Alternans of the ST Segment in Variant Angina

Alternans of the ST segment in Variant Angina* Incidence, Time Course and Relation to Ventricular Arrhythmias during Ambulatory Electrocardiographic Recording Gioia Turitto, M.D.; and Nabil El-Sherif, M.D.

The ST altemans was recorded during at least one ischemic attack with ST elevation in nine of 65 patients with variant angina. The magnitude and duration of ST elevation during ischemic attacks were significantly greater in patients with than in those without ST altemans. It always appeared during the occlusion phase and disappeared during the reperfusion phase of ischemic attacks. In patients with episodic ST altemans, the ischemic attacks showed a greater ST elevation and a longer duration in the presence of ST

altemans than in its absence. The incidence of occlusion phase ventricular arrhythmias was greater in patients with than in those without ST altemans; the incidence of reperfusion phase ventricular arrhythmias was similar in the two groups. The ST altemans always preceded the onset of occlusion phase arrhythmias. Thus, in variant angina, ST a1temans represents an index of the severity of ischemia and a precursor of ventricular arrhythmias.

Electrocardiographic alternans of the ST segment has been repeatedly reported in patients with Prinzmetals variant angina, often in association with ventricular arrhythmias. 1-5 The value of these observations is limited by the fact that they are anecdotal or retrospective and are based on recording methods that may not accurately estimate the frequency of ST alternans (coronary care unit monitoring or conventional electrocardiographic recording). Using ambulatory electrocardiographic recording, we carried out a prospective study on a group of patients with variant angina to assess the following characteristics of ST alternans: (1) incidence; (2) time course; (3) relationship to the magnitude and duration ofST elevation during ischemic attacks; and (4) relationship to the occurrence of ventricular arrhythmias.

of recent «three weeks) myocardial infarction and left ventricular aneurysm. The group consisted of 54 men and 11 women, with a mean age ± standard deviation of 51 ± 8 years (range, 38-71 years).

MATERIALS AND METHODS Patients

The study group was drawn from all patients who underwent inhospital ambulatory electrocardiographic recording for suspected spontaneous angina. The recording was obtained in the absence of any therapy except for sublingual nitrates if needed. Sixty-five patients were selected on the following basis: (I) at least one ischemic attack with transient ST elevation documented during the ambulatory recording; (2) at least one recording of transient ST elevation ~1 mm in one or more standard electrocardiographic leads other than aVR during an episode of spontaneous angina; (3)absence -From the Cardiology Divisions, San Camillo Hospital, Rome, Italy, and State University of New York, Health Science Center and Veterans Administration Medical Center at Brooklyn, Brooklyn, NY. Manuscript received June 1; revision accepted August 24. Reprint requests: Dr. El-Sherij, SUNY Health Science Center, Brooklyn ll200

Ambulatory Electrocardiographic Recording

Ambulatory electrocardiograms were recorded with Avionics portable units (model 445). Two bipolar leads were employed, choosing among CM3 (V3-like), A (aVF-like), CM5(V5-like),andCC5 (~-like). The monitoring period ranged from 24 to 120 h (mean, 42 h). Recordings were analyzed with Avionics replay unit (model 660). The ST segment shifts from baseline and ventricular arrhythmias were detected by examining: (1) the oscilloscopic replay of the tracing scanned at 120 times real-time; (2) the trendgrams of the ST segment, heart rate and ventricular premature complexes printed from both channels; (3)the transcription at a paper speed of25 mmls of all parts of the recording that were judged to be consistent with ischemia or arrhythmia on the basis of the high-speed analysis and the trendgrams. The following definitions were adopted: 1. Ischemic attack: any episode of transient ST elevation ~I mm having gradual onset and regression, lasting at least 30 s. and confirmed by all three methods illustrated. The magnitude ofST elevation was measured 100 ms after the onset of the QRS complex. Each ischemic attack was divided into two phases, based on the evaluation of the real-time tracing: (a) occlusion phase, defined as the onset of ST elevation, including its peak up to the onset of the resolution of ST elevation; (b) reperfusion phase, defined as the onset of the resolution of ST elevation up to the return of the ST segment to the control level. 2. ST segment altemans: a beat-to-beat difference in the magnitude ofSTelevation ~1 mm 100 ms after the onset of the QRS complex. 3. Ventricular arrhythmias: for the purpose of this study, significant ventricular arrhythmias were defined as one or more of the following: a bigeminal or trigeminal ventricular rhythm for ~five consecutive cycles, early ventricular premature complexes (R-on-T), e ventricular couplets, ventricular tachycardia (~3 ventricular premature complexes at a rate > l00/min), and ventricular fibrillation. Ventricular arrhythmias were classified as CHEST I 93 I 3 I MARCH, 1988

