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Spontaneous Angina in the Coronary Care Unit
Spontaneous Angina in the Coronary Care Unit* 1. Frequent Association with Development of Acute Myocardial Infarction John E. Madias, M.D.
We studied 16 patients, 36 to 75 years old, with repetitive episodes of spontaneous angina (SA) associated with transient ST-segment shifts. At onset SA was not IIIISOCiated with changes in systolic blood pressure, heart rate, or double product, but such increases often occurred late. All patients smoked cigarettes; 13 were hypertensive. History of angina at rest or exertion was present in 13 patients, seven of whom had crescendo chest pain before admission. Twelve patients had an acute myocardial infarction (MI). Comp6cations were not uncommon in the setting of MI. Angina persisted in a few patients after MI, and resulted in its extension in three patients. Coronary arteriography performed on eight
of patients who suffered an acute myoS tudies cardial infarction ( MI) after repetitive episodes
of angina at rest have recently been published. 1•2 A previous communication from this Coronary Care Unit ( CCU) constituted a nonconsecutive series of patients2 who had an MI following attacks of spontaneous angina ( SA). We present data on a prospective study of 16 consecutive patients with recurrent attacks of SA, 12 of whom had an MI. MATERIAL AND METHODS
The study population included 16 patients who were admitted to the CCU from January 1978 to April 1979 for evaluation of recurrent attacks of SA, associated with transient ST-segment shifts in the ECG. SA was defined as angina occurring at rest, or chest pain that had awakened the patients from sleep. Ten patients were men and six women. They ranged in age from 36 to 75 years, with a mean age of 53 ± 2.5 ( SEM). Excluded from the study were patients who did not have further episodes of angina following their admission, who were found on entry to the hospital to have suffered an MI, or who had angina without ECG changes. Multiple ECGs and blood pressure recordings were ob0From the Thorndike Memorial Laboratory and the Department of Cardiology, Division of Medicine, Boston City Hospital and Boston University School of Medicine, Boston. Supported in part by the US Public Health Service grant RR-533. Manuscript received September 14; revision accepted November 30. Reprint requests: Dr. Madias, Cardiology, Boston City Hospital, Boston 02118 30
patients revealed significant coronary artery disease in seven. There was a good correlation between the loci of coronary lesions and the transient ECG changes. Nitrates were occasionally ineffective in re6eving symptoms and failed to prevent SA. mgh doses of propranolol were also ineffective. Aortocoronary bypass surgery was performed on three patients. Fifteen patients were discharged asymptomatic. One patient died in the hOBpital. Three additional patients died within the first month after admission. FoUowup in the clinic revealed good response to nitrates in the 12 surviving patients. SA in the CCU may be a good model to study the pathogenesis of myocardial ischemia and acute MI.
tained during and following attacks of chest pain. Systolic blood pressure (SBP), heart rate (HR), and double product ( DP) noted at the onset of chest pain were compared with values of these parameters obtained before the beginning of episodes of SA. DP was defined as the product of SBP and HR and was taken as an estimate of myocardial work. Routine care comprised continuous ECG monitoring, serial recordings of ECG, and blood sampling for cardiac enzymes. Upper normal limits for total creatine kinase ( CK) were 75 IU /L and for myocardial fraction ( MB-CK) less than 4 percent. Drugs were administered as clinically indicated. Nitrates in all avail8'ble forms and propranolol were used to treat anginal episodes. Intravenous ( IV) nitroglycerin and oral nifedipine were used in only two and three patients, respectively. MorPhine was administered as an analgesic if the pain did not respond to nitrates. Eight patients underwent cardiac catheterization and angiography. Surviving patients were followed until July 1981. REsULTS
Details on age, sex, and prevalence of risk factors are shown in Table 1. Three patients were diabetic, eight had elevated levels of lipids, and five had a history of previous MI. Two additional patients had an ECG, but not a history, indicative of an old MI. Family history of MI was present in nine patients. Aortocoronary bypass to the left anterior descending and diagonal vessels had been performed in patient 10 six months before admission. Three patients did not have a history of angina, nine had exertional chest pain, and 13 had angina Spontaneous Angina In the CCU (John E. Iliad/as)
Table 1---Ciinlcel ClaarwcterUdea o/ P......,....,. Spon~aneou Patient No./Age/Sex Hypertension
Smoking
..4,.Pna in alae Coro_..,. Care Uni••
History of Angina
Drugs on Admission
Mode of Presentation
1/49/M
+
2
2/36/M
±
1~
3/59/M
+
2
DIG, NTG, ISDN A-Ex, A-R 4Y IM
4t/62/M
±
2
A-R, A-CR 6M IW A-R in sleep lW
A-R, resting in bed, diaphoresis
5/48/M
+
3
A-R lW
A-R, in sleep, vomitus, diaphoresis
6/55/M
±
A-Ex, A-R 2W lOD A-CR, A-Rin sleep lOD lOD
A-R, resting in bed
PROP,NTG
A-Ex, A-R 3M 2M A-CR 1M
A-R, in sleep, nausea, diaphoresis, fatiguP
A-R, A-CR 8M 7D
A-R, sitting
7t/49/F
I~
A-Ex, A-R 2D 5D
A-R, sitting, vomitus, near syneoJw
HCTZ
8/47/M
+
1/3
PROP, SPIR, NTG, Insulin
Ut/71/F
+
(I
DIG, HCTZ, NTG
10/40/M
+
11/58/M
+
12/46/F
A-R, sitting, diaphoresis
PROP, ISDN, DIP, NTG
A-R, sitting vomitu~.
A-R, watching game on TV, palpitations, nausea, diaphores~ A-Ex, A-R 14M 9M A-CR 5D
A-R, sitting A-R in sleep
131
A-Ex, A-R 4D 4D
A-Ex, walking after breakfast, nausea, diaphoresis
I~
A-Ex 6M
A-Ex, washing floor, diaphoresis, dyspnea
A-Ex 33Y
A-R, sitting, reading, vomitus, diaphoresis, dyspnea
NTG
13/53/M
±
4
14/52/F
±
2
15t/49/F
+
2
PROP,HCTZ
A-R 1Y
A-R, sitting, nausea, dyspnea, lightheadedness
2
DIG, DIP, NTG, Verapamil, Clofibrate
A-Ex, A-R 4Y 4Y A-CR 1W A-R in sleep 1W
A-R, sitting A-R in sleep, nausea
16/75/F
A-Ex, moving boxes, near syncopt>, nausea, dyspnea
*Abbreviations: +-hypertensive with positive history of hypertension; ±-hypertensive and/or left ventricular hypertrophy by ECG with negative history of hyp!'..rtension; Number under smoking indicates packs of cigarettes per day; DIG •digitalis; NTG- nitroglycerin; ISDN - isosorbide dinitrate; HCTZ- hydrochlorothiazide; PROP= propranolol; SPIR -spironolactone; DIP-dipyridamole; A-Ex-angina on exertion; A-R-angina at rest; A-CR-crescendo angina. "History" subscript numbel"'l refer to duration of angina: D•days; W-weeks; M•months; Y-ye&l"'l. t- Patient did not suffer an acute myocardial infarction.
at rest Seven patients had both angina on exertion and at rest, seven had crescendo angina, and three
had chest pain that woke them from sleep. Duration of angina and drug history at the time of admission CHEST I 82 I 1 I JULY, 1882
31
are indicated in Table 1. Patient 16 had discontinued use of all drugs four days before admission. Symptoms that precipitated admission consisted of angina at rest or that woke them from sleep in 13 patients, and angina on exertion in three patients. Details are shown in Table 1. Details on the number of chest pain episodes, their duration, and the time span over which they occurred are presented in Table 2. Duration of episodes of chest pain reported included the residual "aching" that often followed attacks of angina, or express multiple episodes spaced close to each other. While in the hospital four patients ( 3, 6, 8, and 9) awoke from sleep wilth angina. Definite diurnal distribution of chest pain was not noted. Episodes of angina in eight patients occurred both before and after peak rise of CK. Attacks of SA were accompanied primarily by unchanged SBP, HR, and DP values when measured early in the course of chest pain. However, change in these variables was often recorded after the onset of pain (Table 2). Such changes often occurred in the short interval required for the recording of an ECG (Fig 1) or a rhythm strip (Fig
2). Values of SBP and HR were often higher during asymptomatic periods than at the onset of chest pain. Transient ST-segment elevation during chest pain was recorded in 11 of the 16 patients and occurred in anterior leads in five patients (Fig 3), in inferior leads in three patients ( Fig 4), and in both leads in three patients ( Fig 1 ) . Six patients showed both ST-segment elevation and ST-segment depression in the same leads during different attacks of chest pain. Four patients (10, 12, 14, and 16) showed only ST-segment depression, and patient 7 showed only T-wave abnormalities with angina. Transient upright T-waves were recorded in seven patients (Fig 5). Pseudonormalization of inverted T -waves during angina was noted in seven patients. Six patients showed transient inversion of T-waves during chest pain. Peak rise in the CK and its time is indicated in Table 3. Twelve patients had enzymatic alterations c:onsistent with acute MI. Three patients ( 1, 6, and 11) showed two peaks of CK and MB-CK, indicative of exil:ension of MI. Twelve patients suffered an acute MI. Other
Table Z--Frequene:r o/.4ttaelu, and Blood Pre.aure, and Hearl Rare Claan«e• Durin• Sponkrneou .4n«fna in alae Coronary Care Unir* No. of Anginal Episodes
Duration of Anginal Episodes, min
Time Span of Angina Occurrenct>, days
4
15-45
5
2
4
30-40
3
41
3-90
32
4t
35
15-150
30
5
11
15-60
4
-6;+5
X
X
X
6
17
1-60
12
-6; +11
X
X
X
7t
10
1-30
8
26
Yz-40
30
9t
9
20-40
7
10
7
30-90
2
-7;
11
12
5-60
12
4
15-60
13
7
20-90
-3; +4
14
5
20-90
-5;
I5t
7
10-45
9
16
17
15-90
8
Patient No.
