Ventricular arrhythmias, risk

Ventricular arrhythmias risk of sudden death (Figures 8.31-8.33)... 

Cardiac (severe form) acute cardiomyopathy with severe ventricular arrhythmia risk... 

Tachycardia and increased contractility (due to SNS activation) Increase cardiac output Increased MV02 Shortened diastolic filling time P,-Receptor down-regulation, decreased receptor sensitivity Precipitation of ventricular arrhythmias Increased risk of myocardial cell death... 

Intravenous or oral doses of a P-blocker should be administered early in the care of a patient with STE ACS, and then oral agents should be continued indefinitely. Early administration of a P-blocker to patients lacking a contraindication within the first 24 hours of hospitalization is a quality care indicator.2,3 In ACS the benefit of P-blockers mainly results from the competitive blockade of P,-adrenergic receptors located on the myocardium. Pi-Blockade produces a reduction in heart rate, myocardial contractility, and blood pressure, decreasing myocardial oxygen demand. As a result of these effects, P-blockers reduce the risk for recurrent ischemia, increase in infarct size and risk of reinfarction, and occurrence of ventricular arrhythmias in the hours and days following MI.39... 

Because of these effects, /1-blockers reduce the risk for recurrent ischemia, infarct size, risk of reinfarction, and occurrence of ventricular arrhythmias. 

Type Ic drugs profoundly slow conduction velocity while leaving refractoriness relatively unaltered. Although effective for both ventricular and supraventricular arrhythmias, their use for ventricular arrhythmias has been limited by the risk of proarrhythmia. 

Usual maintenance dose for atrial fibrillation is 200 mg/day (may further decrease dose to 100 mg/day with long-term use if patient clinically stable in order to decrease risk of toxicity) usual maintenance dose for ventricular arrhythmias is 300-400 mg/day. 

First, drug-induced lengthening of the QT interval has been associated with the occurrence of ventricular tachyarrhythmias, namely TdP, a polymorphous ventricular arrhythmia that may cause syncope and degenerate into ventricular fibrillation and sudden death although the incidence of TdP is a rare event (usually, less than 1 in 100 000) [32], even a low risk is not justified for drugs with uncertain benefits or drugs providing only symptomatic improvement of a mild disease. 

The decreased work capacity of the in-farcted myocardium leads to a reduction in stroke volume (SV) and hence cardiac output (CO). The fall in blood pressure (RR) triggers reflex activation of the sympathetic system. The resultant stimulation of cardiac 3-adreno-ceptors elicits an increase in both heart rate and force of systolic contraction, which, in conjunction with an a-adren-oceptor-mediated increase in peripheral resistance, leads to a compensatory rise in blood pressure. In ATP-depleted cells in the infarct border zone, resting membrane potential declines with a concomitant increase in excitability that may be further exacerbated by activation of p-adrenoceptors. Together, both processes promote the risk of fatal ventricular arrhythmias. As a consequence of local ischemia, extracellular concentrations of H+ and K+ rise in the affected region, leading to excitation of nociceptive nerve fibers. The resultant sensation of pain, typically experienced by the patient as annihilating, reinforces sympathetic activation. 

The ICH guideline lists the assessment of effects on blood pressure, heart rate and ECG. In vivo, in vitro and/or ex vivo evaluations, including methods for electrical repolarisation and conductance abnormalities, should also be considered. These abnormalities can be associated with risks for fatal ventricular arrhythmias called Torsade de pointes. 

Because of the proarrhythmic effects of propafenone, reserve its use for patients in whom the benefits of treatment outweigh the risks. The use of propafenone is not recommended in patients with less severe ventricular arrhythmias, even if the patients are symptomatic. 

The applicability of the CAST results to other populations (eg, those without recent Ml) is uncertain, but at present, it is prudent to consider the risks of Class 1C agents (including flecainide), coupled with the lack of any evidence of improved survival, generally unacceptable in patients without life-threatening ventricular arrhythmias, even if the patients are experiencing unpleasant, but not life-threatening, symptoms or signs. 

Proarrhythmia Like other antiarrhythmic agents, sotalol can provoke new or worsened ventricular arrhythmias in some patients, including sustained ventricular tachycardia or ventricular fibrillation, with potentially fatal consequences. Because of its effect on cardiac repolarization, is the most common form of proarrhythmia associated with sotalol, occurring in approximately 4% of high-risk patients. 

Hypokalemia Hypokalemia prevention requires particular attention to the following Patients receiving digitalis and diuretics for CHF, hepatic cirrhosis, and ascites in aldosterone excess with normal renal function potassium-losing nephropathy certain diarrheal states or where hypokalemia is an added risk to the patient (eg, history of ventricular arrhythmias). 

Cardiac effects Telithromycin has the potential to prolong the QTc interval in some patients. QTc prolongation may lead to an increased risk for ventricular arrhythmias, including torsades de pointes. 

Sotalol (Betapace) [Antiarrhythmic, Antihypertensive/Beta Blocker] WARNING Monitor pts for 1st 3 d of Rx to 4- risks of arrhythmia Uses Ventricular arrhythmias, AF Action p-Adrenergic blocking agent Dose Adults. 80 mg PO bid may be T to 240-320 mg/d Peds. Neonates 9 mg/m tid... 

Moss AJ, Hall WJ, Cannom DS, et al. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. Multicenter automatic defibrillator implantation trial investigators. N EnglJ Med.Dec 26 1996 335(26) 1933-1940. 

The first implantable cardioverter-defibrillator (ICD) was placed in 1982. Since that time, their use has expanded exponentially. Several large clinical trials have demonstrated the superiority of ICDs compared with pharmacological therapy for the secondary prevention of arrhythmic death and possibly as primary therapy for patients at risk for ventricular arrhythmias. 

Cardiovascular effect. Coconut and coconut oil, administered to 32 coronary heart disease patients in 16 age- and sex-matched healthy controls with no difference in the fat, saturated fat, and cholesterol consumption, produced no effecC h Hydrogenated oil, administered to young male Wistar rats, at a dose of 10% of diet for 10 weeks, produced an increase in the risk of ventricular arrhythmias under conditions of both ischemia and reperfusion. The incidence of ventricular fibrillation was 67% in the oil-... 

Because of mortality risks noted for flecainide and/or encainide (type 1C antiarrhyth-mics), this drug should be reserved for use in patients with life-threatening ventricular arrhythmias. 

Although the literature indicates that seizures and arrhythmias are associated with TCA plasma levels greater than 1,000 ng/mL, the QRS duration might be a better early predictor than plasma levels in overdose cases. For example, in a series of 49 TCA overdoses, seizures occurred only in cases with a QRS duration above 0.10 second, and ventricular arrhythmia was seen with a QRS greater than 0.16 second (430). Thus, for acute overdose, the ECG may provide a reliable and quick measure of risk with TCA drugs however, how well a QRS of less than 0.10 second predicts ultimate safety or how long after ingestion the ECG must be followed, is uncertain (431). 

These are class IC drugs with similar pharmacological profiles and with the same indication range and adverse effects. They are mainly used for the treatment of severe, lifethreatening ventricular tachyarrhythmias, and non-sustained ventricular tachycardia or high-frequency premature ventricular beats. The main adverse effects are cardiovascular, including proarrhythmic actions and severe negative inotropic effects, especially in patients with impaired cardiac function. Both flecainide and encainide increase the risk of sudden death in patients with myocardial infarction and asymptomatic unsustained ventricular arrhythmias. 

---