587

Table l-ClaartICteriatica of Patienta tDitIa or tDit1aout ST

Duration of ambulatory electrocardiographic recording (hours per patient) Location of ST elevation Anterior (%) Inferior (%) Anterior + inferior (%) Total ischemic attacks (n) Ischemic attacks per patient per day Symptomatic ischemic attacks (%) Magnitude of ST elevation at the peak of the ischemic attack (mm) Duration of the ischemic attack (min)

AlterntJ,.,·

Patients with ST-A (n=9)

Patients without ST-A (n=56)

p Value

35±12

43±25

NS

7 (78) 0 2 (22) 172 13.1± 10.3 48 (28) 5.3±4.9

37 (66) 19 (34) 0 1,232 12.4± 13.2 222 (18) 2.5±2.5

NS NS NS NS <0.01 <0.001

4.6±5.8

3.0±3.5

<0.001

*Key: n =number of patients; NS = not significant; ST-A= ST altemans. occlusion or reperfusion arrhythmias, depending on the phase during which they occurred.

Statistical AnaIysis Clinical characteristics of patients with or without ST alternans were compared. In patients with ST alternans, the characteristics of ischemic attacks with or without ST altemans were also compared. The unpaired Student t test was used for continuous variables, while the chi square test was used for discrete variables," A probability value <0.05 was considered statistically significant. Continuous data are expressed as mean ± standard deviation. RESULTS

Among the 65 patients with variant angina, nine (14 percent) had ST alternans during at least one ischemic

11mv

0'00"

3'10"

attack. Comparison between patients with or without ST alternans (Table 1)showed no differences with regard to the duration of the ambulatory electrocardiographic recording, the location of the transient ST elevation, and the number of daily ischemic attacks. On the other hand, the frequency of ischemic attacks accompanied by angina, as well as the magnitude and duration of the ST elevation during ischemic attacks, were significantly greater in patients with ST alternans than in those without ST alternans. Comparison between ischemic attacks with or without ST alternans showed: in nine patients with

ST-A onset ~

....1.!!f continu

FIGURE 1. ST alternans and ventricular arrhythmias, during one episode of variant angina. It may be noted that, 3 min 10 seconds aaer the beginning of the ischemic attack, ST altemans makes its appearance. During the period of maximal altemans, some ventricular premature complexes and couplets, indicated byafTOWS, are visible. ST-A, ST altemans.

588

AItem8ns of ST 8egment In vartant AngIna(Tutltlo,

B~

episodic altemans, ST altemans in 35 of 172 ischemic attacks were recorded. The magnitude and duration of ST elevation were significantly greater during the ischemic attacks with ST alternans than during those without ST alternans (ll.4±7.5 vs 3.7±3.I mm, p
more common in patients with ST alternans than in those without (seven of nine [78 percent] vs ten of 56 [18percent], p
In 71 to 93 percent of cases, 8-12 ST alternans follows coronary artery occlusion in the experimental animal. When coronary occlusion leads to ventricular arrhythmias, these coincide with the period of maximal a1ternans. 8 .11.13 In the clinical setting, ST altemans was seen during episodes of variant angina in 30 percent of 93 patients monitored in the coronary care unit by Rozanski and Kleinfeld." In the present study, 14 percent of 65 patients with variant angina showed ST alternans during ambulatory electrocardiographic recording. The lower frequency of ST alternans in man, as compared with that in the experimental animal, may be: (a) apparent and due to the poor sensitivity of surface recordings, as well as to the limited number of exploring leads during oscilloscopic and ambulatory electro-

Table 2-Ventricular An-laytlamia &corded during 1M Occluaion Gnd &perfuaion PhGla of '.chemic AtttJcb in ftJtienta with or without ST AlterntJna· Patientt

ST-A

Occlusion Phase

Reperfusion Phase

1 2 3 4

+ + + + + + +

Bigeminal, early VPCs, couplets Couplets Bigeminal, trigeminal VPCs Bigeminal VPCs Early VPCs, couplets, VI: VF Bigeminal, early VPCs, couplets Bigeminal VPCs, couplets Bigeminal, early VPCs, couplets, VI: VF Bigeminal, trigeminal, early VPCs, vr Bigeminal, early VPCs, couplets, vr

