J A N U A R Y 1977
The American
Journal
of CARDIOLOGY* VOLUME 39 NUMBER 1
CLINICAL STUDIES
Instantaneous Nonarrhythmic Cardiac Death in Acute Myocardial Infarction
GARY RAIZES, MD GALEN S. WAGNER, MD DONALD B. HACKEL, MD
Durham, North Carolina
From the Departments of Medicine and Pathology, Duke University Medical Center, Durham, N. C. This work was supported in part by Contract PH-43-NHLI-67-1440 from the National Heart, Lung, and Blood Institute, National Institutes of Health, U. S. Public Health Service, Bethesda, Md., and was carried out during the tenure of Research Career Award (K6-HL- 14188) to Dr. Hackel from the National Heart, Lung, and Blood Institute. Manuscript received April 9, 1976; revised manuscript received July 12, 1976, accepted July 14, 1976. Address for reprints: Galen S. Wagner, MD, Box 3327, Duke U.niversity Medical Center, Durham, N.C. 27710.
From a group of 663 patients with acute myocardial infarction, 15 paUents were identified with the syndrome of sudden loss of consciousness not preceded by symptoms of cardiac or respiratory failure or cardiac arrhythmias. The syndrome was accompanied by normal sinus rhythm, as assessed by electrocardiogram, but by neither a palpable pulse nor audible heart sounds. Seven of these patients had postmortem studies, and clinicopathologic correlations are presented. This syndrome has accounted for 68 percent of in-hospital monitored sudden deaths due to myocardial infarction. Four possible mechanisms are reviewed. These patients are presented to Identify the problem of nonarrhythmic cardiac arrest in acute myocardial Infarction and to stimulate new thoughts concerning etiology and management.
Modern methods of coronary care (use of continuous electrocardiographic monitoring, intravenous administration of lidocaine, electrical defibrillation and care by trained nurses) have greatly decreased the incidence of in-hospital sudden death in patients with acute myocardial infarction.l,2 However, use of a computerized data base allows identification and characterization of even the relatively small group of such patients who die in this manner. 3 Sudden death may be due to ventricular fibrillation or asystole, but in a subgroup of patients there is abrupt loss of consciousness without audible heart sounds or palpable pulse, not preceded by evidence of cardiac or respiratory failure and not accompanied by cardiac arrhythmias. This study was performed to document the incidence of this syndrome and to describe both the clinical course and anatomic findings in all patients with this syndrome studied at autopsy. Methods
Clinical data from all patients admitted to the coronary care unit of this institution with symptoms suggesting acute myocardial infarction are entered into a Sigma V computer (Xerox Data Systems). All 1,826 patients admitted during the 5 years from 1970 to 1974 were considered in this evaluation. Acute myocardial infarction was documented in 663 patients by at least three of the four
January 1977 The AmericanJournalof CARDIOLOGY Volume39
1
NONARRHYTHMIC CARDIAC DEATH--RAIZES ET AL.
following criteria: (1) QRS changes in the electrocardiogram, (2) transient elevation of total serum creatine phosphokinase (CPK) levels, (3) greater elevation of lactic dehydrogenase (LDH)I than of LDH2, 4 and (4) presence of hybrid isoenzyme of CPK (MB). 5 The term "posterior" is inclusive of posterior and inferior (diaphragmatic) infarction and "anterior" is inclusive of anteroseptal and anterolateral infarction. The patients are characterized in Table I. In 25 of the 149 patients who died in the hospital (17 percent), death occurred suddenly, as defined: instantaneous death in the absence of symptomatic cardiac (Killip classes III or IV) 1or respiratory failure. Three of these deaths occurred after electrocardiographic monitoring had been discontinued and thus the role of a precipitating arrhythmia cannot be determined. Seven of the remaining 23 instances of sudden death occurred in a setting of serious arrhythmias: ventricular fibrillation in 5 cases, and asystole due to third-degree atrioventricular (A-V) block in 2. Thus, 15 patients had all characteristics of the syndrome described. This subgroup represented 2.3 percent of all patients with documented acute myocardial infarction, 10 percent of those with an in-hospital death and 68 percent of those with an in-hospital monitored sudden death. Of these patients, the severi who underwent autopsy will be described in detail. Twelve-lead electrocardiograms were obtained during the period of attempted resuscitation. Electrocardiographic monitoring with use of a modified V] lead was continuous, but was not used to assess the presence of infarction or ischemia on the basis of QRS or ST-T changes. Postmortem gross and microscopic examination of the heart was carried out. The studies included coronary arteriography using a barium sulfate-gelatin mixture as previously described, s Results
Demographic d a t a and d o c u m e n t a t i o n of prior manifestations of coronary artery disease in the 7 au-
TABLE
I
Patients Admitted to C o r o n a r y Care Unit With Symptoms • o f A c u t e C o r o n a r y Insufficiency Total 1,826
topsy cases are presented in Table H. Data documenting each patient's course in the hospital are p r e s e n t e d in T a b l e III. A brief clinical s u m m a r y for each p a t i e n t follows. C a s e Histories