No. of Anginal Episodes before(-) and after (+) CK Rise
4SBP
4HR
4DP
-2;+2
X
No4
X
-4;
X
X
X
X
X
X
0
-26; +15
t, No4
1. No4
t, No4
!, No4
t, No4
!, No4
X
X
X
X
X
X
0
X
X
X
fl
-4; +8
X
X
X
2
-4;
-7; +19
0 0
!, No4 X
1, No4 X
-6; +11
X
!. No4 X
1. No4
!. No4 X
!, No4 X
!. No4 X X
*Abbreviations: CK=Creatine kinase; 4=change of parameteJ"K during angina compared with values prior to onset of chest pain; SBP-systolic blood pressure (mm Hg); HR=heart rate (beats/min); DP==double product (mm Hg beats/min); t =increase; ! -decrease; X -increase, decrease, or no change during different chest pain episodes. t- Patient did not. suffer an acute myocardial infarction.
32
Spontaneous Angina In the CCU (John E. Mediae)
2
1 ::: \
.
=n :·
'..
:!: "· ..
A .·' .. jl'
•••
: .: !! : ::
'
::.
3 oVR oVL oVF
RS-2
~
1:
". '':. ' ·: :·
::
:
B
c D FIGURE l. Patient 2. (A), Episode of spontaneous angina associated with transient ST-segment elevation. Blood pressure (BP), heart rate (HR) , and double product (DP) increased greatly between recording of lead 1 and rhythm strip (RS-2) , which were separated by 2'. BP 7' before onset of chest pain was 140/95 mm Hg, and HR was 78 beats/min. (B), Three hours after A, and following recurrent attacks of chest pain and cardiac arrest, precordial ECG leads revealed some persisting ST-segment elevation. (C), ECG at discharge showed T-wave inversion and reduction in R waves in leads previously showing ST-segment elevation. (D), ECG 10 months after A showed regeneration of R waves, notably reduced at discharge. Such increase in amplitude was gradual in serial ECGs.
complications are shown in Table 3. Patient 13 died in cardiogenic shock. Patients 6, 8, and 15 underwent intra-aortic balloon counterpulsation, the latter two suffering angina during the procedure. These three patients were subjected to aortocoronary bypass surgery. Comparison of the patients in whom an MI evolved and those without such outcome did not show any differences. Nitrates were administered, often at the maximal
Time
SBP HR
OP
recommended doses and frequency. Propranolol was used at maximal doses indicated in Table 4. This drug was discontinued in patients 3, 4, and 11, who had congestive heart failure. Although all 15 surviving patients were discharged asymptomatic, angina occurred in the hospital in some of these patients while they received a combination of all of the previously described drugs that had effected a reduction of SBP and HR.
5:12'00"om
5:t3'3o'am
115
140 145
130
95 12,350
20,300 ---; -
Leodt 'l ' rr--
FiGuRE
__] \ Ill
,..,.
A
---,--,--
. -~I _....: ' -:----+.:-t --r.
- ' j_-+ -=FA
'
2. Patient 9. (A, B, C), Rhythm ECG strip recorded continuously in a 3channel ECG recorder 2' after onset of an episode of spontaneous angina. Systolic blood pressure ( SBP) and heart rate ( HR) before onset of chest pain were similar to values of A. Within 24" there was an increase in HR, and 1' later HR and double product ( DP) were greatly increased. Moderate rise in SBP was noted. Nitroglycerin was administered just before C.
5:12'24"om
i
:
'
'
.
-
-
·
,
'
: l•··. T-
~ -- - ----~--~~ ,-
1 -
•
L '
t---
t--
1\
I"
8
"lJ! JU
~
~
J.
-.li
c CHEST I 82 I 1 I JULY. 1982
33
Time
9:37am
SBP
100
HR
74 7,400
DP CP
•
3. Patient 8. Systolic blood pressure (SBP) and heart rate (HR) were lower at the onset of episode of spontaneous angina from values obtained before patient's complaint!. of chest pain. By time of ECG tracing (9:40 AM), there was marked increase in SBP and double product (DP) and mild rise in HR. Subsequently, there was decrease in SBP and increase in HR following administration of nitroglycerin (NTG). ST-segment elevation resolved in 15'. ECG at 9:58AM was similar to tracing recorded before this attack of chest pain. T-wave inversion was seen transiently after this episode, but persisted after sequence of several episodes of spontaneous angina. chest pain. CP FIGURE
176
140
124
78
83
84
13,728
11,620
10,416
+++
+++
9=58am
9:47am
9=40am
++
+ + NTG
NTG
+
Eight patients underwent cardiac catheterization and angiography. Seven ·patients had significant coronary artery disease. Details of catheterization data are shown in Table 5. There was a close correlation of the transient ECG changes during angina and significant lesions at coronary arteriography. Collaterals were identified in patients 3, 4, 6, and 8. The first three of these patients showed ST-segment depression during attacks of angina. Seven patients underwent stress testing. One had an adequate negative, and four had an inadequate negative test. These tests were carried out after discharge. One patient had notably different responses to two stress tests (Fig 6), and patient 10 had a negative test five days prior to his admission with SA. Three of the 15 surviving patients died shortly after discharge (Table 4). Follow-up of the 12 surviving patients ranged from 27 (patient 15) to 42 months (patient 1). None of these patients sufTime
SSP
HR
DP
A
3:30am
140
92
12,880
B
4:15am
140
93
13,020
c
4:20am
140
83 54
11,620 7,560
D
4:54am
120
94
11,280
+
NTG
=
fered a recurrence of MI, and three patients ( 3, 14, and 15) currently have rare episodes of angina, which respond to nitroglycerin therapy. Details of therapy after discharge are shown in Table 4. Drugs and dosages listed represent the therapy administered at different phases of the follow-up. DISCUSSION
Acute MI occurs in 20 to 46 percent of patients with recurrent SA. 1•3 Seventy-five percent of our group suffered an MI. This rate would have been lower and the incidence of SA higher if patients with even one episode of SA were included in our study. Continuous recordings of ECG and hemodynamics4-7 would have identified an even larger group of patients with SA or with episodes of silent myocardial ischemia. 6 Therapy for prevention of further episodes of SA must have decreased the number of patients suitable for our protocol. Progression of SA to acute MI and the reasons for oc-
FIGURE 4. Patient 9. (A), ECG during asymptomatic period. (B), Episode of spontaneous angina associated with ST-segment elevation with disappearance of S waves in inferior leads and reciprocal changes in anterior leads. Systolic blood pressure ( SBP), heart rate ( HR), and double product (DP) values were similar to those obtained before onset of chest pain (C), SBP remained stable, but HR of 43 beats/min developed, followed by HR of 83 beats/min, 1°, 2°, and 3° AV block. (D), Following nitroglycerin, HR returned to baseline, then SHP fell somewhat, and HR rose further. All of these parameters soon returned to baseline. Several nitroglycerin tablets were required for abatement of chest pain.
34
Spontaneous Angina In the CCU (John E. Mad/as}
A-1. Day
HR
BP
8
1
-.:..r&w~~'l.ll ... : :
HR
BP
c 27
. l •. ; 1 · : : : · . . ·.· . . . ~~
105/88
'~ ~1Jf~ T~flf& 68
110/90 ••
~
..
j
I
•• 70 130/98
56
45
.
I
l-.
ffiJ '
I
I '
'I
:~ I
'
'II- I
-
_I
I
68
-L;· * =H=I-
~-
.
.~
.. .
I
-
c
.
"
.
L . . ~-: : 65 128/95
1' 1 +·:· ..
·
.
-++!