Bigeminal VPCs Bigeminal, trigeminal VPCs Bigeminal VPCs, couplets, vr Bigeminal, trigeminal VPCs

5

6 7 8 9

10 11 12 13 14 15 16 17 18 19

20

21 22 23 24

25

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

vr

Early VPCs, couplets Bigeminal VPCs, couplets Bigeminal, trigeminal VPCs, couplets Early VPCs, couplets Early VPCs, couplets Couplets

0 0 0 0 0 0 0 0

0 0 0

Couplets Bigeminal VPCs, couplets, vr Couplets Couplets Bigeminal, trigeminal VPCs Bigeminal VPCs, couplets Bigeminal VPCs

0 0 0 Bigeminal VPCs, couplets, VI' Early VPCs, couplets Early VPCs, couplets Early VPCs Bigeminal VPCs, couplets Bigeminal VPCs, couplets Bigeminal VPCs, couplets Couplets

+ == present; 0 == absent; ST-A== ST alternans; VF == ventricular fibrillation; VPCs == ventricular premature complexes; tachycardia. tPatients were not numbered in a chronological sequence but to facilitate the analysis of data.

*Key:

vr == ventricular

CHEST I 83 I 3 I MARCH, 1888

581

cardiographic recordings (in this regard, recording of multiple epicardial electrograms during experimental coronary occlusion have shown that ST aItemans may be limited to only a part of the ischemic region"): (b) real and related to the fact that the mean duration of the ischemic attack (three minutes in our group without aIternans) was too short to induce the appearance of the phenomenon. The high incidence of ST alternans in the series by Rozanski and Kleinfeld' compared with that in the present study may be attributed to the use of different monitoring techniques. In the former study, coronary care unit monitoring was utilized, which markedly underestimates the number of ischemic attacks, as compared with ambulatory electrocardiographic recording." Thus, the ischemic attacks detected by Rozanski and Kleinfeld were likely to be the most severe and symptomatic attacks, which, in our experience, are more frequently associated with ST alternans. The present study has shown that ST alternans is a marker of the severity of ischemia. Among our patients with episodic ST alternans, ST elevation was found to have three times the magnitude and twice the duration during the attacks accompanied by aIternans compared with those without ST alternans. Although the definition of ventricular arrhythmias varied somewhat in different series, the overall incidence of ventricular arrhythmias in the present study of 39 percent is comparable to that reported by Kerin et aILS (42 percent), Previtali et al" (48 percent), and Gabliani et al" (47 percent). The high overall incidence of ventricular arrhythmias in patients with variant angina and ST alternans compared with patients without alternans in our study (78 percent vs 32 percent) is also comparable to that reported by Rozanski and Kleinfeld" (95 percent vs 41 percent). However, the present study is the first to show that occlusion and not reperfusion arrhythmias are Significantly more frequent in patients with than in those without ST alternans. Previous studies have documented a relationship between occlusion arrhythmias and the severity of ischemia as manifested by the degree ofST elevation. 16 In our series, the ST segment was Significantly higher in patients with than in those without ST aIternans. On the other hand, the incidence of reperfusion arrhythmias seems to be related to both the degree and duration of ST elevation during the ischemic attack. 18 In experimentally-induced ischemia, the incidence of reperfusion arrhythmias increases as the period of preceding occlusion is prolonged from a few to up to 30 min." In 60 percent of patients with reperfusion arrhythmias described by Previtali et aI,16 the duration of the ischemic attacks was ten min or more. In our series, the mean duration of ischemic attacks in patients with or without ST alternans was 4.6 and 3.0 590

