Management of Cardiac Arrhythmias in Post-PCI Patients B. G

B. G

Introduction

Percutaneous coronary interventions (PCI) have been the fastest growing major invasive procedure in the past decade. Accompanying the obvious benefit, there are certain risks, including cardiac arrhythmias. A variety of arrhythmias and conduction disturbances can occur during PCI. In general, lethal ventricular arrhythmias, including serious ventricular tachycardia (VT) and ventricular fibrillation (VF), have been reported to occur in 1.5–4.4% of the patients undergoing coronary angioplasty. The frequency of these arrhythmias after primary PCI was analysed in data on 3065 patients from Primary Angioplastic in Myocardial Infarction (PAMI) trials [1].

Ventricular arrhythmias occurred in 133 patients (4.3%). Smoking, lack of preprocedural beta-blockers, shorter time from symptom onset to arrival in emergency room initial thrombolysis in myocardial infarction (TIMI) flow grade 0, and right coronary artery-related infarct were variables indepen- dently associated with a risk of serious ventricular arrhythmias. These patients had higher rates of complications including cardiopulmonary resus- citation and intubation in the catheterisation laboratory, but had similar fre- quencies of major adverse cardiac events in hospital and at 1 year.

These arrhythmias may be the result of excessive catheter manipulation, intracoronary dye injection, new ischaemic events, or reperfusion injury.

Role of Dye Injection and Intracoronary Solutions

Various contrast media have been developed for use in coronary angiogra- phy and PCI. These contrast media may be divided into ionic contrast media

Cardiology Department, Osmangazi University, Eskisehir,Turkey

of high osmolarity, those of low osmolarity, and non-ionic contrast materi- als. The risk of ventricular arrhythmia from intracoronary dye is greatest with the injection of ionic contrast agents into the right coronary artery, par- ticularly in the setting of prolonged injection or a damped pressure tracing.

VF may occur if dye is allowed to remain static in the coronary tree. The incidence of VF during PCI can be significantly decreased by using low- osmolarity non-ionic contrast media lacking calcium-binding additives.

However, in some reports, contrary to the current belief in the overall safety of low-osmolarity ionic contrast agents compared with other agents in diag- nostic coronary angiography procedures, such agents are associated with an increased risk of sustained ventricular arrhythmias [2].

VF is a serious complication during induction of hypothermia for surgi- cal purposes [3]. In a study published 2 years ago, six patients were found to have VF during intracoronary saline, heparin, contrast medium, or nitrate delivery [4]. These medications did not warm up to body temperature.

Immediate intracoronary flush would result in local hypothermia. Thus, to decrease the risk of VF, warmed-up fluid and warmed-up iso-osmolar non- ionic contrast agents must be preferred, especially in patients undergoing PCI on the right coronary artery.

Management of Ventricular Premature Beats

The first period of ventricular premature beats, which usually heralds malig- nant arrhythmias during acute coronary occlusion, develops after a quies- cent period of 1.5–2.5 min and reaches a peak at 5 min. Both re-entrant and non-re-entrant mechanisms contribute to the development of premature beats and malignant ventricular arrhythmias during the early phase of myocardial ischaemia. Complex premature ventricular contractions and occasional non-sustained ventricular tachycardia are seen after 2–3% of apparently uncomplicated angioplasty procedures. These arrhythmias usual- ly abate over 12–36 h and do not, in general, require treatment. However, hypokalaemia and hypomagnesaemia should be ruled out because potassi- um and magnesium may be depleted by diuretic-induced diuresis and may need to be replaced [5].

Arrhythmias Related to Ischaemia

Acute myocardial ischaemia often results in malignant arrhythmias owing to

both the direct effects of ischaemia and the resultant haemodynamic com-

promise during PCI. Some of the most refractory ventricular ectopy is seen

in the setting of profound transmural ischaemia or early myocardial infarc- tion. Venticular fibrillation due to acute ischaemia is a not infrequent com- plication of PCI. As in diagnostic coronary angiography, it is readily treated by defibrillation and death rarely results. There appears to be no relation to the severity of coronary artery disease, and the cause is partially related to the use of contrast agents or post-PCI complications.