~ =t-l· :~
FIGURE 5. Patient 3. (A), Episode of spontaneous angina accompanied by peaking of T-waves and ST-segment depression in anterior ECG leads. Blood pressure ( BP) and heart rate ( HR) rose during short time required for ECG recording. Both BP and HR were higher 2' before onset of chest pain. (B), Another episode of chest pain was associated with transient reduction of R waves in anterior leads. HR did not change during this attack, but BP rose mildly. Episodes of chest pain at A and B were 45' apart, between which nitroglycerin was administered. (C), ECG at discharge. Repolarization alternations and reduction of amplitude of R waves in the precordial leads consistent with myocardial necrosis.
currence of such a complication in a fraction of patients with SA have not been explained as yet. 1· 6 Long-term follow-up of patients with SA surviving the acute phase appears to be benign_:z.s and this was also shown in our study. However, short-term 25-percent mortality in our patients is in agreement with data reported by Conti and Curry. 9 This study did not address the issue of frequency of SA, since our material constituted a subgroup
FiGURE 6. Patient 7. (A), Chest pain was accompanied by deepening of preexisting T -wave inversion in leads V1 to V3 (not shown). Systolic blood pressure ( SBP), heart rate (HR), and double product (DP) were stable compared with values before onset of angina. (B), DP after abatement of angina was unchanged. (C), During negative exercise stress test, the patient reached high levels of SBP, HR, and DP. (D), During 20tTl stress test, patient had chest pain and ST-segment elevation during minor changes in DP. (E), Partial resolution of ECG changes were noted 15" after test ended. (F), ECG returned to normal after the 1' after E; patient became asymptomatic after administration of nitroglycerin. Scintigraphic data were not obtained.
of patients with recurrent attacks of SA. Increasing numbers of patients with SA are detected as the awareness of this syndrome increases. 1•6 Episodes of SA are atypical in the sense that often they are not associated at onset with rise in the SBP and HR, traditionally thought to accompany and, even more important, to mediate myocardial ischemia. 10•15 However, such changes in the determinants of myocardial oxygen consumption come into play
SBP
HR
A
108
63
6,804
8
115
60
6,900
DP
C
4
150
147
22,050
D
34
122
97
11,834
110
69
7,590
E
F
LEAD 2
34 34
CHEST I 82 I 1 I JULY, 1982
35
Table 3--Ensymatie DaiG and ComplieadoM o/ Patienta111itla Spontaneoru ..4qina in lhe Coronary Care Unil* Patient No.
Peak CK, IU/L
MB-CK, %ofCK
Time of Peak CK, days
0
I ,350; 1,145
12;9
2;3
2
1,010
5
2
VF, VT, PVCs, AFb, SB
3
J,a50
24
2
CHF, PVCs, APCs, SVT, VT, LBBB multifocal PCVs, Couplets, 1• AVB
36
(}
6
PACs, multifocal PVCs, LBBB, CHF, VT, 1• AVB, couplets
5
1,000
7
2
Frequent PVCs, pericarditis, Mobitz II AVB, PACs
6 7t
230; 920 4a
\1; 8 0
I; 7
4t
1
Complications VF, VT, SVT, A.Fb, a• AVB, RBBB multifocal PVCs, junctional rhythm
VT, PACs, PVCs, CHF, sinus pauses PVCs, SB PVCs, 1• AVB,
a• AVB, SB
8
550
8
9t
101
(}
3
PVCs, 1o AVB, 2• AVB (Mobitz I and II), a• AVB, CHF, SB
760
8
2
Multifocal PVCs, couplets
4;7
2;5
6.5
a
10 ll
207; 1,550
12
675
Ja
a18
14
1,265
VT, RBBB, LAH, PVCs, CHF CHF, PVCs, hypotension VF, VT, 2• AVB, a• AVB, PACs, SVT, sinus arrest, PVCs, sinus block, SB, hypotension, cardiogenic shock, electromechanical dissociation
12
31.2
2
PVCs, RBBB, SB
15t
69
0
8
PACs
16
480
5
2
CHF, PVCs, 1 o AVB, PACs, hypotension
*Abbreviations: CK=creatine kinase; MB-CK=myocardium specific isoenzyme of CK: VF=ventricular fibrillation; VT-= ventricular tachycardia; A Fb=atrial fibrillation; AVB=AV block, PVC=premature ventricular contraction; PAC=premature atrial contraction; RBBB=right bundle branch block; LBBB=left bundle branch block; LAH=left anterior hemiblock; SVT= supraventricular tachycardia; SB =sinus bradycardia; CHF =congestive heart failure. tPatient did not suffer an acute myocardial infarction.
promptly, and this was well illustrated in our patients whose HR and SBP showed rapid change during chest pain (Fig 1 to 3 and 5). Elaborate techniques are mandatory to dissect the complex temporal interrelations of SA and perturbations of SBP and HR. 1·•·o. 7• 18• 17 However, our study shows that frequent ECG recordings and measurements of blood pressure can offer some insight into the pathogenesis of SA. Episodes of angina in conjunction with ST-segment elevation constitute the prototype of myocardial ischemia resulting from coronary vasospasm. 1 However, some of our patients showed only ST-segment depression during SA. Symptoms in these patients were also attributed to vasospasm, since most of their attacks of SA occurred at DP lower than that noted during asymptomatic periods.18 Recent data indicate that pathogenesis of SA is independent of polarity of ST-segment 38
shifts.t,a,u,te-zt Coronary collaterals, found in patients with SA and ST-segment depression, could have had a preventive effect for development of transmural myocardial ischemia with ST-segment elevation. Propranolol, 22 nitrates, 1•6 calcium blockers,2a. 2• and surgery25 have been proposed for management of SA. Poor response of our patients to therapy may be a feature of patients with recurrent SA. Intravenous nitrates, 7 intracoronary nitroglycerin when feasible, 26 and calcium blockers9•16•23•24 may be indicated in persistent SA. Since anatomic ( atherosclerosis ) and functional (vasospasm ) determinants are operative in the pathogenesis of SA, both surgical and medical therapies have a place in the management of this disease. 9 Functional compromise of coronary How occurs both before1 and after28 establishment of acute MI, so that therapy wi'th IV nitrates 7 and calcium blockers may prevent proSpontaneous Angina In the CCU (John E. Mad/as}
Table ,__Tiaeran and 1'""-p o/ PalienU willa Spontaneoru .4,.Pna in lhe Coronary Care Unil•
Patient No.
Treatment in Hospital
Follow-Up
Treatment After Discharge
1
NTG, ISDN, 240 mg PROP
NTG
Asymptomatic
2
NTG, ISDN, 240 mg PROP
NTG, ISDN, 480 mg PROP, NIFED
Adm (3 wk) for A-R---+ Rare A-R-+Asymptomatic
3
NTG, ISDN, 40 mg PROP
NTG, ISDN
Adm (multiple) for CHF and rare A-R
4t
NTG, ISDN, 40 mg PROP, NIFED
NTG, ISDN, NIFED
Died 7 days after discharge in cardiac arrest
5
NTG, ISDN
NTG, ISDN, 400 mg PROP
Rare A-R (2 mo)---+Asymptomatic-+ Atypical chest pain
6
NTG, ISDN, 1,200 mg PROP
NTG, 40 mg PROP
Asymptomatic
7t
NTG, ISDN, 160 mg PROP
NTG, ISDN, 160 mg PROP, NIFED
Adm (2 mo) forA-Rand A-Ex-+ Asymptomatic-+ Adm (1 yr) for A-R---+Asymptomatic
8
NTG, ISDN, 1,600 mg PROP
NTG, 240 mg PROP
Asymptomatic
9t
NTG, ISDN, NIFED
NTG, ISDN, NIFED
A-R (5 wk)---+Rare A-R-+Asymptomatic
10
NTG, ISDN, 960 mg PROP
NTG, 400 mg PROP
A-R (2 wk)---+Asymptomatic---+ Atypical chest pain
11
NTG, 160 mg PROP
NTG, ISDN
Died on day 31 from extension of myocardial infarction
12
NTG, ISDN
NTG
A-R (2 mo)-+Rare A-R-+Asymptomatic
13
NTG, ISDN
14
NTG, ISDN
NTG
Rare A-R and A-Ex
15t
NTG, ISDN, 320 mg PROP
NTG
A-R (3 wk)-+Asymptomatic---+Rare A-R
16
NTG, ISDN, 320 mg PROP, NIFED
NTG, ISDN, 320 mg PROP, NIFED
Died on day 35 in A-R, ED
Died on day 1 in CS, ED
*Abbreviations: CS ... Cardiogenic shock; ED= electromechanical dissociation; NTG =sublingual nitroglycerin and nitroglycerin ointment; ISDN= isosorbide dinitrate oral, sublingual and chewable forms; PROP= propranolol hydrochloride; Adm = admiEsion to the hospital; NIFED=nifedipine; A-R=angina at rest; CHF=congestive heart failure; and A-Ex=angina on exertion. t=Patient did not suffer an acute myocardial infarction.
