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Trends in Incidence and Mortality Rates of Ventricular Septal Rupture During Acute Myocardial Infarction
Trends in Incidence and Mortality Rates of Ventricular Septal Rupture During Acute Myocardial Infarction Abel E. Moreyra, MD*, Michael S. Huang, DO, Alan C. Wilson, PhD, Yingzi Deng, MD, Nora M. Cosgrove, RN, and John B. Kostis, MD, for the MIDAS Study Group (MIDAS 13) Since the introduction of reperfusion in the treatment of acute myocardial infarction (AMI), rates of ventricular septal rupture (VSR) and associated mortality have decreased, but it is not known if incidence and mortality have continued to decrease. We describe trends in incidence and mortality rates of patients with postinfarction VSR during the previous 2 decades and identify risk factors that predict the development and mortality of this rare but catastrophic complication. We analyzed occurrence and mortality rates in patients with first AMI with (n ⴝ 408) and without VSR (n ⴝ 148,473) who were hospitalized from 1990 to 2007 using the New Jersey Myocardial Infarction Data Acquisition System (MIDAS) database. The annual rate of VSR in AMI was 0.25% to 0.31%. Compared to patients with AMI without VSR, patients with VSR were older, more likely to be women, had increased rate of chronic renal disease, congestive heart failure, and cardiogenic shock, and were less likely to be hypertensive or diabetic (all p values <0.0001). During the 18-year study period, we found no change in hospital and 1-year mortalities, which were 41% and 60% in 1990 to 1992 and 44% and 56% in 2005 to 2007, respectively. The survival benefit associated with VSR surgical repair was seen only in hospital (hazard ratio 0.66, 95% confidence interval 0.45 to 0.95) but not at 30 days or 1 year. In conclusion, despite improvement in medical treatment and revascularization techniques, the rate of VSR complicating AMI has not changed during the previous 2 decades, and the mortality associated with VSR has remained high and relatively constant. © 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 2010;106:1095–1100) Before reperfusion therapy was introduced, the incidence of ventricular septal rupture (VSR) complicating acute myocardial infarction (AMI) was 1% to 3%1,2 and was associated with extremely poor outcome, with in-hospital mortality rates of about 45% for surgically treated patients and 90% for those treated medically.3,4 With the advent of thrombolytic therapy there was a significant decrease in incidence of VSR to approximately 0.2% to 0.4%.5,6 Similarly, when using primary percutaneous coronary intervention as the reperfusion technique, the reported incidence of VSR was 0.2%7 to 0.5%.8 Although this decrease is encouraging, the mortality rate of this complication compared to AMI without VSR has remained high. Several studies1–5 have attempted to identify predictors of survival to optimize treatment decisions for VSR; however, their conclusions were limited by small numbers of patients. This report describes trends in incidence rates and mortality of patients with VSR complicating AMI from 1990 to 2007 and identifies risk factors that predict development and mortality of this rare but catastrophic complication.
UMDNJ–Robert Wood Johnson Medical School, New Brunswick, New Jersey. Manuscript received March 31, 2010; revised manuscript received and accepted June 2, 2010. This work was supported in part by grants from the Robert Wood Johnson Foundation, Princeton, New Jersey, and from the Schering-Plough Foundation, Princeton. *Corresponding author: Tel: 732-235-7855; fax: 732-235-8722. E-mail address: [email protected] (A.E. Moreyra). 0002-9149/10/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2010.06.013
Methods Data for this study were obtained from the Myocardial Infarction Data Acquisition System (MIDAS) database.9,10 This administrative database contains discharge records of all patients admitted to nonfederal acute care hospitals in New Jersey with a cardiovascular disease diagnosis. This database was previously audited using a random sample of charts to verify the accuracy of the information.10 The study was approved by the State of New Jersey Department of Health and Senior Services and Robert Wood Johnson Medical School institutional review boards. The study cohort consists of 148,881 adult patients (ⱖ35 years of age) admitted for the first time to all nonfederal New Jersey hospitals with a diagnosis of acute ST-segment elevation myocardial infarction (excluding non ST-segment elevation infarctions; International Classification of Diseases [ICD] code 410.7) from 1990 to 2007. Four hundred eight patients with VSR complicating AMI were identified by the diagnosis code for acquired VSR (ICD code 429.71, n ⫽ 338) or a procedure code indicating VSR surgical repair (ICD codes 35.53, 35.62, or 35.72, n ⫽ 70) within 28 days after index AMI hospitalization. Primary end points were mortality in hospital, at 30 days, and at 1 year. Covariates included patient demographics and co-morbidities; ST-segment elevation infarction site; anterior, inferior/lateral/posterior, other or unspecified; length of hospital stay; development of cardiogenic shock; and procedures. Risk adjustment included the following factors: presence or absence of diabetes, hypertension, chronic renal www.ajconline.org
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Table 1 Clinical characteristics, complications, location of infarction, and cardiac procedures in study patients compared to other patients with acute myocardial infarction Variable
Age (years) Women White Hypertension Diabetes mellitus Chronic kidney disease Heart failure Atrial fibrillation Cardiogenic shock Cardiac arrest Length of stay (days) Location of infarction Anterior wall Inferior/lateral wall Other/unspecified Cardiac procedures Diagnostic catheterization Percutaneous intervention Coronary artery bypass
VSR
p Value
Yes (n ⫽ 408)
No (n ⫽ 148,473)
71 ⫾ 10 210 (52%) 315 (77%) 116 (28%) 73 (18%) 110 (27%) 185 (45%) 80 (20%) 160 (39%) 25 (6.1%) 12 ⫾ 18
67 ⫾ 14 57,125 (39%) 116,199 (78%) 67,698 (46%) 35,563 (24%) 8,759 (5.9%) 39,632 (27%) 19,059 (13%) 8,771 (5.9%) 6,124 (4.1%) 7⫾9
⬍0.0001 ⬍0.0001 0.26 ⬍0.0001 0.004 ⬍0.0001 ⬍0.0001 ⬍0.0001 ⬍0.0001 0.04 ⬍0.0001
175 (43%) 198 (49%) 35 (8.6%)
54,464 (37%) 73,002 (49%) 21,007 (14%)
0.009 0.80 0.001
241 (59%) 50 (12%) 133 (33%)
53,531 (36%) 27,445 (19%) 7,793 (5.3%)
⬍0.0001 0.001 ⬍0.0001
Values are means ⫾ SDs or numbers of patients (percentages).
