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.

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.

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.

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.

Effect of Cognitive Reserve on the Association of Vascular Brain Injury With Cognition: Analysis of the PURE and CAHHM Studies.

BACKGROUND AND OBJECTIVES: To determine whether cognitive reserve attenuates the association of vascular brain injury with cognition. METHODS: Cross-sectional data were analyzed from 2 harmonized studies: the Canadian Alliance for Healthy Hearts and Healthy Minds (CAHHM) and the Prospective Urban and Rural Epidemiology (PURE) study. Markers of cognitive reserve were education, involvement in social activities, marital status, height, and leisure physical activity, which were combined into a composite score. Vascular brain injury was defined as nonlacunar brain infarcts or high white matter hyperintensity (WMH) burden on MRI. Cognition was assessed using the Montreal Cognitive Assessment Tool (MoCA) and the Digit Symbol Substitution Test (DSST). RESULTS: There were 10,916 participants age 35-81. Mean age was 58.8 years (range 35-81) and 55.8% were female. Education, moderate leisure physical activity, being in a marital partnership, being taller, and participating in social groups were each independently associated with higher cognition, as was the composite cognitive reserve score. Vascular brain injury was associated with lower cognition (ß -0.35 [95% confidence interval [CI] -0.53 to -0.17] for MoCA and ß -2.19 [95% CI -3.22 to -1.15] for DSST) but the association was not modified by the composite cognitive reserve variable (interaction p = 0.59 for MoCA and p = 0.72 for DSST). CONCLUSIONS: Both vascular brain injury and markers of cognitive reserve are associated with cognition. However, the effects were independent such that the adverse effects of covert vascular brain injury were not attenuated by higher cognitive reserve. To improve cognitive brain health, interventions to both prevent cerebrovascular disease and promote positive lifestyles are needed.

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.

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.

2021 Update on Safety of Magnetic Resonance Imaging: Joint Statement From Canadian Cardiovascular Society/Canadian Society for Cardiovascular Magnetic Resonance/Canadian Heart Rhythm Society.

Magnetic resonance imaging (MRI) is often considered the gold-standard test for characterizing cardiac as well as noncardiac structure and function. However, many patients with cardiac implantable electronic devices (CIEDs) and/or severe renal dysfunction are unable to undergo this test because of safety concerns. In the past 10 years, newer-generation CIEDs and gadolinium-based contrast agents (GBCAs) as well as coordinated care between imaging and heart rhythm device teams have mitigated risk to patients and improved access to MRI at many hospitals. The purpose of this statement is to review published data on safety of MRI in patients with conditional and nonconditional CIEDs in addition to patient risks from older and newer GBCAs. This statement was developed through multidisciplinary collaboration of pan-Canadian experts after a relevant and independent literature search by the Canadian Agency for Drugs and Technologies in Health. All recommendations align with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Key recommendations include: (1) the development of standardized protocols for patients with a CIED undergoing MRI; (2) patients with MRI nonconditional pacemakers and pacemaker dependency should be programmed to asynchronous mode and those with MRI nonconditional transvenous defibrillators should have tachycardia therapies turned off during the scan; and (3) macrocyclic or newer linear GBCAs should be used in preference to older GBCAs because of their better safety profile in patients at higher risk of nephrogenic systemic fibrosis.

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).

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.

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.

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.

Cardiovascular risk scoring and magnetic resonance imaging detected subclinical cerebrovascular disease.

