Conduction delay

Orthostatic hypotension and resultant syncope, a common and potentially serious adverse effect of the TCAs, occurs as a result of cq-adrenergic antagonism. Additional side effects include cardiac conduction delays and heart block, especially in patients with preexisting conduction disease. 

Adverse reactions occurring in at least 3% of patients include angina first-degree AV block CHF intraventricular conduction delay palpitations proarrhythmia ventricular tachycardia dizziness fatigue headache constipation dyspepsia nausea/vomiting unusual taste blurred vision dyspnea. About 20% of patients discontinued treatment due to adverse reactions. 

Conduction system abnormalities are common in chronic heart failure, occurring in 15-30% of the population with low left ventricular ejection fraction (LVEF) [1-3]. The prevalence in ischemic heart disease is roughly similar to that seen in other forms of dilated cardiomyopathy. Conduction system disease can occur both at the time of an acute myocardial infarction as well as slowly progressing in chronic ischemic heart disease. Intraventricular conduction delays are associated with a poor prognosis in heart failure, with up to a 70% increase in the risk of death, and are also more prevalent in patients with advanced symptoms [2,4]. In ischemic heart disease, all components of the conduction system are at risk of ischemic injury, from the sinoatrial node to the His-Pukinje system. These conduction system abnormalities have the potential to impair cardiac function by a number of mechanisms. Since conduction abnormalities impair cardiac function, it is logical that pacing therapies to correct or improve these conduction abnormalities may improve cardiac function. 

Intraventricular conduction delay often leads to late activation of the left ventricular free wall with significant mechanical consequences. The mechanical consequences of abnormal electrical activation of the heart have long been recognized [58, 60, 86]. These include dyssynchrony between the atria. 

Secondary mitral regurgitation can be a consequence of intraventricular conduction delay. Secondary mitral regurgitation is a common accompaniment of dilated cardiomyopathy of ischemic etiology. Intraventricular conduction delays can create or exacerbate mitral regurgitation by causing a lack of coordination of the papillary muscles [95]. The geometry of the mitral papillary muscles places one near... 

Shamim W, Francis DP, Yousufuddin M, et al. Intraventricular conduction delay a prognostic marker in chronic heart failure. Int. J. Cardiol. 1999 70 171-8. 

Auricchio A, Kloss M, Trautmann SI, Rodner S, Klein H. Exercise performance following cardiac resynchronization therapy in patients with heart failure and ventricular conduction delay. Am. J. Cardiol. 2002 89 198-203. 

Sade LE, Kanzaki H, Severyn D, Dohi K, Gorcsan J, III. Quantification of radial mechanical dyssynchrony in patients with left bundle branch block and idiopathic dilated cardiomyopathy without conduction delay by tissue displacement imaging. Am. J. Cardiol. 2004 94 514-8. 

Curry CW, Nelson GS, Wyman BT, et al. Mechanical dyssynchrony in dilated cardiomyopathy with intraventricular conduction delay as depicted by 3D tagged magnetic resonance imaging. Circulation 2000 101 4. 

Nelson GS, Curry CW, Wyman BT, et al. Predictors of systolic augmentation from left ventricular preexcitation in patients with dilated cardiomyopathy and intraventricular conduction delay. Circulation 2000 101 2703-9. 

Cazeau S, Leclercq C, Lavergne T, et al. Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay. N. Engl. J. Med. 2001 344 873-80. 

Higgins SL, Hummel JD, Niazi IK, et al. Cardiac resynchronization therapy for the treatment of heart failure in patients with intraventricular conduction delay and malignant ventricular tachyarrhythmias, [see comment]. J. Am. Coll. Cardiol. 2003 42 1454-9. 

Atypical antipsychotics cause fewer EPS than do conventional antipsychotics. Clozapine and quetiapine are the least likely to cause EPS and are therefore recommended for treatment of psychosis in patients with Parkinson s disease. With the notable exception of risperidone, atypical antipsychotics cause substantially less hyperprolactinemia than do conventional antipsychotics. Weight gain is a side effect of all atypical antipsychotics except ziprasidone and aripiprazole. Concerns about cardiac conduction delay with ziprasidone therapy exist and warrant consideration in patients who have... 

Conduction delays, arrhythmias (significant in many overdose cases)... 

Early reports on imipramine noted that some patients developed first-degree heart block, as well as other bundle branch patterns, but it took almost 15 years to clarify that these conduction delays were the only adverse effects at therapeutic plasma concentrations. It is now well documented that increased PR, QRS, or QT intervals occur with all standard TCAs, at or slightly above their therapeutic plasma levels. 

Although the early clinical trials comparing SSRIs with tertiary amine TCAs found the newer agents to have better tolerated side-effect profiles, these differences were less evident when they were compared with secondary amine TCAs (433, 434, 435, 436, 437 and 438). The most important advantage of the SSRIs is the absence of severe adverse effects (e.g., cardiac conduction delays, seizures, postural hypotension) and death from overdose. 

Conduction delays, such as first-degree atrioventricular block... 

Inhibition of Na fast channels, which can inhibit electrically excitable membranes and produce intracardiac conduction delays ( 137)... 

Inhibitors of the renal cation secretion mechanism, eg, cimetidine, prolong the half-life of dofetilide. Since the QT-prolonging effects and risks of ventricular proarrhythmia are directly related to plasma concentration, dofetilide dosage must be based on the estimated creatinine clearance. Treatment with dofetilide should be initiated in hospital after baseline measurement of the rate-corrected QT interval (QTC) and serum electrolytes. A baseline QTC of > 450 ms (500 ms in the presence of an intraventricular conduction delay), bradycardia of < 50 bpm and hypokalemia are relative contraindications to its use. 

Redfern C, Degtyarev M, et al. 2000. Conditional expression of a Gi-coupled receptor causes ventricular conduction delay and a lethal cardiomyopathy. Proc Natl Acad Sci USA 97 4826-4831. 

A 58-year-old woman with lithium toxicity developed an irregular bradycardia (as low as 20 beats/minute), which resolved during hemodialysis persistent sinoatrial conduction delay suggested that she was predisposed to the bradydysrhythmia (131). 

A 52-year-old man with a serum lithium concentration of 4.58 mmol/1 had sinus node dysfunction with multiple atrial extra beats and an intraventricular conduction delay, which normalized following hemodialysis (132). Two patients, a 58-year-old woman and a 74-year-old woman, developed sick sinus syndrome while taking lithium but were able to continue taking it after pacemaker implantation (135,136). 

Two cases of light-headedness or fainting in patients taking olanzapine have been reported (80). Electrocardiograms showed first-degree heart block and AV conduction delay, which normalized after dosage reduction. 

A 38-year-old woman with a psychosis who took 4020 mg of ziprasidone had borderline intraventricular conduction delay (QRS duration 111 ms) the QTC interval was 445 ms (17). She oscillated between being drowsy and calm, and alert and agitated her blood pressure fell from 129/81 to 99/34 mmHg 4 hours later. She also had diarrhea and urinary retention. 

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