When, Why and How to Re-challenge Clozapine in Schizophrenia Following Myocarditis.

Clozapine-induced myocarditis (CIM) is among the most important adverse events limiting the use of clozapine as the most effective treatment for schizophrenia. CIM necessitates the immediate termination of clozapine, often resulting in its permanent discontinuation with considerable detrimental effects on patients' psychopathology and long-term outcome. Consequently, a clozapine re-challenge after CIM is increasingly regarded as a viable alternative, with published reports indicating a success rate of approximately 60%. However, published cases of re-challenges after CIM remain limited. Here, we provide a narrative review of the current state of research regarding the epidemiology, pathophysiology, risk factors, diagnosis and clinical management of CIM as well as a synthesis of current recommendations for re-challenging patients after CIM. This includes a step-by-step guide for this crucial procedure based on the current evidence regarding the pathophysiology and risk factors for CIM. Slow dose titration regimes and addressing risk factors including concomitant valproate and olanzapine are crucial both to prevent CIM and to ensure a safe and successful re-challenge. Furthermore, we discuss the utility of C-reactive protein, troponin, N-terminal-pro hormone and brain natriuretic peptide, therapeutic drug-monitoring and cardiac magnetic resonance imaging for CIM screening and diagnosis as well as for post-CIM re-challenges.

Coronary Artery Disease Assessment via On-Site CT Fractional Flow Reserve in Patients Undergoing Transcatheter Aortic Valve Replacement.

Purpose To examine the clinical feasibility of workstation-based CT fractional flow reserve (CT-FFR) for coronary artery disease (CAD) evaluation during preprocedural planning in patients undergoing transcatheter aortic valve replacement (TAVR). Materials and Methods In this retrospective single-center study, 434 patients scheduled for TAVR between 2018 and 2020 were screened for study inclusion; a relevant proportion of patients (35.0% [152 of 434]) was not suitable for evaluation due to insufficient imaging properties. A total of 112 patients (mean age, 82.1 years ± 6.7 [SD]; 58 [52%] men) were included in the study. Invasive angiography findings, coronary CT angiography results, and Agatston score were acquired and compared with on-site CT-FFR computation for evaluation of CAD and prediction of major adverse cardiovascular events (MACE) within a 24-month follow-up. Results Hemodynamic relevant CAD, as suggested by CT-FFR of 0.80 or less, was found in 41 of 70 (59%) patients with stenosis of 50% or more. MACE occurred in 23 of 112 (20.5%) patients, from which 14 of 23 had stenoses with CT-FFR of 0.80 or less (hazard ratio [HR], 3.33; 95% CI: 1.56, 7.10; P = .002). CT-FFR remained a significant predictor of MACE after inclusion in a multivariable model with relevant covariables (HR, 2.89; 95% CI: 1.22, 6.86; P = .02). An Agatston score of 1000 Agatston units or more (HR, 2.25; 95% CI: 0.98, 5.21; P = .06) and stenoses of 50% or more determined via invasive angiography (HR, 0.94; 95% CI: 0.41, 2.17; P = .88) were not significant predictors of MACE. Conclusion Compared with conventional CAD markers, CT-FFR better predicted adverse outcomes after TAVR. A relevant portion of the screened cohort, however, was not suitable for CT-based CAD evaluation. Keywords: CT, Transcatheter Aortic Valve Implantation/Replacement (TAVI/TAVR), Cardiac, Coronary Arteries, Outcomes Analysis © RSNA, 2024 See also the commentary by Weir-McCall and Pugliese in this issue.

DNMT3A clonal hematopoiesis-driver mutations induce cardiac fibrosis by paracrine activation of fibroblasts.

Hematopoietic mutations in epigenetic regulators like DNA methyltransferase 3 alpha (DNMT3A), play a pivotal role in driving clonal hematopoiesis of indeterminate potential (CHIP), and are associated with unfavorable outcomes in patients suffering from heart failure (HF). However, the precise interactions between CHIP-mutated cells and other cardiac cell types remain unknown. Here, we identify fibroblasts as potential partners in interactions with CHIP-mutated monocytes. We used combined transcriptomic data derived from peripheral blood mononuclear cells of HF patients, both with and without CHIP, and cardiac tissue. We demonstrate that inactivation of DNMT3A in macrophages intensifies interactions with cardiac fibroblasts and increases cardiac fibrosis. DNMT3A inactivation amplifies the release of heparin-binding epidermal growth factor-like growth factor, thereby facilitating activation of cardiac fibroblasts. These findings identify a potential pathway of DNMT3A CHIP-driver mutations to the initiation and progression of HF and may also provide a compelling basis for the development of innovative anti-fibrotic strategies.

