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Glyburide is a second-generation drug of a class called hypoglycemic sulfonylureas. This drug may have potential usefulness in the management of ventricular arrhythmias resulting from myocardial ischemia (abnormal heart rhythms, originating in the ventricle, which are due to inadequate blood flow to the heart muscle). Glyburide blocks channels in the heart muscle known as ATP-sensitive potassium channels. During myocardial ischemia, the heart muscle is starved of oxygen, and these potassium channels allow potassium to flood out into the extracellular space. The external potassium changes the delicate balance across the cell membrane, and results in significant voltage changes; changes which, if severe enough, may result in life-threatening arrhythmias. In experiments on animals, researchers have demonstrated that glyburide attenuated, but did not entirely block, the increase in extracellular potassium which followed experimental myocardial ischemia. This hypoglycemic drug may be useful in cases of malignant ventricular arrhythmia, which result from oxygen starvation. However, it should be emphasized that numerous changes occur in heart muscle during ischemia, including changes in pH, calcium concentration, and noradrenalin. It is not yet known to what degree each of these contributes to the arrhythmias, nor is it known how these factors are affected by glyburide treatment. (Consumer Summary produced by Reliance Medical Information, Inc.)

Calcium channel blockers prevent the movement of calcium into the cell, decreasing arterial blood pressure and oxygen demand by the heart. They are used to treat various heart conditions, including myocardial infarction, the deterioration of heart tissue due to the cessation of blood supply. Studies suggest that calcium channel blockers may have effects on the sympathetic nervous system, which regulates involuntary body functions such as heart contraction and blood pressure during stress. Sympathetic nerves release noradrenaline, which increases heart contraction and heart rate and constricts blood vessels; these effects may increase the energy demands of the heart, and worsen heart problems such as myocardial infarction. Calcium channel blockers may interfere with the release of noradrenaline from sympathetic nerve endings, and this effect would contribute to their therapeutic action in heart disease. The effects of the calcium channel blockers nifedipine and diltiazem, and the beta blocker metoprolol, which chemically blocks the action of noradrenaline, on sympathetic activity were examined in 28 patients within two to six weeks after heart attack. Eight patients received metoprolol, nine patients received diltiazem, and 10 patients received nifedipine. Nifedipine decreased blood pressure, while metoprolol and diltiazem decreased sympathetic activity. The results show that this mechanism of the calcium channel blocker diltiazem may contribute to its therapeutic effect on myocardial infarction. (Consumer Summary produced by Reliance Medical Information, Inc.)

Cardiac K+ channelopathies account for a significant proportion of arrhythmias and sudden cardiac death (SCD) in subjects without structural heart disease. It is well recognized that genetic defects are key factors in many cases, and in practice, the term cardiac channelopathies currently coincides with inherited cardiac channelopathies. However, mounting evidence demonstrate that not only genetic alterations but also autoimmune and inflammatory factors can cause cardiac K+-channel dysfunction and arrhythmias in the setting of a structurally normal heart. In particular, it has been demonstrated that specific autoantibodies as well as inflammatory cytokines can modulate expression and/or function of different K+ channels in the heart, resulting in a disruption of the cardiac action potential and arrhythmias/sudden cardiac death. Awareness about the existence of these newly recognized forms is essential to identify and adequately manage affected patients. In the present review, we focus on autoimmune and inflammatory K+ channelopathies as a novel mechanism for cardiac arrhythmias and analyze the recent advancements in this topic, providing complementary basic, clinical, and population health perspectives. [ABSTRACT FROM AUTHOR]

In the last decade, there have been considerable advances in the understanding of the pathophysiology of malignant ventricular tachyarrhythmias (VT) and sudden cardiac death (SCD). Over 80% of SCD occurs in patients with organic heart disease. However, approximately 10%–15% of SCD occurs in the presence of structurally normal heart, and the majority of these patients are young. In this group of patients, changes in genes encoding cardiac ion channels produce modifications of the function of the channel resulting in an electrophysiological substrate of VT and SCD. Collectively, these disorders are referred to as cardiac ion channelopathies. The four major syndromes in this group are: the long QT syndrome (LQTS), the Brugada syndrome (BrS), the short QT syndrome (SQTS), and the catecholaminergic polymorphic ventricular tachycardia (CPVT). Each of these syndromes includes multiple subtypes with different and sometimes complex cardiac ion channel genetic abnormalities. Many are associated with other somatic and neurological abnormalities besides the risk of VT and SCD. The current management of cardiac ion channelopathies can be summarized as follows: (1) in symptomatic patients, the implantable cardioverter defibrillator (ICD) is the only viable option; (2) in asymptomatic patients, risk stratification is necessary, followed by either the ICD, pharmacotherapy, or a combination of both. A genotype-specific approach to pharmacotherapy requires a thorough understanding of the molecular–cellular basis of arrhythmogenesis in cardiac ion channelopathies as well as the specific drug profile. [ABSTRACT FROM AUTHOR]