P a t i e n t l: An 81 year old man entered the emergency room after 1 1/2 hours of severe substernal chest pain. The electrocardiogram revealed nonspecific ST-T wave changes. Pain persisted during several days with neither electrocardiographic nor isoenzyme changes documenting myocardial infarction. However, on the 11th day severe chest pain recurred and the electrocardiogram revealed S-T segment elevation in leads II, III and aVF. QRS changes in these leads evolved and pain decreased but continued. A transient episode of sinus bradycardia (rate 30 to 40/rain) resolved spontaneously. However, the patient subsequently had a cardiorespiratory arrest in the presence of normal sinus rhythm as assessed by electrocardiogram. P a t i e n t 2: A 55 year old man awoke with severe pain in the arms, back and anterior chest. In the emergency room his blood pressure was 160/110 mm Hg and the electrocardiogram revealed marked S-T segment elevation in leads II, III and aV~ Frequent premature ventricular contractions were observed and controlled with intravenously administered lidocajne (2 mg/min). Recurrent intravenous doses of morphine were required for control of pain. The patient remained hypertensive but in otherwise stable condition for 12 hours. Slowing of heart rate to 45 beats/rain was observed on the monitor. No P waves were apparent but QRS configuration and duration were unchanged. Immediate evaluation revealed a state of cardiorespiratory arrest. P a t i e n t 3: A 55 year old man had a 20 month history of angina that had become unstable during the 3 months before admission. Data from a local hospital had documented coronary insufficiency without acute infarction, and transfer was initiated. The electrocardiogram revealed marked S-T segment depression with T wave inversion in the lateral precordial leads. However, on the day of admission the patient had further severe chest pain. A nurse was in attendance when he suddenly experienced cardiopulmonary arrest despite persistence of normal sinus rhythm.
Survived hospital
P a t i e n t 4: This 45 year old man entered his local hospital with severe chest pain. Data suggested coronary insufficiency without infarction but symptoms recurred the night before his scheduled discharge. Acute myocardial infarction was diagnosed and transfer was initiated. Blood pressure on ad-
Death not sudden 124
TABLE
No acute MI " 1,163 Acute M I 663
P 514 Died in hospital 149 Sudden death 25
Clinical History in Seven Autopsy Cases Death not monitored
P3 Death monitored 22
Case Age (yr) no. & Sex 1 2 3 4 5 6 7
Arrhythmia
D7 No arrhythmia 15
No autopsy Autopsy 7 MI = myocardial infarction.
2
January 1977
II
The American Journal of CARDIOLOGY
81M 55M 55M 45M 67F 72M 67M
History
History
Race
of Angina
of MI
Old MI by ECG
CHF
White White White White White Black White
1 wk No 1 2/3 yr Possible No No No
No No Yes No No No No
Yes No Yes No No No No
No No No No No No No
CHF = congestive heart failure; ECG = electrocardiogram; MI = myocardial infarction.
Volume 39
NONARRHYTHMIC CARDIAC DEATH--RAIZES ET AL.
mission was 180/130 mm Hg and returned to normal after diuresis. The patient was in stable condition until day 3 when an episode of ventricular fibrillation occurred that was quickly electrically converted. He returned to a stable state but I hour later suddenly became cyanotic and unresponsive while his wife was in attendance and while normal sinus rhythm was evident on the electrocardiographic monitor. P a t i e n t 5: This 67 year old woman was admitted after several hours of intermittent chest pain to a local hospital where the electrocardiogram revealed acute diaphragmatic myocardial infarction. Dyspnea was noted; treatment with furosemide and digoxin was begun and transfer was initiated. On admission, second-degree type I and third-degree A-V block were noted. Ventricular rate was 45/min and unresponsive to atropine. A transvenous pacing catheter was inserted and heart rate maintained at 70 beats/rain. Twelve hours later the patient suddenly lost consciousness with neither heart sounds nor pulse despite continued pacemaker capture. P a t i e n t 6: This 72 year old man was hospitalized for repair of bilateral inguinal hernias. Postoperatively hypotension, premature ventricular contractions and new Q waves developed in leads II, III and aVF. Isoenzymes confirmed the diagnosis of acute myocardial infarction. However, chest pain persisted and an episode of ventricular tachycardia was noted on day 6. Pain recurred on day 8 and the electrocardiogram revealed third-degree A-V block. Insertion of a temporary transvenous pacing catheter resulted in return to a stable state. However, approximately i hour later, cardiorespiratory arrest was noted despite continued pacemaker capture at 70/rain. Patient 7: This 67 year old man awoke the day of admission with crushing substernal chest pain. An electrocardiogram at his local hospital revealed acute diaphragmatic infarction, and isoenzymes were diagnostic. Second-degree type I and third-degree A-V block were noted on day 3 and he was transferred. A temporary transvenous pacemaker was inserted, and his condition remained stable until day 10 when he had an episode of ventricular fibrillation that was promptly converted electrically. The patient returned to a stable state but 30 minutes later he complained of severe chest pain. While a nurse was in attendance, sudden cardiorespiratory arrest occurred despite maintenance of sinus rhythm at a rate of 110/rain.
