Research Spotlight

Saint-Val, L., T. Courtin, P. Charles, C. Verny, M. Catala, R. Schiffmann, O. Boespflug-Tanguy and F. Mochel (2019). “GJA1 Variants Cause Spastic Paraplegia Associated with Cerebral Hypomyelination.” AJNR Am J Neuroradiol Apr 25. [Epub ahead of print].

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Oculodentodigital dysplasia is an autosomal dominant disorder due to GJA1 variants characterized by dysmorphic features. Neurologic symptoms have been described in some patients but without a clear neuroimaging pattern. To understand the pathophysiology underlying neurologic deficits in oculodentodigital dysplasia, we studied 8 consecutive patients presenting with hereditary spastic paraplegia due to GJA1 variants. Clinical disease severity was highly variable. Cerebral MR imaging revealed variable white matter abnormalities, consistent with a hypomyelination pattern, and bilateral hypointense signal of the basal ganglia on T2-weighted images and/or magnetic susceptibility sequences, as seen in neurodegeneration with brain iron accumulation diseases. Patients with the more prominent basal ganglia abnormalities were the most disabled ones. This study suggests that GJA1-related hereditary spastic paraplegia is a complex neurodegenerative disease affecting both the myelin and the basal ganglia. GJA1 variants should be considered in patients with hereditary spastic paraplegia presenting with brain hypomyelination, especially if associated with neurodegeneration and a brain iron accumulation pattern.

Rangaswami, J., S. Soman and P. A. McCullough (2019). “Key Updates in Cardio-Nephrology from 2018: Springboard to a Bright Future.” Cardiorenal Med 9(4): 222-228.

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Overall, the field of cardio-nephrology made significant strides in 2018 with novel approaches to the dilemma of pathological heart-kidney interactions, a problem well described and rooted in history. The increasing relevance of this interface was recognized appropriately in publications as well as national conferences in cardiology and nephrology. Notably, collaborative efforts between key organizations such as the American Heart Association (Kidney Council), the American Society of Nephrology, and the Cardiorenal Society of America have been successful in highlighting the importance of this niche field. In a welcome trend deviating from the well-documented exclusion of patients with kidney disease from cardiovascular trials, key trials in cardio-renal medicine such as the International Study of Comparative Health Effectiveness of Medical and Invasive Approaches-CKD (NCT01985360), the Coronary Artery Disease Screening in Kidney Transplant Candidates trial (CARSK) (NCT02082483), the RENAL-AF trial (NCT02942407), and the STOP ACEi trial (SRCTN62869767) will report in the near future, allowing important questions to be answered with randomized controlled data in cardiorenal medicine. Obtaining high-quality data unique to this subset of patients is the biggest service that can ultimately be provided by cardiologists and nephrologists caring for patients with cardiorenal disease. Given the widening scope of the field of cardio-nephrology, efforts to create center-specific cardio-renal teams to accelerate and spearhead clinical care and research in this field are necessary to be able to train physician- scientists of the future to integrate the care of these patients in the best possible way. To that end, the growth of the field witnessed in 2018 is very encouraging. We look forward to participating in the continuation of the growth of cardio-nephrology in 2019 and beyond, to provide the best evidence-based multidisciplinary care for this vulnerable group of patients. (Excerpt from text, p. 226; no abstract available.)

Rangaswami, J., R. O. Mathew, R. Parasuraman, E. Tantisattamo, M. Lubetzky, S. Rao, M. S. Yaqub, K. A. Birdwell, W. Bennett, P. Dalal, R. Kapoor, E. V. Lerma, M. Lerman, N. McCormick, S. Bangalore, P. A. McCullough and D. M. Dadhania (2019). “Cardiovascular disease in the kidney transplant recipient: epidemiology, diagnosis and management strategies.” Nephrol Dial Transplant 34(5): 760-773.