disease, congestive heart failure, cardiogenic shock, and length of hospital stay. Procedures included cardiac catheterization (ICD codes 37.21 to 37.23), angioplasty (ICD codes 36.01, 36.02, 36.05, and 00.66), percutaneous coronary intervention (ICD codes 36.00 to 36.09), VSR surgical repair (ICD codes 35.53, 35.62, and 35.72), and coronary artery bypass graft surgery (ICD codes 36.10 to 36.19, 36.2). We compared demographic, clinical, and cardiac procedures, length of stay, and mortality data for patients with AMI complicated by VSR to those without VSR. Incidence and mortality rates were plotted in 3-year periods. We used Pearson chi-square test for categorical variables and Student’s t test for continuous variables to compare clinical and demographic characteristics. We used the Cochran-Armitage trend test to examine time trends for VSR rates and procedural rates. Kaplan-Meier survival curves (product– limit method) were constructed for patients with VSR with and without surgical repair. We used multivariate logistic regression to analyze potential risk factors and Cox proportional hazards method for survival analyses. All statistical analyses were performed using SAS 9.1 (SAS Institute, Cary, North Carolina). Results From 1990 to 2007, 148,881 patients were hospitalized in New Jersey with ST-segment elevation AMI for the first time, and 408 of these developed VSR. Compared to patients without VSR (Table 1), these patients were older, more likely to be women, and to have higher rate of chronic kidney disease, heart failure, cardiogenic shock, and cardiac arrest. Diagnoses of hypertension and diabetes mellitus
Figure 1. Incidence of VSR complicating AMI from 1990 to 2007 grouped by 3-year periods. Table 2 Risk factors for ventricular septal rupture complicating acute myocardial infarction by multivariate logistic regression analysis Risk Factors in Logistic Model Age (per year) Female vs male gender Admission year (per year) Race White Black Other Infarction sites Anterior wall Inferior/lateral wall Other/unspecified Hypertension(yes vs no) Diabetes mellitus(yes vs no) Chronic kidney disease (yes vs no)
OR (95% CI)* 1.01 (1.01–1.02) 1.59 (1.30–1.95) 1.00 (0.98–1.02) reference 0.91 (0.58–1.43) 1.28 (0.99–1.65) reference 0.93 (0.76–1.14) 0.43 (0.30–0.62) 0.49 (0.39–0.61) 0.67 (0.52–0.87) 5.51 (4.37–6.95)
* Adjusted for all factors in table.
were less common in patients with AMI and VSR. Anterior wall MI was more frequently observed in patients with VSR than in patients without, but that was not true for patients with inferior/lateral wall AMI. Of patients with VSR, anterior wall AMI was seen in 43% of patients, whereas inferior/ lateral location was seen in 49% and other/unspecified in 8.6%. The probability of having VSR in patients with anterior AMI was not different (0.32%) from those with inferior/lateral AMI (0.21%, p ⫽ 0.10). VSR was found to prolong length of hospital stay significantly. For patients with AMI and VSR mean length of stay was 4.7 days longer (65%) than in those without VSR (p ⬍0.0001). Death terminated hospital stay of 50% of patients with VSR compared to 18% of those without VSR. In patients with AMI not complicated by VSR, length of stay steadily decreased in each of the 3-year periods, from 10.1 days in 1990 to 1992 to 5.2 days in 2005 to 2007. In contrast, mean length of stay for patients with AMI complicated by VSR remained unchanged, from 12.8 to 13.5 days. Cardiac catheterization was performed significantly more often, but revascularization by percutaneous coronary intervention was performed less frequently in patients with AMI and VSR.
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Table 3 Trends in unadjusted in-hospital, 30-day, and one-year mortality by three-year periods in patients with acute myocardial infarction with and without ventricular septal rupture 3-Year Period
VSR In-Hospital Death
1990–1992 1993–1995 1996–1998 1999–2001 2002–2004 2005–2007
30-Day Mortality
1-Year Mortality
Yes
No
Yes
No
Yes
No
33 (41%) 42 (49%) 54 (61%) 35 (57%) 23 (42%) 16 (44%)
4,827 (15%) 4,114 (14%) 3,539 (13%) 3,018 (13%) 2,088 (11%) 1,451 (10%)
39 (49%) 45 (52%) 60 (67%) 35 (57%) 27 (49%) 16 (44%)
5,289 (17%) 4,623 (15%) 4,214 (15%) 3,606 (15%) 2,507 (13%) 1,657 (11%)
48 (60%) 57 (66%) 65 (73%) 41 (66%) 34 (62%) 20 (56%)
7,530 (24%) 6,693 (22%) 6,038 (21%) 5,328 (22%) 3,825 (19%) 2,172 (15%)
Values are numbers of patients (percentages).
Figure 2. Patients with AMI complicated (coml.) by VSR (purple bars) or without (w/o) VSR complication (green bars). Trend significance from Cochran-Armitage trend test.
Rate of VSR complicating AMI remained relatively constant, with an overall rate of 0.27% from 1990 to 2007, despite the increasing number of percutaneous coronary intervention procedures (Figure 1). In multivariate analysis, risk factors independently associated with developing VSR after first AMI were increasing age, female gender, and chronic kidney disease (Table 2). In contrast, hypertension and diabetes mellitus were found to be statistically less frequent in patients with VSR. In multivariate analysis, location of infarction and year of admission showed no significant relation to likelihood of developing VSR. Of 408 patients with VSR, 236 patients were treated surgically, the rest were treated medically. In addition to VSR repair, 133 patients received combined coronary artery bypass graft surgery. Of patients who received VSR repair surgery, 147 (62.3%) were operated on within 2 days of admission, and 75 (31.8%) at 3 to 14 days. Fourteen patients (4.2%) underwent surgery later than 14 days and all except 1 were admitted before 1999. Rates of surgical VSR repair throughout the 18-year study period showed no significant changes (p ⫽ 0.24, Cochran-Armitage trend test). Patients treated surgically within 48 hours of admission showed in-hospital mortality from 50% to 77% (average 60%). No trend in death rate decrease was noted during the 18-year
study period. Patients whose surgical repair was delayed ⬎48 hours had a lower in-hospital death rate (38%), probably reflecting selection bias. Table 3 lists unadjusted rates for in-hospital, 30-day, and 1-year deaths in patients with AMI with or without VSR from 1990 to 2007. Although steady decreases in mortality were observed in AMI cases without VSR, this was not seen in cases complicated by VSR, which fluctuated without significant trend. This is further illustrated in Figure 2, which displays in-hospital mortality in different years. Patients with AMI complicated by VSR were nearly 7 times more likely to die in hospital compared to those without (unadjusted odds ratio [OR] 6.83, 95% confidence interval [CI] 5.62 to 8.31). This increased risk persisted after adjustment for baseline co-morbidities and reperfusion by percutaneous coronary intervention or coronary artery bypass graft (adjusted OR 3.76, 95% CI 2.94 to 4.81). After multivariate adjustment, increasing age and shock were the only independent predictors of mortality in patients with AMI complicated by VSR (Table 4). A survival benefit associated with VSR surgical repair was observed only in hospital, but not at 30 days or 1 year (Figure 3). Patients with VSR repair