In recent years, cultured cardiac cell monolayers have become a contemporary experimental preparation for the study of fundamental mechanisms that underlie normal and pathologic electrophysiology at the tissue level. Ion channels and gap junctions in the cardiomyocyte monolayer may be modulated using drugs that suppress or enhance certain channels/junctions, or by genetic silencing or overexpression. The cardiomyocyte monolayer is particularly well suited for studies of functional electrophysiologic properties of mixtures of cardiac and noncardiac cells (eg, myofibroblasts), which otherwise would be difficult to investigate. Optical mapping of monolayers has provided insight into mechanisms that can set the stage for arrhythmias, such as unidirectional conduction block, gap junction uncoupling, ischemia, alternans, and anisotropy, and continues to enhance our understanding of basic electrophysiologic mechanisms. [Copyright &y& Elsevier]

Background: Abnormal intracellular calcium (Cai) kinetics during ischemia/reperfusion (I/R) can alter membrane voltage (Vm) and destabilize wavefront propagation. Objective: We used optical mapping to investigate the hypothesis that early Vm/Cai uncoupling during a ventricular tachyarrhythmia (VT) can play a primary role in perpetuation of VT episodes. Methods: Seventeen Langendorff-perfused guinea pig hearts were subjected to 15 min I/15 min R. Simultaneous optical recordings of Vm and Cai signals were obtained using a dual-photodiode array. Spatiotemporal entropy (E) was used to quantify differences in Vm/Cai kinetics during VT and compare wavefront topology during the first 500 ms of a VT episode. Results: A total of 39 episodes of VT were analyzed; VT was classified as self-terminating (ST, n = 28) and non–self-terminating (NST, n = 11). The ST/VTs were further classified into short ST/VT (1 to 5 s in duration; n = 16) and long ST/VT (>5 s, n = 12). E values for NST/VTs were significantly higher than E values for both short and long ST/VTs separately as well as E values for ST/VTs as a group. Further, E values for long ST/VTs were significantly higher than E values for short ST/VTs. Wave breaks were consistently identified during periods of high E. Conclusion: High E during the first 500 ms of the onset of VT (the first 2 to 3 beats) is significantly correlated with long ST or NST episodes. This may be related to destabilization of wave propagation that helps to perpetuate VT. Early Vm/Cai uncoupling can predestinate the development of a malignant NST/VT. [Copyright &y& Elsevier]

Background: The coexistence of cardiac hypertrophy (H) and ischemia (I) can create a particularly arrhythmogenic substrate. Most studies investigate the effects of global I on H. However, global I is not a good surrogate model of the clinical situation. Objective: The purpose of this study was to investigate the electrophysiological effects of regional I superimposed on H using optical mapping of membrane voltage. Methods: We investigated the guinea pig model of left ventricular H (LVH) induced by suprarenal banding of abdominal aorta. Twelve hearts with or without LVH were mounted in a Langendorff preparation, and regional I was induced by 20 minutes of ligation of the left anterior descending artery. Results: Left ventricle epicardial action potential duration (APD) was significantly prolonged in the LVH group compared with controls. I significantly shortened APD in the I risk zone in both groups, but the percentages of APD shortening (28% vs. 40%) and the magnitudes of shortening (57 ± 18 vs. 105 ± 32 ms) were greater in the LVH group. The greater dispersion of repolarization (DR) across the border of the I zone resulted in arcs of functional conduction block and circulating wave fronts. Tachycardia-dependent APD alternans developed more often in the LVH group, and the area of alternans versus the area of the I zone was significantly larger. Ventricular tachyarrhythmias (VTs) developed in all 12 hearts with LVH including six non-self-terminating VTs, compared with four control hearts with self-terminating VT. Conclusion: Regional I superimposed on LVH resulted in greater DR at the border between the I and non-I zones as well as in a greater tendency to develop APD alternans. Both arrhythmogenic mechanisms correlated with an increased incidence of VT. [Copyright &y& Elsevier]

