Abnormalities Of Impulse Conduction Research Articles

Myocardial injury in dogs: a retrospective analysis on etiological, echocardiographic, electrocardiographic, therapeutic, and outcome findings in 102 cases

IntroductionIn dogs, myocardial injury (MI) is a poorly characterized clinical entity; therefore, this study aimed to provide a detailed description of dogs affected by this condition. Animals, materials, and methodsDogs diagnosed with MI according to the concentration of cardiac troponin I (cTnI) were retrospectively searched. Signalment, diagnostic, therapeutic, and outcome data were retrieved. Dogs were divided into six echocardiographic (dilated cardiomyopathy phenotype; hypertrophic cardiomyopathy phenotype; hypertrophic cardiomyopathy phenotype with systolic dysfunction; abnormal echogenicity only; endocarditis; and no echocardiographic abnormalities suggestive of MI), four electrocardiographic (abnormalities of impulse formation; abnormalities of impulse conduction; abnormalities of ventricular repolarization; and no electrocardiographic abnormalities suggestive of MI), and nine etiological (infective; inflammatory; neoplastic; metabolic; toxic; nutritional; immune-mediated; traumatic/mechanical; and unknown) categories. Statistical analysis was performed to compare cTnI values among different categories and analyze survival. ResultsOne hundred two dogs were included. The median cTnI value was 3.71 ng/mL (0.2–180 ng/mL). Echocardiographic and electrocardiographic abnormalities were documented in 86 of 102 and 89 of 102 dogs, respectively. Among echocardiographic and electrocardiographic categories, the dilated cardiomyopathy phenotype (n = 52) and abnormalities of impulse formation (n = 67) were overrepresented, respectively. Among dogs in which a suspected etiological trigger was identified (68/102), the infective category was overrepresented (n = 20). Among dogs belonging to different echocardiographic, electrocardiographic, and etiological categories, cTnI did not differ significantly. The median survival time was 603 days; only eight of 102 dogs died due to MI. ConclusionsDogs with MI often have an identifiable suspected trigger, show various echocardiographic and electrocardiographic abnormalities, and frequently survive to MI-related complications.

Molecular Basis of Atrial Fibrillation Pathophysiology and Therapy: A Translational Perspective.

Atrial fibrillation (AF) is a highly prevalent arrhythmia, with substantial associated morbidity and mortality. There have been significant management advances over the past 2 decades, but the burden of the disease continues to increase and there is certainly plenty of room for improvement in treatment options. A potential key to therapeutic innovation is a better understanding of underlying fundamental mechanisms. This article reviews recent advances in understanding the molecular basis for AF, with a particular emphasis on relating these new insights to opportunities for clinical translation. We first review the evidence relating basic electrophysiological mechanisms to the characteristics of clinical AF. We then discuss the molecular control of factors leading to some of the principal determinants, including abnormalities in impulse conduction (such as tissue fibrosis and other extra-cardiomyocyte alterations, connexin dysregulation and Na+-channel dysfunction), electrical refractoriness, and impulse generation. We then consider the molecular drivers of AF progression, including a range of Ca2+-dependent intracellular processes, microRNA changes, and inflammatory signaling. The concept of key interactome-related nodal points is then evaluated, dealing with systems like those associated with CaMKII (Ca2+/calmodulin-dependent protein kinase-II), NLRP3 (NACHT, LRR, and PYD domains-containing protein-3), and transcription-factors like TBX5 and PitX2c. We conclude with a critical discussion of therapeutic implications, knowledge gaps and future directions, dealing with such aspects as drug repurposing, biologicals, multispecific drugs, the targeting of cardiomyocyte inflammatory signaling and potential considerations in intervening at the level of interactomes and gene-regulation. The area of molecular intervention for AF management presents exciting new opportunities, along with substantial challenges.

