Assessment of the Spatial QRS-T Angle by Vectorcardiography: Current Data and Perspectives

The concept of the ventricular gradient (VG) was conceived in the 1930s and its calculation yielded information that was not otherwise obtainable. The VG was not utilized by clinicians at large because it was not easy to understand and its computation time-consuming. Spatial vectorcardiography is based on the concept of the VG. Its current major clinical use is to identify primary [heterogeneity of ventricular action potential (VAP) morphology] in the presence of secondary [heterogeneity in ventricular depolarization instants] T-wave abnormalities in an ECG. Nowadays, the calculation of the spatial VG can be computed on the basis of a regular routine ECG and contributes to localization of arrhythmogenic areas in the heart by assessing overall and local VAP duration heterogeneity. Recent population-based studies suggest that the spatial VG is a dominant ECG predictor of future cardiovascular events and death and it is superior to more conventional ECG parameters. Its assessment warrants consideration for intensified primary and secondary prevention efforts and can be included in everyday clinical practice. This review addresses the nature and diagnostic potential of the spatial VG. The main focus is the role of the spatial VG in ECG assessment of dispersion of repolarization, a key factor in arrhythmogeneity

A review of nateglinide in the management of patients with type 2 diabetes

Impaired insulin secretion occurs early in the pathogenesis of type 2 diabetes mellitus (T2DM) and is chronic and progressive, resulting initially in impaired glucose tolerance (IGT) and eventually in T2DM. As most patients with T2DM have both insulin resistance and insulin deficiency, therapy for T2DM should aim to control not only fasting, but also postprandial plasma glucose levels. While oral glucose-lowering treatment with metformin and thiazolidinediones corrects fasting plasma glucose, these agents do not address the problem of mealtime glucose spikes that have been shown to trigger atherogenic processes. Nateglinide is a derivative of the amino acid D-phenylalanine, which acts directly on the pancreatic β-cells to stimulate insulin secretion. Nateglinide monotherapy controls significantly mealtime hyperglycemia and results in improved overall glycemic control in patients with T2DM by reducing glycosylated hemoglobin (HbA1c) levels. The combination of nateglinide with insulin-sensitising agents, such as metformin and thiazolidinediones, targets both insulin deficiency and insulin resistance and results in reductions in HbA1c that could not be achieved by monotherapy with other antidiabetic agents. In prediabetic subjects with IGT, nateglinide restores early insulin secretion and reduces postprandial hyperglycemia. Nateglinide has an excellent safety and tolerability profile and provides a lifetime flexibility that other antidiabetic agents could not accomplish. The aim of this review is to identify nateglinide as an effective “gate-keeper” in T2DM, since it restores early-phase insulin secretion and prevents mealtime glucose spikes throughout the day and to evaluate the results of ongoing research into its potential role in delaying the progression to overt diabetes and reducing its complications and mortality

Diabetic cardiomyopathy: from the pathophysiology of the cardiac myocytes to current diagnosis and management strategies

Diabetic cardiomyopathy (DCM), although a distinct clinical entity, is also a part of the diabetic atherosclerosis process. It may be independent of the coexistence of ischemic heart disease, hypertension, or other macrovascular complications. Its pathological substrate is characterized by the presence of myocardial damage, reactive hypertrophy, and intermediary fibrosis, structural and functional changes of the small coronary vessels, disturbance of the management of the metabolic cardiovascular load, and cardiac autonomic neuropathy. These alterations make the diabetic heart susceptible to ischemia and less able to recover from an ischemic attack. Arterial hypertension frequently coexists with and exacerbates cardiac functioning, leading to the premature appearance of heart failure. Classical and newer echocardiographic methods are available for early diagnosis. Currently, there is no specific treatment for DCM; targeting its pathophysiological substrate by effective risk management protects the myocardium from further damage and has a recognized primary role in its prevention. Its pathophysiological substrate is also the objective for the new therapies and alternative remedies

The Effect of Ingested Macronutrients on Postprandial Ghrelin Response: A Critical Review of Existing Literature Data