AIMS: Cardiovascular risk factors are used for risk stratification in primary prevention. We sought to determine if simple cardiac risk scores are associated with magnetic resonance imaging (MRI)-detected subclinical cerebrovascular disease including carotid wall volume (CWV), carotid intraplaque haemorrhage (IPH), and silent brain infarction (SBI). METHODS AND RESULTS: A total of 7594 adults with no history of cardiovascular disease (CVD) underwent risk factor assessment and a non-contrast enhanced MRI of the carotid arteries and brain using a standardized protocol in a population-based cohort recruited between 2014 and 2018. The non-lab-based INTERHEART risk score (IHRS) was calculated in all participants; the Framingham Risk Score was calculated in a subset who provided blood samples (n = 3889). The association between these risk scores and MRI measures of CWV, carotid IPH, and SBI was determined. The mean age of the cohort was 58 (8.9) years, 55% were women. Each 5-point increase (∼1 SD) in the IHRS was associated with a 9 mm3 increase in CWV, adjusted for sex (P < 0.0001), a 23% increase in IPH [95% confidence interval (CI) 9-38%], and a 32% (95% CI 20-45%) increase in SBI. These associations were consistent for lacunar and non-lacunar brain infarction. The Framingham Risk Score was also significantly associated with CWV, IPH, and SBI. CWV was additive and independent to the risk scores in its association with IPH and SBI. CONCLUSION: Simple cardiovascular risk scores are significantly associated with the presence of MRI-detected subclinical cerebrovascular disease, including CWV, IPH, and SBI in an adult population without known clinical CVD.

Cardiac MRI measurements of pericardial adipose tissue volumes in patients on in-centre nocturnal hemodialysis.

BACKGROUND: Conversion from conventional hemodialysis (CHD) to in-centre nocturnal hemodialysis (INHD) is associated with left ventricular (LV) mass regression, but the underlying mechanisms are not fully understood. Using cardiac MRI (CMR), we examined the effects of INHD on epicardial adipose tissue (EAT) and paracardial adipose tissue (PAT), and the relationships between EAT, PAT and LV remodeling, biomarkers of nutrition, myocardial injury, fibrosis and volume. METHODS: We conducted a prospective multicenter cohort study of 37 patients transitioned from CHD to INHD and 30 patients on CHD (control). Biochemical markers and CMR were performed at baseline and 52 weeks. CMR images were analyzed by independent readers, blinded to order and treatment group. RESULTS: Among 64 participants with complete CMR studies at baseline (mean age 54; 43% women), there were no significant differences in EAT index (60.6 ± 4.3 mL/m2 vs 64.2 ± 5.1 mL/m2, p = 0.99) or PAT index (60.0 ± 5.4 mL/m2 vs 53.2 ± 5.9 mL/m2, p = 0.42) between INHD and CHD groups. Over 52 weeks, EAT index and PAT index did not change significantly in INHD and CHD groups (p = 0.21 and 0.14, respectively), and the changes in EAT index and PAT index did not differ significantly between INHD and CHD groups (p = 0.30 and 0.16, respectively). Overall, changes in EAT index inversely correlated with changes in LV end-systolic volume index (LVESVI) but not LV end-diastolic volume index (LVEDVI), LV mass index (LVMI), and LV ejection fraction (LVEF). Changes in PAT index inversely correlated with changes in LVESVI, LVMI and positively correlated with changes in LVEF. There were no correlations between changes in EAT index or PAT index with changes in albumin, LDL, triglycerides, troponin-I, FGF-23, or NT-proBNP levels over 52 weeks (all p > 0.30). CONCLUSIONS: INHD was not associated with any changes in EAT index and PAT index over 12 months. Changes in EAT index were not significantly associated with changes in markers of LV remodeling, nutrition, myocardial injury, fibrosis, volume status. In contrast, changes in PAT index, which paradoxically is expected to exert less paracrine effect on the myocardium, were correlated with changes in LVESVI, LVMI and LVEF. Larger and longer-term studies may clarify the role of PAT in cardiac remodeling with intensified hemodialysis. CLINICALTRIALS. GOV IDENTIFIER: NCT00718848.

Assessment of left ventricular function by CMR versus MUGA scans in breast cancer patients receiving trastuzumab: a prospective observational study.

