Fibrosis is a consequence of the inflammatory response. When fibrotic tissue becomes excessive, it can have diverse pathophysiological effects on a number of organ systems. The mechanisms underlying fibrosis and approaches to therapy are reviewed.

https://www.nejm.org/doi/suppl/10.1056/NEJMra1300575/suppl_file/nejmra1300575_appendix.pdf

Fibrosis — A Common Pathway to Organ Injury and Failure

Parametric mapping techniques provide a non-invasive tool for quantifying tissue alterations in myocardial disease in those eligible for cardiovascular magnetic resonance (CMR). Parametric mapping with CMR now permits the routine spatial visualization and quantification of changes in myocardial composition based on changes in T1, T2, and T2*(star) relaxation times and extracellular volume (ECV). These changes include specific disease pathways related to mainly intracellular disturbances of the cardiomyocyte (e.g., iron overload, or glycosphingolipid accumulation in Anderson-Fabry disease); extracellular disturbances in the myocardial interstitium (e.g., myocardial fibrosis or cardiac amyloidosis from accumulation of collagen or amyloid proteins, respectively); or both (myocardial edema with increased intracellular and/or extracellular water). Parametric mapping promises improvements in patient care through advances in quantitative diagnostics, inter- and intra-patient comparability, and relatedly improvements in treatment. There is a multitude of technical approaches and potential applications. This document provides a summary of the existing evidence for the clinical value of parametric mapping in the heart as of mid 2017, and gives recommendations for practical use in different clinical scenarios for scientists, clinicians, and CMR manufacturers.

https://link.springer.com/content/pdf/10.1186/s12968-017-0389-8.pdf

Clinical recommendations for cardiovascular magnetic resonance mapping of T1, T2, T2 and extracellular volume: A consensus statement by the Society for Cardiovascular Magnetic Resonance (SCMR) endorsed by the European Association for Cardiovascular Imaging (EACVI)

2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

Rapid innovations in cardiovascular magnetic resonance (CMR) now permit the routine acquisition of quantitative measures of myocardial and blood T1 which are key tissue characteristics. These capabilities introduce a new frontier in cardiology, enabling the practitioner/investigator to quantify biologically important myocardial properties that otherwise can be difficult to ascertain clinically. CMR may be able to track biologically important changes in the myocardium by: a) native T1 that reflects myocardial disease involving the myocyte and interstitium without use of gadolinium based contrast agents (GBCA), or b) the extracellular volume fraction (ECV)–a direct GBCA-based measurement of the size of the extracellular space, reflecting interstitial disease. The latter technique attempts to dichotomize the myocardium into its cellular and interstitial components with estimates expressed as volume fractions. This document provides recommendations for clinical and research T1 and ECV measurement, based on published evidence when available and expert consensus when not. We address site preparation, scan type, scan planning and acquisition, quality control, visualisation and analysis, technical development. We also address controversies in the field. While ECV and native T1 mapping appear destined to affect clinical decision making, they lack multi-centre application and face significant challenges, which demand a community-wide approach among stakeholders. At present, ECV and native T1 mapping appear sufficiently robust for many diseases; yet more research is required before a large-scale application for clinical decision-making can be recommended.

/pdf/myocardial-t1-mapping-and-extracellular-volume-2zxd5q1dbr.pdf

Myocardial T1 mapping and extracellular volume quantification: a Society for Cardiovascular Magnetic Resonance (SCMR) and CMR Working Group of the European Society of Cardiology consensus statement

The longitudinal relaxation time constant (T1) of the myocardium is altered in various disease states due to increased water content or other changes to the local molecular environment. Changes in both native T1 and T1 following administration of gadolinium (Gd) based contrast agents are considered important biomarkers and multiple methods have been suggested for quantifying myocardial T1 in vivo. Characterization of the native T1 of myocardial tissue may be used to detect and assess various cardiomyopathies while measurement of T1 with extracellular Gd based contrast agents provides additional information about the extracellular volume (ECV) fraction. The latter is particularly valuable for more diffuse diseases that are more challenging to detect using conventional late gadolinium enhancement (LGE). Both T1 and ECV measures have been shown to have important prognostic significance. T1-mapping has the potential to detect and quantify diffuse fibrosis at an early stage provided that the measurements have adequate reproducibility. Inversion recovery methods such as MOLLI have excellent precision and are highly reproducible when using tightly controlled protocols. The MOLLI method is widely available and is relatively mature. The accuracy of inversion recovery techniques is affected significantly by magnetization transfer (MT). Despite this, the estimate of apparent T1 using inversion recovery is a sensitive measure, which has been demonstrated to be a useful tool in characterizing tissue and discriminating disease. Saturation recovery methods have the potential to provide a more accurate measurement of T1 that is less sensitive to MT as well as other factors. Saturation recovery techniques are, however, noisier and somewhat more artifact prone and have not demonstrated the same level of reproducibility at this point in time. This review article focuses on the technical aspects of key T1-mapping methods and imaging protocols and describes their limitations including the factors that influence their accuracy, precision, and reproducibility.