Ghrelin is a powerful orexigenic gut hormone with growth hormone releasing activity. It plays a pivotal role for long-term energy balance and short-term food intake. It is also recognized as a potent signal for meal initiation. Ghrelin levels rise sharply before feeding onset, and are strongly suppressed by food ingestion. Postprandial ghrelin response is totally macronutrient specific in normal weight subjects, but is rather independent of macronutrient composition in obese. In rodents and lean individuals, isoenergetic meals of different macronutrient content suppress ghrelin to a variable extent. Carbohydrate appears to be the most effective macronutrient for ghrelin suppression, because of its rapid absorption and insulin-secreting effect. Protein induces prolonged ghrelin suppression and is considered to be the most satiating macronutrient. Fat, on the other hand, exhibits rather weak and insufficient ghrelin-suppressing capacity. The principal mediators involved in meal-induced ghrelin regulation are glucose, insulin, gastrointestinal hormones released in the postabsorptive phase, vagal activity, gastric emptying rate, and postprandial alterations in intestinal osmolarity

Brain imaging evidence of early involvement of subcortical regions in familial and sporadic Alzheimer's disease

Recent brain imaging studies have found changes in subcortical regions in presymptomatic autosomal dominant Alzheimer's disease (ADAD). These regions are also affected in sporadic Alzheimer's disease (sAD), but whether such changes are seen in early-stage disease is still uncertain. In this review, we discuss imaging studies published in the past 12 years that have found evidence of subcortical involvement in early-stage ADAD and/or sAD. Several papers have reported amyloid deposition in the striatum of presymptomatic ADAD mutation carriers, prior to amyloid deposition elsewhere. Altered caudate volume has also been implicated in early-stage ADAD, but findings have been variable. Less is known about subcortical involvement in sAD: the thalamus and striatum have been found to be atrophied in symptomatic patients, but their involvement in the preclinical phase remains unclear, in part due to the difficulties of studying this stage in sporadic disease. Longitudinal imaging studies comparing ADAD mutation carriers with individuals at high-risk for sAD may be needed to elucidate the significance of subcortical involvement in different AD clinical stages

Νέα μέθοδος αντιμετώπισης των χρόνιων διαβητικών ελκών, βασισμένη στη θεραπεία με RGTA matrix: μία τυχαιοποιημένη, ελεγχόμενη μελέτη

Τα έλκη αποτελούν συχνή επιπλοκή του σακχαρώδους διαβήτη (ΣΔ). Τα διαβητικά έλκη χαρακτηρίζονται από αυξημένη δραστηριότητα πρωτεϊνών που διασπούν την εξωκυττάρια θεμέλια ουσία (ΕΘΟ) και δυσχεραίνουν την επούλωση. Τα matrix therapy regenerating agents (RGTA) (CACIPLIQ) είναι χημικά κατασκευασμένα πολυμερή που έχουν σχεδιαστεί ειδικά για να αντικαταστήσουν τη θειική ηπαράνη στα έλκη και έτσι να μιμούνται τη δράση της, προστατεύοντας τις πρωτεΐνες της ΕΘΟ από την αποδόμηση. Στόχος της παρούσας εργασίας ήταν η αξιολόγηση της αποτελεσματικότητας και της ασφάλειας χορήγησης CACIPLIQ σε χρόνια διαβητικά έλκη. Στη μελέτη συμπεριλήφθηκαν 27 ασθενείς με ΣΔ και ενεργό νευροπαθητικό έλκος άκρου ποδός που είχε διάρκεια >6 εβδομάδες. Η μελέτης διήρκησε 16 εβδομάδες και η πρώτη επίσκεψη πραγματοποιήθηκε 2 εβδομάδες πριν την έναρξη της παρέμβασης, ενώ η τελευταία επίσκεψη πραγματοποιήθηκε 4 εβδομάδες μετά το τέλος της παρέμβασης. Συνολικά 13 άτομα τυχαιοποιήθηκαν στην ομάδα που αντιμετωπίσθηκε με τη συνήθη αγωγή και 14 άτομα στην ομάδα που έλαβε επιπλέον CACIPLIQ με τη μορφή εναιωρήματος. Οι ασθενείς των δυο ομάδων δεν διέφεραν σημαντικά ως προς τα δημογραφικά, τα κλινικά και τα εργαστηριακά χαρακτηριστικά τους στην έναρξη της μελέτης. Δεν παρατηρήθηκε σημαντική διαφορά μεταξύ των δυο ομάδων στο πρωτογενές καταληκτικό σημείο που αφορούσε τον αριθμό των ελκών με > 80% μείωση στο μέγεθος του έλκους 10 εβδομάδες μετά τη χορήγηση του εξεταζόμενου φαρμάκου (P = 0.936). Επίσης, δεν παρατηρήθηκε σημαντική διαφορά στα δευτερογενή καταληκτικά σημεία, συμπεριλαμβανομένου και των ανεπιθύμητων συμβαμάτων. Συμπερασματικά, η προσθήκη CACIPLIQ στην καθιερωμένη αγωγή σε νευροπαθητικά έλκη ατόμων με ΣΔ δεν επηρεάζει σημαντικά την έκβαση των ελκών σε σύγκριση με τη συνήθη αγωγή.Ulcers are a common complication of diabetes mellitus (DM). In diabetic ulcers, there is increased activity of proteins that disrupt the extracellular matrix (ECM) and impair wound healing. Matrix therapy regenerating agents (RGTA) (CACIPLIQ) are chemically formulated polymers specifically designed to replace heparin sulfate in ulcers and thereby mimic its action by protecting ECM proteins. The aim of this study was to evaluate the efficacy and safety of CACIPLIQ in chronic neuropathic diabetic ulcers. A total of 27 patients with DM and active foot neuropathic ulcer lasting >6 weeks were recruited. The duration of the study was 16 weeks; the first visit was 2 weeks before the intervention and the last visit was 4 weeks after the end of the intervention. A total of 13 of these patients were randomized to standard care and 14 to CACIPLIQ via spraying as add on standard care. The patients of the two groups did not differ significantly in their demographic, clinical and laboratory characteristics at baseline. No significant difference was found between the two groups regarding the primary endpoint (number of ulcers with >80% reduction in ulcer size 10 weeks after administration of CACIPLIQ) (P = 0.936). Additionally, there was no statistically significant difference in secondary endpoints, including adverse events. In conclusion, the addition of CACIPLIQ to standard wound care in neuropathic diabetic foot ulcers does not impact wound healing in comparison with the standard wound care