Little is known about the comparison of multiple-gated acquisition (MUGA) scanning with cardiovascular magnetic resonance (CMR) for serial monitoring of HER2+ breast cancer patients receiving trastuzumab. The association of cardiac biomarkers with CMR left ventricular (LV) function and volume is also not well studied. Our objectives were to compare CMR and MUGA for left ventricular ejection fraction (LVEF) assessment, and to examine the association between changes in brain natriuretic peptide (NT-BNP) and troponin-I and changes in CMR LV function and volume. This prospective longitudinal two-centre cohort study recruited HER2+ breast cancer patients between January 2010 and December 2013. MUGA, CMR, NT-BNP and troponin-I were performed at baseline, 6, 12, and 18 months after trastuzumab initiation. In total, 41 patients (age 51.7 ± 10.8 years) were enrolled. LVEF comparison between MUGA and CMR demonstrated weak agreement (Lin's correlation coefficient r = 0.46, baseline; r = 0.29, 6 months; r = 0.42, 12 months; r = 0.39, 18 months; all p < 0.05). Bland-Altman plots demonstrated wide LVEF agreement limits (pooled agreement limits 3.0 ± 6.2). Both modalities demonstrated significant LVEF decline at 6 and 12 months from baseline, concomitant with increased LV volumes on CMR. Changes in NT-BNP correlated with changes in LV diastolic volume at 12 and 18 months (p < 0.05), and LV systolic volume at 18 months (p < 0.05). Changes in troponin-I did not correlate with changes in LV function or volume at any timepoint. In conclusion, CMR and MUGA LVEF are not interchangeable, warranting selection and utility of one modality for serial monitoring. CMR is useful due to less radiation exposure and accuracy of LV volume measurements. Changes in NT-BNP correlated with changes in LV volumes.

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.

Left Atrial Remodeling Assessed by Cardiac MRI after Conversion from Conventional Hemodialysis to In-Centre Nocturnal Hemodialysis.

BACKGROUND: Left atrial (LA) volume is a well-established cardiovascular prognosticator in patients with end-stage renal disease. Although dialysis intensification is associated with left ventricular mass regression, there are limited data regarding LA remodeling. Using cardiac magnetic resonance imaging (CMR), we examined changes in LA size and function relative to ventricular remodeling and cardiac biomarkers after dialysis intensification. METHODS: In this prospective 2-centre cohort study, 37 patients receiving conventional hemodialysis (CHD, 4 h/session, 3×/week) were converted to in-centre nocturnal hemodialysis (INHD 7-8 h/session, 3×/week); 30 patients remained on CHD. CMR and biomarkers were performed at baseline and repeated at 52 weeks. RESULTS: After 52 weeks, there were no significant changes in the LA volumes or LA ejection fraction (EF) within either the CHD or INHD group, and no significant differences between the two groups. Correlations existed between changes in LA and LV end-diastolic volume index (EDVi, Spearman's r = 0.69, p < 0.001), LA and LV end-systolic volume index (ESVi, r = 0.44, p = 0.001), LAEF and LVEF (r = 0.28, p = 0.04), LA and RV EDVi (r = 0.51, p < 0.001), LA and RV ESVi (r = 0.29, p = 0.039), and LA ESVi and LV mass index (r = 0.31, p = 0.02). At baseline, indexed LA volumes positively correlated with NT-proBNP, whereas LAEF negatively correlated with NT-proBNP and Troponin I. After 52 weeks, changes in biomarker levels did not correlate with changes in LA volume or EF. CONCLUSION: There was no significant change in LA size or systolic function after conversion to INHD. The significant correlations between LA and ventricular remodeling and cardiac biomarkers suggest common underlying pathophysiologic mechanisms. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00718848.

Determinants of Left Ventricular Characteristics Assessed by Cardiac Magnetic Resonance Imaging and Cardiovascular Biomarkers Related to Kidney Transplantation.

