Why does ischemia cause arrhythmia

The purpose of this chapter is to review some of the metabolic changes associated with cardiac ischaemia, their relevance to electrophysiological instability, and the clinical manifestation and management of some of the more common arrhythmias that follow cardiac ischaemia. Particular attention is given to the peri-infarction period arbitrarily accepted as within 48 h of the index myocardial infarction as arrhythmias are most likely to be seen around this time, and are considered to be non-indicative of long-term prognosis.

In contrast, arrhythmias developing in the post-infarction period after 48 h have been demonstrated to be associated with an adverse outcome. During ischemic ventricular tachycardia, abnormal electrical pulses in the lower chambers, or ventricles, disrupt the normal firing of the SA node, causing the heart to beat rapidly.

The abnormal signals are caused by an area of damaged tissue in the ventricles. The damage to the tissue was caused by a lack of blood flow to the area, known as ischemia. This irregular heartbeat can be seen on an electrocardiogram. A rapid heartbeat does not give the heart enough time to refill with blood before pumping, which causes diminished blood flow to the rest of the body. This may lead to symptoms of dizziness, lightheadedness, unconsciousness and cardiac arrest. The presence of myocardial fibrosis causes slowing of cardiac conduction, resulting in re-entry circuits and subsequent ventricular desynchronisation.

The pathophysiological role of the autonomic nervous system ANS in arrhythmogenesis has been firmly established both experimentally and clinically 3. Within minutes of myocardial ischaemia there is a striking surge of sympathetic nerve activity caused by a combination of pain, anxiety and reflex activation, which has been demonstrated to be inversely related to left ventricular ejection fraction 4.

A general increase in circulating catecholamines can also aggravate myocardial ischaemia, because of positive chronotropic and inotropic actions, therefore establishing a vicious circle. A relative excess in sympathetic over vagal activity is generally pro-arrhythmic because of alterations of the electrophysiological properties of the specialised conducting tissue and the cardiac myocyte Table 1.

Consequently, the risk of developing supraventricular and ventricular tachyarrhythmias is increased. In the early peri-infarction period, cardiac autonomic reflexes can be triggered depending on the site of the myocardial infarction. For instance, acute inferoposterior myocardial ischaemia or infarction often results in bradycardia and hypotension, whereas anterior myocardial ischaemia more frequently evokes tachycardia and hypertension.

There is a greater density of vagal afferent receptors in the inferoposterior wall of the left ventricle, which may be responsible for causing an enhanced vasopressor and cardio-inhibitory reflex Benzold-Jarisch reflex. Therefore, a transient increase in vagal activity, is one of the factors implicated in the development of bradyarrhythmias seen during inferior myocardial infarction.

In the post-infarction period, impaired vagal tone, as documented by decreased baroreflex sensitivity and heart rate variability, has been associated with increased inducibility of sustained monomorphic ventricular tachycardia and with sudden death 5. The mechanisms of ventricular arrhythmias in acute myocardial ischaemia and infarction have been mainly studied using animal models, and have been shown to occur in several distinct phases 6.

The acute phase, which occurs roughly 2—30 min following coronary artery occlusion when changes are still reversible, demonstrates a bimodal distribution and is divided into phases 1a and 1b. Phase 1a arrhythmias occur between 2—10 min. Although several mechanisms have been proposed to explain these arrhythmias, the pathophysiology is most likely to be related to alterations in cellular electrophysiology and re-entrant mechanisms.

Phase 1b arrhythmias occur 10—30 min after acute coronary occlusion and may be related to local accumulation of catecholamines and increased automaticity 6.

The second or delayed phase of ventricular arrhythmias occurs up to 72 h after coronary artery occlusion, with a peak incidence between 12—24 h. These arrhythmias may be caused by abnormal automaticity within surviving Purkinje fibres, triggered activity arising from Purkinje fibres, or re-entry mechanisms involving either the Purkinje fibres or the ischaemic myocardium. Chronic phase arrhythmias developing after 72 h are usually due to re-entry mechanisms.

VPCs commonly develop during periods of ischaemia. They are usually asymptomatic and their presence in the peri-infarction period, regardless of frequency and complexity bigeminy, multiformity, etc bears no relation to mortality or the development of sustained ventricular tachyarrhythmias. Numerous trials have compared prophylactic anti-arrhythmic drugs with placebo for the treatment of VPCs in the peri-infarction and post-infarction periods following a myocardial infarction.

VPCs are treated conservatively by alleviation of any on-going cardiac ischaemia, and correction of electrolyte and metabolic disturbances. The presentation of ventricular tachycardia during acute myocardial infarction depends on the rate of tachycardia, and on left ventricular function. Significant haemodynamic compromise can occur if the tachycardia is fast and sustained, and when there is left ventricular dysfunction.

