- Cardiac autonomic neuropathy: Risk factors, diagnosis and treatment. [Review]
- WJWorld J Diabetes 2018 Jan 15; 9(1):1-24
- Cardiac autonomic neuropathy (CAN) is a serious complication of diabetes mellitus (DM) that is strongly associated with approximately five-fold increased risk of cardiovascular mortality. CAN manifes...
Cardiac autonomic neuropathy (CAN) is a serious complication of diabetes mellitus (DM) that is strongly associated with approximately five-fold increased risk of cardiovascular mortality. CAN manifests in a spectrum of things, ranging from resting tachycardia and fixed heart rate (HR) to development of "silent" myocardial infarction. Clinical correlates or risk markers for CAN are age, DM duration, glycemic control, hypertension, and dyslipidemia (DLP), development of other microvascular complications. Established risk factors for CAN are poor glycemic control in type 1 DM and a combination of hypertension, DLP, obesity, and unsatisfactory glycemic control in type 2 DM. Symptomatic manifestations of CAN include sinus tachycardia, exercise intolerance, orthostatic hypotension (OH), abnormal blood pressure (BP) regulation, dizziness, presyncope and syncope, intraoperative cardiovascular instability, asymptomatic myocardial ischemia and infarction. Methods of CAN assessment in clinical practice include assessment of symptoms and signs, cardiovascular reflex tests based on HR and BP, short-term electrocardiography (ECG), QT interval prolongation, HR variability (24 h, classic 24 h Holter ECG), ambulatory BP monitoring, HR turbulence, baroreflex sensitivity, muscle sympathetic nerve activity, catecholamine assessment and cardiovascular sympathetic tests, heart sympathetic imaging. Although it is common complication, the significance of CAN has not been fully appreciated and there are no unified treatment algorithms for today. Treatment is based on early diagnosis, life style changes, optimization of glycemic control and management of cardiovascular risk factors. Pathogenetic treatment of CAN includes: Balanced diet and physical activity; optimization of glycemic control; treatment of DLP; antioxidants, first of all α-lipoic acid (ALA), aldose reductase inhibitors, acetyl-L-carnitine; vitamins, first of all fat-soluble vitamin B1; correction of vascular endothelial dysfunction; prevention and treatment of thrombosis; in severe cases-treatment of OH. The promising methods include prescription of prostacyclin analogues, thromboxane A2 blockers and drugs that contribute into strengthening and/or normalization of Na+, K+-ATPase (phosphodiesterase inhibitor), ALA, dihomo-γ-linolenic acid (DGLA), ω-3 polyunsaturated fatty acids (ω-3 PUFAs), and the simultaneous prescription of ALA, ω-3 PUFAs and DGLA, but the future investigations are needed. Development of OH is associated with severe or advanced CAN and prescription of nonpharmacological and pharmacological, in the foreground midodrine and fludrocortisone acetate, treatment methods are necessary.
- Type 1 long QT syndrome and psychological stress in a laboratory setting. [Journal Article]
- JHJ Health Psychol 2018 Jan 01; :1359105317751617
- Trait-like sensitivity to stress in long QT syndrome patients has been documented previously. In addition, mental stress has been associated with symptomatic status of long QT syndrome. We examined w...
Trait-like sensitivity to stress in long QT syndrome patients has been documented previously. In addition, mental stress has been associated with symptomatic status of long QT syndrome. We examined whether the symptomatic type 1 long QT syndrome patients would be more sensitive to mental stress compared to asymptomatic patients and whether there would be differences in task-related physiological stress reactions between type 1 long QT syndrome patients and healthy individuals. The study population consisted of 21 symptomatic and 23 asymptomatic molecularly defined KCNQ1 mutation carriers, their 32 non-carrier relatives and 46 non-related healthy controls, with mean ages of 37, 39, 35 and 23 years, respectively. Electrocardiography was utilised to calculate inter-beat interval and high frequency and low frequency heart rate variability. Blood pressure was measured and mean arterial pressure and pulse pressure were calculated. Stress was induced using three different tasks: mental arithmetic, reaction time and public speech. Stress responses of symptomatic and asymptomatic type 1 long QT syndrome patients were not statistically different in any of the stress tasks. Short-term physiological stress reactivity of symptomatic type 1 long QT syndrome patients appears to be normal and does not enhance the risk assessment of asymptomatic mutation carriers.