/pdf/t1-mapping-in-the-heart-accuracy-and-precision-55ar2n6sv0.pdf

T1-mapping in the heart: accuracy and precision

Background—Extracellular matrix expansion may be a fundamental feature of adverse myocardial remodeling, it appears to be treatable, and its measurement may improve risk stratification. Yet, the relationship between mortality and extracellular matrix is not clear because of difficulties with its measurement. To assess its relationship with outcomes, we used novel, validated cardiovascular magnetic resonance techniques to quantify the full spectrum of extracellular matrix expansion not readily detectable by conventional cardiovascular magnetic resonance. Methods and Results—We recruited 793 consecutive patients at the time of cardiovascular magnetic resonance without amyloidosis or hypertrophic cardiomyopathy as well as 9 healthy volunteers (ages 20–50 years). We measured the extracellular volume fraction (ECV) to quantify the extracellular matrix expansion in myocardium without myocardial infarction. ECV uses gadolinium contrast as an extracellular space marker based on T1 measures of blood and myocardium...

Association Between Extracellular Matrix Expansion Quantified by Cardiovascular Magnetic Resonance and Short-Term Mortality

Micronutrient deficiencies such as pellagra are rarely seen after bariatric surgery and can be challenging to diagnose and manage. Alcohol use can precipitate nutritional deficiencies.A 51-year-old woman with a history of Roux-en-Y gastric bypass surgery who later developed an alcohol-use disorder after her diagnosis of breast cancer. She experienced a subacute decline in her physical and cognitive function along with a rash after radiation treatment for breast cancer, lower extremity pain and weakness, anemia, and diarrhea with severe hypokalemia. Workup showed undetectable niacin levels. She initially did not respond to an oral niacin replacement, necessitating intramuscular injections. Alcohol cessation and parenteral B complex replacement led to the resolution of her symptoms and biochemical derangements.Bariatric surgery with concomitant alcohol use can precipitate niacin deficiency-induced liver dysfunction. In the correct clinical setting, screening for alcohol use and checking niacin levels may help avoid extensive testing and can help make the correct diagnosis. Parenteral replacement may be necessary in this setting.Niacin deficiency needs to be considered in patients with bariatric surgery with a history of alcoholism in the correct clinical setting. 

https://doi.org/10.1016/j.aace.2023.04.002

Pellagra Post–Roux-en-Y Gastric Bypass Surgery


 Ectopic adrenocorticotropic hormone (ACTH)-secreting syndrome (EAS) is a rare but often aggressive paraneoplastic syndrome. Patients with EAS typically present with high ACTH levels and rapid clinical progression in the setting of acute cortisol elevation, which can delay diagnosis due to a lack of typical Cushingoid features. High levels of ACTH have also been shown to stimulate the adrenal zona glomerulosa to oversecrete aldosterone. We present the case of a 58-year-old male presenting with new-onset hypertension and severe metabolic alkalosis with spontaneous hypokalemia, in the setting of elevated aldosterone and low renin levels, suggestive of primary aldosteronism. Subsequent biochemical testing, imaging, and pathology, however, revealed suppression of aldosterone with evidence of hypercortisolism in the setting of metastatic small cell lung cancer. This was, therefore, suggestive of pseudo primary aldosteronism in the setting of a paraneoplastic ectopic ACTH-producing syndrome. This case highlights that hypercortisolism, in the setting of EAS, can initially present with a clinical picture suggestive of hyperaldosteronism. The use of a Dexamethasone suppression test can allow the clinician to differentiate between idiopathic bilateral adrenal hyperplasia and ectopic ACTH syndrome.

Jonathan Shakesprere

Papers

Association Between Extracellular Matrix Expansion Quantified by Cardiovascular Magnetic Resonance and Short-Term Mortality

Pellagra Post–Roux-en-Y Gastric Bypass Surgery

Pseudo primary aldosteronism as initial presentation of ectopic ACTH syndrome in metastatic small cell lung cancer

A Real-World Analysis of Autologous Stem Cell Transplantation Utilization in Mantle Cell Lymphoma