gression to myocardial necrosis or may minimize extent of MI, if such a complication is not entirely averted. Interviews of patients with acute MI have disclosed the frequent occurrence of attacks of selflimited angina in the days to weeks before admission. 27 The pathogenesis of such prodromata and their ECG accompaniments are elusive due to the lack of objective information. Attacks of chest pain before admission for acute MI may be similar to the recurrent episodes of SA noted in our patients. SA in the CCU may be a good model for the study of mechanisms of recurrent unprovoked chest pain and the nature of prodromata that precede development of acute MI. Recurrent episodes of SA often lead to MI. These attacks of chest pain are unassociated at their onset with augmentation of determinants of myocardial
oxygen demands. Therapy with propranolol and nitrates does not prevent recurrence of SA. The long-term clinical course is benign, but short-term mortality is high. The routine CCU setting may be adequate to delineate the pathogenesis of episodes of SA. ACKNOWLEDGMENT: I wish to thank Dr. William B. Hood. Jr., Professor of Medicine and Chief of Cardiology at Boston City Hospital, Boston University School of Medicine, for a stimulating and critical review of this manuscript. I am also indebted to Dr. Thomas J. Ryan, Professor of Medicine and Chief of Cardiolog)' at University Hospital, Boston University School of Medicine, for the catheterization and angiographic data of these patients. REFERENCES
1 Maseri A, L•Abbate A, Baroldi G, Chierchia S, Marzilli M, Ballestra AM, et al. Coronary vasospasm as a possible cause of myocardial infarction. A conclusion derived from the study of "preinfarction,. angina. N Engl J Med 1978; 299:1271 CHEST I 82 I 1 I JULY, 1982
37
Table 5--..4rapopaplaie Dala ira Palierab IIIia• Sponaaneou• ..4,.Praa in '"e Coronary Care Unit* Patient No.
Time of Catheterization
Coronary Arteriography
Left Cineventriculography
Ejection Fraction, %
1 2
26 days after MI
20% LAD, OM, LPD, RCA; 30% 1st PLB-LCF
Moderate HYP, septum, apex; AK, part of apex
78
3
95 days after MI
100% LAD, RCA; 45% LCF
Antero-infero-apical HYP; 2-3/4 MR
34
4t
37 days after admission
100% RCA, LCF; 50% LAD, OM;90%0M
Postero-basal-lateral AK; severe HYP, apex, septum, inferolateral
44
6
7 days after MI
100% RCA; 90% LAD; 30% 1st DIAG; 80% 1st OM; 40% 2nd OM
Moderate anterolateral, mild apical HYP
60
7t
245 days after admission
25% DIAG; 70% RCA
Normal
61
8
26 days after MI
50% RCA, 2nd OM; 99% LAD, 1st DIAG; 90% LCF
Moderate anterolateral basal, severe apical, septal HYP
68
236 days prior to MI
20% RCA; 30% LCA; 100% 1st and 2nd DIAG 100% LAD; Bypass to 1st and 2nd DIAG patent
Moderate anterolateral HYP
68
Apical-septal-basal AK; moderate apical, anterolateral HYP
59
Normal; 2/4 MR
90
5
9t 10
43 days after MI 11
12 13 14 15t
11 days after admission
80% RCA; 50% LAD, 2nd Diag: LCF
16 *Abbreviations: MI =myocardial infarction; LAD= left anterior descending; OM= obtuse marginal; LPD =left posterior descending; RCA=right coronary artery; PLB=posterolateral branch; LCF=left circumflex; DIAG=diagonal; HYP=hypokinesis; AK=akinesis; and MR=mitral regurgitation. t ""Patient did not suffer an acute myocardial infarction. 2 Madias JE. The syndrome of variant angina culminating in acute myocardial infarction. Circulation 1979; 59:297306
3 Biagini A, Carpeggioeni C, Mazzei G, Zachelli GC, Buzziogoli G, L'Abbate A, et al. Myocardial cell damage during vasospastic anginal attacks with promptly reversible electrocardiographic changes ( abstr). Am J Cardiol 1980; 45:455 4 Guazzi M, Polese A, Fiorentini C, Magrini F, Bartorelli C. Left ventricular performance and related hemodynamic changes in Prinzmetal's variant angina pectoris. Br Heart J 1971; 33:84-94 5 Maseri A, Mimmo R, Chierchia S, Marchesi C, Pesola A, L'Abbate A. Coronary artery spasm as a cause of acute myocardial ischemia in man. Chest 1975; 58:625-33 6 Maseri A, Severi S, DeNes M, L'Abbate A, Chierchia S, Marzilli M, et al. Variant angina: one aspect of a continuous spectrum of vasospastic myocardial ischemia. Am J Cardiol 1978; 43:1019-35 7 Distante A, Maseri A, Severi S, Biagini A, Chierchia S. Management of vasospastic angina at rest with continuous 38
8 9 10 11 12 13
14
infusion of isosorbide dinitrate: A double crossover study in a coronary care unit. Am J Cardiol1979; 44:533-39 Severi S, Davies G, Maseri A, Aazzulo P, L'Abbate A. Long-term prognosis of "variant" angina with medical treatment. Am J Cardiol1980; 46:226 Conti CR, Curry RC Jr. Coronary artery spasm and myocardial ischemia. Mod Con Cardiovasc Dis 1980; 49:1-6 Roughgarten JW, Newman EV. Circulatory changes during the pain of angina pectoris, 1772-1964: a critical review. Am J Med 1966; 41:935-46 Roughgarten JW. Circulatory changes associated with spontaneous angina pectoris. Am J Med 1966; 41:947-61 Robinson BR. Relation of heart rate and systolic blood pressure to the onset of pain in angina pectoris. Circulation 1967; 35:1073-83 Sarnoff SJ, Braunwald E, Welch GH Jr, Case RB, Stainsbury WN, Marcuz R. Determinants of oxygen consumption of the heart with special reference to the tension time index. Am J Physiol 1958; 192:148-56 Sonnenblick EH, Ross J Jr, Braunwald E. Oxygen consumption of the heart: newer concepts of its multifacSpontaneous Angina In the CCU (John E. Mad/aa)
torial determination. Am J Cardiol 1968; 22:328-36 15 Littler WA, Honour AJ, Sleight P, Slott FD. Direct arterial pressure and electrocardiogram in unrestricted patients with angina pectoris. Circulation 1973; 48: 125-34 16 Parodi 0, Maseri A, Simonetti I. Management of unstable angina at rest by verapamil: a double blind crossover study in a coronary care unit. Br Heart J 1979; 41:164-74 17 Guazzi M, Polese A, Fiorentini C, Magrini F, Olivari MR, Bartorelli C. Left and right heart hemodynamics during spontaneous angina pectoris: comparison between angina with ST-segment depression and angina with ST-segment elevation. Br. Heart J 1975; 37:601-13 18 Berndt TB, Fitzgerald J, Harrison DC, Schroeder JS. Hemodynamic changes at the onset of spontaneous versus pacing-induced angina. Am J Cardiol 1977; 39: 784-88 19 Maseri G, DeNes DM, Parodi 0, Biagini A. Coronary vasospasm in angina pectoris. Lancet 1977; 1:713-17 20 Maseri A, Parodi 0, Severi S, Pesola A. Transient transmural reduction of myocardial blood How, demonstrated by thallium-201 scintigraphy, as a cause of variant angina. Circulation 1976; 54:280-88 21 Parodi 0, Uthurralt N, Severi S, Bencivelli W, Michel-
assi C, L'Abbate A, et al. Transient reduction of regional myocardial perfusion during angina at rest with STsegment depression or normalization of negative Twaves. Circulation 1981; 63: 1238-47 22 Guazzi M, Magrini F, Fiorentini C, Polese A. Clinical electrocardiographic and hemodynamic effects of longterm use of propranolol in Prinzmetal's variant angina pectoris. Br Heart J 1971; 33:889-94 23 Heupler FA, Proudfit WL. Nifedipine therapy for refractory coronary arterial spasm. Am J Cardiol 1979; 44:798-803 24 Goldberg S, Reichek N, Wilson J. Hirshfeld JW Jr, Muller J, Kastor JA. Nifedipine in the treatment of Prinzmetal's (variant) angina. Am J Cardiol 1979; 44: 804-10
25 Shubrooks S, Bete J. Hutter A, Block P, Buckley M, Daggeti W, et al. Variant angina pectoris: clinical and anatomic spectrum and results of coronary bypass surgery. Am J Cardiol 1975; 36:142-47 26 Oliva PB, Breckinridge JC. Arteriographic evidence of coronary arterial spasm in acute myocardial infarction. Circulation 1977; 56:366-74 27 Solomon HA, Edwards AL, Killip T. Prodromata in acute myocardial infarction. Circulation 1969; 40:403-71
Cardiovascular Medicine and Surgery in the 1980s This anniversary symposium of the Texas Heart Institute and the German Heart Center will be held September 20-23 in Athens, Greece. For information, contact the Office of the Medical Director, Texas Heart Institute, PO Box 20269, Houston 77225 (713: 791-2157).
Allergy and Clinical Immunology The Association for the Care of Asthma will sponsor this postgraduate course at Dunfey's Hotel and Conference Center at Hyannis on Cape Cod, Massachusetts, August 6-8. For information, write Mr. Harold IHt, Executive Director, ACA, Box 568, Spring Valley Road, Ossining, New York 10562 (914: 762-1941).