- Hydroquinidine Prevents Life-Threatening Arrhythmic Events in Patients With Short QT Syndrome. [Journal Article]
- JACCJ Am Coll Cardiol 2017 Dec 19; 70(24):3010-3015
- CONCLUSIONS: We demonstrated for the first time that treatment with HQ was associated with a lower incidence of LAE in SQTS patients. These data point to the importance that quinidine, that in several countries has been removed from the market, remains available worldwide for patients with SQTS. In the present study, therapy with HQ has been proven to be safe, with a relatively low rate of side effects.
- Characteristics of electromechanical window in anesthetized rabbit models of short QT and long QT syndromes. [Journal Article]
- JTJ Toxicol Sci 2017; 42(5):579-587
- The current regulatory guidelines recommend the use of QT interval to assess the risk of arrhythmogenic potential of new chemical entities. Recently, the electromechanical window (EMW), the differenc...
The current regulatory guidelines recommend the use of QT interval to assess the risk of arrhythmogenic potential of new chemical entities. Recently, the electromechanical window (EMW), the difference in duration between electrical and mechanical systole, has been proposed as markers for drug-induced torsades de pointes (TdP); however, data of EMW in short QT model are not available. This study aimed to characterize the EMW as a marker for drug-induced ventricular arrhythmias in anesthetized rabbit model of long QT syndrome type 2 (LQT2) and short QT syndrome (SQTS) infused with reference compounds known to lengthen or shorten QT intervals. After rabbits were anesthetized with isoflurane, body surface electrocardiograms and left ventricular pressure were recorded. The LQT2 was produced by intravenous infusion with dofetilide (n = 6), quinidine (n = 6) and sotalol (n = 6) whereas the SQTS was induced by intravenous escalating concentrations of nicorandil (n = 7), pinacidil (n = 5) and cromakalim (n = 5). The EMW in anesthetized rabbits ranged from 1.3 to 53.3 msec. All three drugs known to lengthen QT intervals prolonged QT and QTcF interval while the EMW was markedly decreased to negative values. Pinacidil significantly produced QT and QTcF shortening and significantly abbreviated the EMW (p < 0.05). This study demonstrated that the EMW is associated with QT intervals (p < 0.001). It is negative in the presence of QT-prolonging drugs while it is more positive in the presence of QT-shortening drugs. The results suggest that the EMW in anesthetized rabbits can be used in drug safety evaluation in addition to the QT interval.
- Positional cloning of quantitative trait nucleotides for blood pressure and cardiac QT-interval by targeted CRISPR/Cas9 editing of a novel long non-coding RNA. [Journal Article]
- PGPLoS Genet 2017; 13(8):e1006961
- Multiple GWAS studies have reported strong association of cardiac QT-interval to a region on HSA17. Interestingly, a rat locus homologous to this region is also linked to QT-intervals. The high resol...
Multiple GWAS studies have reported strong association of cardiac QT-interval to a region on HSA17. Interestingly, a rat locus homologous to this region is also linked to QT-intervals. The high resolution positional mapping study located the rat QT-interval locus to a <42.5kb region on RNO10. This region contained no variants in protein-coding sequences, but a prominent contiguous 19bp indel polymorphism was noted within a novel predicted long non-coding RNA (lncRNA), which we named as Rffl-lnc1. To assess the candidacy of this novel lncRNA on QT-interval, targeted CRISPR/Cas9 based genome-engineering approaches were applied on the rat strains used to map this locus. Targeted disruption of the rat Rffl-lnc1 locus caused aberrant, short QT-intervals and elevated blood pressure. Further, to specifically examine the significance of the 19bp polymorphism within the Rffl-lnc1 locus, a CRISPR/Cas9 based targeted knock-in rescue model was constructed by inserting the 19bp into the strain which contained the deletion polymorphism. The knock-in alleles successfully rescued the aberrant QT-interval and blood pressure phenotypes. Further studies revealed that the 19bp polymorphism was necessary and sufficient to recapitulate the phenotypic effect of the previously mapped <42.5kb rat locus. To our knowledge, this study is the first demonstration of a combination of both CRISPR/Cas9 based targeted disruption as well as CRISPR/Cas9 based targeted knock-in rescue approaches applied for a mammalian positional cloning study, which defines the quantitative trait nucleotides (QTNs) within a rat long non-coding RNA as being important for the pleiotropic regulation of both cardiac QT-intervals and blood pressure.
