Multimodality Imaging in Arrhythmogenic Right Ventricular Cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare, heritable myocardial disease associated with the development of ventricular arrhythmias, heart failure, and sudden cardiac death in early adulthood. Multimodality imaging is a central component in the diagnosis and evaluation of ARVC. Diagnostic criteria established by an international task force in 2010 include noninvasive parameters from echocardiography and cardiac magnetic resonance imaging. These criteria identify right ventricular structural abnormalities, chamber and outflow tract dilation, and reduced right ventricular function as features of ARVC. Echocardiography is a widely available and cost-effective technique, and it is often selected for initial evaluation. Beyond fulfillment of diagnostic criteria, features such as abnormal tricuspid annular plane excursion, increased right ventricular basal diameter, and abnormal strain patterns have been described. 3-dimensional echocardiography may also expand opportunities for structural and functional assessment of ARVC. Cardiac magnetic resonance has the ability to assess morphological and functional cardiac features of ARVC and is also a core modality in evaluation, however, tissue characterization of the right ventricle is limited by spatial resolution and low specificity for detection of pathological changes. Nonetheless, the ability of cardiac magnetic resonance to identify left ventricular involvement, offer high negative predictive value, and provide a reproducible structural evaluation of the right ventricle enhance the ability and scope of the modality. In this review, the prognostic significance of multimodality imaging is outlined, including the supplemental value of multidetector computed tomography and nuclear imaging. Strengths and weaknesses of imaging techniques, as well as future direction of multimodality assessment, are also described.

Right Ventricular Strain Predicts Structural Disease Progression in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy.

Background Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited condition associated with ventricular arrhythmias and myocardial dysfunction; however, limited data exist on identifying patients at highest risk. The purpose of the study was to determine whether measures of right ventricular (RV) dysfunction on echocardiogram including RV strain were predictive of structural disease progression in ARVC. Methods and Results A retrospective analysis of serial echocardiograms from 40 patients fulfilling 2010 task force criteria for ARVC was performed to assess structural progression defined by an increase in proximal RV outflow tract dimensions (parasternal short or long axis) or decrease in RV fractional area change. Echocardiograms were analyzed for RV free-wall peak longitudinal systolic strain using 2-dimensional speckle tracking. Risk of structural progression and 5-year change in RV outflow tract measurements were compared with baseline RV strain. Of the 40 ARVC patients, 61% had structural progression with an increase in the mean parasternal short-axis RV outflow tract dimension from 36.2 to 38.5 mm (P=0.022) and 68% by increase in parasternal long-axis RV outflow tract dimension from 36.1 to 39.2 mm (P=0.001). RV fractional area change remained stable over time. Baseline RV strain was significantly associated with the risk of structural progression and 5-year rate of change. Patients with an RV strain more positive than -20% had a higher risk (odds ratio: 18.4; 95% CI, 2.7-125.8; P=0.003) of structural progression. Conclusions RV free wall strain is associated with the rate of structural progression in patients with ARVC. It may be a useful marker in determining which patients require closer follow-up and treatment.

Vasculopathy, inflammation, and blood flow in leg ulcers of patients with sickle cell anemia.

Chronic leg ulcers are frequent and debilitating complications of sickle cell anemia. Inadequate blood supply has been postulated to be an important factor in their occurrence and delayed healing. Little is known about their microcirculatory and histopathological changes. We evaluated the microcirculation of lower extremity ulcers with laser speckle contrast imaging and infrared thermography and obtained clinical and laboratory characteristics in 18 adults with sickle cell anemia and chronic leg ulcers. Skin biopsies were obtained in four subjects. Subjects had markers of severe disease, anemia, high degree of hemolysis, inflammation, and thrombophilia. The highest blood flow was present in the ulcer bed, progressively less in the immediate periwound area, and an unaffected control skin area in the same extremity. Microscopic examination showed evidence of venostasis, inflammation, and vasculopathy. Blood vessels were increased in number, had activated endothelium and evidence of thrombosis/recanalization. High blood flow may be due to chronic inflammation, cutaneous vasodilatation, venostasis, and in situ thrombosis. These changes in skin microcirculation are similar to chronic venous ulcers in the non-sickle cell disease (SCD) population, thus suggesting that leg ulcers may be another end-organ complication with endothelial dysfunction that appears in patients with SCD at a younger age and with higher frequency than in the general population.

