Electrophysiological and Biochemical mechanisms
Acute myocardial ischaemia is accompanied by significant intracellular and extracellular ionic and metabolic alterations of the myocardial syncytium. Extracellular changes include: elevated potassium, lysophosphoglycerides and adenosine concentrations, increased lactate and carbon dioxide production, acidosis, and catecholamine release. Concomitantly, intracellular changes include: acidosis, elevated cyclic adenosine monophosphate (cAMP), and elevated concentrations of calcium, magnesium, and sodium ions. These biochemical and metabolic changes alter inward and outward transmembrane ionic current fluxes, causing profound alterations of the resting membrane and action potential characteristics of the myocyte. Changes such as depolarisation of the resting membrane potential, diminished upstroke velocity, slowed conduction, decreased excitability, shortening of the action potential duration, altered refractoriness, dispersion of repolarisation, and abnormal automaticity, can all occur.The resultant biochemical and electrical changes do not all occur at once but evolve temporally, providing the electrophysiological trigger and anatomic substrate necessary to induce arrhythmias through virtually all known arrhythmogenic mechanisms . A history of a previous myocardial infarction with scar formation further contributes to this arrhythmogenic milieu. The presence of myocardial fibrosis causes slowing of cardiac conduction, resulting in re-entry circuits and subsequent ventricular desynchronisation.
Fig. 1
Influence of cardiac ischaemia on arrhythmogenesis.
Fig. 1
Influence of cardiac ischaemia on arrhythmogenesis.
Autonomic nervous system
The pathophysiological role of the autonomic nervous system (ANS) in arrhythmogenesis has been firmly established both experimentally and clinically. 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. 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 .Consequently, the risk of developing supraventricular and ventricular tachyarrhythmias is increased.
Electrophysiological effects of the sympathetic nervous system
• Shifts pacemaker from sinus node to junctional region
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| • Increases Purkinje fibre automaticity |
| • Alters P wave morphology and shortens QT interval |
| • Shortens PR interval |
| • Increase after-depolarisations (facilitating triggered activity) |
| • Enhances re-entry during acute myocardial ischaemia |
| • Decreases ventricular fibrillation threshold |
| • Shifts pacemaker from sinus node to junctional region |
|---|
| • Increases Purkinje fibre automaticity |
| • Alters P wave morphology and shortens QT interval |
| • Shortens PR interval |
| • Increase after-depolarisations (facilitating triggered activity) |
| • Enhances re-entry during acute myocardial ischaemia |
| • Decreases ventricular fibrillation threshold |
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.
Ventricular arrhythmias
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. 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. 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.
Ventricular premature complexes (VPCs)
VPCs commonly develop during periods of ischaemia. In the early peri-infarction period, the incidence of VPCs has been reported to vary between 10–93%. 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. In contrast, their presence in the post-infarction period (usually >10 per h) is a strong predictor of all cause and arrhythmic mortality.
Ventricular arrhythmias
Ventricular tachycardia (VT) is defined as three or more consecutive cardiac depolarisation arising below the atrioventricular node, with an RR interval of less than 500 ms (>120 beats/min). VT is estimated to occur in 3–39% of patients in the peri-infarction period. 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. VT is described as being ‘monomorphic’ if the QRS complexes have one morphology; multiple monomorphic if there are two or more runs of different QRS morphologies, but each run has a uniform QRS complex; and polymorphic if the QRS morphology is variable during one episode .
Fig. 3
Polymorphic VT: note the frequent changes in QRS complex morphology.
Fig. 3
Polymorphic VT: note the frequent changes in QRS complex morphology.
Accelerated idioventricular rhythm (slow ventricular tachycardia)
This rhythm is caused by an abnormally firing ventricular focus, which usurps sinus node pacemaker dominance and further depress sinoatrial node automaticity .By definition, the heart rate is less than 120 beats/min. It occurs very commonly during myocardial infarction and has been shown to be particularly associated with reperfusion of the myocardium following thrombolytic therapy.
Fig. 2
Accelerated idioventricular rhythm at a rate of approximately 80 beats per min.
Non-sustain Ventricular Tachycardia
The incidence of NSVT (monomorphic) in the peri-infarction period has generally been reported to occur in 1–7% of patients. 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. However, a recent study by Cheema et al has found that the time of onset of NSVT from admission (≥13 h and ≤24 h) as well as specific NSVT characteristics (association with previous MI or faster heart rates) were significant predictors of long-term survival.
Substantial data have demonstrated that NSVT in the post-infarction period increases the risk of sudden cardiac death by at least 2-fold. This risk is further increased to more than 5-fold in patients with left ventricular dysfunction (ejection fraction <0.40).
Sustained VT
Peri-infarction sustained VT has an incidence of 0.3–1.9%. 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 0.3–2% of patients in the peri-infarction period. The prognosis is similar to patients with sustained VT.
Ventricular fibrillation
Ventricular fibrillation is characterized by rapid, disorganized, 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. It has been reported to occur in 3% of acute MI with approximately 60% of episodes occurring within 4 h and 80% within 12 h
Supraventricular arrhythmias
Sinus bradycardia
Sinus tachycardia
Sinus tachycardia occurs in about 30% of patients with acute myocardial infarction. 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.
Atrial tachyarrhythmias
The incidence of atrial tachyarrhythmias during the peri-infarction period is estimated at 10–20%, with atrial fibrillation being the commonest atrial tachyarrhythmia (occurs in 10–15% of cases). Atrial flutter occurs in less than 5% of patients. These arrhythmias usually occur within 72 h of the index infarction with less than 3% arising in the very early phase (<3 h).
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 and, therefore, the threshold for cardiac catheterisation should be low.
Factors associated with the development of peri-infarction atrial fibrillation include: atrial infarction/ischaemia, sinus node dysfunction, older age, metabolic abnormalities, pericarditis, pericardial effusion, right ventricular infarction, congestive heart failure, higher peak cardiac enzyme concentration, increased heart rate, diabetes mellitus, history of hypertension and inotropic drugs. 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.
Conduction disturbances
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.
First degree AV block is the most common conduction disturbance occurring in up to 14% of patients with acute myocardial infarction. 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. Iatrogenic causes of first degree heart block include drugs such as β-blockers, calcium antagonists and digoxin. Mobitz type 1 heart block (Wenckebach) is present in 4–10% of patients with acute myocardial infarction and accounts for about 90% of patients with second degree heart block. 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. Complete heart block (CHB) has an incidence of about 6% and is more common with inferior/posterior infarctions. CHB occurring in association with anterior myocardial infarctions implies extensive myocardial damage and has a worse prognosis. CHB complicating either inferior or anterior wall myocardial infarctions is independently associated with mortality and in-hospital complications.
Conduction disturbances involving the left and right bundle branches occur in 10–24% of patients with acute myocardial infarction. Persistent bundle branch block is an independent marker of mortality, whereas, transient blocks which recover normal conduction during hospitalisation have similar prognosis to patients who never develop this complication.
Left anterior hemiblock occurs in 3–5% of acute myocardial infarctions and mortality is slightly increased. Left posterior hemiblock occurs in 1–2% of cases and, because of its large size, disturbances of this conduction pathway reflect significant myocardial damage, and it is associated with a higher mortality.