min, respectively. This can possibly explain our finding that the incidence of reperfusion arrhythmias was not statistically different in patients with or without ST alternans. In summary, although the present study has shed no light on the electrophysiologic mechanism of ST alternans, it shows that in patients with variant angina, ST alternans represents a marker of the severity of ischemia and is associated with a high incidence of ventricular arrhythmias. They commonly develop before or at the peak of ST elevation. REFERENCES 1 Williams RR, Wagner GS, Peter RH. ST-segment alternans in Prinzmetals angina: a report of two cases. Ann Intern Med 1974; 81:51-54 2 Kleinfeld MJ, Rozanski JJ. Alternans of the ST segment in Prinzmetal's angina. Circulation 1977; 55:574-77 3 Rozanski JJ, Meller J, Kleinfeld M, Castellanos A, Kupersmith J. Nonmechanical ST-segment alternans in Prinzmetals angina. Ann Intern Med 1978; 89:76-77 4 Rozanski JJ, Kleinfeld M. Alternans of the ST segment and T wave: a sign of electrical instability in Prinzmetals angina. PACE 1982; 5:359-65 5 Belie N, Gardin JM. ECG manifestations of myocardial ischemia. Arch Intern Med 1980; 140:1162-65 6 Naito M, Michelson EL, Kaplinsky E, Dreifus LS, David D, Blenko TM. Role of early cycle ventricular extrasystoles in initiation of ventricular tachycardia and fibrillation: evaluation of the R on T phenomenon during acute ischemia in a canine model. Am J Cardioll982; 49:317-22 7 Armitage P Statistical methods in medical research. Oxford: Blackwell Scientific Publications, 1971;131-40 8 Downar E, Janse MJ, Durrer D. The effect of acute coronary artery occlusion on subepicardial transmembrane potentials in the intact porcine heart. Circulation 1977; 56:217-24 9 Kleber AG, Janse MJ, van Capelle FJL, Durrer D. Mechanism and time course of S-T and T-Q segment changes during acute regional myocardial ischemia in the pig heart determined by extracellular and intracellular recordings. Circ Res 1978; 42: 603-13 10 Cinca J, Janse MJ, Morena H, Candell J, Valle Durrer D. Mechanism and time course of the early electrical changes during acute coronary artery occlusion: an attempt to correlate the early ECG changes in man to the cellular electrophysiology in the pig. Chest 1980; 77:499-505 11 Janse MJ, van Capelle FJL, Morsink H, Kl~ber AG, WilmsSchopman F, Cardinal R, et ale Flow of "injury" current and patterns of excitation during early ventricular arrhythmias in acute regional myocardial ischemia in isolated porcine and canine hearts: Evidence for two different arrhythmogenic mechanisms. Circ Res 1980; 47:151-65 12 Hashimoto H, Suzuki K, Miyake S, Nakashima M. Effects of calcium antagonists on the electrical alternans of the ST segment and on associated mechanical alternans during acute coronary occlusion in dogs. Circulation 1983; 68:667-72 13 Hashimoto H, Asano M, Nakashima M. Potentiating effects of a ventricular premature beat on the alternation of the ST-T complex of epicardial electrograms and the incidence of ventricular arrhythmias during acute coronary occlusion in dogs. J Electrocardiol 1984; 17:289-302 14 Biagini A, L'Abbate A, Mazzei MG, Testa R, Michelassi C, Antonelli R, et al. Inaffidabilita' del monitoraggio elettrocardiograflco in unita' di cura coronarica per il riconoscimento di

v

Altemans of ST Segmentin V8r1ant Angina (Turltto, a-Sherif)

episodi eliischemia miocardica. C Ita! Cardioll980; 10:1449-53 15 Kerin NZ, Rubenfire M, Willens H}, Rao ~ Cascade PN. The mechanism of dysrhythmias in variant angina pectoris: occlusive versus reperfusion. Am Heart J 1983; 106:1332-40 16 Previtali M, IOeny C, Salerno JA, Chimienti M, Pancitoli C, Maranzoni E, et a1. Ventricular tachyarrhythmias in Prinzmetal's variant angina: clinicalsignificance and relation to the degree and time course of S-T segment elevation. Am J Cardiol 1983; 52:19-25

17 Cabliani CI, Winniford MD, Fulton KL, Johnson SM, Mauritson DR, Hillis LD. Ventricular ectopic activity with spontaneous variant angina: frequency and relation to transient ST segment deviation. Am Heart J 1985; 110:40-43 18 Balke ~ Kaplinslcy E, Michelson EL, Naito M, Dreifus LS. Reperfusion ventricular tachyarrhythmias: correlation with antecedent coronary artery occlusion tachyarrhythmias and duration of myocardial ischemia. Am Heart J 1981; 101:449-S6

Plan to Attend

54th Annual SCientific Assembly Anaheim

October 3-7, 1988

CHEST I 83 I 3 I MARCH. 1988

181