Cardiac Involvement Due to COVID-19: Insights from Imaging and Histopathology.

Lingering cardiac symptoms are increasingly recognised complications of severe acute respiratory syndrome coronavirus 2 infection, now referred to as post-acute cardiovascular sequelae of COVID-19 (PASC). In the acute phase, cardiac injury is driven by cytokine release and stems from ischaemic and thrombotic complications, resulting in myocardial necrosis. Patients with pre-existing cardiac conditions are particularly vulnerable. Myocarditis due to a direct viral infection is rare. Chronic symptoms relate to either worsening of pre-existing heart disease (PASC - cardiovascular disease) or delayed chronic inflammatory condition due to heterogenous immune dysregulation (PASC - cardiovascular syndrome), the latter affecting a broad segment of previously well people. Both PASC presentations are associated with increased cardiovascular risk, long-term disability and reduced quality of life. The recognition and management of PASC in clinical settings remains a considerable challenge. Sensitive diagnostic methods are needed to detect subtler inflammatory changes that underlie the persistent symptoms in PASC - cardiovascular syndrome, alongside considerable clinical experience in inflammatory cardiac conditions.

Single-nuclear transcriptome profiling identifies persistent fibroblast activation in hypertrophic and failing human hearts of patients with longstanding disease.

AIMS: Cardiac fibrosis drives the progression of heart failure in ischaemic and hypertrophic cardiomyopathy. Therefore, the development of specific anti-fibrotic treatment regimens to counteract cardiac fibrosis is of high clinical relevance. Hence, this study examined the presence of persistent fibroblast activation during longstanding human heart disease at a single-cell resolution to identify putative therapeutic targets to counteract pathological cardiac fibrosis in patients. METHODS AND RESULTS: We used single-nuclei RNA sequencing with human tissues from two samples of one healthy donor, and five hypertrophic and two failing hearts. Unsupervised sub-clustering of 7110 nuclei led to the identification of 7 distinct fibroblast clusters. De-convolution of cardiac fibroblast heterogeneity revealed a distinct population of human cardiac fibroblasts with a molecular signature of persistent fibroblast activation and a transcriptional switch towards a pro-fibrotic extra-cellular matrix composition in patients with established cardiac hypertrophy and heart failure. This sub-cluster was characterized by high expression of POSTN, RUNX1, CILP, and a target gene adipocyte enhancer-binding protein 1 (AEBP1) (all P < 0.001). Strikingly, elevated circulating AEBP1 blood level were also detected in a validation cohort of patients with confirmed cardiac fibrosis and hypertrophic cardiomyopathy by cardiac magnetic resonance imaging (P < 0.01). Since endogenous AEBP1 expression was increased in patients with established cardiac hypertrophy and heart failure, we assessed the functional consequence of siRNA-mediated AEBP1 silencing in human cardiac fibroblasts. Indeed, AEBP1 silencing reduced proliferation, migration, and fibroblast contractile capacity and α-SMA gene expression, which is a hallmark of fibroblast activation (all P < 0.05). Mechanistically, the anti-fibrotic effects of AEBP1 silencing were linked to transforming growth factor-beta pathway modulation. CONCLUSION: Together, this study identifies persistent fibroblast activation in patients with longstanding heart disease, which might be detected by circulating AEBP1 and therapeutically modulated by its targeted silencing in human cardiac fibroblasts.

ESC Congress 2022 Imaging Highlights.

Cardiac imaging is an ever-evolving area, with imaging parameters and application in constant re-evaluation. This was reflected in many imaging debates and by the increased number of scientific contributions at the European Society of Cardiology Congress in 2022. While clinical trials tried to answer clinical questions related to the performance of different imaging modalities, many high-quality presentations focused on new imaging biomarkers in different scenarios, such as heart failure with preserved ejection fraction, valvular heart disease or long COVID. This highlights the need for the translation of cardiac imaging technology from research interests towards established measures of clinical practice.