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Kidney transplantation (KT) is the optimal therapy for end-stage kidney disease (ESKD), resulting in significant improvement in survival as well as quality of life when compared with maintenance dialysis. The burden of cardiovascular disease (CVD) in ESKD is reduced after KT; however, it still remains the leading cause of premature patient and allograft loss, as well as a source of significant morbidity and healthcare costs. All major phenotypes of CVD including coronary artery disease, heart failure, valvular heart disease, arrhythmias and pulmonary hypertension are represented in the KT recipient population. Pre-existing risk factors for CVD in the KT recipient are amplified by superimposed cardio-metabolic derangements after transplantation such as the metabolic effects of immunosuppressive regimens, obesity, posttransplant diabetes, hypertension, dyslipidemia and allograft dysfunction. This review summarizes the major risk factors for CVD in KT recipients and describes the individual phenotypes of overt CVD in this population. It highlights gaps in the existing literature to emphasize the need for future studies in those areas and optimize cardiovascular outcomes after KT. Finally, it outlines the need for a joint ‘cardio-nephrology’ clinical care model to ensure continuity, multidisciplinary collaboration and implementation of best clinical practices toward reducing CVD after KT.

Raj, S. D., M. Shurafa, Z. Shah, K. M. Raj, M. D. C. Fishman and V. M. Dialani (2019). “Primary and Secondary Breast Lymphoma: Clinical, Pathologic, and Multimodality Imaging Review.” Radiographics 39(3): 610-625.

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Breast lymphoma is a rare hematologic neoplasm that originates in the breast lymphoid tissue and includes primary breast lymphoma (PBL) and secondary breast lymphoma (SBL). PBL involves the breast lymphoid tissue in the absence of previously identified extramammary lymphoma and widespread disease. SBL is the most common metastasis to the breast, accounting for 17% of metastatic disease to the breast. PBL and SBL usually demonstrate imaging phenotypes that overlap with those of primary breast carcinoma, which makes a prospective diagnosis of breast lymphoma challenging. These nonspecific imaging features include an iso- to hyperdense oval mass or masses at mammography, a hypoechoic or mixed-echogenicity hypervascular mass at US, an enhancing mass with type II kinetics at MRI, and high fluorine 18-fluorodeoxyglucose avidity at PET. In cases of suspected lymphoma, reviewing the clinical history, using appropriate biopsy techniques, and evaluating for multiplicity, bilaterality, and distant disease are critical for diagnosis and management. A patient with PBL generally has an earlier clinical presentation with a palpable abnormality and a solitary imaging finding. In contrast, multiple masses in an older patient and an occult clinical presentation favor an SBL diagnosis.

Packer, M. and P. A. Grayburn (2019). “Neurohormonal and Transcatheter Repair Strategies for Proportionate and Disproportionate Functional Mitral Regurgitation in Heart Failure.” JACC Heart Fail May 3. [Epub ahead of print].

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Functional mitral regurgitation (MR) is present to varying degrees in most patients with chronic heart failure (HF) and left ventricular (LV) systolic, and in ~ 30% its magnitude is hemodynamically meaningful. A critical determinant of MR in these patients is the degree of LV dilatation. Remodeling and enlargement of the LV leads to displacement of the papillary muscles and widening and flattening of the mitral annulus, which (together with a reduction in closing forces) impairs the coaptation of the mitral valve (MV) leaflets. However, independent of LV end-diastolic volume (LVEDV), ventricular dyssynchrony contributes importantly to functional MR. In patients with meaningful QRS prolongation, dyssynchrony causes unequal contraction of papillary muscle bearing walls, preventing coordinated closure of the MV leaflets; amelioration of the conduction delay by cardiac resynchronization reduces MR. Additionally, irrespective of the presence of electric conduction delay, localized LV remodeling can cause apical and posterior displacement of the papillary muscles and dysschronous contraction of the leaflet-supporting structures independent of global LV dysfunction. (Excerpt from text of article-in-press, not paginated; no abstract available.)