Arrhythmic Complications and Patient Characteristics

Vessel calibre is one of the important factors in the genesis of arrhythmias in PCI. Huang et al. observed that a small calibre of the right coronary artery and associated ST segment changes played important roles in the patients who experienced VF during the PCI. They suggested that the cause of acute ischaemia might be the size of the guiding catheter. Most of the catheters they used in patients with VF were 7F, except in two cases where a 6F catheter was used. So, small-size catheters should be preferred especially in high-risk patients [4].

The risk of cardiac arrhythmias in PCI is more pronounced in patients with heart failure. Three years ago, DeGeare et al. investigated the predictive value of Killip classification in patients undergoing primary PCI for acute myocardial infarction. Killip classification predicted the incidence of arrhythmias in those patients. This classification was a predictor of mortali- ty in their study. Killip classification on hospital admission was a simple and useful independent predictor of in-hospital and 6-month mortality in patients with acute myocardial infarction who were undergoing primary PCI [6].

Importance of QT Dispersion and Heart Rate Variability

QT dispersion may serve as a measure of variability in ventricular recovery time and may be a means of identifying patients at risk of lethal ventricular arrhythmias and sudden death with coronary artery disease. Ashikaga et al.

showed that increased QTc dispersion may predict the risk of lethal ventricu- lar arrhythmias during angioplasty. The fact that successful angioplasty decreased QTc dispersion indicates that part of increased QTc dispersion is related to myocardial ischaemia in patients with coronary artery disease [7].

Thus, in patients with QTc dispersion we should be alert for serious ventric-

ular arrhythmias. Nicorandil may precondition the myocardium and may

prevent the occurrence of ventricular arrhythmias after coronary angioplas-

ty by suppressing the increase in QT dispersion [8].

Abrupt coronary occlusion may cause a wide range of autonomic reac- tions as evidenced by changes in heart rate, blood pressure, and heart rate variability (HRV). Coronary occlusion-induced increase in HRV seems to have a protective effect against the occurrence of complex ventricular arrhythmias during the early stage of abrupt coronary occlusion, suggesting that vagal activation may modify the outcome of acute coronary events with coronary artery disease [9].

Reperfusion Arrhythmias

Reperfusion arrhythmias may be one of the manifestations of reperfusion injury. These arrhythmias are common in patients undergoing PCI, which include accelerated idioventricular rhy thms, VT, and VF. Reperfusion arrhythmias, in addition to their importance as a marker of successful reper- fusion, need special attention because haemodynamics may rapidly deterio- rate during VT or VF.

Intracellular calcium overload is believed to play a critical role in the development of reperfusion arrhythmias. Accumulation of calcium in the cell causes damage to the respiratory chain and decreases ATP production, lead- ing to depletion of mitochondrial energy [10]. The oxygen paradox is closely linked to the calcium overload or calcium paradox, since oxygen mediates the uptake of calcium by mitochondria [11]. Oxygen also leads to cell damage during reperfusion through the formation of oxygen radicals [12]. The role of free radicals in the genesis of reperfusion arrhythmias is uncertain. Free-rad- ical-induced damage occurs in the 10 min after reperfusion [13]. Reduced levels of free radical scavengers have been observed within 3 h of angioplasty in patients with acute myocardial infarction [14].

Some strategies may be helpful for the prevention and treatment of reperfusion arrhythmias, but their beneficial affects are limited. Today we know a little about the effectiveness of antioxidant therapy. The results have largely been mixed and the investigation remains focused at the animal level.

Magnesium can be a choice, but there are conflicting data on its benefit.

Numerous studies have examined the efficacy of vasodilators as cardiopro-

tective agents in ischaemic reperfusion injury. Intracoronary adenosine and

papaverine may be effective as cardioprotective agents. Human studies with

papaverine have also demonstrated success in improving angiographically

documented TIMI flow grades in epicardial arteries [15]. Calcium channel

blockers may block intracellular calcium overload and have positive effects

on vascular flow. The effects have been demonstrated during the administra-

tion of nifedine and verapamil [16]. Two years ago Yoshida et al. showed that

administration of dipyridamole can prevent and terminate reperfusion

arrhythmias such as accelerated idioventricular rhythms and VT. They con- cluded that cAMP-mediated triggered activity may, at least in part, be responsible for reperfusion arrhythmias [17].