VT increases myocardial oxygen demand, which may result in exacerbation of ischaemia and possible infarct extension. Occasionally, VT is the presenting feature of an otherwise silent myocardial infarction the presence of a scar provides a stable substrate capable of maintaining a re-entrant tachycardia mechanism.

VT is conventionally classified according to its temporal and morphological characteristics. VT is described as non-sustained NSVT , if the duration is less than 30 s, and sustained if it lasts more than 30 s or requires termination within 30 s because of haemodynamic compromise. The treatment of ventricular tachyarrhythmias should target both the cause of the arrhythmia upstream approach as well as the arrhythmic expression of the pathology downstream approach.

In other words, in patients with significant coronary artery disease, revascularisation and haemodynamic optimisation should be considered in the first instance to prevent ventricular arrhythmias and their complications. This rhythm is caused by an abnormally firing ventricular focus, which usurps sinus node pacemaker dominance and further depress sinoatrial node automaticity Fig.

It occurs very commonly during myocardial infarction and has been shown to be particularly associated with reperfusion of the myocardium following thrombolytic therapy. Accelerated idioventricular rhythm at a rate of approximately 80 beats per min. This rhythm is usually benign and has no adverse effect on mortality.

Most episodes are transient and require no treatment. If the rhythm causes haemodynamic compromise, for example due to loss of atrioventricular synchrony, increasing the atrial rate with atropine or atrial pacing is indicated. Limited data are available regarding the prognostic significance of NSVT in the peri-infarction period. Earlier studies have suggested that NSVT had no adverse effect on either in-hospital or 1-year survival 15 , Substantial data have demonstrated that NSVT in the post-infarction period increases the risk of sudden cardiac death by at least 2-fold 19 , If episodes of NSVT are frequent, rapid, prolonged or associated with significant symptoms, the administration of lidocaine or amiodarone can be considered.

Drugs used in the peri-infarction and post-infarction periods to treat arrhythmias. Although the occurrence of NSVT in the post-infarction period is a prognostic marker, its suppression or treatment with anti-arrhythmic drugs has been disappointing 11 — Although amiodarone reduced arrhythmic mortality, there was no corresponding reduction in all cause mortality.

Further adequately powered, prospective studies are needed to confirm this interaction. In the late post-infarction period, the advent of implantable cardioverter defibrillators ICD has changed clinical practice.

The treatment of NSVT outside this carefully selected patient group remains less defined. Peri-infarction sustained VT has an incidence of 0. It is associated with a higher in-hospital mortality, but is not considered to be a prognostic factor among hospital survivors The occurrence of sustained monomorphic VT is an uncommon arrhythmia in the peri-infarction period.

When present, it usually signifies previous myocardial scarring or may be a sign of extensive myocardial damage In the setting of acute myocardial infarction, polymorphic VT is not usually related to QT interval prolongation, sinus bradycardia, pauses or electrolyte abnormalities.

When present, it usually implies recurrent myocardial ischaemia. It has been reported to occur in 0. The prognosis is similar to patients with sustained VT. Rapid treatment of sustained VT is mandatory because of the deleterious effect on cardiac output, the exacerbation of myocardial ischaemia, and the risk of degeneration into ventricular fibrillation. If there is haemodynamic compromise, synchronised direct current cardioversion DCC should be implemented.

If the patient is haemodynamically stable, pharmacological termination can be attempted. Although lidocaine, which has an acceptable safety profile, has been traditionally used for treating stable monomorphic VT, studies have suggested that it is relatively ineffective for termination of VT 26 and less effective against VT than IV procainamide 27 or IV sotalol Studies investigating the use of amiodarone to treat haemodynamically stable VT are minimal; however, it is effective in treating unstable VT and VF 29 and consequently it is considered an acceptable agent to treat stable VT.

The new Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care 30 has de-emphasised the use of lidocaine as a first-line agent for the treatment of stable monomorphic VT, recommending either intravenous sotalol or intravenous procainamide as first-line agents in patients with normal left ventricular function.

In patients with left ventricular dysfunction, either amiodarone or lidocaine is recommended as a first-line agent as they cause the least additional impairment of LV function If not already administered or contra-indicated, patients with recurrent VT should be established on intravenous amiodarone. In patients who continue to display arrhythmias despite the use of amiodarone at recommended doses, supplemental infusions can be considered Burst overdrive pacing can also be used to terminate refractory VT.

Atrial or ventricular pacing at rates marginally higher than the intrinsic sinus rate physiological overdrive can help prevent bradycardia-related ventricular arrhythmias. Peri-infarction polymorphic VT is uncommon and its treatment is the same for sustained VT. However, these arrhythmias are less responsive to class 1 agents and may be suppressed with intravenous amiodarone Ventricular fibrillation is characterised by rapid, disorganised, multiple re-entrant wavelets in the ventricle, resulting in no uniform ventricular contraction and no cardiac output.

