Genistein Supplementation and Cardiac Function in Postmenopausal Women with Metabolic Syndrome: Results from a Pilot Strain-Echo Study.

Genistein, a soy-derived isoflavone, may improve cardiovascular risk profile in postmenopausal women with metabolic syndrome (MetS), but few literature data on its cardiac effects in humans are available. The aim of this sub-study of a randomized double-blind case-control study was to analyze the effect on cardiac function of one-year genistein dietary supplementation in 22 post-menopausal patients with MetS. Participants received 54 mg/day of genistein (n = 11) or placebo (n = 11) in combination with a Mediterranean-style diet and regular exercise. Left ventricular (LV) systolic function was assessed as the primary endpoint, according to conventional and strain-echocardiography measurements. Also, left atrial (LA) morphofunctional indices were investigated at baseline and at the final visit. Results were expressed as median with interquartile range (IQ). A significant improvement of LV ejection fraction (20.3 (IQ 12.5) vs. -1.67 (IQ 24.8); p = 0.040)), and LA area fractional change (11.1 (IQ 22.6) vs. 2.8 (9.5); p = 0.034)) were observed in genistein patients compared to the controls, following 12 months of treatment. In addition, body surface area indexed LA systolic volume and peak LA longitudinal strain significantly changed from basal to the end of the study in genistein-treated patients. One-year supplementation with 54 mg/day of pure genistein improved both LV ejection fraction and LA remodeling and function in postmenopausal women with MetS.

Increased expression of markers of early atherosclerosis in patients with inflammatory bowel disease.

BACKGROUND & AIMS: Recent studies documented an increased cardiovascular risk in patients with inflammatory bowel disease (IBD). Our study aimed at investigating the prevalence of intima-media thickness (IMT) of the carotid arteries and the arterial stiffness indices as markers of early atherosclerosis in young IBD patients. METHODS: We recruited 68 consecutive IBD patients, and 38 matched healthy controls less than 45years old (median age 31.6±8.1years). Clinical and demographic features, cardiovascular risk factors, history of cardiovascular events, concomitant therapies were registered on a dedicate database. Carotid IMT was evaluated by using high resolution B-mode ultrasonography. Arterial stiffness was assessed by measurement of carotid-femoral Pulse Wave Velocity (PWV) and Augmentation Index (AIx). RESULTS: Total cholesterol (P<0.013) and LDL-cholesterol (P<0.019) levels were significantly lower in IBD patients compared to controls. Carotid IMT was higher in IBD than in controls (P<0.047), but there was no statistically significant difference among Crohn's Disease (CD) and Ulcerative Colitis (UC) patients. Moreover, PWV and AIx were significantly higher in patients as compared to controls (P<0.006 and P<0.004 respectively). No medication seemed to affect vascular measurements, though stiffness parameters were significantly higher in patients treated with 5-ASA (11.9 (9.7) vs 18.2 (10.2), P<0.021), suggesting a lack of efficacy of 5-ASA in protecting IBD patients from early atherogenesis. CONCLUSIONS: Young IBD patients show an increase in subclinical markers of atherosclerosis. Future studies need to address whether these markers result in an increased risk of cardiovascular events in these patient.