Role of Inhibition of the Renin–Angiotensin–Aldosterone System

In the normal heart, locally derived angiotensin II may modulate coronary blood flow, inotropy, and chronotropy [18–21], whereas under pathological conditions the renin–angiotensin–aldosterone system (RAS) may influence ventricular growth and myocardial metabolism, induce ventricular arrhyth- mias during ischaemia and reperfusion injury, and contribute to post-infarc- tion ventricular remodelling [22]. We also know that bradykinin accumulation is a potent cardioprotective mechanism underlying RAS inhibition in ischaemia and reperfusion injury. A role for RAS in reperfusion arrhythmias was suggested by studies in angiotensin II type 1a receptor knockout mice which, compared to wild-type mice, showed less reperfusion arrhythmia despite a similar infarct size. In addition, administration of a selective angiotensin II type 1 receptor before ischaemia blocked reperfusion arrhyth- mias [23]. An experimental study showed us that losartan attenuates myocar- dial ischaemia-induced ventricular arrhythmias and reperfusion injury in hypertension, and may be useful in the treatment of ventricular arrhythmias induced by acute myocardial infarction and attenuation of reperfusion injury [24]. Intracoronary enalaprilat infusion in the infarct-related artery is feasible in the setting of primary angioplasty and is safe and well tolerated [25].

Effective cardiac RAS inhibition can be achieved by low-dose intracoronary enalaprilat, which primarily causes a potentiation of bradykinin [25].

Preconditioning and Arrhythmias

The incidence of serious ventricular arrhythmias in the presence of intra-

coronary thrombus was high in a report [26]. Sudden obstruction of the

coronary artery without pre-existing coronary artery narrowing was associ-

ated with a higher incidence of VF than was obstruction occurring in associ-

ation with pre-existing stenoses [26]. The profibrillatory effect of thrombus

was not detectable in another report. Experimental studies have suggested

that the phenomenon of ischaemic preconditioning may increase the VF

threshold [27] and reduce the incidence of ischaemic and reperfusion

arrhythmias [28]. The mitochondrial KATP channel seems to be important

in prevention of myocardium by preconditioning. A study in dogs suggests

that preconditioning may exert an antiarrhythmic effect during ischaemia by

modifying cardiac autonomic receptor mechanisms, which results in an improved parasympathetic balance. A preceding short vessel occlusion–

reperfusion cycle increases the electrical stability of ischaemic myocardium, so the repeated coronary artery occlusions during PCI protect against ischaemia-induced ventricular arrhythmias [29].

Benefits of Intra-aortic Balloon Counterpulsation

Intra-aortic balloon counterpulsation (IABC) has been used following pri- mary PCI in high risk patients in an attempt to improve outcomes by increasing coronary blood flow reserve, decreasing preload and afterload, and augmenting systemic pressure [30]. In high risk patients prophylactic use of IABC may decrease the incidence of VF, especially in patients with cardiogenic shock [30]. Intra-aortic balloon counterpulsation used before primary PCI provides benefit to patients with cardiogenic shock by reducing the incidence of catheterisation laboratory events, including VT. So, we rec- ommend the use of IABC in patients with cardiogenic shock who are under- going primary PCI.

Supraventricular Arrhythmias and Atrial Fibrillation

Supraventricular arrhythmias including atrial fibrillation (AF) may be induced by PCI, but they are not as frequent as ventricular arrhythmias.

However, AF especially has prognostic significance in patients treated with PCI. Because the patency of infarct-related artery is better, primary PCI is superior to thrombolytic therapy in restoring sinus rhythm in patients with acute myocardial infarction who have developed AF [31].

Kinjo et al. investigated the prognostic significance of AF and atrial flut- ter in patients with acute myocardial infarction treated with PCI. In their study, the patients with AF were older, were in higher Killip classes, had higher rates of previous myocardial infarction and previous cerebrovascular accident, had systolic blood pressure of less than 100 mmHg and heart rates of 100 beats/min or more, were less likely to smoke, and had a higher preva- lence of multivessel disease and poorer reperfusion of infarct-related artery than those without AF. Atrial fibrillation was a common complication in patients with acute myocardial infarction who are treated with PCI and inde- pendently influenced 1-year mortality, they said [32].