Clinical F e a t u r e s
Five of the seven patients had no history of typical angina or historic or electrocardiographic evidence of prior myocardial infarction. T h e two remaining patients had both a history of angina and QRS changes in the electrocardiogram. None of the patients had symptoms suggesting congestive heart failure before admission (Table II).
The patients can be classified into three groups regarding time between onset of infarction and sudden death (Table III). T w o patients died on the day of infarction, two on days 2 or 3 and three others on days 7 t h r o u g h 10. Serial serum C P K determinations docum e n t e d this variation in time after initial infarction. In all of the six with QRS changes, posterior diaphragmatic location was documented. T h e last venous blood sample before d e a t h (obtained within 24 hours of d e a t h in all cases) revealed normal electrolytes in all patients and elevated blood urea nitrogen in only one. T h e final vital sign evaluation before cardiac arrest revealed normal data in all patients with the exception of continued high blood pressure in two. Two patients had a recurrence of precordial pain during the minutes to hours preceding cardiovascular collapse. C o m p u t e r i z e d records of the 514 patients who survived hospitalization with acute infarction were reviewed to determine if there was any instance of survival after n o n a r r h y t h m i c cardiac arrest. T h i r t y - e i g h t of' these patients had a cardiac arrest during continuous electrocardiographic monitoring. In 36 instances this was due to ventricular fibrillation and, in 2 others, to ventricular asystole due to third-degree A-V block. Thus, there were no instances of successful resuscitation after n o n a r r h y t h m i c cardiac arrest. Acute cardiac rupture is one probable cause of the s y n d r o m e described; therefore, p o s t m o r t e m examination of all hearts of patients who died in the coronary care unit during the 10 years from 1965 through 1974 were reviewed for this finding. T h r e e instances of cardiac r u p t u r e were d o c u m e n t e d among 128 cases available, b u t the terminal events in these patients did not m e e t criteria for this syndrome.
TABLE III Clinical Course in Seven Autopsy Cases
Case no.
Infarct Day
CPK
Pain With Terminal Event
1 2 3 4 5 6 7
1 1 2 3 7 8 10
N ? N N i" t t
Hours None Minutes None None None None
Killip Class
Last BP (mm Hg)
Last Pulse Rate (per min)
Last Urinary Output (cc/hr)
Last BUN (mg/ 100 m l ) *
Last Serum K+ (mEq/ liter)
200/110 150/110 120/80 105/70 145/80 110/60 110/80
72 88 78 96 70 70 108
55 ? ? 30 55 1 05 95
20 8 12 23 19 16 55
4.8 3.5 3.9 4.7 5.4 4.8 4.0
ECG Location of Acute MI (QRS) PMI PMI None PM I PMI PMI PMI
* Upper limit o f normal: 20 mg/100 ml. t = increasing; 8P = blood pressure; BUN = blood urea nitrogen; CPK = creatine phosphokinase; MI = myocardial infarction; N = w i t h i n normal limits; PMI = posterior-inferior (diaphragmatic) myocardial infarction.
January 1977
The American Journal of CARDIOLOGY
Volume 39
3
NONARRHYTHMIC CARDIAC DEATH--RAIZES ET AL.
TABLE IV Pathologic Data in Seven Cases Acute I n f a r c t i o n A t h e r o s c l e r o t i c O c c l u s i o n (%) Case no.