Background: The correlation between spontaneous calcium oscillations (S-CaOs) and arrhythmogenesis has been investigated in a number of theoretical and experimental in vitro models. There is an obvious lack of studies that directly investigate how the kinetics of S-CaOs correlates with a specific arrhythmia in the in vivo heart. Objectives: The purpose of the study is to investigate the correlation between the kinetics of S-CaOs and arrhythmogenesis in the intact heart using an experimental model of ischemia/reperfusion (I/R). Methods: Perfused Langendorff guinea pig (GP) hearts were subjected to global I/R (10-15 minutes/10-15 minutes). The heart was stained with a voltage-sensitive dye (RH237) and loaded with a Ca2+ indicator (Rhod-2 AM). Membrane voltage (Vm) and intracellular calcium transient (CaiT) were simultaneously recorded with an optical mapping system of two 16 × 16 photodiode arrays. S-CaOs were considered to arise from a localized focal site within the mapped surface when these preceded the associated membrane depolarizations by 2-15 ms. Results: In 135 episodes of ventricular arrhythmias from 28 different GP experiments, 23 were linked to S-CaOs that were considered to arise from or close to the mapped epicardial window. Self-limited or sustained S-CaOs had a cycle length of 130-430 ms and could trigger propagated ventricular depolarizations. Self-limited S-CaOs that followed the basic beat action potential (AP)/CaiT closely resembled phase 3 early afterdepolarizations. Fast S-CaOs could remain confined to a localized site (concealed) or exhibit varying conduction patterns. This could manifest as (1) an isolated premature beat (PB), bigeminal, or trigeminal rhythm; (2) ventricular tachycardia (VT) when a regular 2:1 conduction from the focal site develops; or (3) ventricular fibrillation (VF) when a complex conduction pattern results in wave break and reentrant excitation. Conclusions: The study examined, for the first time in the intact heart, the correlation between the kinetics of focal S-CaOs during I/R and arrhythmogenesis. S-CaOs may remain concealed or manifest as PBs, VT, or VF. A “benign looking” PB during I/R may represent “the tip of the iceberg” of an underlying potentially serious arrhythmic mechanism. [Copyright &y& Elsevier]

Ambulatory ECG (AECG) is very commonly employed in a variety of clinical contexts to detect cardiac arrhythmias and/or arrhythmia patterns which are not readily obtained from the standard ECG. Accurate and timely characterization of arrhythmias is crucial to direct therapies that can have an important impact on diagnosis, prognosis or patient symptom status. The rhythm information derived from the large variety of AECG recording systems can often lead to appropriate and patient-specific medical and interventional management. The details in this document provide background and framework from which to apply AECG techniques in clinical practice, as well as clinical research. [ABSTRACT FROM AUTHOR]

The T2* technique, used for quantifying myocardial iron content (MIC), has limitations in detecting early myocardial iron overload (MIO). The in vivo mapping of the myocardial T1 relaxation time is a promising alternative for the early detection and management of MIO. 32 β-thalassemia major (βTM) patients aged 11.5 ± 4 years and 32 healthy controls were recruited and underwent thorough clinical and laboratory assessments. The mid-level septal iron overload was measured through T1 mapping using a modified Look-Locker inversion recovery sequence with a 3 (3 s) 3 (3 s) 5 scheme. Septum was divided at the mentioned level into 3 zones corresponding to segments 8 and 9 in the cardiac segmentation model. 21.9 % of βTM had clinical cardiac morbidity. The cut-off of T1 mapping of hepatic and myocardium to differentiate between the patients and control groups was ≤466 and ≥ 923 ms respectively. The T1 technique was able to detect 4 patients with high MIC, two of them were not detected by the T2* technique. There was a statistically significant correlation between the average T1 values of the studied zones in patients with βTM and the liver iron content (LIC), the T1 values within segment 8 of the liver, age of patients, the age at first transfusion, age of splenectomy and serum ferritin value. The addition of the T1 mapping sequence to the conventional T2* technique was able to increase the efficacy of the MIC detection protocol by earlier detection of MIO. This would guide chelation therapy to decrease myocardial morbidity. [ABSTRACT FROM AUTHOR]