Atrial fibrillation during PCI tends to revert spontaneously over a period

of minutes to hours, but may require additional therapy if it produces

ischaemia or haemodynamic instability. Intravenous beta-blockers (e.g.

esmolol, metoprolol), calcium channel blockers (e.g. verapamil), or digoxin may be given and up-titrated until adequate control of ventricular response is achieved. Electrical cardioversion is rarely required.

Conduction Defects and Heart Blocks

New conduction defects occur in about 0.9% of the patients undergoing coronary angioplasty [33]. Of these, right bundle branch block was the most common, followed by first-degree atrioventricular block. These defects almost always disappeared without treatment before the time of hospital dis- charge, but occasionally required the elimination of drugs depressing car- diac activity [5].

When complete heart block develops, atropine is rarely helpful in the set- ting of inadequate escape and deterioration, but should be given anyway.

Coughing may help support the circulation and maintain consciousness while a temporary pacing catheter is inserted.

Conclusions

Either ventricular or atrial arrhythmias or conduction disturbances can be observed during PCI. Some of them occur as a complication of the proce- dure, but many of the arrhythmias are related to reperfusion injury. The patient’s characteristics, the type of the procedure, the features of the target vessel and the type of the lesion play an important role in the occurrence of arrhythmias. The majority of the arrhythmias tend to revert spontaneously, but when necessary, special treatment must be given promptly.

References

1. Mehta RH, Harjai KJ, Grines L et al (2004) Sustained ventricular tachycardia or fibrillation in the cardiac catheterisation laboratory among patients receiving pri- mary percutaneous coronary intervention: incidence, predictors, and outcomes. J Am Coll Cardiol 43:1765–1772

2. Hajj-Ali R, Ezzeddine R, Jadonath R et al (2001) Use of low-osmolar ionic contrast agents increases the risk of sustained ventricular arrhythmias during diagnostic coronary angiography. Am J Cardiol 88 (5A): TCT298 Suppl.

3. Kearns JB, Murnaghan MF (1969) Ventricular fibrillation during hypothermia. J Physiol Lond, 203(1):51P-53P

4. Huang JL, Ting CT, Chen YT, Chen SA (2002) Mechanisms of ventricular fibrilla-

tion during coronary angioplasty: increased incidence for the small orifice caliber

of the right coronary artery. Int J Cardiol 82:221–228

5. Ellis SG (1994) Elective coronary angioplasty: technique and complications. In:

Topol EJ (ed) Textbook of interventional cardiology. Saunders, Philadelphia, pp 186–206

6. DeGeare WS, Boura JA, Grines LL et al (2001) Predictive value of the Killip classifi- cation in patients undergoing primary percutaneous coronary intervention for acute myocardial infarction. Am J Cardiol 87:1035–1038

7. Ashikaga T, Nishizaki M, Arita M et al (1998) Increased QTc dispersion predicts lethal venticular arrhythmias complicating coronary angioplasty. Am J Cardiol 82:814–816

8. Kato T, Kamiyama T, Maruyama M et al (2001) Nicorandil, a potent cardioprotecti- ve agent, reduces QT dispersion during coronary angioplasty. Am Heart J 141:940–943

9. Airaksinen KE, Ylitalo A, Nimela MJ et al (1999) Heart rate variability and occur- rence of ventricular arrhythmias during balloon occlusion of a major coronary artery. Am J Cardiol 83:1000–1005

10. Matsuma K, Jeremy RW, Schaper J et al (1998) Progression of myocardial necrosis during reperfusion of ischemic myocardium. Circulation 97:795–804

11. Opie LH, Coetzee WA ( 1988) Role of calcium ions in reperfusion arrhythmias:

Relevance to pharmacologic intervention. Cardiovasc Drugs Ther 2:623–636 12. Hearse DJ, Tosak A (1988) Free radicals and calcium. Simultaneous interacting trig-

gers as determinants of vulnerability to reperfusion-induced arrhythmias in the rat heart. J Mol Cell Cardiol 20:213–223

13. Ambrosio G, Weisfeldt ML, Jacobus WE et al (1987) Evidence for a reversible oxy- gen mediated component of reperfusion injury: reduction by recombinant human superoxide dismutase administered at the time of reflow. Circulation 75:282–291 14. Lafont A, Marwick TH, Chisolm GM et al (1996) Decreased free radical scavengers

with reperfusion after coronary angioplasty in patients with acute myocardial infarction. Am Heart J 1996 131:219–23