Epicardial fat, cardiac geometry and cardiac function in patients with non-alcoholic fatty liver disease: association with the severity of liver disease.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) has been associated with increased cardiovascular risk, including coronary artery disease and cardiac dysfunction. In addition, recent evidence highlighted the possible role of epicardial fat as a new cardiometabolic risk factor. We tested the correlation between epicardial fat, alterations in cardiac geometry and function, and severity of liver damage, in patients with biopsy-proven NAFLD. METHODS: The anthropometric, biochemical and metabolic features were recorded in 147 consecutive biopsy-proven NAFLD cases (Kleiner score). Epicardial fat thickness was measured by echocardiography. RESULTS: Epicardial fat was higher in patients with severe vs. milder fibrosis (8.5 ± 3.0 vs. 7.2 ± 2.3 mm; p=0.006); this association was maintained at multivariate logistic regression analysis (OR 1.22, 95%C.I. 1.01-1.47; p=0.04) after correction for gender, age >50 years, visceral obesity, IFG/diabetes, non-alcoholic steatohepatitis and severe steatosis. Of note, 37.1% of patients with epicardial fat >7 mm (median value) had severe liver fibrosis, compared to 18.3% of the cases with lower epicardial fat (p=0.01). As for echocardiographic indices, after adjusting for cardiometabolic confounders, diastolic posterior-wall thickness (p=0.01), left ventricular mass (p=0.03), relative wall thickness (p=0.02), and left atrial volume (0.04), as well as ejection fraction (p=0.004), lower lateral TDI e' (p=0.009), E/A ratio (0.04) (cardiac geometry alterations and diastolic dysfunction) were linked to severe liver fibrosis. CONCLUSIONS: In patients with NAFLD, a higher epicardial fat thickness is associated with the severity of liver fibrosis, in keeping with a possible pathogenic role of ectopic fat depots in whole body organ damage. In addition, morphological and functional cardiac alterations are more pronounced according to the severity of fibrosis. Further studies are needed to validate our results.

A re-entry tachycardia triggered by the spontaneous interruption of an atrial tachycardia.

The common atrioventricular nodal re-entry tachycardia is the most common form of paroxysmal supraventricular tachycardia. It starts frequently with a supraventricular ectopic beat that, on finding the fast pathway in refractory period, travels in the slow pathway as to appear as a prolongation of the PR interval on the ECG. In this study, we show a singular case of a common atrioventricular nodal re-entry tachycardia triggered by the spontaneous interruption of an atrial tachycardia.

Hypoadiponectinemia, cardiometabolic comorbidities and left ventricular hypertrophy.

This study was designed to evaluate the prevalence of cardiometabolic comorbidities and the changes in left ventricular geometry and function in 135 subjects subgrouped according to low or normal total adiponectin plasma (ADPN) levels. Left ventricular (LV) internal diameter/height, total LV mass (LVM) and LVM index (LVMI), relative wall thickness (RWT), LV ejection fraction by echocardiography and diastolic parameters by pulsed-wave Doppler were calculated. Body mass index (BMI) (p < 0.0001), waist-to-hip ratio (p < 0.03), triglycerides (p < 0,001), prevalence of obesity (p < 0.005), visceral obesity (p < 0.003), left ventricular hypertrophy (LVH) (p < 0.001), metabolic syndrome (p < 0.0003) and coronary artery disease (CAD) (p < 0.003) were significantly increased and high-density lipoprotein-cholesterol (p < 0.001) was significantly reduced in hypo-ADPN than normal-ADPN subjects. LVM, LVMI, interventricular septum thickness and RWT were significantly (p < 0.0001) higher and left ventricular ejection fraction was significantly (p < 0.0002) lower in hypo-ADPN than normal-ADPN patients. LVMI correlated directly with BMI (p < 0.001), mean blood pressure (p < 0.001), metabolic syndrome (MetS) (p < 0.001) and inversely with ADPN (p < 0.0001). The prevalence of LVH (p < 0.001) and CAD (p < 0.01) was higher in subjects with normal-ADPN and MetS, while the presence of MetS did not change this finding in hypo ADPN group. Both models of regression analysis indicated that ADPN and BMI resulted independently associated with LVMI. In conclusion, our data seem to indicate that hypoadiponectinemia might be associated with an increased prevalence both of clinical comorbidities and increased LVMI. In this subset of subjects, ADPN and BMI, more than MetS, are able to explain cardiac damage. Accordingly, ADPN might become a new target in the management of cardiometabolic risk.

Immune-inflammatory markers and arterial stiffness indexes in subjects with acute ischemic stroke with and without metabolic syndrome.