LCA
LAD
LCx
RCA
1 2 3 4 5 6 7
0 0 100 50 0 75 10
80 0 100 50 60 90 75
0 0 100 90 0 100 80
100 75 75 95 100 95 100
Thrombotic Occlusion None RCA RCA RCA RCA None RCA
Fibrotic Infarct
Ant
Post
Right Ventricle Involved
None None A n t - p o s t SE I A n t - p o s t SE I None Post t r a n s m u r a l A n t SEI
--+ -----
+ + + + + + +
-+ + + + + +
Transmural + + -+ + -+
+ , - - = a n a t o m i c i n f a r c t i o n d o c u m e n t e d or n o t d o c u m e n t e d , respectively. A n t = a n t e r i o r ; L A D = l e f t a n t e r i o r d e s c e n d i n g c o r o n a r y a r t e r y ; L C A = l e f t m a i n c o r o n a r y a r t e r y ; L C x = l e f t c i r c u m f l e x c o r o n a r y a r t e r y ; Post = p o s t e r i o r ; R C A = r i g h t c o r o n a r y a r t e r y ; SEI = s u b e n d o c a r d i a l i n f a r c t i o n .
Pathologic Findings (Table IV) Among the seven patients there were no instances of cerebral or pulmonary findings that would suggest a noncardiac cause of death. There were no instances of pericardial tamponade or of rupture of any cardiovascular structure. There was no significant pulmonary edema and no evidence of pulmonary embolism. I n s t a n c e s of one, two a n d three vessel coronary artery occlusive disease were noted. Two of the seven patients had only one coronary vessel with subtotal (75 percent or greater) or total occlusion. In all five patients with acute thrombotic occlusion the occlusion was in the right coronary artery; these five and the two additional patients had acute posterior myocardial infarction documented anatomically. In six of the seven cases, the posterior right ventricular free wall was involved, and in five the posterior left ventricular infarction extended transmurally. Discussion
This study documents the presence of a syndrome in a small (2.3 percent) subgroup of hospitalized patients with acute myocardial infarction that accounts for a majority (68 percent) of all those who die suddenly. This sequence of events may conceivably be produced by at least four different mechanisms: (1) cardiac or aortic rupture, (2) extension of myocardial infarction, (3) reflex sympathetic inhibition, or (4) idiopathic electricomechanical dissociation. Postmortem examinations eliminated the possibility of cardiac or aortic rupture within this subgroup of patients. However, although nonarrhythmic cardiac arrest did not occur in three instances of cardiac rupture in this institution, it is likely that this clinical sequence would occur in some instances of such a catastrophic event. Neither 12 lead electrocardiograms nor serum isoenzyme determinations are available to confirm or deny the role of extension of myocardial infarction in the etiology of this syndrome. However, recurrent precordial pain was evident in two patients, and in both the nurse was preparing to administer medication for relief
4
January 1977
The American Journal of CARDIOLOGY
of pain at the time of cardiovascular collapse. The absence of pain is not sufficient to eliminate consideration of recurrent infarction in the remaining patients. Electromechanical Dissociation
Jennings et al. 7 have documented the disappearance of myocardial contractions distal to an area of coronary occlusion after a period of 15 seconds. This change occurred despite the persistence of a regular sinus rhythm. Thus, if a large enough area were rendered ischemic, electricomechanical dissociation might be appareht and the syndrome observed here could result. During the brief interval between coronary occlusion and loss of contractility, no sensation of pain might be appreciated. A latency period of 7 to 50 seconds after excitation of the nerve fibers responsible for transmission of sensation from the myocardium has been documented, s The time from the onset of the terminal event until death is so brief that the absence of hyperacute pathologic evidence of infarction does not serve to eliminate electromechanical dissociation as a possible cause of death. Indeed, Jennings and Sommers et al. 9,1° documented that at least 20 minutes of coronary occlusion is required to produce any demonstrable cell death in the dog. The only thrombotic occlusions demonstrated at autopsy occurred in vessels supplying areas where the electrocardiogram had indicated the presence of the initial infarction and where the presence was documented by organizing necrosis. One might expect that a region with electricomechanical dissociation of size sufficient to produce this syndrome would occur only with occlusion Df a second coronary artery. However, the absence of any such occlusion persisting at postmortem examination does not serve to eliminate this etiologic possibility. Walston et al. 11 failed to identify acute coronary occlusion in one third (12 of 37) of patients dying of acute myocardial infarction. R e f l e x sympathetic inhibition: Acute increase in parasympathetic or withdrawal of sympathetic activity must be considered a possible trigger mechanism for this syndromeJ 2-14 The greater incidence of infarction
Volume 39
NONARRHYTHMIC CARDIAC DEATH--RAIZES ET AL.