Untreated, the arrhythmia is lethal and it is the main mechanism of sudden cardiac death. The only definitive treatment for VF is defibrillation. Therefore, the priority is to minimise any delay between the onset of cardiac arrest and the administration of defibrillation shocks. The treatment of VF is now standardised to local and national resuscitation protocols. Results of the recently published ARREST study, showed that the early use of intravenous amiodarone after 3 failed DC shocks, can increase the number of survivors In treating peri-infarction ventricular tachyarrhythmias VT and VF , it is common clinical practice to continue anti-arrhythmic drug infusions for 24—48 h and to discontinue the infusion provided there is no arrhythmic recurrence.

In patients who are adequately revascularised and who refuse device therapy, pace mapping to identify the arrhythmogenic zone combined with radiofrequency ablation has been shown to be an acceptable strategy in that small proportion of patients with a single tachycardia focus on the endocardial surface Aborted SCD is, in the majority of cases, caused by life-threatening ventricular tachyarrhythmias.

A number of randomised, clinical trials have now demonstrated the superiority of the ICD over anti-arrhythmic drug therapy mostly or exclusively amiodarone in survivors of aborted SCD Aborted SCD is invariably associated with structural heart disease, which in the adult population is most frequently CAD.

Although the exact role of cardiac ischaemia in the pathogenesis of SCD is not clearly defined, it is believed to be the trigger that initiates arrhythmogenesis. Therefore, reversal or prevention of ischaemia should avoid the occurrence of the arrhythmia.

A recently published study investigating the effects of coronary artery revascularisation in patients with sustained ventricular arrhythmias in the chronic phase of a myocardial infarction demonstrated that arrhythmia recurrence is still high following revascularisation, particularly in patients with reduced left ventricular function It is more common with inferior wall myocardial infarction and is often due to hypervagotonia.

Treatment is only necessary when there are symptoms or evidence of haemodynamic compromise. Most cases respond well to intravenous atropine 0. Persistent symptomatic bradycardia despite atropine is an indication for temporary cardiac pacing. It can aggravate myocardial ischaemia by increasing myocardial oxygen consumption as well as reducing diastolic coronary artery perfusion time. Sinus tachycardia is also a manifestation of significant ventricular dysfunction, on-going cardiac ischaemia, inadequate analgesia, anxiety, pyrexia and hypovolaemia.

Management is aimed at treating the underlying causes. Atrial fibrillation has been shown to be independently associated with in-hospital and long-term mortality, re-infarction rates, ventricular arrhythmias, advanced atrioventricular conduction disturbances, asystole, cardiogenic shock, and ischaemic strokes. It is also more likely to be associated with extensive coronary artery disease and poor reperfusion of the infarct related artery 42 ,43 and, therefore, the threshold for cardiac catheterisation should be low.

The development of atrial fibrillation within 24 h is usually associated with inferior wall myocardial infarction from right coronary artery occlusion. In contrast, atrial fibrillation developing more than 24 h afterwards is associated with anterior wall myocardial infarction and left ventricular dysfunction. The early treatment of atrial tachyarrhythmias is important as increased ventricular rates and loss of atrial systole result in a significant reduction in cardiac output and an increase in cardiac ischaemia.

When there is significant haemodynamic compromise, then DC cardioversion is indicated. Alternatively, pharmacological cardioversion to sinus rhythm can be attempted with amiodarone or dofetilide 44 , Dofetilide has recently been shown to be effective in cardioverting atrial fibrillation in the post-infarction period in patients with left ventricular dysfunction without affecting all-cause, cardiac and arrhythmic mortality However, dofetilide is associated with an increased incidence of torsades de pointes and close ECG monitoring is mandatory when it is administered.

Although newer class III agents such as ibutilide and azimilide have been successful in the treatment of atrial fibrillation, data concerning their efficacy and safety in the peri-infarction period are currently limited. Elective DC cardioversion should be considered if the patient remains in atrial fibrillation after the acute infarction period has passed.

Atrial fibrillation is associated with an increased risk of thrombo-embolism, and provided there are no contra-indications, all patients should be heparinised and considered for oral anticoagulation if atrial fibrillation persists or is paroxysmal.

Myocardial ischaemia can produce a broad range of conduction disturbances, involving both the atrioventricular node and infranodal structures. Although early reperfusion with thrombolysis can shorten the duration of AV block and reduce the need for temporary pacing, it has not reduced the incidence of atrioventricular block, which has remained relatively constant It is usually associated with inferior myocardial infarction and may be a manifestation of hypervagotonia or functional damage of the AV node.

First degree heart block that is below the His bundle is more commonly associated with anterior myocardial infarction and has a worse prognosis. It is usually transient and is more common following inferior infarctions. Mobitz type 2 heart block is less common and is more associated with anterior infarction, indicating damage to the AV junction or His bundle The QRS complexes are usually wide implying bundle branch involvement and may herald the onset of complete heart block.