Matrix metalloproteinase-2 gene polymorphism is not associated with increased glioblastoma multiforme susceptibility: an Indian institutional experience.

BACKGROUND: Glioblastoma multiforme (GBM) is a highly malignant central nervous system tumor that is extremely refractory to therapy due to its rapid growth and local invasive potential. The ability of glioma cells to invade the surrounding tissue has been attributed to the expression of matrix metalloproteinase-2 (MMP-2) in human gliomas. The -1306C/T polymorphism in the MMP-2 gene has been found to be associated with gastric adenocarcinoma, lung cancer and various other cancers including GBM. Racial and ethnic variations are known in such genetic polymorphisms. AIMS: This prospective, case control study was aimed to find out an association of MMP-2 gene polymorphism with susceptibility to develop glioblastoma in Indian population. MATERIAL AND METHODS: MMP-2 gene polymorphism was studied using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 110 GBM patients and 150 healthy controls. The SPSS 17.0 statistical software (Chicago, IL, USA) was used for data management and analysis. RESULTS AND CONCLUSIONS: A significant association of MMP-2 (-1306C/T) polymorphism with GBM (P = 0.475) was not found, suggesting that MMP-2 (-1306C/T) polymorphism is not associated with increased GBM susceptibility.

Association of matrix metalloproteinase-1 gene polymorphism with glioblastoma multiforme in a northern Indian population.

Matrix metalloproteinase-1 (MMP-1) is known to be involved in the pathogenesis of glioma. It damages the extra-cellular matrix to produce invasiveness in cancer tissue, and hence has a direct effect in cancer invasion. The study aims to explore the association of single nucleotide polymorphism of -1607 MMP-1 gene with susceptibility to glioblastoma multiforme (GBM) in northern Indian subjects. One hundred and ten GBM patients and 150 healthy controls were included in this study. 1607 MMP-1 gene was studied by PCR-RFLP; different genotypes being combinations of 1G and 2G allele (1G/1G, 1G/2G and 2G/2G). 2G/2G genotype was significantly associated with GBM patients (OR, 2.24; P = 0.016; 95% CI, 1.16-4.30) as compared to controls. Prevalence of the 2G allele of -1607 MMP-1 polymorphism was significantly greater in GBM patients as compared to controls (62.3 vs 48.3%, OR, 1.76; P = 0.002; 95% CI, 1.23-2.52). This study suggests that the 2G/2G genotype and 2G allele of -1607 MMP-1 polymorphism are associated with an increased susceptibility for developing GBM.

An intramedullary tuberculous abscess of the conus in a 5-year-old child presenting with urinary dysfunction.

OBJECTIVE: To report a case of the primary presence of an intramedullary tuberculous abscess in the conus medullaris with neither a history of contact nor tuberculous infection elsewhere in the body. CASE DESCRIPTION: A 5-year-old boy progressed from urinary hesitancy and frequency to complete urinary retention over the course of 1 month. He was seronegative for human immunodeficiency virus. Magnetic resonance imaging (MRI) showed a D11-L1, well-circumscribed, intramedullary mass within the conus, which was hypointense on T1-weighted imaging and hyperintense on T2-weighted imaging with a thin-walled enhancing capsule. A D11-L2 laminectomy revealed a tense dura and expanded cord with no arachnoidal adhesions. A midline myelotomy and capsular fenestration released thick yellowish, creamy pus. The histology showed loose aggregates of epithelioid cells and a mixed leukocyte population including polymorphonuclear leukocytes and mononuclear cells without formed granulomas. Ziehl-Neelsen staining showed acid-fast bacilli of Mycobacterium tuberculosis. The patient showed rapid improvement of sphincteric function with four-drug antituberculous therapy (ATT). CONCLUSIONS: To the best of the authors' knowledge, an intramedullary conus tuberculous abscess in a young child presenting with urinary dysfunction has never been reported. Perhaps hematogenous spread of M. tuberculosis within the conus, encapsulated proliferation and caseating necrosis (owing to delayed-type hypersensitivity), and an osmotic increase in the fluid content were responsible for its genesis and for the lack of arachnoidal adhesions around the cord. Surgical decompression of the abscess established the diagnosis, increased penetrability of ATT, and decreased the biologic load of bacteria, achieving a good recovery.