Pathogenesis of sudden unexpected death in a clinical trial of patients with myocardial infarction and left ventricular dysfunction, heart failure, or both

Anne-Catherine Pouleur; Ebrahim Barkoudah; Hajime Uno; Hicham Skali; Peter V Finn; Steven L Zelenkofske; Yuri N Belenkov; Viacheslav Mareev; Eric J Velazquez; Jean L Rouleau; Aldo P Maggioni; Lars Køber; Robert M Califf; John J V McMurray; Marc A Pfeffer; Scott D Solomon; VALIANT Investigators

doi:http://dx.doi.org/10.1161/CIRCULATIONAHA.110.940619

Pathogenesis of sudden unexpected death in a clinical trial of patients with myocardial infarction and left ventricular dysfunction, heart failure, or both

Anne-Catherine Pouleur, Ebrahim Barkoudah, Hajime Uno, Hicham Skali, Peter V Finn, Steven L Zelenkofske, Yuri N Belenkov, Viacheslav Mareev, Eric J Velazquez, Jean L Rouleau, Aldo P Maggioni, Lars Køber, Robert M Califf, John J V McMurray, Marc A Pfeffer, Scott D Solomon, VALIANT Investigators

160 Citations (Scopus)

Abstract

Background: The frequency of sudden unexpected death is highest in the early post-myocardial infarction (MI) period; nevertheless, 2 recent trials showed no improvement in mortality with early placement of an implantable cardioverter-defibrillator after MI. Methods and Results: To better understand the pathophysiological events that lead to sudden death after MI, we assessed autopsy records in a series of cases classified as sudden death events in patients from the VALsartan In Acute myocardial infarctioN Trial (VALIANT). Autopsy records were available in 398 cases (14% of deaths). We determined that 105 patients had clinical circumstances consistent with sudden death. On the basis of the autopsy findings, we assessed the probable cause of sudden death and evaluated how these causes varied with time after MI. Of 105 deaths considered sudden on clinical grounds, autopsy suggested the following causes: 3 index MIs in the first 7 days (2.9%); 28 recurrent MIs (26.6%); 13 cardiac ruptures (12.4%); 4 pump failures (3.8%); 2 other cardiovascular causes (stroke or pulmonary embolism; 1.9%); and 1 noncardiovascular cause (1%). Fifty-four cases (51.4%) had no acute specific autopsy evidence other than the index MI and were thus presumed arrhythmic. The percentage of sudden death due to recurrent MI or rupture was highest in the first month after the index MI. By contrast, after 3 months, the percentage of presumed arrhythmic death was higher than recurrent MI or rupture (x²=23.3, P<0.0001). Conclusions: Recurrent MI or cardiac rupture accounts for a high proportion of sudden death in the early period after acute MI, whereas arrhythmic death may be more likely subsequently. These findings may help explain the lack of benefit of early implantable cardioverter-defibrillator therapy.

Original language	English
Journal	Circulation
Volume	122
Issue number	6
Pages (from-to)	597-602
Number of pages	6
ISSN	0009-7322
DOIs	https://doi.org/10.1161/CIRCULATIONAHA.110.940619
Publication status	Published - 10 Aug 2010

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Pouleur, A-C., Barkoudah, E., Uno, H., Skali, H., Finn, P. V., Zelenkofske, S. L., Belenkov, Y. N., Mareev, V., Velazquez, E. J., Rouleau, J. L., Maggioni, A. P., Køber, L., Califf, R. M., McMurray, J. J. V., Pfeffer, M. A., Solomon, S. D., & VALIANT Investigators (2010). Pathogenesis of sudden unexpected death in a clinical trial of patients with myocardial infarction and left ventricular dysfunction, heart failure, or both. Circulation, 122(6), 597-602. https://doi.org/10.1161/CIRCULATIONAHA.110.940619

Pouleur, A-C, Barkoudah, E, Uno, H, Skali, H, Finn, PV, Zelenkofske, SL, Belenkov, YN, Mareev, V, Velazquez, EJ, Rouleau, JL, Maggioni, AP, Køber, L, Califf, RM, McMurray, JJV, Pfeffer, MA, Solomon, SD & VALIANT Investigators 2010, 'Pathogenesis of sudden unexpected death in a clinical trial of patients with myocardial infarction and left ventricular dysfunction, heart failure, or both', Circulation, vol. 122, no. 6, pp. 597-602. https://doi.org/10.1161/CIRCULATIONAHA.110.940619

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title = "Pathogenesis of sudden unexpected death in a clinical trial of patients with myocardial infarction and left ventricular dysfunction, heart failure, or both",

abstract = "Background: The frequency of sudden unexpected death is highest in the early post-myocardial infarction (MI) period; nevertheless, 2 recent trials showed no improvement in mortality with early placement of an implantable cardioverter-defibrillator after MI. Methods and Results: To better understand the pathophysiological events that lead to sudden death after MI, we assessed autopsy records in a series of cases classified as sudden death events in patients from the VALsartan In Acute myocardial infarctioN Trial (VALIANT). Autopsy records were available in 398 cases (14% of deaths). We determined that 105 patients had clinical circumstances consistent with sudden death. On the basis of the autopsy findings, we assessed the probable cause of sudden death and evaluated how these causes varied with time after MI. Of 105 deaths considered sudden on clinical grounds, autopsy suggested the following causes: 3 index MIs in the first 7 days (2.9%); 28 recurrent MIs (26.6%); 13 cardiac ruptures (12.4%); 4 pump failures (3.8%); 2 other cardiovascular causes (stroke or pulmonary embolism; 1.9%); and 1 noncardiovascular cause (1%). Fifty-four cases (51.4%) had no acute specific autopsy evidence other than the index MI and were thus presumed arrhythmic. The percentage of sudden death due to recurrent MI or rupture was highest in the first month after the index MI. By contrast, after 3 months, the percentage of presumed arrhythmic death was higher than recurrent MI or rupture (x2=23.3, P<0.0001). Conclusions: Recurrent MI or cardiac rupture accounts for a high proportion of sudden death in the early period after acute MI, whereas arrhythmic death may be more likely subsequently. These findings may help explain the lack of benefit of early implantable cardioverter-defibrillator therapy.",