15. Ishihara M, Sato H, Tateishi H et al (1996) Attenuation of the no-reflow phenome- non after coronary angioplasty for acute myocardial infarction with intracoronary papaverine. Am Heart J 132:959–963

16. Tillmanns H, Neumann FJ, Parekh et al (1990) Pharmacologic effects on coronary microvessels during myocardial ischemia. Eur Heart J 11:B10–B15

17. Yoshida Y, Hirai M, Yamada T et al (2000) Arrhythmic efficacy of dipyridamole in treatment of reperfusion arrhythmias. Circulation 101:624–630

18. Saito K, Gutkind JS, Saaverda JM (1987) Angiotensin II binding sites in the conduc- tion system of rat hearts. Am J Physiol 253:1618–1622

19. Xiang JZ, Scholkens BA, Ganten D, Unger T (1984) Effects of sympathetic nerve sti- mulation is attenuated by the converting enzyme inhibitor Hoe 498 in isolated rab- bit hearts. Clin Exp Hypertens 6:1853–1857

20. Xiang JZ, Linz W, Becker H et al (1985) Effects of converting enzyme inhibitors:

ramipril and enalapril on peptide action and sympathetic neurotransmission in the isolated heart. Eur J Pharmacol 113:215–223

21. Rogers TB, Gaa ST, Allen IS (1986) Identification and characterization of functional angiotensin II receptors on cultured heart myocytes. J Pharmacol Exp Ther 236:438–444

22. Dostal DE, Baker KM (1993) Evidence for a role of an intracardiac renin-angioten- sin system in normal and failing hearts. Trends Cardiovasc Med 3:67–74

23. Harada K, Komuro I, Hayashi D et al (1998) Angiotensin II type 1a receptor is

involved in the occurrence of reperfusion arrhythmias. Circulation 97:315–317

24. Lee YM, Peng YY, Ding YA et al (1997) Losartan attenuates myocardial ischemia- induced ventricular arrhythmias and reperfusion injury in spontaneously hyper- tensive rats. Am J Hypertens 10:852–858

25. Kurz T, Schafer U, Dendorfer A et al (2001) Effects of intracoronary low dose enala- prilat as an adjunct to primary percutaneous transluminal coronary angiography in acute myocardial infarction. Am J Cardiol 88:1351–1357

26. Coronel R, Wilms-Schopman FJ, Janse MJ (1997) Profibrillatory effects of intraco- ronary thrombus in acute regional ischemia of the in situ porcine heart.

Circulation 96:3985–3991

27. Gulker H, Kramer B, Stephan K et al (1977) Changes in ventricular fibrillation thre- shold during regional short-term coronary occlusion and release. Basic Res Cardiol 72:547–562

28. Lawson CS, Hearse DJ (1996) Anti-arrhythmic protection by ischemic preconditio- ning in anesthetised dogs and rats. Cardiovasc Res 31:655–662

29. Airaksinen KEJ, Huikuri HV (1997) Antiarrhythmic effect of repeated coronary occlusion during balloon angioplasty. J Am Coll Cardiol 29:1035–1038

30. Brodie BR, Stuckey TD, Hansen C et al (1999) Intra-aortic balloon counterpulsa- tion before primary percutaneous transluminal coronary angioplasty reduces catheterization laboratory events in high-risk patients with acute myocardial infarction. Am J Cardiol 84:18–23

31. Gorenek B, Birdane A, Unalir A et al (2000) Restoring sinus rhythm in patients with atrial fibrillation complicating acute myocardial infarction: comparison of outco- mes of primary angioplasty and thrombolytic therapy (abstract). Eur J Heart Fail, Suppl 1:32

32. Kinjo K, Sato H, Sato H et al (2003) Prognostic significance of atrial fibrillation/atrial flutter in patients with acute myocardial infarction treated with percutaneous coronary intervention. Am J Cardiol 92:1150–1154

33. Bredlau CE, Roubin GS, Leimgruber PP et al 81985) In-hospital mortality in

patients undergoing elective coronary angioplasty. Circulation 72:1044–1052