limited to the posterior myocardium (6 of 7 patients) was in marked contrast to the incidence in the remaining autopsy coronary care unit patients (22 of 72) (P
The American
Journal
of CARDIOLOGY* VOLUME 39 NUMBER 1
CLINICAL STUDIES
Instantaneous Nonarrhythmic Cardiac Death in Acute Myocardial Infarction
GARY RAIZES, MD GALEN S. WAGNER, MD DONALD B. HACKEL, MD
Durham, North Carolina
From the Departments of Medicine and Pathology, Duke University Medical Center, Durham, N. C. This work was supported in part by Contract PH-43-NHLI-67-1440 from the National Heart, Lung, and Blood Institute, National Institutes of Health, U. S. Public Health Service, Bethesda, Md., and was carried out during the tenure of Research Career Award (K6-HL- 14188) to Dr. Hackel from the National Heart, Lung, and Blood Institute. Manuscript received April 9, 1976; revised manuscript received July 12, 1976, accepted July 14, 1976. Address for reprints: Galen S. Wagner, MD, Box 3327, Duke U.niversity Medical Center, Durham, N.C. 27710.
From a group of 663 patients with acute myocardial infarction, 15 paUents were identified with the syndrome of sudden loss of consciousness not preceded by symptoms of cardiac or respiratory failure or cardiac arrhythmias. The syndrome was accompanied by normal sinus rhythm, as assessed by electrocardiogram, but by neither a palpable pulse nor audible heart sounds. Seven of these patients had postmortem studies, and clinicopathologic correlations are presented. This syndrome has accounted for 68 percent of in-hospital monitored sudden deaths due to myocardial infarction. Four possible mechanisms are reviewed. These patients are presented to Identify the problem of nonarrhythmic cardiac arrest in acute myocardial Infarction and to stimulate new thoughts concerning etiology and management.
Modern methods of coronary care (use of continuous electrocardiographic monitoring, intravenous administration of lidocaine, electrical defibrillation and care by trained nurses) have greatly decreased the incidence of in-hospital sudden death in patients with acute myocardial infarction.l,2 However, use of a computerized data base allows identification and characterization of even the relatively small group of such patients who die in this manner. 3 Sudden death may be due to ventricular fibrillation or asystole, but in a subgroup of patients there is abrupt loss of consciousness without audible heart sounds or palpable pulse, not preceded by evidence of cardiac or respiratory failure and not accompanied by cardiac arrhythmias. This study was performed to document the incidence of this syndrome and to describe both the clinical course and anatomic findings in all patients with this syndrome studied at autopsy. Methods
Clinical data from all patients admitted to the coronary care unit of this institution with symptoms suggesting acute myocardial infarction are entered into a Sigma V computer (Xerox Data Systems). All 1,826 patients admitted during the 5 years from 1970 to 1974 were considered in this evaluation. Acute myocardial infarction was documented in 663 patients by at least three of the four
January 1977 The AmericanJournalof CARDIOLOGY Volume39
1
NONARRHYTHMIC CARDIAC DEATH--RAIZES ET AL.
following criteria: (1) QRS changes in the electrocardiogram, (2) transient elevation of total serum creatine phosphokinase (CPK) levels, (3) greater elevation of lactic dehydrogenase (LDH)I than of LDH2, 4 and (4) presence of hybrid isoenzyme of CPK (MB). 5 The term "posterior" is inclusive of posterior and inferior (diaphragmatic) infarction and "anterior" is inclusive of anteroseptal and anterolateral infarction. The patients are characterized in Table I. In 25 of the 149 patients who died in the hospital (17 percent), death occurred suddenly, as defined: instantaneous death in the absence of symptomatic cardiac (Killip classes III or IV) 1or respiratory failure. Three of these deaths occurred after electrocardiographic monitoring had been discontinued and thus the role of a precipitating arrhythmia cannot be determined. Seven of the remaining 23 instances of sudden death occurred in a setting of serious arrhythmias: ventricular fibrillation in 5 cases, and asystole due to third-degree atrioventricular (A-V) block in 2. Thus, 15 patients had all characteristics of the syndrome described. This subgroup represented 2.3 percent of all patients with documented acute myocardial infarction, 10 percent of those with an in-hospital death and 68 percent of those with an in-hospital monitored sudden death. Of these patients, the severi who underwent autopsy will be described in detail. Twelve-lead electrocardiograms were obtained during the period of attempted resuscitation. Electrocardiographic monitoring with use of a modified V] lead was continuous, but was not used to assess the presence of infarction or ischemia on the basis of QRS or ST-T changes. Postmortem gross and microscopic examination of the heart was carried out. The studies included coronary arteriography using a barium sulfate-gelatin mixture as previously described, s Results
Demographic d a t a and d o c u m e n t a t i o n of prior manifestations of coronary artery disease in the 7 au-
TABLE
I
Patients Admitted to C o r o n a r y Care Unit With Symptoms • o f A c u t e C o r o n a r y Insufficiency Total 1,826
topsy cases are presented in Table H. Data documenting each patient's course in the hospital are p r e s e n t e d in T a b l e III. A brief clinical s u m m a r y for each p a t i e n t follows. C a s e Histories