Computed tomography-based pericoronary adipose tissue attenuation in patients undergoing TAVR: a novel method for risk assessment.

Objectives: This study aims to assess the attenuation of pericoronary adipose tissue (PCAT) surrounding the proximal right coronary artery (RCA) in patients with aortic stenosis (AS) and undergoing transcatheter aortic valve replacement (TAVR). RCA PCAT attenuation is a novel computed tomography (CT)-based marker for evaluating coronary inflammation. Coronary artery disease (CAD) in TAVR patients is common and usually evaluated prior to intervention. The most sensible screening method and consequential treatment approach are unclear and remain a matter of ceaseless discussion. Thus, interest remains for safe and low-demand predictive markers to identify patients at risk for adverse outcomes postaortic valve replacement. Methods: This single-center retrospective study included patients receiving a standard planning CT scan prior to TAVR. Conventional CAD diagnostic tools, such as coronary artery calcium score and significant stenosis via invasive coronary angiography and coronary computed tomography angiography, were determined in addition to RCA PCAT attenuation using semiautomated software. These were assessed for their relationship with major adverse cardiovascular events (MACE) during a 24-month follow-up period. Results: From a total of 62 patients (mean age: 82 ± 6.7 years), 15 (24.2%) patients experienced an event within the observation period, 10 of which were attributed to cardiovascular death. The mean RCA PCAT attenuation was higher in patients enduring MACE than that in those without an endpoint (-69.8 ± 7.5 vs. -74.6 ± 6.2, P = 0.02). Using a predefined cutoff of >-70.5 HU, 20 patients (32.3%) with high RCA PCAT attenuation were identified, nine (45%) of which met the endpoint within 2 years after TAVR. In a multivariate Cox regression model including conventional CAD diagnostic tools, RCA PCAT attenuation prevailed as the only marker with significant association with MACE (P = 0.02). After dichotomization of patients into high- and low-RCA PCAT attenuation groups, high attenuation was related to greater risk of MACE (hazard ration: 3.82, P = 0.011). Conclusion: RCA PCAT attenuation appears to have predictive value also in a setting of concomitant AS in patients receiving TAVR. RCA PCAT attenuation was more reliable than conventional CAD diagnostic tools in identifying patients at risk for MACE .

Cardiac Imaging Biomarkers in Chronic Kidney Disease.

Uremic cardiomyopathy (UC), the peculiar cardiac remodeling secondary to the systemic effects of renal dysfunction, is characterized by left ventricular (LV) diffuse fibrosis with hypertrophy (LVH) and stiffness and the development of heart failure and increased rates of cardiovascular mortality. Several imaging modalities can be used to obtain a non-invasive assessment of UC by different imaging biomarkers, which is the focus of the present review. Echocardiography has been largely employed in recent decades, especially for the determination of LVH by 2-dimensional imaging and diastolic dysfunction by pulsed-wave and tissue Doppler, where it retains a robust prognostic value; more recent techniques include parametric assessment of cardiac deformation by speckle tracking echocardiography and the use of 3D-imaging. Cardiac magnetic resonance (CMR) imaging allows a more accurate assessment of cardiac dimensions, including the right heart, and deformation by feature-tracking imaging; however, the most evident added value of CMR remains tissue characterization. T1 mapping demonstrated diffuse fibrosis in CKD patients, increasing with the worsening of renal disease and evident even in early stages of the disease, with few, but emerging, prognostic data. Some studies using T2 mapping highlighted the presence of subtle, diffuse myocardial edema. Finally, computed tomography, though rarely used to specifically assess UC, might provide incidental findings carrying prognostic relevance, including information on cardiac and vascular calcification. In summary, non-invasive cardiovascular imaging provides a wealth of imaging biomarkers for the characterization and risk-stratification of UC; integrating results from different imaging techniques can aid a better understanding of the physiopathology of UC and improve the clinical management of patients with CKD.

Native T1 is predictive of cardiovascular death/heart failure events and all-cause mortality irrespective of the patient's volume status.

