Assessment of cardiac sympathetic activity by MIBG imaging in patients with heart failure: a clinical appraisal

Cardiac sympathetic activity can be assessed by (123)I-labelled meta-iodobenzylguanidine (MIBG) scintigraphy. Abnormalities of sympathetic cardiac activity have been shown in patients with heart failure, resulting in reduced MIBG uptake. Abnormal MIBG uptake predicts cardiac death, arrhythmias and all-cause mortality in patients with heart failure with a prognostic power incremental to that of conventional risk markers, and may identify patients at low risk of arrhythmias despite current guideline indications for implantable cardioverter defibrillator or patients at high risk for arrhythmias not fulfilling implantable cardioverter defibrillator indications. Prospective outcome studies are needed to assess whether MIBG imaging will have an impact on the mortality and morbidity of patients with heart failure.     

PNPLA3 rs738409C/G polymorphism in cirrhosis: relationship with the aetiology of liver disease and hepatocellular carcinoma occurrence

Background and aim: The PNPLA3 rs738409 C>G polymorphism has been found to be strongly associated with non‐alcoholic fatty liver disease and with alcoholic liver disease. Whether the PNPLA3 rs738409 polymorphism could be a risk factor for the development of hepatocellular carcinoma (HCC) in cirrhosis patients is unknown. Methods: This study included 483 (344 males) consecutive Italian patients of Caucasian ethnicity affected by cirrhosis, of whom 279 had undergone transplantation for end‐stage liver disease while 204 had been referred to our liver and transplant unit for the diagnosis of cirrhosis. The aetiologies were hepatitis C virus=209, hepatitis B virus=76, alcohol=166, metabolic=32. Ile148Met rs738409 transversion was genotyped using an restriction fragment length polymorphism‐based assay. Results: The genotype frequencies of the rs738409 polymorphism were distributed differently in patients with cirrhosis C/C=168, C/G=220, G/G=95 vs controls C/C=218, C/G=175, G/G=35 (P<0.0001). Among cirrhotics, the G allele was over‐represented in alcoholic/metabolic (0.505) vs viral (0.368, P<0.001) liver disease. Patients with cirrhosis complicated by HCC were more likely to be G/G homozygotes (38/141) than the remaining patients (57/342, P<0.02). At multivariate analysis, the PNPLA3 rs738409 polymorphism was confirmed to be an independent predictor of HCC occurrence (odds ratio 1.76, 95% confidence interval 1.06–2.92, P<0.05). HCC rates increased from 13/116 (11.2%; female C/^* carriers), to 97/295 (32.9%; male C/^*carriers and female G/G homozygotes), to 31/72 (43.1%; male G/G homozygotes) (P<0.0001). Conclusions: The PNPLA3 rs738409 C>G polymorphism is associated with cirrhosis. In synergy with gender, this polymorphism is a strong predictor of HCC occurrence among patients with cirrhosis.     

Influence of corevalve revalving system implantation on mitral valve function

Objectives : The purpose of this study is to verify whether transcatheter aortic valve implantation (TAVI) determined changes in mitral valve (MV) function, in terms of mitral regurgitation (MR) and stenosis. Background : Little data is available regarding the effects of TAVI on global MV function, often derived from analysis primarily focused on clinical and aortic related outcomes. Methods : From May 2008 to March 2010, 73 patients with severe symptomatic aortic stenosis underwent TAVI with the CoreValve ReValving System. The study population consisted of 58 patients (27 males, mean age 82 ± 7 years) who underwent transthoracic echocardiography at least ≥1 month after implantation (mean follow‐up 7.8 ± 5.4 months). Results : In patients with a left ventricular dysfunction (ejection fraction, EF, <45%) at the baseline, EF significantly increased from 37 ± 6% to 48 ± 7% after TAVI (P = 0.003). Before TAVI, 42 patients had no or mild MR, 13 mild‐to‐moderate, and 3 moderate or moderate‐to‐severe. During follow‐up, the MR degree was unchanged in the majority of patients (55%), 12% reduced, and 33% worsened. Variables associated with worsening in MR were depth of aortic prosthesis (P = 0.02 for the distance between the ventricular end and the right coronary cusp; P = 0.04 for mean distance right‐left coronary cusps) and left atrium area at the baseline (P = 0.02). After TAVI, six patients (10%) developed mild or moderate mitral stenosis, often in a native valve with anterior calcifications. Conclusions : In the majority of patients no significant changes occurred in the degree of MR in native valve, but we found that if the aortic valve was deeply implanted in the left ventricle outflow tract, a worsening in MR can be observed. A mitral stenosis development must be sought in patients with heavy calcifications of the anterior leaflet. © 2011 Wiley‐Liss, Inc.     