OBJECTIVE: The aim of our study was to evaluate the associations between arterial stiffness indexes and immune-inflammatory markers in subjects with acute ischemic stroke with and without metabolic syndrome. MATERIALS/METHODS: We enrolled 130 patients with acute ischemic stroke and metabolic syndrome, 127 patients with acute ischemic stroke without metabolic syndrome and 120 control subjects without acute stroke. Applanation tonometry was used to record the augmentation index (Aix) and pulse wave velocity (PWV). We also evaluated plasma levels of C-reactive protein (CRP), Interleukin-1beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), Interleukin-6 (IL-6) and Interleukin-10 (IL-10), E-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), von Willebrand Factor (vWF) plasma levels, tissue plasminogen activator (TPA) and plasminogen activator inhibitor-1 (PAI-1). RESULTS: In subjects with acute ischemic stroke and metabolic syndrome we observed higher median plasma values of immuno-inflammatory markers. In acute ischemic stroke patients and metabolic syndrome in relation of each TOAST subtype we observed a more significant positive correlation between PWV and immuno-inflammatory markers. CONCLUSIONS: Stroke subjects with acute ischemic stroke and metabolic syndrome showed a higher degree of immuno-inflammatory and arterial stiffness indexes possibly due to metabolic background of these types of patients that trigger a more intense immune-inflammatory activation irrespective of stroke subtype, whereas being related to stroke subtype in subjects without metabolic syndrome.

Information management and complementary alternative medicine: the anatomy of information about CAMs through PubMed.

In recent years, there has been a growing interest about complementary and alternative medicine (CAM), and the use of CAM interventions has become more common among people. For these reasons, health professionals must be able to effectively manage information in this field of knowledge according to an evidence-based point of view. This study assessed the anatomy of the available information about CAMs using PubMed, to give practical instructions to manage information in this field. We also analyzed the anatomy of information according to each alternative medicine branch, narrow and broad search methods, subset filters for indexed-for-Medline and non-indexed citations, and different publication types including randomized controlled trials (RCTs) and meta-analyses. Our results demonstrated that the use of CAMs subset (supplied by PubMed search engine) leads to a great number of citations determining an information overload. Our data reveal that it would be more useful to search for the CAM separately, identifying specific items and study design. Moreover, we found the largest number of randomized clinical trials and meta-analyses related to herbal medicine and acupuncture, neither RCTs nor meta-analyses were available for bach and flower remedies, auriculoacupuncture, iridology, and pranotherapy. For the first time, our study gives a comprehensive view of the anatomy of information regarding CAMs and each branch of them. We suggest a methodological approach to face with searching information about this emerging issue from an evidence-based point of view. Finally, our data pointed out some "grey zones" since neither RCTs nor meta-analyses were available for some CAMs.

PNPLA3 GG genotype and carotid atherosclerosis in patients with non-alcoholic fatty liver disease.

BACKGROUND AND AIM: To evaluate if the presence of carotid atherosclerosis in patients with NAFLD, could be related to gene variants influencing hepatic fat accumulation and the severity of liver damage. METHODS: We recorded anthropometric, metabolic and histological data(Kleiner score) of 162 consecutive, biopsy-proven Sicilian NAFLD patients. Intima-media thickness(IMT), IMT thickening(IMT≥1 mm) and carotid plaques(focal thickening of >1.3 mm at the level of common carotid artery) were evaluated using ultrasonography. IL28B rs12979860 C>T, PNPLA3 rs738409 C>G, GCKR rs780094 C>T, LYPLAL1 rs12137855 C>T, and NCAN rs2228603 C>T single nucleotide polymorphisms were also assessed. The results were validated in a cohort of 267 subjects with clinical or histological diagnosis of NAFLD from Northern Italy, 63 of whom had follow-up examinations. RESULTS: Carotid plaques, IMT thickening and mean maximum IMT were similar in the two cohorts, whereas the prevalence of diabetes, obesity, NASH, and PNPLA3 GG polymorphism(21%vs.13%, p = 0.02) were significantly higher in the Sicilian cohort. In this cohort, the prevalence of carotid plaques and IMT thickening was higher in PNPLA3 GG compared to CC/CG genotype(53%vs.32%, p = 0.02; 62%vs.28%, p<0.001, respectively). These associations were confirmed at multivariate analyses (OR2.94;95%C.I. 1.12-7.71, p = 0.02, and OR4.11;95%C.I. 1.69-9.96, p = 0.002, respectively), although have been observed only in patients <50years. Also in the validation cohort, PNPLA3 GG genotype was independently associated with IMT thickening in younger patients only (OR: 6.00,95%C.I. 1.36-29, p = 0.01), and to IMT progression (p = 0.05) in patients with follow-up examinations. CONCLUSION: PNPLA3 GG genotype is associated with higher severity of carotid atherosclerosis in younger patients with NAFLD. Mechanisms underlying this association, and its clinical relevance need further investigations.