combined with revascularization by coronary artery bypass grafting did not show any survival benefit (for surgical repair alone, OR 0.69, 95% CI 0.44 to 1.08; for surgical repair plus coronary artery bypass graft, OR 0.81, 95% CI 0.56 to 1.17). Discussion We identified 408 cases of postinfarction VSR that occurred in New Jersey between 1990 and 2007. From this large observational study we were able make several observations: (1) VSR incidence rate fluctuated but did not decrease, (2) despite significant increases in revascularization procedures and improvement in medical therapies, mortality associated with this complication did not change, (3) surgical repair was significantly associated with lower mortality in hospital but not at 30 days or 1 year compared to medical treatment, and (4) rate of VSR complicating AMI appears to be significantly higher in patients with chronic renal disease but, in contrast to other reports, lower in patients with diabetes and hypertension. VSR was first described by Latham11 in 1847 at autopsy. In a trial comparing 4 thrombolytic strategies for AMI, the
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Table 4 Risk factors for mortality in patients with acute myocardial infarction complicated by ventricular septal rupture Factor in Cox Model* Age Female vs male gender Admission year (per year) Race White Black Other Infarction site Anterior wall Inferior/lateral wall Other/unspecified Coexisting conditions Renal failure Shock Hypertension Diabetes mellitus Atrial fibrillation Cardiac procedures Percutaneous intervention Surgical repair of septum
In-Hospital Mortality (95% CI)
30-Day Mortality (95% CI)
1-Year Mortality (95% CI)
1.02 (1.01–1.04) 1.16 (0.84–1.60) 1.00 (0.96–1.03)
1.03 (1.02–1.05) 1.31 (0.98–1.76) 0.99 (0.96–1.02)
1.04 (1.02–1.05) 1.15 (0.89–1.50) 0.99 (0.96–1.01)
reference 0.99 (0.45–2.18) 1.07 (0.71–1.61)
reference 0.90 (0.48–1.71) 1.20 (0.85–1.69)
reference 0.96 (0.54–1.70) 1.06 (0.76–1.47)
reference 1.31 (0.93–1.83) 1.72 (0.98–3.05)
reference 1.21 (0.90–1.61) 1.23 (0.72–2.10)
reference 1.14 (0.87–1.48) 0.97 (0.59–1.60)
1.04 (0.74–1.46) 2.55 (1.84–3.54) 1.15 (0.81–1.64) 0.82 (0.51–1.30) 0.80 (0.54–1.18)
1.08 (0.79–1.46) 2.48 (1.84–3.33) 1.02 (0.74–1.40) 0.91 (0.61–1.35) 0.91 (0.61–1.35)
1.05 (0.79–1.40) 2.18 (1.66–2.86) 0.91 (0.68–1.23) 0.87 (0.60–1.25) 0.87 (0.60–1.25)
1.07 (0.66–1.71) 0.66 (0.45–0.95)
1.11 (0.73–1.67) 0.86 (0.63–1.18)
1.12 (0.76–1.65) 0.90 (0.68–1.20)
* Hazard ratios adjusted for all factors in table.
Figure 3. Kaplan-Meier survival plots for patients with AMI complicated by VSR that is surgically treated (blue lines) or medically treated (red lines) (A) in hospital and (B) 1-year follow-up.
incidence of VSR was 0.4% to 0.6%.12 The introduction of primary angioplasty had similar benefit; reports of the impact of primary percutaneous coronary intervention cited an incidence of VSR from 0.2% to 0.5%.7,8 Because VSR is dependent on complete transmural septal infarction,2 de-
creasing ischemic injury and infarct size with prompt reperfusion preserves overall left ventricular integrity. Our study covers a period in which reperfusion therapies were well established, and the incidence of VSR (0.2%) is consistent with studies from the reperfusion era. Figueras et al13 reported a progressive decrease in the incidence of cardiac rupture (including VSR) after AMI from 1977 to 2006 and attributed it to the increasing rate of reperfusion therapy and increased use of  blockers, angiotensin-converting enzyme inhibitors, and aspirin. Our study does not confirm such a progressive decrease. Risk factors associated with developing VSR have been evaluated in multiple studies.5,6 Factors include hypertension, advanced age, female gender, absence of angina or history of MI, anterior location of infarction, and high Killip class. In this study, we confirmed that advanced age, female gender, and congestive heart failure are associated with an increased risk of VSR. We did not find any difference in the development of VSR between anterior and inferior/lateral infarction. Contrary to other studies,5,6 we found a lower incidence of hypertension and diabetes in patients with VSR. Concentric myocardial hypertrophy in patients with hypertension may possibly confer some protection against septal rupture. Previous studies have reported a wide range (11% to 39%) in prevalence of diabetes in VSR populations.4,6,7,13,14 VSR has been reported to occur more frequently in single-vessel disease and absent collateral circulation.14 –16 The apparently protective effect of diabetes against the development of VSR may possibly arise from multivessel disease with collateral circulation providing blood supply to the ischemic septum and preventing its rupture. We found that a history of chronic kidney disease increased the risk of VSR nearly fivefold. A possible explanation for this association is that patients with chronic renal disease frequently do not present with typical symptoms for
Coronary Artery Disease/Postinfarction Ventricular Septal Rupture
AMI.17 This may delay diagnosis and treatment, resulting in an increased VSR incidence rate. Another possible factor contributing to increased risk for VSR development in patients with AMI and chronic renal disease is that they receive adjunctive and reperfusion therapies for AMI less frequently than those with normal renal function.18 Despite advances in pharmacologic and percutaneous reperfusion procedures for AMI and better surgical techniques for VSR repair, we found that mortality rate for AMI complicated by VSR remained high and unchanged from 1990 to 2007. The explanation for the lack of decrease in mortality is unclear. The sudden and severe hemodynamic deterioration imposed by this complication may overwhelm any available medical and surgical resources. It remains to be seen whether wider use of left ventricular assist devices to bridge patients to surgery or heart transplantation will decrease mortality. Overall in-hospital, 30-day, and 1-year mortality rates in our study were 50%, 54%, and 65%, respectively. These mortality rates are similar to those reported by others,7,19,20 from 23% to as high as 87% in the Should We Emergently Revascularize Occluded Coronaries in Cardiogenic Shock? (SHOCK) registry.14 We found no significant difference in adjusted mortality rates at 30 days or 1 year for patients with VSR who underwent surgical repair compared to those who were treated medically. One study reported improved outcomes in patients treated surgically in recent years compared to early surgical results and to medical treatment.4 We did not find any improving trends in mortality of surgically treated patients during this 18-year span. However, it should be emphasized that records from an administrative database lack many variables that are needed to accurately assess patients’ clinical status and to draw conclusions from factors determining short- and long-term outcomes of patients treated medically and surgically. Risk factors associated with increased mortality have been extensively studied and include advanced age,21 total occlusion of infarct-related artery22 and inotrope requirements,23 early repair of VSR,20,23 