Myotonic dystrophy type 1 (DM1) is a multiorgan disorder with significant cardiac involvement. ECG abnormalities, including arrhythmias, occur in 80 % of DM1 patients and are the second-most common cause of death after respiratory complications; however, the mechanisms underlying the arrhythmogenesis remain unclear. The objective of this study was to investigate the basis of the electrophysiological abnormalities in DM1 using the DMSXL mouse model. ECG parameters were evaluated at baseline and post flecainide challenge. Calcium transient and action potential parameters were evaluated in Langendorff-perfused hearts using fluorescence optical mapping. Calcium transient/sparks were evaluated in ventricular myocytes via confocal microscopy. Protein and mRNA levels for calcium handling proteins were evaluated using western blot and RT-qPCR, respectively. DMSXL mice showed arrhythmic events on ECG including premature ventricular contractions and sinus block. DMSXL mice showed increased calcium transient time to peak without any change to voltage parameters. Calcium alternans and both sustained and non-sustained ventricular tachyarrhythmias were readily inducible in DMSXL mice. The confocal experiments also showed calcium transient alternans and increased frequency of calcium sparks in DMSXL cardiomyocytes. These calcium abnormalities were correlated with increased RyR2 phosphorylation without changes to the other calcium handling proteins. The DMSXL mouse model of DM1 exhibited enhanced arrhythmogenicity associated with abnormal intracellular calcium handling due to hyperphosphorylation of RyR2, pointing to RyR2 as a potential new therapeutic target in DM1 treatment. [Display omitted] • DM1 patients have reduced life expectancy due to cardiac causes; however, the underlying mechanisms are unclear. • The DMSXL mouse model of DM1 was more prone to VTs and exhibited arrhythmic events including PVCs and sinus block. • These arrhythmic events were associated with abnormal intracellular calcium transients/sparks in DMSXL mice. • Our findings suggest a significant arrhythmogenic role for RyR2/phospho-RyR2, which provide novel therapeutic targets. [ABSTRACT FROM AUTHOR]

This consensus guideline was prepared on behalf of the International Society for Holter and Noninvasive Electrocardiology and is cosponsored by the Japanese Circulation Society, the Computers in Cardiology Working Group on e-Cardiology of the European Society of Cardiology, and the European Cardiac Arrhythmia Society. It discusses the electrocardiographic phenomenon of T-wave alternans (TWA) (i.e., a beat-to-beat alternation in the morphology and amplitude of the ST-segment or T-wave). This statement focuses on its physiological basis and measurement technologies and its clinical utility in stratifying risk for life-threatening ventricular arrhythmias. Signal processing techniques including the frequency-domain Spectral Method and the time-domain Modified Moving Average method have demonstrated the utility of TWA in arrhythmia risk stratification in prospective studies in >12,000 patients. The majority of exercise-based studies using both methods have reported high relative risks for cardiovascular mortality and for sudden cardiac death in patients with preserved as well as depressed left ventricular ejection fraction. Studies with ambulatory electrocardiogram-based TWA analysis with Modified Moving Average method have yielded significant predictive capacity. However, negative studies with the Spectral Method have also appeared, including 2 interventional studies in patients with implantable defibrillators. Meta-analyses have been performed to gain insights into this issue. Frontiers of TWA research include use in arrhythmia risk stratification of individuals with preserved ejection fraction, improvements in predictivity with quantitative analysis, and utility in guiding medical as well as device-based therapy. Overall, although TWA appears to be a useful marker of risk for arrhythmic and cardiovascular death, there is as yet no definitive evidence that it can guide therapy. [ABSTRACT FROM AUTHOR]

This investigation was performed to evaluate the feasibility of detecting repolarization alternans with the heart rate elevated with a bicycle exercise protocol. Sensitive spectral signal-processing techniques are able to detect beat-to-beat alternation of the amplitude of the T wave, which is not visible on standard electrocardiogram. Previous animal and human investigations using atrial or ventricular pacing have demonstrated that T-wave alternans is a marker of vulnerability to ventricular arrhythmias. Using a spectral analysis technique incorporating noise reduction signal-processing software, we evaluated electrical alternans at rest and with the heart rate elevated during a bicycle exercise protocol. In this study we defined optimal criteria for electrical alternans to separate patients from those without inducible arrhythmias. Alternans and signal-averaged electrocardiographic results were compared with the results of vulnerability to ventricular arrhythmias as defined by induction of sustained ventricular tachycardia or fibrillation at electrophysiologic evaluation. In 27 patients alternans recorded at rest and with exercise had a sensitivity of 89%, specificity of 75%, and overall clinical accuracy of 80% (p <0.003). In this patient population the signal-averaged electrocardiogram was not a significant predictor of arrhythmia vulnerability. This is the first study to report that repolarization alternans can be detected with heart rate elevated with a bicycle exercise protocol. Alternans measured using this technique is an accurate predictor of arrhythmia inducibility. [ABSTRACT FROM AUTHOR]

We report 2 cases of exudative left pleural effusion following radiofrequency catheter ablation of cardiac arrhythmias complicated by cardiac perforation. We suggest that radiofrequency ablation may be a previously unsuspected cause of postcardiac injury syndrome. [ABSTRACT FROM AUTHOR]