CHEST I 82 I 1 I JULY, 1982
39
We studied 16 patients, 36 to 75 years old, with repetitive episodes of spontaneous angina (SA) associated with transient ST-segment shifts. At onset SA was not IIIISOCiated with changes in systolic blood pressure, heart rate, or double product, but such increases often occurred late. All patients smoked cigarettes; 13 were hypertensive. History of angina at rest or exertion was present in 13 patients, seven of whom had crescendo chest pain before admission. Twelve patients had an acute myocardial infarction (MI). Comp6cations were not uncommon in the setting of MI. Angina persisted in a few patients after MI, and resulted in its extension in three patients. Coronary arteriography performed on eight
of patients who suffered an acute myoS tudies cardial infarction ( MI) after repetitive episodes
of angina at rest have recently been published. 1•2 A previous communication from this Coronary Care Unit ( CCU) constituted a nonconsecutive series of patients2 who had an MI following attacks of spontaneous angina ( SA). We present data on a prospective study of 16 consecutive patients with recurrent attacks of SA, 12 of whom had an MI. MATERIAL AND METHODS
The study population included 16 patients who were admitted to the CCU from January 1978 to April 1979 for evaluation of recurrent attacks of SA, associated with transient ST-segment shifts in the ECG. SA was defined as angina occurring at rest, or chest pain that had awakened the patients from sleep. Ten patients were men and six women. They ranged in age from 36 to 75 years, with a mean age of 53 ± 2.5 ( SEM). Excluded from the study were patients who did not have further episodes of angina following their admission, who were found on entry to the hospital to have suffered an MI, or who had angina without ECG changes. Multiple ECGs and blood pressure recordings were ob0From the Thorndike Memorial Laboratory and the Department of Cardiology, Division of Medicine, Boston City Hospital and Boston University School of Medicine, Boston. Supported in part by the US Public Health Service grant RR-533. Manuscript received September 14; revision accepted November 30. Reprint requests: Dr. Madias, Cardiology, Boston City Hospital, Boston 02118 30
patients revealed significant coronary artery disease in seven. There was a good correlation between the loci of coronary lesions and the transient ECG changes. Nitrates were occasionally ineffective in re6eving symptoms and failed to prevent SA. mgh doses of propranolol were also ineffective. Aortocoronary bypass surgery was performed on three patients. Fifteen patients were discharged asymptomatic. One patient died in the hOBpital. Three additional patients died within the first month after admission. FoUowup in the clinic revealed good response to nitrates in the 12 surviving patients. SA in the CCU may be a good model to study the pathogenesis of myocardial ischemia and acute MI.
tained during and following attacks of chest pain. Systolic blood pressure (SBP), heart rate (HR), and double product ( DP) noted at the onset of chest pain were compared with values of these parameters obtained before the beginning of episodes of SA. DP was defined as the product of SBP and HR and was taken as an estimate of myocardial work. Routine care comprised continuous ECG monitoring, serial recordings of ECG, and blood sampling for cardiac enzymes. Upper normal limits for total creatine kinase ( CK) were 75 IU /L and for myocardial fraction ( MB-CK) less than 4 percent. Drugs were administered as clinically indicated. Nitrates in all avail8'ble forms and propranolol were used to treat anginal episodes. Intravenous ( IV) nitroglycerin and oral nifedipine were used in only two and three patients, respectively. MorPhine was administered as an analgesic if the pain did not respond to nitrates. Eight patients underwent cardiac catheterization and angiography. Surviving patients were followed until July 1981. REsULTS
Details on age, sex, and prevalence of risk factors are shown in Table 1. Three patients were diabetic, eight had elevated levels of lipids, and five had a history of previous MI. Two additional patients had an ECG, but not a history, indicative of an old MI. Family history of MI was present in nine patients. Aortocoronary bypass to the left anterior descending and diagonal vessels had been performed in patient 10 six months before admission. Three patients did not have a history of angina, nine had exertional chest pain, and 13 had angina Spontaneous Angina In the CCU (John E. Iliad/as)
Table 1---Ciinlcel ClaarwcterUdea o/ P......,....,. Spon~aneou Patient No./Age/Sex Hypertension
Smoking
..4,.Pna in alae Coro_..,. Care Uni••
History of Angina
Drugs on Admission
Mode of Presentation
1/49/M
+
2
2/36/M
±
1~
3/59/M
+
2
DIG, NTG, ISDN A-Ex, A-R 4Y IM
4t/62/M
±
2
A-R, A-CR 6M IW A-R in sleep lW
A-R, resting in bed, diaphoresis
5/48/M
+
3
A-R lW
A-R, in sleep, vomitus, diaphoresis
6/55/M
±
A-Ex, A-R 2W lOD A-CR, A-Rin sleep lOD lOD
A-R, resting in bed
PROP,NTG
A-Ex, A-R 3M 2M A-CR 1M
A-R, in sleep, nausea, diaphoresis, fatiguP
A-R, A-CR 8M 7D
A-R, sitting
7t/49/F
I~
A-Ex, A-R 2D 5D
A-R, sitting, vomitus, near syneoJw
HCTZ
8/47/M
+
1/3
PROP, SPIR, NTG, Insulin
Ut/71/F
+
(I
DIG, HCTZ, NTG
10/40/M
+
11/58/M
+
12/46/F
A-R, sitting, diaphoresis
PROP, ISDN, DIP, NTG
A-R, sitting vomitu~.
A-R, watching game on TV, palpitations, nausea, diaphores~ A-Ex, A-R 14M 9M A-CR 5D
A-R, sitting A-R in sleep
131
A-Ex, A-R 4D 4D
A-Ex, walking after breakfast, nausea, diaphoresis
I~
A-Ex 6M
A-Ex, washing floor, diaphoresis, dyspnea
A-Ex 33Y
A-R, sitting, reading, vomitus, diaphoresis, dyspnea
NTG
13/53/M
±
4
14/52/F
±
2
15t/49/F
+
2
PROP,HCTZ
A-R 1Y
A-R, sitting, nausea, dyspnea, lightheadedness
2
DIG, DIP, NTG, Verapamil, Clofibrate
A-Ex, A-R 4Y 4Y A-CR 1W A-R in sleep 1W
A-R, sitting A-R in sleep, nausea
16/75/F
A-Ex, moving boxes, near syncopt>, nausea, dyspnea
*Abbreviations: +-hypertensive with positive history of hypertension; ±-hypertensive and/or left ventricular hypertrophy by ECG with negative history of hyp!'..rtension; Number under smoking indicates packs of cigarettes per day; DIG •digitalis; NTG- nitroglycerin; ISDN - isosorbide dinitrate; HCTZ- hydrochlorothiazide; PROP= propranolol; SPIR -spironolactone; DIP-dipyridamole; A-Ex-angina on exertion; A-R-angina at rest; A-CR-crescendo angina. "History" subscript numbel"'l refer to duration of angina: D•days; W-weeks; M•months; Y-ye&l"'l. t- Patient did not suffer an acute myocardial infarction.
at rest Seven patients had both angina on exertion and at rest, seven had crescendo angina, and three
had chest pain that woke them from sleep. Duration of angina and drug history at the time of admission CHEST I 82 I 1 I JULY, 1882
31
are indicated in Table 1. Patient 16 had discontinued use of all drugs four days before admission. Symptoms that precipitated admission consisted of angina at rest or that woke them from sleep in 13 patients, and angina on exertion in three patients. Details are shown in Table 1. Details on the number of chest pain episodes, their duration, and the time span over which they occurred are presented in Table 2. Duration of episodes of chest pain reported included the residual "aching" that often followed attacks of angina, or express multiple episodes spaced close to each other. While in the hospital four patients ( 3, 6, 8, and 9) awoke from sleep wilth angina. Definite diurnal distribution of chest pain was not noted. Episodes of angina in eight patients occurred both before and after peak rise of CK. Attacks of SA were accompanied primarily by unchanged SBP, HR, and DP values when measured early in the course of chest pain. However, change in these variables was often recorded after the onset of pain (Table 2). Such changes often occurred in the short interval required for the recording of an ECG (Fig 1) or a rhythm strip (Fig
2). Values of SBP and HR were often higher during asymptomatic periods than at the onset of chest pain. Transient ST-segment elevation during chest pain was recorded in 11 of the 16 patients and occurred in anterior leads in five patients (Fig 3), in inferior leads in three patients ( Fig 4), and in both leads in three patients ( Fig 1 ) . Six patients showed both ST-segment elevation and ST-segment depression in the same leads during different attacks of chest pain. Four patients (10, 12, 14, and 16) showed only ST-segment depression, and patient 7 showed only T-wave abnormalities with angina. Transient upright T-waves were recorded in seven patients (Fig 5). Pseudonormalization of inverted T -waves during angina was noted in seven patients. Six patients showed transient inversion of T-waves during chest pain. Peak rise in the CK and its time is indicated in Table 3. Twelve patients had enzymatic alterations c:onsistent with acute MI. Three patients ( 1, 6, and 11) showed two peaks of CK and MB-CK, indicative of exil:ension of MI. Twelve patients suffered an acute MI. Other
Table Z--Frequene:r o/.4ttaelu, and Blood Pre.aure, and Hearl Rare Claan«e• Durin• Sponkrneou .4n«fna in alae Coronary Care Unir* No. of Anginal Episodes
Duration of Anginal Episodes, min
Time Span of Angina Occurrenct>, days
4
15-45
5
2
4
30-40
3
41
3-90
32
4t
35
15-150
30
5
11
15-60
4
-6;+5
X
X
X
6
17
1-60
12
-6; +11
X
X
X
7t
10
1-30
8
26
Yz-40
30
9t
9
20-40
7
10
7
30-90
2
-7;
11
12
5-60
12
4
15-60
13
7
20-90
-3; +4
14
5
20-90
-5;
I5t
7
10-45
9
16
17
15-90
8
Patient No.
