not the change in PON1 arylesterase, was inversely correlated with the change in left ventricular volume (ml/m2.7) (p = 0.0146 and 0.0114 for diastolic and systolic, respectively) and with the change in hemoglobin (p = 0.0042). Conclusion: Both PON1 mass and arylesterase activity are increased by kidney transplantation. The increase in PON1 mass is consistent with a novel relationship to the increase in hemoglobin and decrease in left ventricular volume and NT-proBNP seen when kidney function is restored.

Metformin for early comorbid glucose dysregulation and schizophrenia spectrum disorders: a pilot double-blind randomized clinical trial.

Patients with schizophrenia have exceedingly high rates of metabolic comorbidity including type 2 diabetes and lose 15-20 years of life due to cardiovascular diseases, with early accrual of cardiometabolic disease. In this study, thirty overweight or obese (Body Mass Index (BMI) > 25) participants under 40 years old with schizophrenia spectrum disorders and early comorbid prediabetes or type 2 diabetes receiving antipsychotic medications were randomized, in a double-blind fashion, to metformin 1500 mg/day or placebo (2:1 ratio; n = 21 metformin and n = 9 placebo) for 4 months. The primary outcome measures were improvements in glucose homeostasis (HbA1c, fasting glucose) and insulin resistance (Matsuda index-derived from oral glucose tolerance tests and homeostatic model of insulin resistance (HOMA-IR)). Secondary outcome measures included changes in weight, MRI measures of fat mass and distribution, symptom severity, cognition, and hippocampal volume. Twenty-two patients (n = 14 metformin; n = 8 placebo) completed the trial. The metformin group had a significant decrease over time in the HOMA-IR (p = 0.043) and fasting blood glucose (p = 0.007) vs. placebo. There were no differences between treatment groups in the Matsuda index, HbA1c, which could suggest liver-specific effects of metformin. There were no between group differences in other secondary outcome measures, while weight loss in the metformin arm correlated significantly with decreases in subcutaneous, but not visceral or hepatic adipose tissue. Our results show that metformin improved dysglycemia and insulin sensitivity, independent of weight loss, in a young population with prediabetes/diabetes and psychosis spectrum illness, that is at extremely high risk of early cardiovascular mortality. Trial Registration: This protocol was registered with clinicaltrials.gov (NCT02167620).