Left Hepatic Vein and Persistent Left Superior Vena Cava Drainage into the Coronary Sinus with Subaortic Valve Stenosis

Persistent left superior vena cava (PLSVC) and left hepatic vein drainage into the coronary sinus is a very rare combination of thoracic venous anomalies. A literature search revealed only two previously reported cases. PLSVC is associated with congenital heart disease and impulse conduction abnormalities. Subaortic valve stenosis is among these abnormalities. We present an extremely rare case of a 19-year-old woman who presented with PLSVC and left hepatic vein drainage into the coronary sinus associated with subaortic valve stenosis. The vascular anomalies were noted on a computed tomography angiogram of the chest performed for a history of shortness of breath. The patient had been previously diagnosed with and underwent treatment for subaortic valve stenosis at ages 2 and 8. PLSVC increases the incidence of congenital heart disease.

Characterization of Left Atrial Tachyarrhythmias in Patients Following Atrial Fibrillation Ablation:Correlation of surface ECG with Intracardiac Mapping.

With expected success rates in excess of 80% for achieving long term arrhythmia control, catheter based ablation has become a popular treatment strategy in the management of patients with atrial fibrillation (AF). However, the success of AF ablation has been tempered by the occurrence of post procedure left atrial tachycardias and / or flutters, which can be seen in up to 30% of the patients. These arrhythmias are perpetuated either due to abnormalities of impulse formation (abnormal automaticity / triggered activity), or abnormalities of impulse conduction (micro / macroreentry). Regardless of the underlying mechanism, these tachycardias manifest distinct "P" or flutter waves on the surface ECG, recognition of which may facilitate their characterization / localization. However, because of the frequent overlap in the morphology of P waves, intracardiac mapping is often the only way to distinguish them apart. This is accomplished using a combination of activation, entrainment and electroanatomic mapping techniques. Tachycardias resulting from abnormalities of impulse formation and / or microreentry are characteristically focal and usually confined in and around pulmonary vein (PV) segments which have reconnected (septal aspect of right PVs and anterior aspect of left PVs). In contrast, macroreentrant tachycardias manifest a large circuit dimension involving zone(s) of slow conduction. These are most commonly seen to occur around the mitral valve but can develop in any part of the left atrium where "gaps" across prior ablation lesion sets create altered conduction. Successful ablation of focal tachycardias is usually accomplished by isolating the reconnected PV segment(s). In case of macroreentrant arrhythmias however, a more extensive ablation approach is typically required in order to achieve conduction block across isthmus of the circuit. Using these strategies, the majority of left atrial tachycardias occurring post AF ablation can be successfully cured with excellent long term results.

The Ladder Diagram (A 100+ Year History)

The ladder diagram (also called a laddergram) remains a popular visual aid when graphically representing the mechanism of arrhythmia. It disentangles atrial and ventricular electrical activity and gives explicit representation to the sinoatrial and atrioventricular nodes. More than 100 years after the first published ladder diagrams, this report reviews their origins, development, and limitations. Ladderlike diagrams have existed since 1885, first applied to venous and arterial pulsation timing or waveform tracings and later in 1920 alongside electrocardiograms to explain the generation and propagation of electrical impulses in the heart. Two examples are presented in which the underlying mechanism of arrhythmia either was predicted by a ladder diagram and later confirmed by intracardiac recordings (atrioventricular nodal reentrant tachycardia) or underwent evolution of its ladder diagram depiction as the pathophysiology became better understood (atrial flutter). In general, the ladder diagram represents well abnormalities of impulse conduction but is less explicit with abnormalities of impulse formation. In conclusion, the surprising scarcity of major changes since the introduction of the ladder diagram testifies to its power to deal with a range of arrhythmogenic mechanisms that were unknown at the time of its development.

Cardiopulmonary Support in Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is an X-linked, rapidly progressive myopathy affecting the limb muscles, the respiratory muscles, the heart, the intestines, and the brain. Since about 90% of DMD patients die from muscular respiratory failure or cardiomyopathy, early and adequate therapy is essential. Ventilatory failure from muscle weakness requires mechanical support for ventilation and coughing as soon as there is symptomatic nocturnal hypoventilation. Today noninvasive positive-pressure ventilation (NIPPV) is the method of choice for supportive long-term mechanical ventilation in DMD. For assisted coughing, various methods are available, among which the mechanical in-exsufflator is the most widely used device. There is large nonrandomized clinical trial evidence that NIPPV improves quality of life and prolongs the lives of DMD patients if medical, social, economic, and ethical issues, raised by the availability of long-term NIPPV, are adequately addressed. Cardiac involvement in DMD manifests as impulse generation or impulse conduction abnormalities or cardiomyopathy. Cardiac abnormalities in DMD respond well to adequate therapy. Though DMD is ultimately a fatal disease, quality of life and life expectancy can be markedly improved if cardiopulmonary manifestations are adequately treated.