preoperative shock,14 and impaired right ventricular function.24 The 2 risk factors that have been most consistently reported to have the strongest association with mortality are early surgical treatment and shock. In agreement with other studies,14,25 shock was associated with the highest risk of mortality. A major concern in early VSR repair is that necrotic myocardium is too fragile for repair of septal rupture. In our study we found a high mortality in patients operated within 48 hours of admission. However, this does not mean that early surgery was inappropriate. It is not possible to know from this administrative database if the lower mortality rates in patients operated later were because of selection bias (patients being less “sick”) or whether connective tissue developed at margins of the infarcted muscle facilitating the surgical repair. Conflicting results on the survival benefit of concomitant revascularization by coronary artery bypass graft during VSR repair have been reported in the literature.15,19,22,23 In our study patients with VSR repair combined with revascularization by coronary artery bypass grafting did not show any survival benefit. Our results concur with several reports24 –28 in showing that inferior wall AMI with VSR is
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associated with increased mortality compared to anterior wall AMI but the association is not significant. Administrative databases such as MIDAS lack specific details of anatomic findings, pharmacologic treatments, and procedures as noted previously, but they are widely inclusive in time span and population representation and do not have the limitations of selected populations of clinical trials and prospective, detailed registries. With rates similar to those in other reports, there are several strengths to this study including having the largest number of reported VSR cases, up to an 18-year follow-up, and being based on a statewide population encompassing all hospitalized AMIs. This is the largest reported series of patients with VSR complicating AMI. Our study shows that the rate of occurrence has remained constant since reperfusion was introduced for treatment of AMI. We report for the first time that chronic renal disease is an additional independent risk factor for development of VSR. Despite improvements in medical treatment and revascularization techniques during the previous 2 decades, the mortality rate of this lethal AMI complication has not changed and remains a formidable challenge. 1. Pohjola-Sintonen S, Muller JE, Stone PH, Willich SN, Antman EM, Davis VG, Parker CB, Braunwald E. Ventricular septal and free wall rupture complicating acute myocardial infarction: experience in the Multicenter Investigation of Limitation of Infarct Size. Am Heart J 1989;117:809 – 818. 2. Topaz O, Taylor AL. Interventricular septal rupture complicating acute myocardial infarction: from pathophysiologic features to the role of invasive and noninvasive diagnostic modalities in current management. Am J Med 1992;93:683– 688. 3. Davies RH, Dawkins KD, Skillington PD, Lewington V, Monro JL, Lamb RK, Gray HH, Conway N, Ross JK, Whitaker L. Late functional results after surgical closure of acquired ventricular septal defect. J Thorac Cardiovasc Surg 1993;106:592–598. 4. Poulsen SH, Praestholm M, Munk K, Wierup P, Egeblad H, NielsenKudsk JE. Ventricular septal rupture complicating acute myocardial infarction: clinical characteristics and contemporary outcome. Ann Thorac Surg 2008;85:1591–1596. 5. Birnbaum Y, Fishbein MC, Blanche C, Siegel RJ. Ventricular septal rupture after acute myocardial infarction. N Engl J Med 2002;347:1426 – 1432. 6. Crenshaw BS, Granger CB, Birnbaum Y, Pieper KS, Morris DC, Kleiman NS, Vahanian A, Califf RM, Topol EJ. Risk factors, angiographic patterns, and outcomes in patients with ventricular septal defect complicating acute myocardial infarction. GUSTO-I (Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries) Trial Investigators. Circulation 2000;101:27–32. 7. Yip HK, Fang CY, Tsai KT, Chang HW, Yeh KH, Fu M, Wu CJ. The potential impact of primary percutaneous coronary intervention on ventricular septal rupture complicating acute myocardial infarction. Chest 2004;125:1622–1628. 8. Katayama T, Nakashima H, Takagi C, Honda Y, Suzuki S, Iwasaki Y, Yamamoto T, Yoshioka M, Yano K. Serum amyloid a protein as a predictor of cardiac rupture in acute myocardial infarction patients following primary coronary angioplasty. Circ J 2006;70:530 –535. 9. Kostis WJ, Demissie K, Marcella SW, Shao YH, Wilson AC, Moreyra AE. Weekend versus weekday admission and mortality from myocardial infarction. N Engl J Med 2007;356:1099 –1109. 10. Kostis JB, Wilson AC, O’Dowd K, Gregory P, Chelton S, Cosgrove NM, Chirala A, Cui T. Sex differences in the management and long-term outcome of acute myocardial infarction. A statewide study. MIDAS Study Group. Myocardial Infarction Data Acquisition System. Circulation 1994;90:1715–1730. 11. Latham P. Lectures on Subjects Connected with Clinical Medicine Comprising Disease of the Heart, Volume 2. London: Langman, Recs, Orme, Brown, Green and Langman, 1847:163–164.
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12. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. The GUSTO investigators. N Engl J Med 1993;329:673– 682. 13. Figueras J, Alcalde O, Barrabes JA, Serra V, Alguersuari J, Cortadellas J, Lidon RM. Changes in hospital mortality rates in 425 patients with acute ST-elevation myocardial infarction and cardiac rupture over a 30-year period. Circulation 2008;118:2783–2789. 14. Menon V, Webb JG, Hillis LD, Sleeper LA, Abboud R, Dzavik V, Slater JN, Forman R, Monrad ES, Talley JD, Hochman JS. Outcome and profile of ventricular septal rupture with cardiogenic shock after myocardial infarction: a report from the SHOCK Trial Registry. SHould we emergently revascularize Occluded Coronaries in cardiogenic shocK? J Am Coll Cardiol 2000;36(suppl A):1110 –1116. 15. Pretre R, Rickli H, Ye Q, Benedikt P, Turina MI. Frequency of collateral blood flow in the infarct-related coronary artery in rupture of the ventricular septum after acute myocardial infarction. Am J Cardiol 2000;85:497– 499, A410. 16. Skehan JD, Carey C, Norrell MS, de Belder M, Balcon R, Mills PG. Patterns of coronary artery disease in post-infarction ventricular septal rupture. Br Heart J 1989;62:268 –272. 17. Sosnov J, Lessard D, Goldberg RJ, Yarzebski J, Gore JM. Differential symptoms of acute myocardial infarction in patients with kidney disease: a community-wide perspective. Am J Kidney Dis 2006;47:378 –384. 18. Wright RS, Reeder GS, Herzog CA, Albright RC, Williams BA, Dvorak DL, Miller WL, Murphy JG, Kopecky SL, Jaffe AS. Acute myocardial infarction and renal dysfunction: a high-risk combination. Ann Intern Med 2002;137:563–570. 19. Deja MA, Szostek J, Widenka K, Szafron B, Spyt TJ, Hickey MS, Sosnowski AW. Post infarction ventricular septal defect— can we do better? Eur J Cardiothorac Surg 2000;18:194 –201. 20. Pretre R, Ye Q, Grunenfelder J, Lachat M, Vogt PR, Turina MI. Operative results of “repair” of ventricular septal rupture after acute myocardial infraction. Am J Cardiol 1999;84:785–788.