NT pro BNP plasma level and atrial volume are linked to the severity of liver cirrhosis.

BACKGROUND AND AIMS: Plasma levels of NT-pro-BNP, a natriuretic peptide precursor, are raised in the presence of fluid retention of cardiac origin and can be used as markers of cardiac dysfunction. Recent studies showed high levels of NT pro BNP in patients with cirrhosis. We assessed NT pro-BNP and other parameters of cardiac dysfunction in patients with cirrhosis, with or without ascites, in order to determine whether the behaviour of NT pro BNP is linked to the stage of liver disease or to secondary cardiac dysfunction. METHODS: Fifty eight consecutive hospitalized patients mostly with viral or NAFLD-related cirrhosis were studied. All underwent abdominal ultrasound and upper GI endoscopy. Cardiac morpho-functional changes were evaluated by echocardiography and NT-pro-BNP plasma levels determined upon admission. Twenty-eight hypertensive patients, without evidence of liver disease served as controls. RESULTS: Fifty eight cirrhotic patients (72% men) with a median age of 62 years (11% with mild arterial hypertension and 31% with type 2 diabetes) had a normal renal function (mean creatinine 0.9 mg/dl, range 0.7-1.06). As compared to controls, cirrhotic patients had higher NT pro-BNP plasma levels (365.2±365.2 vs 70.8±70.6 pg/ml; p<0.001). Left atrial volume (LAV) (61.8±26.3 vs 43.5±14.1 ml; p = 0.001), and left ventricular ejection fraction (62.7±6.9 vs. 65.5±4%,; p = 0.05) were also altered in cirrhotic patients that in controls. Patients with F2-F3 oesophageal varices as compared to F0/F1, showed higher e' velocity (0.91±0.23 vs 0.66±0.19 m/s, p<0.001), and accordingly a higher E/A ratio (1.21±0.46 vs 0.89±0.33 m/s., p = 0.006). CONCLUSION: NT-pro-BNP plasma levels are increased proportionally to the stage of chronic liver disease. Advanced cirrhosis and high NT-pro-BNP levels are significantly associated to increased LAV and to signs of cardiac diastolic dysfunction. NT pro-BNP levels could hence be an useful prognostic indicators of early decompensation of cirrhosis.

Genistein and endothelial function in postmenopausal women with metabolic syndrome.

BACKGROUND: Previous data have suggested that genistein could exert beneficial effects on endothelial function and on predictors of cardiovascular risk in healthy postmenopausal women. In a randomized clinical trial, we studied the effects of genistein on endothelial function in postmenopausal women with metabolic syndrome (MS). METHODS: Twenty postmenopausal women with MS, according to modified NCEP-ATP III criteria were randomly assigned to receive placebo or genistein (54 mg/day) for 6 months, along with a Mediterranean-style diet. Postmenopausal women without MS (n = 15), served as controls. The primary goal was the assessment of endothelial function by flow-mediated vasodilation (FMD) of brachial artery; moreover, time-to-peak dilation in the FMD response has been evaluated. Secondary outcomes were fasting glucose, fasting insulin, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, visfatin, adiponectin and homocysteine blood levels. Data on adverse events were also recorded. RESULTS: After 6 months of treatment, FMD at 50s and peak FMD significantly increased in genistein recipients compared with placebo. Moreover, genistein significantly decreased the blood levels of total cholesterol, triglycerides, homocysteine and visfatin compared with placebo, while blood adiponectin levels were increased. Genistein recipients neither experienced more side-adverse effects than placebo nor discontinued the study. CONCLUSIONS: Six months of treatment with genistein effectively improves brachial artery flow-mediated vasodilation in postmenopausal women with metabolic syndrome.