Association of matrix γ-carboxyglutamic acid protein levels with insulin resistance and Lp(a) in diabetes: A cross-sectional study.

AIMS: The risk of cardiovascular disease (CVD) and mortality is increased in patients with chronic kidney disease (CKD), with a background role of vascular calcification in the development of CVD also reported. Studies have demonstrated that high lipoprotein(a) (Lp(a)) levels accelerate the development of atherosclerolsis and are potentially involved in the vascular calcification. Matrix Gla Protein (MGP) seems to play an important role in vascular calcification. The aim of the study was to examine the potential association of MGP concentrations with Lp(a) and insulin resistance. METHODS: The study involved 100patients divided in four groups: 25 with both CKD stage 4 and Type2 Diabetes (DM) (Group-A), 25 with CKD4 without DM (Group-B), 25 non uremic patients with DM (Group-C) and 25 healthy subjects (Group-D). Serum glucose, Lp(a), MGP, plasma HBA1c and insulin were measured in all patients. Insulin resistance was estimated by the homeostasis model assessment equation (HOMA-IR). RESULTS: A significant positive linear association between MGP and Lp(a) levels (r=0.272, p=0.006) was noted, as well as between MGP and HOMA-IR levels (r=0.308, p=0.002). However, no significant linear association between Lp(a) and HOMA-IR levels was recorded. A similar positive association between MGP and insulin levels (r=0.204, p=0.042) was also found. CONCLUSION: This study concluded that diabetes coexisting with renal disease leads to extreme vascular calcification expressed by elevated MGP levels, resulting in higher frequency of cardiovascular disease in comparison to CKD patients without diabetes. The detected Lp(a) and MGP association in CKD4 patients may also represent the key to the complicated mechanism of their coexisting accelerated atherosclerosis and vascular calcification

Cardiac Autonomic Function Correlates with Arterial Stiffness in the Early Stage of Type 1 Diabetes

Arterial stiffness is increased in type 1 diabetes (T1D), before any clinical complications of the disease are evident. The aim of the present paper was to investigate the association between cardiac autonomic function and arterial stiffness in a cohort of young T1D patients, without history of hypertension and any evidence of macrovascular and/or renal disease. Large artery stiffness was assessed by measurement of carotid-femoral pulse wave velocity (PWV). Cardiac autonomic function was assessed by the cardiovascular tests proposed by Ewing and Clarke. Patients with a high cardiac autonomic neuropathy score (≥4) had significantly higher PWV than those with a low score (0-1). A negative, heart rate-independent, correlation between PWV and heart rate variation during respiration was observed (r = −0.533,  P < 0.001). In multivariable analysis, E/I index was the strongest correlate of PWV (β-coefficient = −0.326, P = 0.002). Cardiac parasympathetic function is a strong predictor of large arterial stiffness, in young T1D patients free of macrovascular and renal complications