21. David TE, Armstrong S. Surgical repair of postinfarction ventricular septal defect by infarct exclusion. Semin Thorac Cardiovasc Surg 1998;10:105–110. 22. Barker TA, Ramnarine IR, Woo EB, Grayson AD, Au J, Fabri BM, Bridgewater B, Grotte GJ. Repair of post-infarct ventricular septal defect with or without coronary artery bypass grafting in the northwest of England: a 5-year multi-institutional experience. Eur J Cardiothorac Surg 2003;24:940 –946. 23. Labrousse L, Choukroun E, Chevalier JM, Madonna F, Robertie F, Merlico F, Coste P, Deville C. Surgery for post infarction ventricular septal defect (VSD): risk factors for hospital death and long term results. Eur J Cardiothorac Surg 2002;21:725–731. 24. Cummings RG, Califf R, Jones RN, Reimer KA, Kong YH, Lowe JE. Correlates of survival in patients with postinfarction ventricular septal defect. Ann Thorac Surg 1989;47:824 – 830. 25. Anderson DR, Adams S, Bhat A, Pepper JR. Post-infarction ventricular septal defect: the importance of site of infarction and cardiogenic shock on outcome. Eur J Cardiothorac Surg 1989;3:554 –557. 26. Cox FF, Morshuis WJ, Plokker HW, Kelder JC, van Swieten HA, Brutel de la Riviere A, Knaepen PJ, Vermeulen FE. Early mortality after surgical repair of postinfarction ventricular septal rupture: importance of rupture location. Ann Thorac Surg 1996;61:1752– 1758. 27. Deville C, Fontan F, Chevalier JM, Madonna F, Ebner A, Besse P. Surgery of post-infarction ventricular septal defect: risk factors for hospital death and long-term results. Eur J Cardiothorac Surg 1991; 5:167–175. 28. Moore CA, Nygaard TW, Kaiser DL, Cooper AA, Gibson RS. Postinfarction ventricular septal rupture: the importance of location of infarction and right ventricular function in determining survival. Circulation 1986;74:45–55.
UMDNJ–Robert Wood Johnson Medical School, New Brunswick, New Jersey. Manuscript received March 31, 2010; revised manuscript received and accepted June 2, 2010. This work was supported in part by grants from the Robert Wood Johnson Foundation, Princeton, New Jersey, and from the Schering-Plough Foundation, Princeton. *Corresponding author: Tel: 732-235-7855; fax: 732-235-8722. E-mail address: [email protected] (A.E. Moreyra). 0002-9149/10/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2010.06.013
Methods Data for this study were obtained from the Myocardial Infarction Data Acquisition System (MIDAS) database.9,10 This administrative database contains discharge records of all patients admitted to nonfederal acute care hospitals in New Jersey with a cardiovascular disease diagnosis. This database was previously audited using a random sample of charts to verify the accuracy of the information.10 The study was approved by the State of New Jersey Department of Health and Senior Services and Robert Wood Johnson Medical School institutional review boards. The study cohort consists of 148,881 adult patients (ⱖ35 years of age) admitted for the first time to all nonfederal New Jersey hospitals with a diagnosis of acute ST-segment elevation myocardial infarction (excluding non ST-segment elevation infarctions; International Classification of Diseases [ICD] code 410.7) from 1990 to 2007. Four hundred eight patients with VSR complicating AMI were identified by the diagnosis code for acquired VSR (ICD code 429.71, n ⫽ 338) or a procedure code indicating VSR surgical repair (ICD codes 35.53, 35.62, or 35.72, n ⫽ 70) within 28 days after index AMI hospitalization. Primary end points were mortality in hospital, at 30 days, and at 1 year. Covariates included patient demographics and co-morbidities; ST-segment elevation infarction site; anterior, inferior/lateral/posterior, other or unspecified; length of hospital stay; development of cardiogenic shock; and procedures. Risk adjustment included the following factors: presence or absence of diabetes, hypertension, chronic renal www.ajconline.org
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Table 1 Clinical characteristics, complications, location of infarction, and cardiac procedures in study patients compared to other patients with acute myocardial infarction Variable
Age (years) Women White Hypertension Diabetes mellitus Chronic kidney disease Heart failure Atrial fibrillation Cardiogenic shock Cardiac arrest Length of stay (days) Location of infarction Anterior wall Inferior/lateral wall Other/unspecified Cardiac procedures Diagnostic catheterization Percutaneous intervention Coronary artery bypass
VSR
p Value
Yes (n ⫽ 408)
No (n ⫽ 148,473)
71 ⫾ 10 210 (52%) 315 (77%) 116 (28%) 73 (18%) 110 (27%) 185 (45%) 80 (20%) 160 (39%) 25 (6.1%) 12 ⫾ 18
67 ⫾ 14 57,125 (39%) 116,199 (78%) 67,698 (46%) 35,563 (24%) 8,759 (5.9%) 39,632 (27%) 19,059 (13%) 8,771 (5.9%) 6,124 (4.1%) 7⫾9
⬍0.0001 ⬍0.0001 0.26 ⬍0.0001 0.004 ⬍0.0001 ⬍0.0001 ⬍0.0001 ⬍0.0001 0.04 ⬍0.0001
175 (43%) 198 (49%) 35 (8.6%)
54,464 (37%) 73,002 (49%) 21,007 (14%)
0.009 0.80 0.001
241 (59%) 50 (12%) 133 (33%)
53,531 (36%) 27,445 (19%) 7,793 (5.3%)
⬍0.0001 0.001 ⬍0.0001
Values are means ⫾ SDs or numbers of patients (percentages).
disease, congestive heart failure, cardiogenic shock, and length of hospital stay. Procedures included cardiac catheterization (ICD codes 37.21 to 37.23), angioplasty (ICD codes 36.01, 36.02, 36.05, and 00.66), percutaneous coronary intervention (ICD codes 36.00 to 36.09), VSR surgical repair (ICD codes 35.53, 35.62, and 35.72), and coronary artery bypass graft surgery (ICD codes 36.10 to 36.19, 36.2). We compared demographic, clinical, and cardiac procedures, length of stay, and mortality data for patients with AMI complicated by VSR to those without VSR. Incidence and mortality rates were plotted in 3-year periods. We used Pearson chi-square test for categorical variables and Student’s t test for continuous variables to compare clinical and demographic characteristics. We used the Cochran-Armitage trend test to examine time trends for VSR rates and procedural rates. Kaplan-Meier survival curves (product– limit method) were constructed for patients with VSR with and without surgical repair. We used multivariate logistic regression to analyze potential risk factors and Cox proportional hazards method for survival analyses. All statistical analyses were performed using SAS 9.1 (SAS Institute, Cary, North Carolina). Results From 1990 to 2007, 148,881 patients were hospitalized in New Jersey with ST-segment elevation AMI for the first time, and 408 of these developed VSR. Compared to patients without VSR (Table 1), these patients were older, more likely to be women, and to have higher rate of chronic kidney disease, heart failure, cardiogenic shock, and cardiac arrest. Diagnoses of hypertension and diabetes mellitus
Figure 1. Incidence of VSR complicating AMI from 1990 to 2007 grouped by 3-year periods. Table 2 Risk factors for ventricular septal rupture complicating acute myocardial infarction by multivariate logistic regression analysis Risk Factors in Logistic Model Age (per year) Female vs male gender Admission year (per year) Race White Black Other Infarction sites Anterior wall Inferior/lateral wall Other/unspecified Hypertension(yes vs no) Diabetes mellitus(yes vs no) Chronic kidney disease (yes vs no)
OR (95% CI)* 1.01 (1.01–1.02) 1.59 (1.30–1.95) 1.00 (0.98–1.02) reference 0.91 (0.58–1.43) 1.28 (0.99–1.65) reference 0.93 (0.76–1.14) 0.43 (0.30–0.62) 0.49 (0.39–0.61) 0.67 (0.52–0.87) 5.51 (4.37–6.95)
* Adjusted for all factors in table.