BACKGROUND: Cardiac magnetic resonance (CMR) imaging accurately and precisely measures left ventricular (LV) mass and function. Identifying mechanisms by which LV mass change and functional improvement occur in some end-stage kidney disease (ESKD) patients may help to appropriately target kidney transplant (KT) recipients for further investigation and intervention. The concentration of serum adiponectin, a cardiovascular biomarker, increases in cardiac failure, its production being enhanced by B-type natriuretic peptide (BNP), and both serum adiponectin and BNP concentrations decline posttransplantation. OBJECTIVE: We tested the hypothesis that kidney transplantation alters LV characteristics that relate to serum adiponectin concentrations. DESIGN: Prospective and observational cohort study. SETTING: The study was performed at 3 adult kidney transplant and dialysis centers in Ontario, Canada. PATIENTS: A total of 82 KT candidate subjects were recruited (39 to the KT group and 43 to the dialysis group). Predialysis patients were excluded. MEASUREMENTS: Subjects underwent CMR with a 1.5-tesla whole-body magnetic resonance scanner using a phased-array cardiac coil and retrospective vectorographic gating. LV mass, LV ejection fraction (LVEF), LV end-systolic volume (LVESV), and LV end-diastolic volume (LVEDV) were measured by CMR pre-KT and again 12 months post-KT (N = 39), or 12 months later if still receiving dialysis (N = 43). LV mass, LVESV, and LVEDV were indexed for height (m2.7) to calculate left ventricular mass index (LVMI), left ventricular end-systolic volume index (LVESVI), and left ventricular end-diastolic volume index (LVEDVI), respectively. Serum total adiponectin and N-terminal proBNP (NT-proBNP) concentrations were measured at baseline, 3 months, and 12 months. METHODS: We performed a prospective 1:1 observational study comparing KT candidates with ESKD either receiving a living donor organ (KT group) or waiting for a deceased donor organ (dialysis group). RESULTS: Left ventricular mass index change was -1.98 ± 5.5 and -0.36 ± 5.7 g/m2.7 for KT versus dialysis subjects (P = .44). Left ventricular mass change was associated with systolic blood pressure (SBP) (P = .0008) and average LV mass (P = .0001). Left ventricular ejection fraction did not improve (2.9 ± 6.6 vs 0.7 ± 4.9 %, P = .09), while LVESVI and LVEDVI decreased more post-KT than with continued dialysis (-3.36 ± 5.6 vs -0.22 ± 4.4 mL/m2.7, P < .01 and -4.9 ± 8.5 vs -0.3 ± 9.2 mL/m2.7, P = .02). Both adiponectin (-7.1 ± 11.3 vs -0.11 ± 7.9 µg/mL, P < .0001) and NT-proBNP (-3811 ± 8130 vs 1665 ± 20013 pg/mL, P < .0001) declined post-KT. Post-KT adiponectin correlated with NT-proBNP (P = .001), but not estimated glomerular filtration rate (eGFR) (P = .13). Change in adiponectin did not correlate with change in LVEF in the KT group (Spearman ρ = 0.16, P = .31) or dialysis group (Spearman ρ = 0.19, P = .21). LIMITATIONS: Few biomarkers of cardiac function were measured to fully contextualize their role during changing kidney function. Limited intrapatient biomarker sampling and CMR measurements precluded constructing dose-response curves of biomarkers to LV mass and function. The CMR timing in relation to dialysis was not standardized. CONCLUSIONS: The LVESVI and LVEDVI but not LVMI or LVEF improve post-KT. LVMI and LVEF change is independent of renal function and adiponectin. As adiponectin correlates with NT-proBNP post-KT, improved renal function through KT restores the normal heart-endocrine axis.