No. of Anginal Episodes before(-) and after (+) CK Rise
4SBP
4HR
4DP
-2;+2
X
No4
X
-4;
X
X
X
X
X
X
0
-26; +15
t, No4
1. No4
t, No4
!, No4
t, No4
!, No4
X
X
X
X
X
X
0
X
X
X
fl
-4; +8
X
X
X
2
-4;
-7; +19
0 0
!, No4 X
1, No4 X
-6; +11
X
!. No4 X
1. No4
!. No4 X
!, No4 X
!. No4 X X
*Abbreviations: CK=Creatine kinase; 4=change of parameteJ"K during angina compared with values prior to onset of chest pain; SBP-systolic blood pressure (mm Hg); HR=heart rate (beats/min); DP==double product (mm Hg beats/min); t =increase; ! -decrease; X -increase, decrease, or no change during different chest pain episodes. t- Patient did not. suffer an acute myocardial infarction.
32
Spontaneous Angina In the CCU (John E. Mediae)
2
1 ::: \
.
=n :·
'..
:!: "· ..
A .·' .. jl'
•••
: .: !! : ::
'
::.
3 oVR oVL oVF
RS-2
~
1:
". '':. ' ·: :·
::
:
B
c D FIGURE l. Patient 2. (A), Episode of spontaneous angina associated with transient ST-segment elevation. Blood pressure (BP), heart rate (HR) , and double product (DP) increased greatly between recording of lead 1 and rhythm strip (RS-2) , which were separated by 2'. BP 7' before onset of chest pain was 140/95 mm Hg, and HR was 78 beats/min. (B), Three hours after A, and following recurrent attacks of chest pain and cardiac arrest, precordial ECG leads revealed some persisting ST-segment elevation. (C), ECG at discharge showed T-wave inversion and reduction in R waves in leads previously showing ST-segment elevation. (D), ECG 10 months after A showed regeneration of R waves, notably reduced at discharge. Such increase in amplitude was gradual in serial ECGs.
complications are shown in Table 3. Patient 13 died in cardiogenic shock. Patients 6, 8, and 15 underwent intra-aortic balloon counterpulsation, the latter two suffering angina during the procedure. These three patients were subjected to aortocoronary bypass surgery. Comparison of the patients in whom an MI evolved and those without such outcome did not show any differences. Nitrates were administered, often at the maximal
Time
SBP HR
OP
recommended doses and frequency. Propranolol was used at maximal doses indicated in Table 4. This drug was discontinued in patients 3, 4, and 11, who had congestive heart failure. Although all 15 surviving patients were discharged asymptomatic, angina occurred in the hospital in some of these patients while they received a combination of all of the previously described drugs that had effected a reduction of SBP and HR.
5:12'00"om
5:t3'3o'am
115
140 145
130
95 12,350
20,300 ---; -
Leodt 'l ' rr--
FiGuRE
__] \ Ill
,..,.
A
---,--,--
. -~I _....: ' -:----+.:-t --r.
- ' j_-+ -=FA
'
2. Patient 9. (A, B, C), Rhythm ECG strip recorded continuously in a 3channel ECG recorder 2' after onset of an episode of spontaneous angina. Systolic blood pressure ( SBP) and heart rate ( HR) before onset of chest pain were similar to values of A. Within 24" there was an increase in HR, and 1' later HR and double product ( DP) were greatly increased. Moderate rise in SBP was noted. Nitroglycerin was administered just before C.
5:12'24"om
i
:
'
'
.
-
-
·
,
'
: l•··. T-
~ -- - ----~--~~ ,-
1 -
•
L '
t---
t--
1\
I"
8
"lJ! JU
~
~
J.
-.li
c CHEST I 82 I 1 I JULY. 1982
33
Time
9:37am
SBP
100
HR
74 7,400
DP CP
•
3. Patient 8. Systolic blood pressure (SBP) and heart rate (HR) were lower at the onset of episode of spontaneous angina from values obtained before patient's complaint!. of chest pain. By time of ECG tracing (9:40 AM), there was marked increase in SBP and double product (DP) and mild rise in HR. Subsequently, there was decrease in SBP and increase in HR following administration of nitroglycerin (NTG). ST-segment elevation resolved in 15'. ECG at 9:58AM was similar to tracing recorded before this attack of chest pain. T-wave inversion was seen transiently after this episode, but persisted after sequence of several episodes of spontaneous angina. chest pain. CP FIGURE
176
140
124
78
83
84
13,728
11,620
10,416
+++
+++
9=58am
9:47am
9=40am
++
+ + NTG
NTG
+
Eight patients underwent cardiac catheterization and angiography. Seven ·patients had significant coronary artery disease. Details of catheterization data are shown in Table 5. There was a close correlation of the transient ECG changes during angina and significant lesions at coronary arteriography. Collaterals were identified in patients 3, 4, 6, and 8. The first three of these patients showed ST-segment depression during attacks of angina. Seven patients underwent stress testing. One had an adequate negative, and four had an inadequate negative test. These tests were carried out after discharge. One patient had notably different responses to two stress tests (Fig 6), and patient 10 had a negative test five days prior to his admission with SA. Three of the 15 surviving patients died shortly after discharge (Table 4). Follow-up of the 12 surviving patients ranged from 27 (patient 15) to 42 months (patient 1). None of these patients sufTime
SSP
HR
DP
A
3:30am
140
92
12,880
B
4:15am
140
93
13,020
c
4:20am
140
83 54
11,620 7,560
D
4:54am
120
94
11,280
+
NTG
=
fered a recurrence of MI, and three patients ( 3, 14, and 15) currently have rare episodes of angina, which respond to nitroglycerin therapy. Details of therapy after discharge are shown in Table 4. Drugs and dosages listed represent the therapy administered at different phases of the follow-up. DISCUSSION
Acute MI occurs in 20 to 46 percent of patients with recurrent SA. 1•3 Seventy-five percent of our group suffered an MI. This rate would have been lower and the incidence of SA higher if patients with even one episode of SA were included in our study. Continuous recordings of ECG and hemodynamics4-7 would have identified an even larger group of patients with SA or with episodes of silent myocardial ischemia. 6 Therapy for prevention of further episodes of SA must have decreased the number of patients suitable for our protocol. Progression of SA to acute MI and the reasons for oc-
FIGURE 4. Patient 9. (A), ECG during asymptomatic period. (B), Episode of spontaneous angina associated with ST-segment elevation with disappearance of S waves in inferior leads and reciprocal changes in anterior leads. Systolic blood pressure ( SBP), heart rate ( HR), and double product (DP) values were similar to those obtained before onset of chest pain (C), SBP remained stable, but HR of 43 beats/min developed, followed by HR of 83 beats/min, 1°, 2°, and 3° AV block. (D), Following nitroglycerin, HR returned to baseline, then SHP fell somewhat, and HR rose further. All of these parameters soon returned to baseline. Several nitroglycerin tablets were required for abatement of chest pain.
34
Spontaneous Angina In the CCU (John E. Mad/as}
A-1. Day
HR
BP
8
1
-.:..r&w~~'l.ll ... : :
HR
BP
c 27
. l •. ; 1 · : : : · . . ·.· . . . ~~
105/88
'~ ~1Jf~ T~flf& 68
110/90 ••
~
..
j
I
•• 70 130/98
56
45
.
I
l-.
ffiJ '
I
I '
'I
:~ I
'
'II- I
-
_I
I
68
-L;· * =H=I-
~-
.
.~
.. .
I
-
c
.
"
.
L . . ~-: : 65 128/95
1' 1 +·:· ..
·
.
-++!