Genistein in the metabolic syndrome: results of a randomized clinical trial.

CONTEXT: This study was performed to evaluate the effects of genistein on metabolic and cardiovascular risk factors in Caucasian postmenopausal subjects with metabolic syndrome (MetS). OBJECTIVE: Our objective was to assess the effects of genistein on surrogate endpoints associated with diabetes and cardiovascular disease. DESIGN AND SETTING: This was a randomized, double-blind, placebo-controlled trial at 3 university medical centers in Italy. PATIENTS: Patients included 120 postmenopausal women with MetS according to modified Third Report of the National Cholesterol Education Program (NCEP), Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) criteria. INTERVENTION: After a 4-week stabilization period, postmenopausal women with MetS were randomly assigned to receive placebo (n = 60) or 54 mg genistein daily (n = 60) for 1 year. MAIN OUTCOME MEASURES: The primary outcome was homeostasis model assessment for insulin resistance (HOMA-IR) at 1 year. Secondary outcomes were fasting glucose, fasting insulin, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, visfatin, adiponectin, and homocysteine levels. Data on adverse events were also recorded. RESULTS: At 1 year in genistein recipients, fasting glucose, fasting insulin, and HOMA-IR (mean from 4.5 to 2.7; P < .001) decreased and were unchanged in placebo recipients. Genistein statistically increased HDL-C (mean from 46.4 to 56.8 mg/dL) and adiponectin and decreased total cholesterol, LDL-C (mean from 108.8 to 78.7 mg/dL), triglycerides, visfatin, and homocysteine (mean from 14.3 to 11.7 µmol/L) blood levels. Systolic and diastolic blood pressure was also reduced in genistein recipients. Genistein recipients neither experienced more side adverse effects than placebo nor discontinued the study. CONCLUSION: One year of treatment with genistein improves surrogate endpoints associated with risk for diabetes and cardiovascular disease in postmenopausal women with MetS.

Cholesterol-adjusted vitamin E serum levels are associated with cardiovascular events in patients with non-valvular atrial fibrillation.

BACKGROUND: Non-valvular atrial fibrillation is associated with an increase in thromboembolism, i.e. stroke, and atherosclerotic events, i.e. myocardial infarction. Vitamin E possesses anti-coagulant as well as anti-atherosclerotic properties. Our aim was to assess whether vitamin E is associated with cardiovascular events in patients with non-valvular atrial fibrillation. METHODS: Serum levels of cholesterol-adjusted vitamin E were measured in 1012 patients with non-valvular atrial fibrillation. Patients were followed for a mean time of 27.0 months, and cardiovascular events, such as cardiovascular death and fatal and nonfatal stroke or myocardial infarction, were recorded. RESULTS: During the follow-up period, cardiovascular events occurred in 109 (11%) patients (18 fatal and 14 nonfatal myocardial infarction; 13 fatal and 19 nonfatal ischemic strokes; 45 cardiovascular deaths). Lower vitamin E serum levels were found in patients who experienced cardiovascular events compared to those who did not (3.8±1.2 vs. 4.4±1.8 µmol/mmol cholesterol; p<0.001). Using a Cox proportional hazard model, age, diabetes, history of stroke and myocardial infarction and vitamin E serum levels (HR 0.77; 95% CI: 0.67-0.89; p=0.001) independently predicted cardiovascular events. Patients with vitamin E<4.2 µmol/mmol cholesterol (median values) had an increased risk of cardiovascular events (HR 1.87; 95% CI: 1.25-2.80: p=0.002). CONCLUSIONS: Low vitamin E serum levels are associated with an increased risk of cardiovascular events in patients with non-valvular atrial fibrillation.