Background: Native T1 has become a pivotal parameter of tissue composition that is assessed by cardiac magnetic resonance (CMR). It characterizes diseased myocardium and can be used for prognosis estimation. Recent publications have shown that native T1 is influenced by short-term fluctuations of volume status due to hydration or hemodialysis. Methods: Patients from a prospective BioCVI all-comers clinical CMR registry were included, and native T1 and plasma volume status (PVS) were determined according to Hakim's formula as surrogate markers of patient volume status. The primary endpoint was defined as combined endpoint of cardiovascular death or hospitalization for heart failure events, the secondary endpoint was defined as all-cause mortality. Results: A total of 2,047 patients were included since April 2017 [median (IQR); age 63 (52-72) years, 33% female]. There was a significant although weak influence of PVS on native T1 (ß = 0.11, p < 0.0001). Patients with volume expansion (PVS > -13%) showed significantly higher values for tissue markers than non-volume-overloaded patients [PVS ≤ -13%; median (IQR); native T1 1,130 (1,095-1,170) vs. 1,123 (1,086-1,166) ms, p < 0.003; and T2 39 (37-40) vs. 38 (36-40) ms, p < 0.0001]. In Cox regression analysis both native T1 and PVS were independently predictive of the primary endpoint and all-cause mortality. Conclusion: Despite a weak effect of PVS on native T1, its predictive power was not affected in a large, all-comers cohort.

Myocardial oedema contributes to interstitial expansion and associates with mechanical and electrocardiographic changes in takotsubo syndrome: a CMR T1 and T2 mapping study.

AIMS: myocardial oedema is largely represented in takotsubo syndrome (TTS) and may contribute to alter the myocardium morphology and function. The aim of the study is to describe relationships between oedema, mechanical, and electrical abnormalities in TTS. METHODS AND RESULTS: the study included n = 32 hospitalized TTS patients and n = 23 controls. Cardiac magnetic resonance (CMR) with tissue mapping and feature tracking was performed with concomitant 12-lead electrocardiogram (ECG) recording. Mean age of TTS was 72 ± 12 years old, 94% women. Compared with controls, patients had higher left ventricular (LV) mass, worse systolic function, higher septal native T1 (1116 ± 73 msec vs. 970 ± 23 msec, P < 0.001), T2 (56 ± 5 msec vs. 46 ± 2 msec, P < 0.001), and extracellular volume (ECV) fraction (32 ± 5% vs. 24 ± 1%, P < 0.001). TTS patients had higher apicobasal gradient of T2 values (12 ± 6 msec vs. 2 ± 6 msec, P < 0.001); basal LV wall displayed higher native T1, T2, and ECV (all P < 0.002) but similar circumferential strain against controls (-23 ± 3% vs. -24 ± 4%, P = 0.351). In the TTS cohort, septal T2 values showed significant correlations with native T1 (r = 0.609, P < 0.001), ECV (r = 0.689, P < 0.001), left ventricular ejection fraction (r = -0.459, P = 0.008) and aVR voltage (r = -0.478, P = 0.009). Negative T-wave voltage and QTc length correlated with apicobasal T2 mapping gradient (r = 0.499, P = 0.007 and r = 0.372, P = 0.047, respectively) but not with other tissue mapping measurements. CONCLUSIONS: CMR T1 and T2 mapping demonstrated increased myocardial water content conditioning interstitial expansion in acute TTS, detected even outside areas of abnormal wall motion. Oedema burden and distribution associated with mechanical and electrocardiographic changes, making it a potential prognostic marker and therapeutic target in TTS.

Myocardial tissue changes detected by cardiac MRI in a patient with suspected systemic sarcoidosis.

BACKGROUND: The role of cardiac magnetic resonance imaging in the early management of chronic cardiac inflammatory conditions is growing. Our case enlightens the benefit of quantitative mapping in the monitoring and treatment guidance in systemic sarcoidosis. CASE PRESENTATION: We report about a 29-year-old man with an ongoing dyspnea and bihilar lymphadenopathy, suggesting sarcoidosis. Cardiac magnetic resonance showed high mapping values, but no scarring. In follow-ups, cardiac remodeling was noted; cardioprotective treatment normalized cardiac function and mapping markers. Definitive diagnosis was achieved in extracardiac lymphatic tissue during a relapse. CONCLUSION: This case shows the role that mapping markers can play in the detection and treatment at early stage of systemic sarcoidosis.