P a t i e n t l: An 81 year old man entered the emergency room after 1 1/2 hours of severe substernal chest pain. The electrocardiogram revealed nonspecific ST-T wave changes. Pain persisted during several days with neither electrocardiographic nor isoenzyme changes documenting myocardial infarction. However, on the 11th day severe chest pain recurred and the electrocardiogram revealed S-T segment elevation in leads II, III and aVF. QRS changes in these leads evolved and pain decreased but continued. A transient episode of sinus bradycardia (rate 30 to 40/rain) resolved spontaneously. However, the patient subsequently had a cardiorespiratory arrest in the presence of normal sinus rhythm as assessed by electrocardiogram. P a t i e n t 2: A 55 year old man awoke with severe pain in the arms, back and anterior chest. In the emergency room his blood pressure was 160/110 mm Hg and the electrocardiogram revealed marked S-T segment elevation in leads II, III and aV~ Frequent premature ventricular contractions were observed and controlled with intravenously administered lidocajne (2 mg/min). Recurrent intravenous doses of morphine were required for control of pain. The patient remained hypertensive but in otherwise stable condition for 12 hours. Slowing of heart rate to 45 beats/rain was observed on the monitor. No P waves were apparent but QRS configuration and duration were unchanged. Immediate evaluation revealed a state of cardiorespiratory arrest. P a t i e n t 3: A 55 year old man had a 20 month history of angina that had become unstable during the 3 months before admission. Data from a local hospital had documented coronary insufficiency without acute infarction, and transfer was initiated. The electrocardiogram revealed marked S-T segment depression with T wave inversion in the lateral precordial leads. However, on the day of admission the patient had further severe chest pain. A nurse was in attendance when he suddenly experienced cardiopulmonary arrest despite persistence of normal sinus rhythm.
Survived hospital
P a t i e n t 4: This 45 year old man entered his local hospital with severe chest pain. Data suggested coronary insufficiency without infarction but symptoms recurred the night before his scheduled discharge. Acute myocardial infarction was diagnosed and transfer was initiated. Blood pressure on ad-
Death not sudden 124
TABLE
No acute MI " 1,163 Acute M I 663
P 514 Died in hospital 149 Sudden death 25
Clinical History in Seven Autopsy Cases Death not monitored
P3 Death monitored 22
Case Age (yr) no. & Sex 1 2 3 4 5 6 7
Arrhythmia
D7 No arrhythmia 15
No autopsy Autopsy 7 MI = myocardial infarction.
2
January 1977
II
The American Journal of CARDIOLOGY
81M 55M 55M 45M 67F 72M 67M
History
History
Race
of Angina
of MI
Old MI by ECG
CHF
White White White White White Black White
1 wk No 1 2/3 yr Possible No No No
No No Yes No No No No
Yes No Yes No No No No
No No No No No No No
CHF = congestive heart failure; ECG = electrocardiogram; MI = myocardial infarction.
Volume 39
NONARRHYTHMIC CARDIAC DEATH--RAIZES ET AL.
mission was 180/130 mm Hg and returned to normal after diuresis. The patient was in stable condition until day 3 when an episode of ventricular fibrillation occurred that was quickly electrically converted. He returned to a stable state but I hour later suddenly became cyanotic and unresponsive while his wife was in attendance and while normal sinus rhythm was evident on the electrocardiographic monitor. P a t i e n t 5: This 67 year old woman was admitted after several hours of intermittent chest pain to a local hospital where the electrocardiogram revealed acute diaphragmatic myocardial infarction. Dyspnea was noted; treatment with furosemide and digoxin was begun and transfer was initiated. On admission, second-degree type I and third-degree A-V block were noted. Ventricular rate was 45/min and unresponsive to atropine. A transvenous pacing catheter was inserted and heart rate maintained at 70 beats/rain. Twelve hours later the patient suddenly lost consciousness with neither heart sounds nor pulse despite continued pacemaker capture. P a t i e n t 6: This 72 year old man was hospitalized for repair of bilateral inguinal hernias. Postoperatively hypotension, premature ventricular contractions and new Q waves developed in leads II, III and aVF. Isoenzymes confirmed the diagnosis of acute myocardial infarction. However, chest pain persisted and an episode of ventricular tachycardia was noted on day 6. Pain recurred on day 8 and the electrocardiogram revealed third-degree A-V block. Insertion of a temporary transvenous pacing catheter resulted in return to a stable state. However, approximately i hour later, cardiorespiratory arrest was noted despite continued pacemaker capture at 70/rain. Patient 7: This 67 year old man awoke the day of admission with crushing substernal chest pain. An electrocardiogram at his local hospital revealed acute diaphragmatic infarction, and isoenzymes were diagnostic. Second-degree type I and third-degree A-V block were noted on day 3 and he was transferred. A temporary transvenous pacemaker was inserted, and his condition remained stable until day 10 when he had an episode of ventricular fibrillation that was promptly converted electrically. The patient returned to a stable state but 30 minutes later he complained of severe chest pain. While a nurse was in attendance, sudden cardiorespiratory arrest occurred despite maintenance of sinus rhythm at a rate of 110/rain.