Anderson-Fabry disease: a multiorgan disease.

Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by a deficiency of the enzyme α-galactosidase A. FD causes glycolipids, such as globotriaosylceramide (Gb3), to accumulate in the vascular endothelium of several organs (Fig. 2), including the skin, kidneys, nervous system, and heart, thereby triggering inflammation and fibrosis. These processes generally result in organ dysfunction, which is usually the first clinical evidence of FD. Patients with classic FD have various symptoms, eg, acroparesthesias, hypohidrosis, angiokeratomas, corneal opacities, cerebrovascular lesions, cardiac disorders, andrenal dysfunction.However, evolving knowledge about the natural course of disease suggests that it is more appropriate to describe FD as a disease with a wide spectrum of heterogeneously progressive clinical phenotypes. Indeed, most female heterozygotes develop symptoms due to yet undetermined mechanisms and a high percentage of females develops vital organ involvement including the kidneys, heart and/or brain about a decade later than males. Renal failure is a serious complication of this disease. Fabry nephropathy lesions are present and progress in childhood while the disease commonly remains silent by routine clinical measures. Early and timely diagnosis of Fabry nephropathy is crucial since late initiation of enzyme replacement therapy may not halt progressive renal dysfunction. This may be challenging due to difficulties in diagnosis of Fabry disease in children and absence of a sensitive non-invasive biomarker of early Fabry nephropathy. Accurate measurement of glomerular filtration rate and regular assessment for proteinuria and microalbuminuria are useful, though not sensitive enough to detect early lesions in the kidney. The principal clinical manifestations in Fabry disease consist of artery associated complications (such as cerebral disease and nephropathy), but the pathophysiology of this specific vasculopathy is unclear. Several studies indicate that the specific vascular lesions that are present in Fabry disease occur as a result of vascular dysfunction with major components being endothelial dysfunction, alterations in cerebral perfusion and a pro-thrombotic phenotype. Fabry cardiac involvement has several clinical manifestations (Table 10): concentric left ventricular hypertrophy without left ventricular dilation and severe loss of left ventricular systolic function, mitral and aortic valvulopathy, disorders of the atrioventricular conduction or repolarization, and compromised diastolic function. The neurological manifestations of Fabry disease include both peripheral nervous system and CNS involvement, with globotriaosylceramide accumulation found in Schwann cells and dorsal root ganglia together with deposits in CNS neurones. The main involvement of the CNS is attributable to cerebrovasculopathy, with an increased incidence of stroke. The abnormal neuronal accumulation of glycosphingolipid appears to have little clinical effect on the natural history of Fabry disease, with the possible exception of some reported mild cognitive abnormalities. The pathogenesis of Fabry vasculopathy remains poorly understood, but probably relates, in part, to abnormal functional control of the vessels, secondary to endothelial dysfunction as a consequence of α-galactosidase A deficiency. The diagnosis of Fabry disease is made in hemizygous males after the detection of the presence of angiokeratomas (Fig. 19 A, B), irregularities in sweating, edema, scant body hair, painful sensations, and of cardiovascular, intestinal, renal, ophthalmologic, phlebologic, and respiratory involvement. A deficiency of alpha-gal A in serum, leukocytes, tears, tissue specimens, or cultured skin fibroblasts further supports the diagnosis in male patients. Since heterozygous women show angiokeratomas in only about 30% of cases and may have alpha-gal A levels within normal range, genetic analysis is recommended. The resultant storage of undegraded glycolipids leads to the progressive development of potentially life-threatening manifestations affecting multiple organ systems in the body. The Mainz Severity Score Index (MSSI) (Table 12), a scoring system for patients with Fabry disease has been proven to be representative in patients with 'classic' Fabry disease and may be useful for monitoring clinical improvement in patients receiving enzyme replacement therapy. The MSSI of patients with AFD was significantly higher than that of patients with other severe debilitating diseases.