Multimodality Imaging in HIV-Associated Cardiovascular Complications: A Comprehensive Review.

Human immunodeficiency virus (HIV) infection is a leading cause of mortality and morbidity worldwide. The introduction of antiretroviral therapy (ART) has significantly reduced the risk of developing acquired immune deficiency syndrome and increased life expectancy, approaching that of the general population. However, people living with HIV have a substantially increased risk of cardiovascular diseases despite long-term viral suppression using ART. HIV-associated cardiovascular complications encompass a broad spectrum of diseases that involve the myocardium, pericardium, coronary arteries, valves, and systemic and pulmonary vasculature. Traditional risk stratification tools do not accurately predict cardiovascular risk in this population. Multimodality imaging plays an essential role in the evaluation of various HIV-related cardiovascular complications. Here, we emphasize the role of multimodality imaging in establishing the diagnosis and aetiopathogenesis of various cardiovascular manifestations related to chronic HIV disease. This review also provides a critical appraisal of contemporary data and illustrative cases.

Cancer patients with venous thromboembolism: Diagnostic and prognostic value of elevated D-dimers.

BACKGROUND: D-dimer testing is known to have a high sensitivity at simultaneously low specificity, resulting in nonspecific elevations in a variety of conditions. METHODS: This retrospective study sought to assess diagnostic and prognostic features of D-dimers in cancer patients referred to the emergency department for suspected pulmonary embolism (PE) and deep vein thrombosis (DVT). In total, 526 patients with a final adjudicated diagnosis of PE (n = 83) and DVT (n = 69) were enrolled, whereas 374 patients served as the comparative group, in which venous thromboembolism (VTE) has been excluded. RESULTS: For the identification of VTE, D-dimers yielded the highest positive predictive value of 96% (95% confidence interval (CI), 85-99) at concentrations of 9.9 mg/L and a negative predictive value of 100% at .6 mg/L (95% CI, 97-100). At the established rule-out cut-off level of .5 mg/L, D-dimers were found to be very sensitive (100%) at a moderate specificity of nearly 65%. Using an optimised cut-off value of 4.9 mg/L increased the specificity to 95% for the detection of life-threatening VTE at the cost of moderate sensitivities (64%). During a median follow-up of 30 months, D-dimers positively correlated with the reoccurrence of VTE (p = .0299) and mortality in both cancer patients with VTE (p < .0001) and without VTE (p = .0008). CONCLUSIONS: Although D-dimer testing in cancer patients is discouraged by current guidelines, very high concentrations above the 10-fold upper reference limit contain diagnostic and prognostic information and might be helpful in risk assessment, while low concentrations remain useful for ruling out VTE.

Long-term cardiac pathology in individuals with mild initial COVID-19 illness.

Cardiac symptoms are increasingly recognized as late complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in previously well individuals with mild initial illness, but the underlying pathophysiology leading to long-term cardiac symptoms remains unclear. In this study, we conducted serial cardiac assessments in a selected population of individuals with Coronavirus Disease 2019 (COVID-19) with no previous cardiac disease or notable comorbidities by measuring blood biomarkers of heart injury or dysfunction and by performing magnetic resonance imaging. Baseline measurements from 346 individuals with COVID-19 (52% females) were obtained at a median of 109 days (interquartile range (IQR), 77-177 days) after infection, when 73% of participants reported cardiac symptoms, such as exertional dyspnea (62%), palpitations (28%), atypical chest pain (27%) and syncope (3%). Symptomatic individuals had higher heart rates and higher imaging values or contrast agent accumulation, denoting inflammatory cardiac involvement, compared to asymptomatic individuals. Structural heart disease or high levels of biomarkers of cardiac injury or dysfunction were rare in symptomatic individuals. At follow-up (329 days (IQR, 274-383 days) after infection), 57% of participants had persistent cardiac symptoms. Diffuse myocardial edema was more pronounced in participants who remained symptomatic at follow-up as compared to those who improved. Female gender and diffuse myocardial involvement on baseline imaging independently predicted the presence of cardiac symptoms at follow-up. Ongoing inflammatory cardiac involvement may, at least in part, explain the lingering cardiac symptoms in previously well individuals with mild initial COVID-19 illness.