author = "Anne-Catherine Pouleur and Ebrahim Barkoudah and Hajime Uno and Hicham Skali and Finn, {Peter V} and Zelenkofske, {Steven L} and Belenkov, {Yuri N} and Viacheslav Mareev and Velazquez, {Eric J} and Rouleau, {Jean L} and Maggioni, {Aldo P} and Lars K{\o}ber and Califf, {Robert M} and McMurray, {John J V} and Pfeffer, {Marc A} and Solomon, {Scott D} and K{\o}ber, {Lars Valeur}",

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TY - JOUR

T1 - Pathogenesis of sudden unexpected death in a clinical trial of patients with myocardial infarction and left ventricular dysfunction, heart failure, or both

AU - Pouleur, Anne-Catherine

AU - Barkoudah, Ebrahim

AU - Uno, Hajime

AU - Skali, Hicham

AU - Finn, Peter V

AU - Zelenkofske, Steven L

AU - Belenkov, Yuri N

AU - Mareev, Viacheslav

AU - Velazquez, Eric J

AU - Rouleau, Jean L

AU - Maggioni, Aldo P

AU - Køber, Lars

AU - Califf, Robert M

AU - McMurray, John J V

AU - Pfeffer, Marc A

AU - Solomon, Scott D

AU - VALIANT Investigators

PY - 2010/8/10

Y1 - 2010/8/10

N2 - Background: The frequency of sudden unexpected death is highest in the early post-myocardial infarction (MI) period; nevertheless, 2 recent trials showed no improvement in mortality with early placement of an implantable cardioverter-defibrillator after MI. Methods and Results: To better understand the pathophysiological events that lead to sudden death after MI, we assessed autopsy records in a series of cases classified as sudden death events in patients from the VALsartan In Acute myocardial infarctioN Trial (VALIANT). Autopsy records were available in 398 cases (14% of deaths). We determined that 105 patients had clinical circumstances consistent with sudden death. On the basis of the autopsy findings, we assessed the probable cause of sudden death and evaluated how these causes varied with time after MI. Of 105 deaths considered sudden on clinical grounds, autopsy suggested the following causes: 3 index MIs in the first 7 days (2.9%); 28 recurrent MIs (26.6%); 13 cardiac ruptures (12.4%); 4 pump failures (3.8%); 2 other cardiovascular causes (stroke or pulmonary embolism; 1.9%); and 1 noncardiovascular cause (1%). Fifty-four cases (51.4%) had no acute specific autopsy evidence other than the index MI and were thus presumed arrhythmic. The percentage of sudden death due to recurrent MI or rupture was highest in the first month after the index MI. By contrast, after 3 months, the percentage of presumed arrhythmic death was higher than recurrent MI or rupture (x2=23.3, P<0.0001). Conclusions: Recurrent MI or cardiac rupture accounts for a high proportion of sudden death in the early period after acute MI, whereas arrhythmic death may be more likely subsequently. These findings may help explain the lack of benefit of early implantable cardioverter-defibrillator therapy.

AB - Background: The frequency of sudden unexpected death is highest in the early post-myocardial infarction (MI) period; nevertheless, 2 recent trials showed no improvement in mortality with early placement of an implantable cardioverter-defibrillator after MI. Methods and Results: To better understand the pathophysiological events that lead to sudden death after MI, we assessed autopsy records in a series of cases classified as sudden death events in patients from the VALsartan In Acute myocardial infarctioN Trial (VALIANT). Autopsy records were available in 398 cases (14% of deaths). We determined that 105 patients had clinical circumstances consistent with sudden death. On the basis of the autopsy findings, we assessed the probable cause of sudden death and evaluated how these causes varied with time after MI. Of 105 deaths considered sudden on clinical grounds, autopsy suggested the following causes: 3 index MIs in the first 7 days (2.9%); 28 recurrent MIs (26.6%); 13 cardiac ruptures (12.4%); 4 pump failures (3.8%); 2 other cardiovascular causes (stroke or pulmonary embolism; 1.9%); and 1 noncardiovascular cause (1%). Fifty-four cases (51.4%) had no acute specific autopsy evidence other than the index MI and were thus presumed arrhythmic. The percentage of sudden death due to recurrent MI or rupture was highest in the first month after the index MI. By contrast, after 3 months, the percentage of presumed arrhythmic death was higher than recurrent MI or rupture (x2=23.3, P<0.0001). Conclusions: Recurrent MI or cardiac rupture accounts for a high proportion of sudden death in the early period after acute MI, whereas arrhythmic death may be more likely subsequently. These findings may help explain the lack of benefit of early implantable cardioverter-defibrillator therapy.

U2 - http://dx.doi.org/10.1161/CIRCULATIONAHA.110.940619

DO - http://dx.doi.org/10.1161/CIRCULATIONAHA.110.940619

M3 - Journal article

SN - 0009-7322

VL - 122

SP - 597

EP - 602

JO - Circulation

JF - Circulation

IS - 6

ER -

Pathogenesis of sudden unexpected death in a clinical trial of patients with myocardial infarction and left ventricular dysfunction, heart failure, or both

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