- In silico assessment of the effects of quinidine, disopyramide and E-4031 on short QT syndrome variant 1 in the human ventricles. [Journal Article]
- PlosPLoS One 2017; 12(6):e0179515
- CONCLUSIONS: The simulated pharmacological actions of quinidine exhibited antiarrhythmic effects on SQT1. This study substantiates a causal link between quinidine and QT interval prolongation in SQT1 and suggests that quinidine may be a potential pharmacological agent for treating SQT1 patients.
- Shortening of the Short Refractory Periods in Short QT Syndrome. [Journal Article]
- JAJ Am Heart Assoc 2017 May 31; 6(6)
- CONCLUSIONS: Patients with SQTS have shorter ventricular RP than controls, both at baseline during various cycle lengths and after premature extrastimuli. A cut-off value of 200 ms at the right ventricular outflow tract during 600- and 500-ms basic cycle length may help in detecting true SQTS from normal subjects with borderline QT values.
- The Spectrum of Ambulatory Electrocardiographic Monitoring. [Review]
- HLHeart Lung Circ 2017; 26(11):1160-1174
- Since its introduction as a clinical investigative tool, the 12-lead electrocardiograph (ECG) has been the gold standard for recognition of cardiac arrhythmias. The resting 12-lead ECG, however, give...
Since its introduction as a clinical investigative tool, the 12-lead electrocardiograph (ECG) has been the gold standard for recognition of cardiac arrhythmias. The resting 12-lead ECG, however, gives only a rhythm snapshot in time, whereas arrhythmias maybe short-lived, paroxysmal and even asymptomatic making documentation in many patients very difficult. To overcome this, ambulatory ECG monitoring has been developed as a means of recording the ECG in patients over a set period of time, whether it be short-, medium- or long-term. With the miniaturisation of recording devices and advances in solid state technology, there has been a recent revolution in hardware design, so that the boundaries between these time-dependent devices have become blurred. Not surprisingly, the indications for monitoring have broadened as the quality and range of monitoring devices have become available. In this review, the indications for ambulatory ECG monitoring with emphasis on non-arrhythmic indications such as ST segment analysis, heart rate variability, signal averaged ECGs, diurnal QT and QTc analysis, obstructive sleep apnoea and vectorcardiography will be discussed. Also, the types of electrode systems used, lead placement, monitoring hardware, data collection, analysis and presentation as well as cost effectiveness of the investigation will be covered.
- Novel trigenic CACNA1C/DES/MYPN mutations in a family of hypertrophic cardiomyopathy with early repolarization and short QT syndrome. [Journal Article]
- JTJ Transl Med 2017 Apr 20; 15(1):78
- CONCLUSIONS: The study reveals a novel CACNA1C mutation underlying the unique ER pattern ECGs with SQTS. It also shows the rare trigenic mutations are the pathogenic substrates for the complicated clinical manifestation in HCM patients.
New Search Next
- Validation of automatic measurement of QT interval variability. [Journal Article]
- PlosPLoS One 2017; 12(4):e0175087
- CONCLUSIONS: Artificially constructed ECGs with a variety of disturbances allow validation of QTV measurement procedures. The FSA algorithm provides highly accurate STV estimates under varying signal conditions, and performs much better than traditional beat-by-beat analysis. The fully automatic operation of the FSA algorithm enables STV measurement in large sets of ECGs.