The German National Pandemic Cohort Network (NAPKON): rationale, study design and baseline characteristics.

The German government initiated the Network University Medicine (NUM) in early 2020 to improve national research activities on the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic. To this end, 36 German Academic Medical Centers started to collaborate on 13 projects, with the largest being the National Pandemic Cohort Network (NAPKON). The NAPKON's goal is creating the most comprehensive Coronavirus Disease 2019 (COVID-19) cohort in Germany. Within NAPKON, adult and pediatric patients are observed in three complementary cohort platforms (Cross-Sectoral, High-Resolution and Population-Based) from the initial infection until up to three years of follow-up. Study procedures comprise comprehensive clinical and imaging diagnostics, quality-of-life assessment, patient-reported outcomes and biosampling. The three cohort platforms build on four infrastructure core units (Interaction, Biosampling, Epidemiology, and Integration) and collaborations with NUM projects. Key components of the data capture, regulatory, and data privacy are based on the German Centre for Cardiovascular Research. By April 01, 2022, 34 university and 40 non-university hospitals have enrolled 5298 patients with local data quality reviews performed on 4727 (89%). 47% were female, the median age was 52 (IQR 36-62-) and 50 pediatric cases were included. 44% of patients were hospitalized, 15% admitted to an intensive care unit, and 12% of patients deceased while enrolled. 8845 visits with biosampling in 4349 patients were conducted by April 03, 2022. In this overview article, we summarize NAPKON's design, relevant milestones including first study population characteristics, and outline the potential of NAPKON for German and international research activities.Trial registration https://clinicaltrials.gov/ct2/show/NCT04768998 . https://clinicaltrials.gov/ct2/show/NCT04747366 . https://clinicaltrials.gov/ct2/show/NCT04679584.

Cardiovascular Magnetic Resonance for Rejection Surveillance After Cardiac Transplantation.

BACKGROUND: Endomyocardial biopsy (EMB) is the gold standard method for surveillance of acute cardiac allograft rejection (ACAR) despite its invasive nature. Cardiovascular magnetic resonance (CMR)-based myocardial tissue characterization allows detection of myocarditis. The feasibility of CMR-based surveillance for ACAR-induced myocarditis in the first year after heart transplantation is currently undescribed. METHODS: CMR-based multiparametric mapping was initially assessed in a prospective cross-sectional fashion to establish agreement between CMR- and EMB-based ACAR and to determine CMR cutoff values between rejection grades. A prospective randomized noninferiority pilot study was then undertaken in adult orthotopic heart transplant recipients who were randomized at 4 weeks after orthotopic heart transplantation to either CMR- or EMB-based rejection surveillance. Clinical end points were assessed at 52 weeks. RESULTS: Four hundred one CMR studies and 354 EMB procedures were performed in 106 participants. Forty heart transplant recipients were randomized. CMR-based multiparametric assessment was highly reproducible and reliable at detecting ACAR (area under the curve, 0.92; sensitivity, 93%; specificity, 92%; negative predictive value, 99%) with greater specificity and negative predictive value than either T1 or T2 parametric CMR mapping alone. High-grade rejection occurred in similar numbers of patients in each randomized group (CMR, n=7; EMB, n=8; P=0.74). Despite similarities in immunosuppression requirements, kidney function, and mortality between groups, the rates of hospitalization (9 of 20 [45%] versus 18 of 20 [90%]; odds ratio, 0.091; P=0.006) and infection (7 of 20 [35%] versus 14 of 20 [70%]; odds ratio, 0.192; P=0,019) were lower in the CMR group. On 15 occasions (6%), patients who were randomized to the CMR arm underwent EMB for clarification or logistic reasons, representing a 94% reduction in the requirement for EMB-based surveillance. CONCLUSIONS: A noninvasive CMR-based surveillance strategy for ACAR in the first year after orthotopic heart transplantation is feasible compared with EMB-based surveillance. REGISTRATION: HREC/13/SVH/66 and HREC/17/SVH/80. AUSTRALIAN NEW ZEALAND CLINICAL TRIALS REGISTRY: ACTRN12618000672257.

Determination of scar area using native and post-contrast T1 mapping: Agreement with late gadolinium enhancement.