were less common in patients with AMI and VSR. Anterior wall MI was more frequently observed in patients with VSR than in patients without, but that was not true for patients with inferior/lateral wall AMI. Of patients with VSR, anterior wall AMI was seen in 43% of patients, whereas inferior/ lateral location was seen in 49% and other/unspecified in 8.6%. The probability of having VSR in patients with anterior AMI was not different (0.32%) from those with inferior/lateral AMI (0.21%, p ⫽ 0.10). VSR was found to prolong length of hospital stay significantly. For patients with AMI and VSR mean length of stay was 4.7 days longer (65%) than in those without VSR (p ⬍0.0001). Death terminated hospital stay of 50% of patients with VSR compared to 18% of those without VSR. In patients with AMI not complicated by VSR, length of stay steadily decreased in each of the 3-year periods, from 10.1 days in 1990 to 1992 to 5.2 days in 2005 to 2007. In contrast, mean length of stay for patients with AMI complicated by VSR remained unchanged, from 12.8 to 13.5 days. Cardiac catheterization was performed significantly more often, but revascularization by percutaneous coronary intervention was performed less frequently in patients with AMI and VSR.
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Table 3 Trends in unadjusted in-hospital, 30-day, and one-year mortality by three-year periods in patients with acute myocardial infarction with and without ventricular septal rupture 3-Year Period
VSR In-Hospital Death
1990–1992 1993–1995 1996–1998 1999–2001 2002–2004 2005–2007
30-Day Mortality
1-Year Mortality
Yes
No
Yes
No
Yes
No
33 (41%) 42 (49%) 54 (61%) 35 (57%) 23 (42%) 16 (44%)
4,827 (15%) 4,114 (14%) 3,539 (13%) 3,018 (13%) 2,088 (11%) 1,451 (10%)
39 (49%) 45 (52%) 60 (67%) 35 (57%) 27 (49%) 16 (44%)
5,289 (17%) 4,623 (15%) 4,214 (15%) 3,606 (15%) 2,507 (13%) 1,657 (11%)
48 (60%) 57 (66%) 65 (73%) 41 (66%) 34 (62%) 20 (56%)
7,530 (24%) 6,693 (22%) 6,038 (21%) 5,328 (22%) 3,825 (19%) 2,172 (15%)
Values are numbers of patients (percentages).
Figure 2. Patients with AMI complicated (coml.) by VSR (purple bars) or without (w/o) VSR complication (green bars). Trend significance from Cochran-Armitage trend test.
Rate of VSR complicating AMI remained relatively constant, with an overall rate of 0.27% from 1990 to 2007, despite the increasing number of percutaneous coronary intervention procedures (Figure 1). In multivariate analysis, risk factors independently associated with developing VSR after first AMI were increasing age, female gender, and chronic kidney disease (Table 2). In contrast, hypertension and diabetes mellitus were found to be statistically less frequent in patients with VSR. In multivariate analysis, location of infarction and year of admission showed no significant relation to likelihood of developing VSR. Of 408 patients with VSR, 236 patients were treated surgically, the rest were treated medically. In addition to VSR repair, 133 patients received combined coronary artery bypass graft surgery. Of patients who received VSR repair surgery, 147 (62.3%) were operated on within 2 days of admission, and 75 (31.8%) at 3 to 14 days. Fourteen patients (4.2%) underwent surgery later than 14 days and all except 1 were admitted before 1999. Rates of surgical VSR repair throughout the 18-year study period showed no significant changes (p ⫽ 0.24, Cochran-Armitage trend test). Patients treated surgically within 48 hours of admission showed in-hospital mortality from 50% to 77% (average 60%). No trend in death rate decrease was noted during the 18-year
study period. Patients whose surgical repair was delayed ⬎48 hours had a lower in-hospital death rate (38%), probably reflecting selection bias. Table 3 lists unadjusted rates for in-hospital, 30-day, and 1-year deaths in patients with AMI with or without VSR from 1990 to 2007. Although steady decreases in mortality were observed in AMI cases without VSR, this was not seen in cases complicated by VSR, which fluctuated without significant trend. This is further illustrated in Figure 2, which displays in-hospital mortality in different years. Patients with AMI complicated by VSR were nearly 7 times more likely to die in hospital compared to those without (unadjusted odds ratio [OR] 6.83, 95% confidence interval [CI] 5.62 to 8.31). This increased risk persisted after adjustment for baseline co-morbidities and reperfusion by percutaneous coronary intervention or coronary artery bypass graft (adjusted OR 3.76, 95% CI 2.94 to 4.81). After multivariate adjustment, increasing age and shock were the only independent predictors of mortality in patients with AMI complicated by VSR (Table 4). A survival benefit associated with VSR surgical repair was observed only in hospital, but not at 30 days or 1 year (Figure 3). Patients with VSR repair combined with revascularization by coronary artery bypass grafting did not show any survival benefit (for surgical repair alone, OR 0.69, 95% CI 0.44 to 1.08; for surgical repair plus coronary artery bypass graft, OR 0.81, 95% CI 0.56 to 1.17). Discussion We identified 408 cases of postinfarction VSR that occurred in New Jersey between 1990 and 2007. From this large observational study we were able make several observations: (1) VSR incidence rate fluctuated but did not decrease, (2) despite significant increases in revascularization procedures and improvement in medical therapies, mortality associated with this complication did not change, (3) surgical repair was significantly associated with lower mortality in hospital but not at 30 days or 1 year compared to medical treatment, and (4) rate of VSR complicating AMI appears to be significantly higher in patients with chronic renal disease but, in contrast to other reports, lower in patients with diabetes and hypertension. VSR was first described by Latham11 in 1847 at autopsy. In a trial comparing 4 thrombolytic strategies for AMI, the
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Table 4 Risk factors for mortality in patients with acute myocardial infarction complicated by ventricular septal rupture Factor in Cox Model* Age Female vs male gender Admission year (per year) Race White Black Other Infarction site Anterior wall Inferior/lateral wall Other/unspecified Coexisting conditions Renal failure Shock Hypertension Diabetes mellitus Atrial fibrillation Cardiac procedures Percutaneous intervention Surgical repair of septum
In-Hospital Mortality (95% CI)
30-Day Mortality (95% CI)
1-Year Mortality (95% CI)
1.02 (1.01–1.04) 1.16 (0.84–1.60) 1.00 (0.96–1.03)
1.03 (1.02–1.05) 1.31 (0.98–1.76) 0.99 (0.96–1.02)
1.04 (1.02–1.05) 1.15 (0.89–1.50) 0.99 (0.96–1.01)
reference 0.99 (0.45–2.18) 1.07 (0.71–1.61)
reference 0.90 (0.48–1.71) 1.20 (0.85–1.69)
reference 0.96 (0.54–1.70) 1.06 (0.76–1.47)
reference 1.31 (0.93–1.83) 1.72 (0.98–3.05)
reference 1.21 (0.90–1.61) 1.23 (0.72–2.10)
reference 1.14 (0.87–1.48) 0.97 (0.59–1.60)
1.04 (0.74–1.46) 2.55 (1.84–3.54) 1.15 (0.81–1.64) 0.82 (0.51–1.30) 0.80 (0.54–1.18)
1.08 (0.79–1.46) 2.48 (1.84–3.33) 1.02 (0.74–1.40) 0.91 (0.61–1.35) 0.91 (0.61–1.35)
1.05 (0.79–1.40) 2.18 (1.66–2.86) 0.91 (0.68–1.23) 0.87 (0.60–1.25) 0.87 (0.60–1.25)
1.07 (0.66–1.71) 0.66 (0.45–0.95)
1.11 (0.73–1.67) 0.86 (0.63–1.18)
1.12 (0.76–1.65) 0.90 (0.68–1.20)
* Hazard ratios adjusted for all factors in table.