Ionic mechanisms of ischemia‐related ventricular arrhythmias

The aim of this review is the utmost simplification of the cellular electrophysiologic background of ischemia-related arrhythmias. In the acute and subacute phase of myocardial infarction, arrhythmias can be caused by an abnormal impulse generation, abnormal automaticity or triggered activity caused by early or delayed afterdepolarizations (EAD and DAD), or by abnormalities of impulse conduction (i.e., reentry). This paper addresses therapeutic intervention aimed at preventing the depolarization of "pathologic" slow fibers, counteracting the inward calcium (Ca) influx that takes place through the L-type channels (Ca antagonists), or hyperpolarizing the diastolic membrane action potential, increasing potassium (K) efflux (K-channel openers) in arrhythmias generated by an abnormal automaticity (ectopic tachycardias or accelerated idioventricular rhythms). If the cause enhanced impulse generation is related to triggered activity, and since both EAD and DAD are dependent on calcium currents that can appear during a delayed repolarization, the therapeutic options are to shorten the repolarization phase through K-channel openers or Ca antagonists, or to suppress the inward currents directly responsible for the afterdepolarization with Ca blockers. Magnesium seems to represent a reasonable choice, as it is able to shorten the action potential duration and to function as a Ca antagonist. Abnormalities of impulse conduction (re-entry) account for the remainder of arrhythmias that occur in the acute and subacute phase of ischemia and for most dysrhythmias that develop during the chronic phase. Reentrant circuits due to ischemia are usually Na channel-dependent. Drug choice will depend on the length of the excitable gap: in case of a short gap (ventricular fibrillation, polymorphic ventricular tachycardia, etc.), the refractory period has been identified as the most vulnerable parameter, and therefore a correct therapeutic approach will be based on drugs able to prolong the effective refractory period (K-channel blockers, such as class III antiarrhythmic drugs); on the other hand, for those arrhythmias characterized by a long excitable gap (most of the monomorphic ventricular tachycardias), the most appropriate therapeutic intervention consists of depressing ventricular excit-ability and conduction by use of sodium-channel blockers such as mexiletine and lidocaine. Compared with other class I antiarrhythmic agents, these drugs minimally affect refractoriness and exhibit a use-dependent effect and a voltage dependent action (i.e., more pronounced on the ischemic tissue because of its partial depolarization).

Antiarrhythmic treatment: An overview

Atrial and ventricular arrhythmias cause significant morbidity and mortality. Abnormalities of impulse generation, e.g., abnormal automaticity or triggered activity, or abnormalities of impulse conduction, e.g., atrioventricular block or reentry, are the prime mechanisms of atrial or ventricular arrhythmias. The ventricular arrhythmias are of special interest because they are a key element in sudden cardiac death, the number 1 public health problem in the U.S. Electrocardiographic recording or provocative testing, e.g., exercise or programmed ventricular stimulation, are used to detect and classify ventricular arrhythmias. Drugs with different mechanisms of action are being rapidly developed to combat cardiac arrhythmias. Ventricular arrhythmias can be defined as benign, potentially malignant or malignant. Benign ventricular arrhythmias require no drug treatment; potentially malignant arrhythmias are subject to drug prophylaxis; and the malignant ventricular arrhythmias require aggressive therapy with drugs, surgery or electronic devices. The management of the malignant ventricular arrhythmias should be evaluated by 1 of 2 programmatic approaches: electrophysiologic or Holter/exercise. Both are complex, costly and inconvenient, but both are excellent for identifying effective treatment for malignant ventricular arrhythmias.

Mechanisms of cardiac arrhythmias.

The mechanisms involved in the disruption of the rate and rhythm of the heart have classically been categorized' as those due to abnormalities in impulse formation (automaticity) or those due to abnormalities in impulse conduction (59, 66). Current knowledge has expanded these concepts to include additional mechanisms of arrhythmogenesis that are just beginning to be understood. Many of these new concepts have recently been rev iewed