Dilated cardiomyopathy with conduction defects in a patient with partial merosin deficiency due to mutations in the laminin‐α2‐chain gene: A chance association or a novel phenotype?

Patients with a partial reduction of merosin due to mutations in the laminin‐α2 chain gene usually present with a mild form of congenital muscular dystrophy or a limb‐girdle–like muscular dystrophy. To our knowledge, cardiac impairment has never been reported in such patients. A longitudinal study of a patient with partial laminin‐α2 deficiency secondary to mutations in the LAMA2 gene revealed dilated cardiomyopathy with ventricular arrhythmias. Is this a chance association or a novel phenotype? Muscle Nerve, 2011     

Redox imbalance of red blood cells impacts T lymphocyte homeostasis: implication in carotid atherosclerosis

Oxidative stress and immune/inflammatory responses are key pathogenetic factors of atherosclerotic disease. In this contest, mechanisms that regulate survival and death of immune cells may be relevant. Previous studies have demonstrated that red blood cells (RBCs) are physiologically able to inhibit apoptosis and to promote proliferation of activated T lymphocytes from healthy subjects. The aim of the present study was to evaluate whether RBCs from patients with carotid atherosclerosis maintain their property to modulate T cell homeostasis. Peripheral blood lymphocytes (PBLs) obtained from healthy subjects were activated in vitro by phytohemagglutinin in the presence/absence of RBCs from patients with carotid atherosclerosis or of in vitro oxidised RBCs from healthy subjects. Levels of reactive oxygen species (ROS) and aging markers of RBCs as well as susceptibility to apoptosis of PBLs were evaluated by flow cytometry. PBL proliferation was evaluated by 3H-methyl-thymidine incorporation assay whereas secretion of cytokines, analysed in view of their key role in T cell function, was assessed by ELISA. Levels of ROS and phosphatidyl-serine externalisation, a sign of RBC aging, resulted significantly higher in RBCs from patients than in those from healthy subjects, whereas surface glycophorin A expression and reduced glutathione content did the opposite. Unlike RBCs obtained from healthy subjects, RBCs from patients and in vitro oxidised RBCs did not protect activated T lymphocytes from apoptosis. Hence, RBCs from patients with carotid atherosclerosis, probably due to their oxidative imbalance, impact T cell integrity and function. Our results suggest a new regulatory role for RBCs in atherosclerosis.     

Identification of three novel plasminogen (PLG) gene mutations in a series of 23 patients with low PLG activity

Inherited severe hypoplasminogenaemia is a multisystemic disorder leading to deficient extravascular fibrinolysis. As a clinical consequence wound healing capacity of mucous membranes is markedly impaired leading to ligneous conjunctivitis and several other manifestations. Here we report the molecular genetic and clinical findings on 23 new cases with severe hypoplasminogenaemia. Homozygous or compound-heterozygous mutations in the plasminogen (PLG) gene were found in 16 of 23 patients (70%), three of which were novel mutations reported here for the first time (C166Y, Y264S, IVS10-7T/G). Compared to 79 previously published cases, clinical manifestations of the current group of patients showed higher percentages of ligneous periodontitis, congenital hydrocephalus, and involvement of the female genital tract. In contrast, involvement of the gastrointestinal or urogenital tract was not observed in any of the cases. Patients originated to a large extent (61%) from Turkey and the Middle East, and showed a comparably frequent occurrence of consanguinity of affected families and a greater female to male ratio than was derived from previous reports in the literature. Individual treatment of ligneous conjunctivitis included topical plasminogen or heparin eye drops, topical or systemic fresh frozen plasma, and surgical removal of ligneous pseudomembranes, mostly with modest or transient efficacy. In conclusion, the present study underscores the broad range of clinical manifestations in PLG-deficient patients with a trend to regional differences. Transmission of genetic and clinical data to the recently established Plasminogen Deficiency Registry should help to determine the prevalence of the disease and to develop more efficient treatment strategies.     

What’s growing on? The growing teratoma syndrome

Background

The growing teratoma syndrome (GTS) consists of a mature teratoma paradoxically enlarging during or after chemotherapy for malignant nongerminomatous germ cell tumors.

Methods and results

We report two cases of GTS occurring in association with NSGCT of the pineal gland. Although an unusual event, clinicians and radiologists should be aware of its natural history.

Conclusions

When normalized tumor markers after chemotherapy are associated with imaging features of a growing mass, the hypothesis of GTS must be taken in consideration. When early diagnosed, GTS can be managed surgically with good results.