The purpose of this study is to ascertain agreement in measurements of the scar area between late gadolinium enhancement (LGE), native and post-contrast T1 mapping in patients with known ischemic heart disease. 132 patients (age 60 ± 11 yrs, male 82%) were included in the study. Corresponding 3 short axis slices images of LGE, native and post contrast T1 mapping were used. Scar area was evaluated semi- quantitatively with FWHM methods, in which scar is automatically determined by specialized post-processing software. Agreement per culprit vessel was also assessed. Concordance and inter- intraobserver reproducibility were assessed with Bland-Altman analysis. The results show that scar area amounted to 12.6% of myocardium for LGE, 9.1% for native (p < 0.05) and 19.4% (p < 0.05) for post-contrast T1 mapping. LAD and RCA territory infarcts showed statistical discrepancy for both T1 acquisitions. Intraobserver differences in infarct size were comparable at 0.39% ± 0.28, 2.93% ± 0.03 and 0.97% ± 0.01 respectively (p≫0.05). Interobserver differences were 5.56% ± 0.91 for LGE, 11.87% ± 3.21 (p < 0.05) for native and 5.55% ± 2.87 (p≫0.05) for post-contrast T1 mapping. In conclusion, native T1 acquisitions systematically underestimated infarct size in comparison to LGE, while post-contrast T1 overestimated it. Variances in measurements were most pronounced for LAD and RCA territory infarcts. Intraobserver reproducibility was similar with both methods, whereas interobserver variability for native T1 mapping acquisition was worse.

Cardiac biomarkers in chronic kidney disease are independently associated with myocardial edema and diffuse fibrosis by cardiovascular magnetic resonance.

BACKGROUND: High sensitivity cardiac troponin T (hs-cTnT) and NT-pro-brain natriuretic peptide (NT-pro BNP) are often elevated in chronic kidney disease (CKD) and associated with both cardiovascular remodeling and outcome. Relationship between these biomarkers and quantitative imaging measures of myocardial fibrosis and edema by T1 and T2 mapping remains unknown. METHODS: Consecutive patients with established CKD and estimated glomerular filtration rate (eGFR) < 59 ml/min/1.73 m2 (n = 276) were compared to age/sex matched patients with eGFR ≥ 60 ml/min/1.73 m2 (n = 242) and healthy controls (n = 38). Comprehensive cardiovascular magnetic resonance (CMR) with native T1 and T2 mapping, myocardial ischemia and scar imaging was performed with venous sampling immediately prior to CMR. RESULTS: Patients with CKD showed significant cardiac remodeling in comparison with both healthy individuals and non-CKD patients, including a stepwise increase of native T1 and T2 (p < 0.001 between all CKD stages). Native T1 and T2 were the sole imaging markers independently associated with worsening CKD in patients [B = 0.125 (95% CI 0.022-0.235) and B = 0.272 (95% CI 0.164-0.374) with p = 0.019 and < 0.001 respectively]. At univariable analysis, both hs-cTnT and NT-pro BNP significantly correlated with native T1 and T2 in groups with eGFR 30-59 ml/min/1.73 m2 and eGFR < 29 ml/min/1.73 m2 groups, with associations being stronger at lower eGFR (NT-pro BNP (log transformed, lg10): native T1 r = 0.43 and r = 0.57, native T2 r = 0.39 and r = 0.48 respectively; log-transformed hs-cTnT(lg10): native T1 r = 0.23 and r = 0.43, native T2 r = 0.38 and r = 0.58 respectively, p < 0.001 for all, p < 0.05 for interaction). On multivariable analyses, we found independent associations of native T1 with NT-pro BNP [(B = 0.308 (95% CI 0.129-0.407), p < 0.001 and B = 0.334 (95% CI 0.154-0.660), p = 0.002 for eGFR 30-59 ml/min/1.73 m2 and eGFR < 29 ml/min/1.73 m2, respectively] and of T2 with hs-cTnT [B = 0.417 (95% CI 0.219-0.650), p < 0.001 for eGFR < 29 ml/min/1.73 m2]. CONCLUSIONS: We demonstrate independent associations between cardiac biomarkers with imaging markers of interstitial expansion, which are CKD-group specific. Our findings indicate the role of diffuse non-ischemic tissue processes, including excess of myocardial fluid in addition to diffuse fibrosis in CKD-related adverse remodeling.