Clinical F e a t u r e s
Five of the seven patients had no history of typical angina or historic or electrocardiographic evidence of prior myocardial infarction. T h e two remaining patients had both a history of angina and QRS changes in the electrocardiogram. None of the patients had symptoms suggesting congestive heart failure before admission (Table II).
The patients can be classified into three groups regarding time between onset of infarction and sudden death (Table III). T w o patients died on the day of infarction, two on days 2 or 3 and three others on days 7 t h r o u g h 10. Serial serum C P K determinations docum e n t e d this variation in time after initial infarction. In all of the six with QRS changes, posterior diaphragmatic location was documented. T h e last venous blood sample before d e a t h (obtained within 24 hours of d e a t h in all cases) revealed normal electrolytes in all patients and elevated blood urea nitrogen in only one. T h e final vital sign evaluation before cardiac arrest revealed normal data in all patients with the exception of continued high blood pressure in two. Two patients had a recurrence of precordial pain during the minutes to hours preceding cardiovascular collapse. C o m p u t e r i z e d records of the 514 patients who survived hospitalization with acute infarction were reviewed to determine if there was any instance of survival after n o n a r r h y t h m i c cardiac arrest. T h i r t y - e i g h t of' these patients had a cardiac arrest during continuous electrocardiographic monitoring. In 36 instances this was due to ventricular fibrillation and, in 2 others, to ventricular asystole due to third-degree A-V block. Thus, there were no instances of successful resuscitation after n o n a r r h y t h m i c cardiac arrest. Acute cardiac rupture is one probable cause of the s y n d r o m e described; therefore, p o s t m o r t e m examination of all hearts of patients who died in the coronary care unit during the 10 years from 1965 through 1974 were reviewed for this finding. T h r e e instances of cardiac r u p t u r e were d o c u m e n t e d among 128 cases available, b u t the terminal events in these patients did not m e e t criteria for this syndrome.
TABLE III Clinical Course in Seven Autopsy Cases
Case no.
Infarct Day
CPK
Pain With Terminal Event
1 2 3 4 5 6 7
1 1 2 3 7 8 10
N ? N N i" t t
Hours None Minutes None None None None
Killip Class
Last BP (mm Hg)
Last Pulse Rate (per min)
Last Urinary Output (cc/hr)
Last BUN (mg/ 100 m l ) *
Last Serum K+ (mEq/ liter)
200/110 150/110 120/80 105/70 145/80 110/60 110/80
72 88 78 96 70 70 108
55 ? ? 30 55 1 05 95
20 8 12 23 19 16 55
4.8 3.5 3.9 4.7 5.4 4.8 4.0
ECG Location of Acute MI (QRS) PMI PMI None PM I PMI PMI PMI
* Upper limit o f normal: 20 mg/100 ml. t = increasing; 8P = blood pressure; BUN = blood urea nitrogen; CPK = creatine phosphokinase; MI = myocardial infarction; N = w i t h i n normal limits; PMI = posterior-inferior (diaphragmatic) myocardial infarction.
January 1977
The American Journal of CARDIOLOGY
Volume 39
3
NONARRHYTHMIC CARDIAC DEATH--RAIZES ET AL.
TABLE IV Pathologic Data in Seven Cases Acute I n f a r c t i o n A t h e r o s c l e r o t i c O c c l u s i o n (%) Case no.