~ =t-l· :~
FIGURE 5. Patient 3. (A), Episode of spontaneous angina accompanied by peaking of T-waves and ST-segment depression in anterior ECG leads. Blood pressure ( BP) and heart rate ( HR) rose during short time required for ECG recording. Both BP and HR were higher 2' before onset of chest pain. (B), Another episode of chest pain was associated with transient reduction of R waves in anterior leads. HR did not change during this attack, but BP rose mildly. Episodes of chest pain at A and B were 45' apart, between which nitroglycerin was administered. (C), ECG at discharge. Repolarization alternations and reduction of amplitude of R waves in the precordial leads consistent with myocardial necrosis.
currence of such a complication in a fraction of patients with SA have not been explained as yet. 1· 6 Long-term follow-up of patients with SA surviving the acute phase appears to be benign_:z.s and this was also shown in our study. However, short-term 25-percent mortality in our patients is in agreement with data reported by Conti and Curry. 9 This study did not address the issue of frequency of SA, since our material constituted a subgroup
FiGURE 6. Patient 7. (A), Chest pain was accompanied by deepening of preexisting T -wave inversion in leads V1 to V3 (not shown). Systolic blood pressure ( SBP), heart rate (HR), and double product (DP) were stable compared with values before onset of angina. (B), DP after abatement of angina was unchanged. (C), During negative exercise stress test, the patient reached high levels of SBP, HR, and DP. (D), During 20tTl stress test, patient had chest pain and ST-segment elevation during minor changes in DP. (E), Partial resolution of ECG changes were noted 15" after test ended. (F), ECG returned to normal after the 1' after E; patient became asymptomatic after administration of nitroglycerin. Scintigraphic data were not obtained.
of patients with recurrent attacks of SA. Increasing numbers of patients with SA are detected as the awareness of this syndrome increases. 1•6 Episodes of SA are atypical in the sense that often they are not associated at onset with rise in the SBP and HR, traditionally thought to accompany and, even more important, to mediate myocardial ischemia. 10•15 However, such changes in the determinants of myocardial oxygen consumption come into play
SBP
HR
A
108
63
6,804
8
115
60
6,900
DP
C
4
150
147
22,050
D
34
122
97
11,834
110
69
7,590
E
F
LEAD 2
34 34
CHEST I 82 I 1 I JULY, 1982
35
Table 3--Ensymatie DaiG and ComplieadoM o/ Patienta111itla Spontaneoru ..4qina in lhe Coronary Care Unil* Patient No.
Peak CK, IU/L
MB-CK, %ofCK
Time of Peak CK, days
0
I ,350; 1,145
12;9
2;3
2
1,010
5
2
VF, VT, PVCs, AFb, SB
3
J,a50
24
2
CHF, PVCs, APCs, SVT, VT, LBBB multifocal PCVs, Couplets, 1• AVB
36
(}
6
PACs, multifocal PVCs, LBBB, CHF, VT, 1• AVB, couplets
5
1,000
7
2
Frequent PVCs, pericarditis, Mobitz II AVB, PACs
6 7t
230; 920 4a
\1; 8 0
I; 7
4t
1
Complications VF, VT, SVT, A.Fb, a• AVB, RBBB multifocal PVCs, junctional rhythm
VT, PACs, PVCs, CHF, sinus pauses PVCs, SB PVCs, 1• AVB,
a• AVB, SB
8
550
8
9t
101
(}
3
PVCs, 1o AVB, 2• AVB (Mobitz I and II), a• AVB, CHF, SB
760
8
2
Multifocal PVCs, couplets
4;7
2;5
6.5
a
10 ll
207; 1,550
12
675
Ja
a18
14
1,265
VT, RBBB, LAH, PVCs, CHF CHF, PVCs, hypotension VF, VT, 2• AVB, a• AVB, PACs, SVT, sinus arrest, PVCs, sinus block, SB, hypotension, cardiogenic shock, electromechanical dissociation
12
31.2
2
PVCs, RBBB, SB
15t
69
0
8
PACs
16
480
5
2
CHF, PVCs, 1 o AVB, PACs, hypotension
*Abbreviations: CK=creatine kinase; MB-CK=myocardium specific isoenzyme of CK: VF=ventricular fibrillation; VT-= ventricular tachycardia; A Fb=atrial fibrillation; AVB=AV block, PVC=premature ventricular contraction; PAC=premature atrial contraction; RBBB=right bundle branch block; LBBB=left bundle branch block; LAH=left anterior hemiblock; SVT= supraventricular tachycardia; SB =sinus bradycardia; CHF =congestive heart failure. tPatient did not suffer an acute myocardial infarction.
promptly, and this was well illustrated in our patients whose HR and SBP showed rapid change during chest pain (Fig 1 to 3 and 5). Elaborate techniques are mandatory to dissect the complex temporal interrelations of SA and perturbations of SBP and HR. 1·•·o. 7• 18• 17 However, our study shows that frequent ECG recordings and measurements of blood pressure can offer some insight into the pathogenesis of SA. Episodes of angina in conjunction with ST-segment elevation constitute the prototype of myocardial ischemia resulting from coronary vasospasm. 1 However, some of our patients showed only ST-segment depression during SA. Symptoms in these patients were also attributed to vasospasm, since most of their attacks of SA occurred at DP lower than that noted during asymptomatic periods.18 Recent data indicate that pathogenesis of SA is independent of polarity of ST-segment 38
shifts.t,a,u,te-zt Coronary collaterals, found in patients with SA and ST-segment depression, could have had a preventive effect for development of transmural myocardial ischemia with ST-segment elevation. Propranolol, 22 nitrates, 1•6 calcium blockers,2a. 2• and surgery25 have been proposed for management of SA. Poor response of our patients to therapy may be a feature of patients with recurrent SA. Intravenous nitrates, 7 intracoronary nitroglycerin when feasible, 26 and calcium blockers9•16•23•24 may be indicated in persistent SA. Since anatomic ( atherosclerosis ) and functional (vasospasm ) determinants are operative in the pathogenesis of SA, both surgical and medical therapies have a place in the management of this disease. 9 Functional compromise of coronary How occurs both before1 and after28 establishment of acute MI, so that therapy wi'th IV nitrates 7 and calcium blockers may prevent proSpontaneous Angina In the CCU (John E. Mad/as}
Table ,__Tiaeran and 1'""-p o/ PalienU willa Spontaneoru .4,.Pna in lhe Coronary Care Unil•
Patient No.
Treatment in Hospital
Follow-Up
Treatment After Discharge
1
NTG, ISDN, 240 mg PROP
NTG
Asymptomatic
2
NTG, ISDN, 240 mg PROP
NTG, ISDN, 480 mg PROP, NIFED
Adm (3 wk) for A-R---+ Rare A-R-+Asymptomatic
3
NTG, ISDN, 40 mg PROP
NTG, ISDN
Adm (multiple) for CHF and rare A-R
4t
NTG, ISDN, 40 mg PROP, NIFED
NTG, ISDN, NIFED
Died 7 days after discharge in cardiac arrest
5
NTG, ISDN
NTG, ISDN, 400 mg PROP
Rare A-R (2 mo)---+Asymptomatic-+ Atypical chest pain
6
NTG, ISDN, 1,200 mg PROP
NTG, 40 mg PROP
Asymptomatic
7t
NTG, ISDN, 160 mg PROP
NTG, ISDN, 160 mg PROP, NIFED
Adm (2 mo) forA-Rand A-Ex-+ Asymptomatic-+ Adm (1 yr) for A-R---+Asymptomatic
8
NTG, ISDN, 1,600 mg PROP
NTG, 240 mg PROP
Asymptomatic
9t
NTG, ISDN, NIFED
NTG, ISDN, NIFED
A-R (5 wk)---+Rare A-R-+Asymptomatic
10
NTG, ISDN, 960 mg PROP
NTG, 400 mg PROP
A-R (2 wk)---+Asymptomatic---+ Atypical chest pain
11
NTG, 160 mg PROP
NTG, ISDN
Died on day 31 from extension of myocardial infarction
12
NTG, ISDN
NTG
A-R (2 mo)-+Rare A-R-+Asymptomatic
13
NTG, ISDN
14
NTG, ISDN
NTG
Rare A-R and A-Ex
15t
NTG, ISDN, 320 mg PROP
NTG
A-R (3 wk)-+Asymptomatic---+Rare A-R
16
NTG, ISDN, 320 mg PROP, NIFED
NTG, ISDN, 320 mg PROP, NIFED
Died on day 35 in A-R, ED
Died on day 1 in CS, ED
*Abbreviations: CS ... Cardiogenic shock; ED= electromechanical dissociation; NTG =sublingual nitroglycerin and nitroglycerin ointment; ISDN= isosorbide dinitrate oral, sublingual and chewable forms; PROP= propranolol hydrochloride; Adm = admiEsion to the hospital; NIFED=nifedipine; A-R=angina at rest; CHF=congestive heart failure; and A-Ex=angina on exertion. t=Patient did not suffer an acute myocardial infarction.
gression to myocardial necrosis or may minimize extent of MI, if such a complication is not entirely averted. Interviews of patients with acute MI have disclosed the frequent occurrence of attacks of selflimited angina in the days to weeks before admission. 27 The pathogenesis of such prodromata and their ECG accompaniments are elusive due to the lack of objective information. Attacks of chest pain before admission for acute MI may be similar to the recurrent episodes of SA noted in our patients. SA in the CCU may be a good model for the study of mechanisms of recurrent unprovoked chest pain and the nature of prodromata that precede development of acute MI. Recurrent episodes of SA often lead to MI. These attacks of chest pain are unassociated at their onset with augmentation of determinants of myocardial
oxygen demands. Therapy with propranolol and nitrates does not prevent recurrence of SA. The long-term clinical course is benign, but short-term mortality is high. The routine CCU setting may be adequate to delineate the pathogenesis of episodes of SA. ACKNOWLEDGMENT: I wish to thank Dr. William B. Hood. Jr., Professor of Medicine and Chief of Cardiology at Boston City Hospital, Boston University School of Medicine, for a stimulating and critical review of this manuscript. I am also indebted to Dr. Thomas J. Ryan, Professor of Medicine and Chief of Cardiolog)' at University Hospital, Boston University School of Medicine, for the catheterization and angiographic data of these patients. REFERENCES
1 Maseri A, L•Abbate A, Baroldi G, Chierchia S, Marzilli M, Ballestra AM, et al. Coronary vasospasm as a possible cause of myocardial infarction. A conclusion derived from the study of "preinfarction,. angina. N Engl J Med 1978; 299:1271 CHEST I 82 I 1 I JULY, 1982
37
Table 5--..4rapopaplaie Dala ira Palierab IIIia• Sponaaneou• ..4,.Praa in '"e Coronary Care Unit* Patient No.