Figure 3. Kaplan-Meier survival plots for patients with AMI complicated by VSR that is surgically treated (blue lines) or medically treated (red lines) (A) in hospital and (B) 1-year follow-up.
incidence of VSR was 0.4% to 0.6%.12 The introduction of primary angioplasty had similar benefit; reports of the impact of primary percutaneous coronary intervention cited an incidence of VSR from 0.2% to 0.5%.7,8 Because VSR is dependent on complete transmural septal infarction,2 de-
creasing ischemic injury and infarct size with prompt reperfusion preserves overall left ventricular integrity. Our study covers a period in which reperfusion therapies were well established, and the incidence of VSR (0.2%) is consistent with studies from the reperfusion era. Figueras et al13 reported a progressive decrease in the incidence of cardiac rupture (including VSR) after AMI from 1977 to 2006 and attributed it to the increasing rate of reperfusion therapy and increased use of  blockers, angiotensin-converting enzyme inhibitors, and aspirin. Our study does not confirm such a progressive decrease. Risk factors associated with developing VSR have been evaluated in multiple studies.5,6 Factors include hypertension, advanced age, female gender, absence of angina or history of MI, anterior location of infarction, and high Killip class. In this study, we confirmed that advanced age, female gender, and congestive heart failure are associated with an increased risk of VSR. We did not find any difference in the development of VSR between anterior and inferior/lateral infarction. Contrary to other studies,5,6 we found a lower incidence of hypertension and diabetes in patients with VSR. Concentric myocardial hypertrophy in patients with hypertension may possibly confer some protection against septal rupture. Previous studies have reported a wide range (11% to 39%) in prevalence of diabetes in VSR populations.4,6,7,13,14 VSR has been reported to occur more frequently in single-vessel disease and absent collateral circulation.14 –16 The apparently protective effect of diabetes against the development of VSR may possibly arise from multivessel disease with collateral circulation providing blood supply to the ischemic septum and preventing its rupture. We found that a history of chronic kidney disease increased the risk of VSR nearly fivefold. A possible explanation for this association is that patients with chronic renal disease frequently do not present with typical symptoms for
Coronary Artery Disease/Postinfarction Ventricular Septal Rupture
AMI.17 This may delay diagnosis and treatment, resulting in an increased VSR incidence rate. Another possible factor contributing to increased risk for VSR development in patients with AMI and chronic renal disease is that they receive adjunctive and reperfusion therapies for AMI less frequently than those with normal renal function.18 Despite advances in pharmacologic and percutaneous reperfusion procedures for AMI and better surgical techniques for VSR repair, we found that mortality rate for AMI complicated by VSR remained high and unchanged from 1990 to 2007. The explanation for the lack of decrease in mortality is unclear. The sudden and severe hemodynamic deterioration imposed by this complication may overwhelm any available medical and surgical resources. It remains to be seen whether wider use of left ventricular assist devices to bridge patients to surgery or heart transplantation will decrease mortality. Overall in-hospital, 30-day, and 1-year mortality rates in our study were 50%, 54%, and 65%, respectively. These mortality rates are similar to those reported by others,7,19,20 from 23% to as high as 87% in the Should We Emergently Revascularize Occluded Coronaries in Cardiogenic Shock? (SHOCK) registry.14 We found no significant difference in adjusted mortality rates at 30 days or 1 year for patients with VSR who underwent surgical repair compared to those who were treated medically. One study reported improved outcomes in patients treated surgically in recent years compared to early surgical results and to medical treatment.4 We did not find any improving trends in mortality of surgically treated patients during this 18-year span. However, it should be emphasized that records from an administrative database lack many variables that are needed to accurately assess patients’ clinical status and to draw conclusions from factors determining short- and long-term outcomes of patients treated medically and surgically. Risk factors associated with increased mortality have been extensively studied and include advanced age,21 total occlusion of infarct-related artery22 and inotrope requirements,23 early repair of VSR,20,23 preoperative shock,14 and impaired right ventricular function.24 The 2 risk factors that have been most consistently reported to have the strongest association with mortality are early surgical treatment and shock. In agreement with other studies,14,25 shock was associated with the highest risk of mortality. A major concern in early VSR repair is that necrotic myocardium is too fragile for repair of septal rupture. In our study we found a high mortality in patients operated within 48 hours of admission. However, this does not mean that early surgery was inappropriate. It is not possible to know from this administrative database if the lower mortality rates in patients operated later were because of selection bias (patients being less “sick”) or whether connective tissue developed at margins of the infarcted muscle facilitating the surgical repair. Conflicting results on the survival benefit of concomitant revascularization by coronary artery bypass graft during VSR repair have been reported in the literature.15,19,22,23 In our study patients with VSR repair combined with revascularization by coronary artery bypass grafting did not show any survival benefit. Our results concur with several reports24 –28 in showing that inferior wall AMI with VSR is