LCA
LAD
LCx
RCA
1 2 3 4 5 6 7
0 0 100 50 0 75 10
80 0 100 50 60 90 75
0 0 100 90 0 100 80
100 75 75 95 100 95 100
Thrombotic Occlusion None RCA RCA RCA RCA None RCA
Fibrotic Infarct
Ant
Post
Right Ventricle Involved
None None A n t - p o s t SE I A n t - p o s t SE I None Post t r a n s m u r a l A n t SEI
--+ -----
+ + + + + + +
-+ + + + + +
Transmural + + -+ + -+
+ , - - = a n a t o m i c i n f a r c t i o n d o c u m e n t e d or n o t d o c u m e n t e d , respectively. A n t = a n t e r i o r ; L A D = l e f t a n t e r i o r d e s c e n d i n g c o r o n a r y a r t e r y ; L C A = l e f t m a i n c o r o n a r y a r t e r y ; L C x = l e f t c i r c u m f l e x c o r o n a r y a r t e r y ; Post = p o s t e r i o r ; R C A = r i g h t c o r o n a r y a r t e r y ; SEI = s u b e n d o c a r d i a l i n f a r c t i o n .
Pathologic Findings (Table IV) Among the seven patients there were no instances of cerebral or pulmonary findings that would suggest a noncardiac cause of death. There were no instances of pericardial tamponade or of rupture of any cardiovascular structure. There was no significant pulmonary edema and no evidence of pulmonary embolism. I n s t a n c e s of one, two a n d three vessel coronary artery occlusive disease were noted. Two of the seven patients had only one coronary vessel with subtotal (75 percent or greater) or total occlusion. In all five patients with acute thrombotic occlusion the occlusion was in the right coronary artery; these five and the two additional patients had acute posterior myocardial infarction documented anatomically. In six of the seven cases, the posterior right ventricular free wall was involved, and in five the posterior left ventricular infarction extended transmurally. Discussion
This study documents the presence of a syndrome in a small (2.3 percent) subgroup of hospitalized patients with acute myocardial infarction that accounts for a majority (68 percent) of all those who die suddenly. This sequence of events may conceivably be produced by at least four different mechanisms: (1) cardiac or aortic rupture, (2) extension of myocardial infarction, (3) reflex sympathetic inhibition, or (4) idiopathic electricomechanical dissociation. Postmortem examinations eliminated the possibility of cardiac or aortic rupture within this subgroup of patients. However, although nonarrhythmic cardiac arrest did not occur in three instances of cardiac rupture in this institution, it is likely that this clinical sequence would occur in some instances of such a catastrophic event. Neither 12 lead electrocardiograms nor serum isoenzyme determinations are available to confirm or deny the role of extension of myocardial infarction in the etiology of this syndrome. However, recurrent precordial pain was evident in two patients, and in both the nurse was preparing to administer medication for relief
4
January 1977
The American Journal of CARDIOLOGY
of pain at the time of cardiovascular collapse. The absence of pain is not sufficient to eliminate consideration of recurrent infarction in the remaining patients. Electromechanical Dissociation
Jennings et al. 7 have documented the disappearance of myocardial contractions distal to an area of coronary occlusion after a period of 15 seconds. This change occurred despite the persistence of a regular sinus rhythm. Thus, if a large enough area were rendered ischemic, electricomechanical dissociation might be appareht and the syndrome observed here could result. During the brief interval between coronary occlusion and loss of contractility, no sensation of pain might be appreciated. A latency period of 7 to 50 seconds after excitation of the nerve fibers responsible for transmission of sensation from the myocardium has been documented, s The time from the onset of the terminal event until death is so brief that the absence of hyperacute pathologic evidence of infarction does not serve to eliminate electromechanical dissociation as a possible cause of death. Indeed, Jennings and Sommers et al. 9,1° documented that at least 20 minutes of coronary occlusion is required to produce any demonstrable cell death in the dog. The only thrombotic occlusions demonstrated at autopsy occurred in vessels supplying areas where the electrocardiogram had indicated the presence of the initial infarction and where the presence was documented by organizing necrosis. One might expect that a region with electricomechanical dissociation of size sufficient to produce this syndrome would occur only with occlusion Df a second coronary artery. However, the absence of any such occlusion persisting at postmortem examination does not serve to eliminate this etiologic possibility. Walston et al. 11 failed to identify acute coronary occlusion in one third (12 of 37) of patients dying of acute myocardial infarction. R e f l e x sympathetic inhibition: Acute increase in parasympathetic or withdrawal of sympathetic activity must be considered a possible trigger mechanism for this syndromeJ 2-14 The greater incidence of infarction
Volume 39
NONARRHYTHMIC CARDIAC DEATH--RAIZES ET AL.
limited to the posterior myocardium (6 of 7 patients) was in marked contrast to the incidence in the remaining autopsy coronary care unit patients (22 of 72) (P