Time of Catheterization
Coronary Arteriography
Left Cineventriculography
Ejection Fraction, %
1 2
26 days after MI
20% LAD, OM, LPD, RCA; 30% 1st PLB-LCF
Moderate HYP, septum, apex; AK, part of apex
78
3
95 days after MI
100% LAD, RCA; 45% LCF
Antero-infero-apical HYP; 2-3/4 MR
34
4t
37 days after admission
100% RCA, LCF; 50% LAD, OM;90%0M
Postero-basal-lateral AK; severe HYP, apex, septum, inferolateral
44
6
7 days after MI
100% RCA; 90% LAD; 30% 1st DIAG; 80% 1st OM; 40% 2nd OM
Moderate anterolateral, mild apical HYP
60
7t
245 days after admission
25% DIAG; 70% RCA
Normal
61
8
26 days after MI
50% RCA, 2nd OM; 99% LAD, 1st DIAG; 90% LCF
Moderate anterolateral basal, severe apical, septal HYP
68
236 days prior to MI
20% RCA; 30% LCA; 100% 1st and 2nd DIAG 100% LAD; Bypass to 1st and 2nd DIAG patent
Moderate anterolateral HYP
68
Apical-septal-basal AK; moderate apical, anterolateral HYP
59
Normal; 2/4 MR
90
5
9t 10
43 days after MI 11
12 13 14 15t
11 days after admission
80% RCA; 50% LAD, 2nd Diag: LCF
16 *Abbreviations: MI =myocardial infarction; LAD= left anterior descending; OM= obtuse marginal; LPD =left posterior descending; RCA=right coronary artery; PLB=posterolateral branch; LCF=left circumflex; DIAG=diagonal; HYP=hypokinesis; AK=akinesis; and MR=mitral regurgitation. t ""Patient did not suffer an acute myocardial infarction. 2 Madias JE. The syndrome of variant angina culminating in acute myocardial infarction. Circulation 1979; 59:297306
3 Biagini A, Carpeggioeni C, Mazzei G, Zachelli GC, Buzziogoli G, L'Abbate A, et al. Myocardial cell damage during vasospastic anginal attacks with promptly reversible electrocardiographic changes ( abstr). Am J Cardiol 1980; 45:455 4 Guazzi M, Polese A, Fiorentini C, Magrini F, Bartorelli C. Left ventricular performance and related hemodynamic changes in Prinzmetal's variant angina pectoris. Br Heart J 1971; 33:84-94 5 Maseri A, Mimmo R, Chierchia S, Marchesi C, Pesola A, L'Abbate A. Coronary artery spasm as a cause of acute myocardial ischemia in man. Chest 1975; 58:625-33 6 Maseri A, Severi S, DeNes M, L'Abbate A, Chierchia S, Marzilli M, et al. Variant angina: one aspect of a continuous spectrum of vasospastic myocardial ischemia. Am J Cardiol 1978; 43:1019-35 7 Distante A, Maseri A, Severi S, Biagini A, Chierchia S. Management of vasospastic angina at rest with continuous 38
8 9 10 11 12 13
14
infusion of isosorbide dinitrate: A double crossover study in a coronary care unit. Am J Cardiol1979; 44:533-39 Severi S, Davies G, Maseri A, Aazzulo P, L'Abbate A. Long-term prognosis of "variant" angina with medical treatment. Am J Cardiol1980; 46:226 Conti CR, Curry RC Jr. Coronary artery spasm and myocardial ischemia. Mod Con Cardiovasc Dis 1980; 49:1-6 Roughgarten JW, Newman EV. Circulatory changes during the pain of angina pectoris, 1772-1964: a critical review. Am J Med 1966; 41:935-46 Roughgarten JW. Circulatory changes associated with spontaneous angina pectoris. Am J Med 1966; 41:947-61 Robinson BR. Relation of heart rate and systolic blood pressure to the onset of pain in angina pectoris. Circulation 1967; 35:1073-83 Sarnoff SJ, Braunwald E, Welch GH Jr, Case RB, Stainsbury WN, Marcuz R. Determinants of oxygen consumption of the heart with special reference to the tension time index. Am J Physiol 1958; 192:148-56 Sonnenblick EH, Ross J Jr, Braunwald E. Oxygen consumption of the heart: newer concepts of its multifacSpontaneous Angina In the CCU (John E. Mad/aa)
torial determination. Am J Cardiol 1968; 22:328-36 15 Littler WA, Honour AJ, Sleight P, Slott FD. Direct arterial pressure and electrocardiogram in unrestricted patients with angina pectoris. Circulation 1973; 48: 125-34 16 Parodi 0, Maseri A, Simonetti I. Management of unstable angina at rest by verapamil: a double blind crossover study in a coronary care unit. Br Heart J 1979; 41:164-74 17 Guazzi M, Polese A, Fiorentini C, Magrini F, Olivari MR, Bartorelli C. Left and right heart hemodynamics during spontaneous angina pectoris: comparison between angina with ST-segment depression and angina with ST-segment elevation. Br. Heart J 1975; 37:601-13 18 Berndt TB, Fitzgerald J, Harrison DC, Schroeder JS. Hemodynamic changes at the onset of spontaneous versus pacing-induced angina. Am J Cardiol 1977; 39: 784-88 19 Maseri G, DeNes DM, Parodi 0, Biagini A. Coronary vasospasm in angina pectoris. Lancet 1977; 1:713-17 20 Maseri A, Parodi 0, Severi S, Pesola A. Transient transmural reduction of myocardial blood How, demonstrated by thallium-201 scintigraphy, as a cause of variant angina. Circulation 1976; 54:280-88 21 Parodi 0, Uthurralt N, Severi S, Bencivelli W, Michel-
assi C, L'Abbate A, et al. Transient reduction of regional myocardial perfusion during angina at rest with STsegment depression or normalization of negative Twaves. Circulation 1981; 63: 1238-47 22 Guazzi M, Magrini F, Fiorentini C, Polese A. Clinical electrocardiographic and hemodynamic effects of longterm use of propranolol in Prinzmetal's variant angina pectoris. Br Heart J 1971; 33:889-94 23 Heupler FA, Proudfit WL. Nifedipine therapy for refractory coronary arterial spasm. Am J Cardiol 1979; 44:798-803 24 Goldberg S, Reichek N, Wilson J. Hirshfeld JW Jr, Muller J, Kastor JA. Nifedipine in the treatment of Prinzmetal's (variant) angina. Am J Cardiol 1979; 44: 804-10
25 Shubrooks S, Bete J. Hutter A, Block P, Buckley M, Daggeti W, et al. Variant angina pectoris: clinical and anatomic spectrum and results of coronary bypass surgery. Am J Cardiol 1975; 36:142-47 26 Oliva PB, Breckinridge JC. Arteriographic evidence of coronary arterial spasm in acute myocardial infarction. Circulation 1977; 56:366-74 27 Solomon HA, Edwards AL, Killip T. Prodromata in acute myocardial infarction. Circulation 1969; 40:403-71
Cardiovascular Medicine and Surgery in the 1980s This anniversary symposium of the Texas Heart Institute and the German Heart Center will be held September 20-23 in Athens, Greece. For information, contact the Office of the Medical Director, Texas Heart Institute, PO Box 20269, Houston 77225 (713: 791-2157).
Allergy and Clinical Immunology The Association for the Care of Asthma will sponsor this postgraduate course at Dunfey's Hotel and Conference Center at Hyannis on Cape Cod, Massachusetts, August 6-8. For information, write Mr. Harold IHt, Executive Director, ACA, Box 568, Spring Valley Road, Ossining, New York 10562 (914: 762-1941).
CHEST I 82 I 1 I JULY, 1982
39