Neurological complications of Anderson-Fabry disease.

Characteristic clinical manifestations of AFD such as acroparesthesias, angiokeratoma, corneal opacity, hypo/ and anhidrosis, gastrointestinal symptoms, renal and cardiac dysfunctions can occur in male and female patients, although heterozygous females with AFD usually seem to be less severely affected. The most prominent CNS manifestations consist of cerebrovascular events such as transient ischaemic attacks (TIAs) and (recurrent) strokes. For the most part, CNS complications in AFD have been attributed to cerebral vasculopathy, including anatomical abnormalities. The natural history of Fabry patients includes transitory cerebral ischaemia and strokes, even in very young persons of both genders. The mechanism is partly due to vascular endothelial accumulation of Gb-3. White matter lesions (WML) on occur MRI. Both males and females can be safely treated with enzyme replacement; and thus screening for Fabry disease of young stroke populations should be considered. There are, however, no hard data of treatment effect on mortality and morbidity. Stroke in Anderson-Fabry disease study of 721 patients with cryptogenic stroke, aged 18-55 years, showed a high prevalence of Fabry disease in this group: 5% (21/432) of men and 3% (7/289) of women. Combining results of both sexes showed that 4% of young patients with stroke of previously unknown cause had Fabry disease, corresponding to about 1-2% of the general population of young stroke patients. Cerebral micro- and macro-vasculopathy have been described in Fabry disease. Neuronal globotriaosylceramide accumulation in selective cortical and brain stem areas including the hippocampus has been reported by autopsy studies in FD, but clinical surrogates as well as the clinical relevance of these findings have not been investigated so far. Another Neurologic hallmark of Fabry disease (FD) includes small fiber neuropathy as well as cerebral micro- and macroangiopathy with premature stroke. Cranial MRI shows progressive white matter lesions (WML) at an early age, increased signal intensity in the pulvinar, and tortuosity and dilatation of the larger vessels. Conventional MRI shows a progressive load of white matter lesions (WMLs) due to cerebral vasculopathy in the course of FD. Another study has been conducted to quantify brain structural changes in clinically affected male and female patients with FD. The peripheral neuropathy in Fabry disease manifests as neuropathic pain, reduced cold and warm sensation and possibly gastrointestinal disturbances. Patients with Fabry disease begin having pain towards the end of the first decade of life or during puberty. Children as young as 6 years of age have complained of pain often associated with febrile illnesses with reduced heat and exercise tolerance. The patients describe the pain as burning that is often associated with deep ache or paresthesiae. Some patients also have joint pain. A high proportion of patients with Fabry disease is at increased risk of developing neuropsychiatric symptoms, such as depression and neuropsychological deficits. Due to both somatic and psychological impairment, health-related quality of life (QoL) is considerably reduced in patients with Fabry disease. Targeted screening for Fabry disease among young individuals with stroke seems to disclose unrecognized cases and may therefore very well be recommended as routine in the future. Furthermore, ischemic stroke is related to inflammation and arterial stiffness and no study had addressed this relationship in patients with AF disease and cerebrovascular disease, so this topic could represent a possible future research line.

Supraventricular tachycardias: proposal of a diagnostic algorithm for the narrow complex tachycardias.

The narrow complex tachycardias (NCTs) are defined by the presence in a 12-lead electrocardiogram (ECG) of a QRS complex duration less than 120ms and a heart rate greater than 100 beats per minute; those are typically of supraventricular origin, although rarely narrow complex ventricular tachycardias have been reported in the literature. As some studies document, to diagnose correctly the NCTs is an arduous exercise because sometimes those have similar presentation on the ECG. In this paper, we have reviewed the physiopathological, clinical, and ECG findings of all known supraventricular tachycardias and, in order to reduce the possible diagnostic errors on the ECG, we have proposed a quick and accurate diagnostic algorithm for the differential diagnosis of NCTs.