CONTEXTE: L'imagerie par résonnance magnétique (IRM) cardiaque mesure avec précision et exactitude la masse et la fonction du ventricule gauche (VG). L'identification des mécanismes par lesquels la variation de la masse et l'amélioration de la fonction du VG se produisent chez certains patients atteints d'insuffisance rénale terminale (IRT) pourrait contribuer à cibler adéquatement les receveurs d'une greffe rénale, en vue d'investiguer et d'intervenir de façon plus poussée. La concentration d'adiponectine sérique, un biomarqueur cardiovasculaire, augmente lors d'une défaillance cardiaque, sa production étant rehaussée par le peptide natriurétique de type B (BNP), et les concentrations d'adiponectine et de BNP diminuent après la transplantation. OBJECTIF: Nous avons testé l'hypothèse selon laquelle la greffe rénale modifierait les caractéristiques du VG et que ceci serait en lien avec la concentration d'adiponectine sérique. TYPE D'ÉTUDE: Il s'agit d'une étude de cohorte observationnelle et prospective. CADRE: L'étude a eu lieu dans trois centres de dialyse et de transplantation rénale pour adultes en Ontario (Canada). SUJETS: Un total de 82 candidats à la greffe ont été recrutés (39 patients dans le groupe transplantation rénale [TR] et 43 sujets dans le groupe de patients dialysés [dialyse]). Les patients en pré-dialyse ont été exclus. MESURES: Les sujets ont été soumis à une IRM à l'aide d'un scanner pour le corps entier de 1,5 Tesla utilisant une bobine cardiaque en réseau phasé et une synchronisation d'images vectographiques rétrospective. La masse du VG, la fraction d'éjection du VG (FEVG), le volume télésystolique du VG (VTSVG) et le volume télédiastolique du VG (VTDVG) ont été mesurés par IRM avant la greffe et 12 mois post-greffe (n=39) ou 12 mois plus tard si le patient était toujours dialysé (n=43). La masse du VG, le VTSVG et le VTDGV ont été indexés pour la taille du patient (m2,7) pour les calculs respectifs de l'indice de masse du VG (IMVG), de l'indice de volume télésystolique du VG (IVTSVG) et de l'indice de volume télédiastolique du VG (IVTDVG). Les concentrations sériques totales d'adiponectine et de NT-proBNP ont été mesurées au début de l'étude, après 3 mois et après 12 mois. MÉTHODOLOGIE: Nous avons procédé à une étude observationnelle prospective comparant, dans un rapport d'un pour un (1:1), des candidats à la greffe rénale atteints d'IRT qui devaient soit recevoir un rein d'un donneur vivant (groupe de TR), soit attendre un organe d'un donneur décédé (groupe de dialyse). RÉSULTATS: Les variations de l'IMVG se situaient à -1,98 ± 5,5 g/m2.7 pour le groupe TR et à -0,36 ± 5,7 g/m2.7 pour le groupe dialysé (p=0,44). Les variations dans la masse du VG ont été associées à la pression artérielle systolique (p=0,0008) et à la masse moyenne du VG (p=0,0001). La FEVG ne s'est pas améliorée (2,9 ± 6,6 % [TR] contre 0,7 ± 4,9 % [dialyse], p=0.09), alors que l'IVTSVG (-3,36 ± 5,6 ml/m2,7 [TR] contre -0,22 ± 4,4 ml/m2,7 [dialyse], p<0,01) et l'IVTDVG (-4,9 ± 8,5 ml/m2,7 [TR] contre -0,3 ± 9,2 ml/m2,7 [dialyse], p=0.02) ont diminué davantage chez les greffés que chez les patients qui poursuivaient la dialyse. L'adiponectine (-7,1 ± 11,3 µg/ml [TR] contre -0,11 ± 7,9 µg/ml [dialyse], p<0,0001) et le NT-proBNP (-3 811 ± 8 130 pg/ml [TR] contre 1 665 ± 20 013 pg/ml [dialyse], p<0,0001) ont diminué après la greffe. Les concentrations d'adiponectine post-greffe ont corrélé avec les taux de NT-proBNP (p=0,001), mais pas avec le débit de filtration glomérulaire estimé (DFGe) (p=0,13). Les variations dans les taux d'adiponectine n'ont pas corrélé avec les changements observés pour la FEVG (coefficient de corrélation des rangs de Spearman = 0,16; p=0,31 [TR] et 0,19; p=0,21 [dialyse]). LIMITES DE L'ÉTUDE: Trop peu de biomarqueurs de la fonction cardiaque ont été mesurés pour permettre de contextualiser pleinement leur rôle lors d'un changement dans la fonction rénale. L'échantillonnage limité de biomarqueurs intra-patients de même que le faible nombre de mesures d'IRM ont empêché l'établissement de courbes dose-réponse des biomarqueurs pour la masse et la fonction du VG. Enfin, la synchronisation de l'IRM par rapport à la dialyse n'était pas standardisée. CONCLUSION: Contrairement à l'IMVG et à la FEVG, l'IVTSVG et l'IVTDVG se sont améliorés après la greffe rénale. Les variations observées pour l'IMVG et la FEVG sont indépendantes de la fonction rénale et de la concentration sérique d'adiponectine. Étant donné que l'adiponectine corrèle avec le NT-proBNP post-greffe, l'amélioration de la fonction rénale par la greffe rétablit l'axe normal cœur-système endocrinien.