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associated with increased mortality compared to anterior wall AMI but the association is not significant. Administrative databases such as MIDAS lack specific details of anatomic findings, pharmacologic treatments, and procedures as noted previously, but they are widely inclusive in time span and population representation and do not have the limitations of selected populations of clinical trials and prospective, detailed registries. With rates similar to those in other reports, there are several strengths to this study including having the largest number of reported VSR cases, up to an 18-year follow-up, and being based on a statewide population encompassing all hospitalized AMIs. This is the largest reported series of patients with VSR complicating AMI. Our study shows that the rate of occurrence has remained constant since reperfusion was introduced for treatment of AMI. We report for the first time that chronic renal disease is an additional independent risk factor for development of VSR. Despite improvements in medical treatment and revascularization techniques during the previous 2 decades, the mortality rate of this lethal AMI complication has not changed and remains a formidable challenge. 1. Pohjola-Sintonen S, Muller JE, Stone PH, Willich SN, Antman EM, Davis VG, Parker CB, Braunwald E. Ventricular septal and free wall rupture complicating acute myocardial infarction: experience in the Multicenter Investigation of Limitation of Infarct Size. Am Heart J 1989;117:809 – 818. 2. Topaz O, Taylor AL. Interventricular septal rupture complicating acute myocardial infarction: from pathophysiologic features to the role of invasive and noninvasive diagnostic modalities in current management. Am J Med 1992;93:683– 688. 3. Davies RH, Dawkins KD, Skillington PD, Lewington V, Monro JL, Lamb RK, Gray HH, Conway N, Ross JK, Whitaker L. Late functional results after surgical closure of acquired ventricular septal defect. J Thorac Cardiovasc Surg 1993;106:592–598. 4. Poulsen SH, Praestholm M, Munk K, Wierup P, Egeblad H, NielsenKudsk JE. Ventricular septal rupture complicating acute myocardial infarction: clinical characteristics and contemporary outcome. Ann Thorac Surg 2008;85:1591–1596. 5. Birnbaum Y, Fishbein MC, Blanche C, Siegel RJ. Ventricular septal rupture after acute myocardial infarction. N Engl J Med 2002;347:1426 – 1432. 6. Crenshaw BS, Granger CB, Birnbaum Y, Pieper KS, Morris DC, Kleiman NS, Vahanian A, Califf RM, Topol EJ. Risk factors, angiographic patterns, and outcomes in patients with ventricular septal defect complicating acute myocardial infarction. GUSTO-I (Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries) Trial Investigators. Circulation 2000;101:27–32. 7. Yip HK, Fang CY, Tsai KT, Chang HW, Yeh KH, Fu M, Wu CJ. The potential impact of primary percutaneous coronary intervention on ventricular septal rupture complicating acute myocardial infarction. Chest 2004;125:1622–1628. 8. Katayama T, Nakashima H, Takagi C, Honda Y, Suzuki S, Iwasaki Y, Yamamoto T, Yoshioka M, Yano K. Serum amyloid a protein as a predictor of cardiac rupture in acute myocardial infarction patients following primary coronary angioplasty. Circ J 2006;70:530 –535. 9. Kostis WJ, Demissie K, Marcella SW, Shao YH, Wilson AC, Moreyra AE. Weekend versus weekday admission and mortality from myocardial infarction. N Engl J Med 2007;356:1099 –1109. 10. Kostis JB, Wilson AC, O’Dowd K, Gregory P, Chelton S, Cosgrove NM, Chirala A, Cui T. Sex differences in the management and long-term outcome of acute myocardial infarction. A statewide study. MIDAS Study Group. Myocardial Infarction Data Acquisition System. Circulation 1994;90:1715–1730. 11. Latham P. Lectures on Subjects Connected with Clinical Medicine Comprising Disease of the Heart, Volume 2. London: Langman, Recs, Orme, Brown, Green and Langman, 1847:163–164.
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12. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. The GUSTO investigators. N Engl J Med 1993;329:673– 682. 13. Figueras J, Alcalde O, Barrabes JA, Serra V, Alguersuari J, Cortadellas J, Lidon RM. Changes in hospital mortality rates in 425 patients with acute ST-elevation myocardial infarction and cardiac rupture over a 30-year period. Circulation 2008;118:2783–2789. 14. Menon V, Webb JG, Hillis LD, Sleeper LA, Abboud R, Dzavik V, Slater JN, Forman R, Monrad ES, Talley JD, Hochman JS. Outcome and profile of ventricular septal rupture with cardiogenic shock after myocardial infarction: a report from the SHOCK Trial Registry. SHould we emergently revascularize Occluded Coronaries in cardiogenic shocK? J Am Coll Cardiol 2000;36(suppl A):1110 –1116. 15. Pretre R, Rickli H, Ye Q, Benedikt P, Turina MI. Frequency of collateral blood flow in the infarct-related coronary artery in rupture of the ventricular septum after acute myocardial infarction. Am J Cardiol 2000;85:497– 499, A410. 16. Skehan JD, Carey C, Norrell MS, de Belder M, Balcon R, Mills PG. Patterns of coronary artery disease in post-infarction ventricular septal rupture. Br Heart J 1989;62:268 –272. 17. Sosnov J, Lessard D, Goldberg RJ, Yarzebski J, Gore JM. Differential symptoms of acute myocardial infarction in patients with kidney disease: a community-wide perspective. Am J Kidney Dis 2006;47:378 –384. 18. Wright RS, Reeder GS, Herzog CA, Albright RC, Williams BA, Dvorak DL, Miller WL, Murphy JG, Kopecky SL, Jaffe AS. Acute myocardial infarction and renal dysfunction: a high-risk combination. Ann Intern Med 2002;137:563–570. 19. Deja MA, Szostek J, Widenka K, Szafron B, Spyt TJ, Hickey MS, Sosnowski AW. Post infarction ventricular septal defect— can we do better? Eur J Cardiothorac Surg 2000;18:194 –201. 20. Pretre R, Ye Q, Grunenfelder J, Lachat M, Vogt PR, Turina MI. Operative results of “repair” of ventricular septal rupture after acute myocardial infraction. Am J Cardiol 1999;84:785–788.
21. David TE, Armstrong S. Surgical repair of postinfarction ventricular septal defect by infarct exclusion. Semin Thorac Cardiovasc Surg 1998;10:105–110. 22. Barker TA, Ramnarine IR, Woo EB, Grayson AD, Au J, Fabri BM, Bridgewater B, Grotte GJ. Repair of post-infarct ventricular septal defect with or without coronary artery bypass grafting in the northwest of England: a 5-year multi-institutional experience. Eur J Cardiothorac Surg 2003;24:940 –946. 23. Labrousse L, Choukroun E, Chevalier JM, Madonna F, Robertie F, Merlico F, Coste P, Deville C. Surgery for post infarction ventricular septal defect (VSD): risk factors for hospital death and long term results. Eur J Cardiothorac Surg 2002;21:725–731. 24. Cummings RG, Califf R, Jones RN, Reimer KA, Kong YH, Lowe JE. Correlates of survival in patients with postinfarction ventricular septal defect. Ann Thorac Surg 1989;47:824 – 830. 25. Anderson DR, Adams S, Bhat A, Pepper JR. Post-infarction ventricular septal defect: the importance of site of infarction and cardiogenic shock on outcome. Eur J Cardiothorac Surg 1989;3:554 –557. 26. Cox FF, Morshuis WJ, Plokker HW, Kelder JC, van Swieten HA, Brutel de la Riviere A, Knaepen PJ, Vermeulen FE. Early mortality after surgical repair of postinfarction ventricular septal rupture: importance of rupture location. Ann Thorac Surg 1996;61:1752– 1758. 27. Deville C, Fontan F, Chevalier JM, Madonna F, Ebner A, Besse P. Surgery of post-infarction ventricular septal defect: risk factors for hospital death and long-term results. Eur J Cardiothorac Surg 1991; 5:167–175. 28. Moore CA, Nygaard TW, Kaiser DL, Cooper AA, Gibson RS. Postinfarction ventricular septal rupture: the importance of location of infarction and right ventricular function in determining survival. Circulation 1986;74:45–55.