1591

DOI: 10.1016/j.athoracsur.2008.01.010 2008;85:1591-1596 Ann Thorac Surg

and Jens Erik Nielsen-Kudsk Steen Hvitfeldt Poulsen, Michael Prstholm, Kim Munk, Per Wierup, Henrik Egeblad

Characteristics and Contemporary OutcomeVentricular Septal Rupture Complicating Acute Myocardial Infarction: Clinical

http://ats.ctsnetjournals.org/cgi/content/full/85/5/1591located on the World Wide Web at:

The online version of this article, along with updated information and services, is

Print ISSN: 0003-4975; eISSN: 1552-6259. Southern Thoracic Surgical Association. Copyright 2008 by The Society of Thoracic Surgeons.

is the official journal of The Society of Thoracic Surgeons and theThe Annals of Thoracic Surgery

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Ventricular septal rupture in acute myocardial infarc-tion (AMI) is a well-recognized mechanical compli-cation associated with a very high mortality [13]. Theusinc0.2occthrouwaapinlatshtion [4, 68]. After introduction of thrombolysis andprimary percutaneous coronary intervention, the clinicalcharacteristics and course in unselected postinfarctionveamsisavOcregan[9,ma

complete in each and every patient. In the GUSTO-I trial,the patient profile was biased due to the particularenrolment criteria used in this study [9, 10]. Data fromthetalGUthecontalchainfl

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We reviewed the medical records of 64 consecutive patientsadmitted to our tertiary cardiac center with ventricularseptal rupture complicating AMI during the period from

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Cntricular septal defect patients have mainly been ex-ined in relatively small studies or in subgroup analy-. Data in larger selected postinfarction populations areailable from the SHould we emergently revascularizecluded Coronaries for cardiogenic shocK? (SHOCK)istry trial and the Global Utilization of Streptokinase

d TPA for Occluded Coronary Arteries (GUSTO-I) trial10]. However, in the SHOCK trial only patients withnifest shock were included and data were far from

January 1993 to December 2002. Data were collected retro-spectively. Individual consent for participation was there-fore not obtained. This approach was approved by the localethical committee. The diagnosis of AMI was based ontypical clinical symptoms, electrocardiographic signs ofinfarction, and a documented elevation of cardiac enzymes(creatine kinase and creatine kinase MB fraction) to at leasttwice the upper normal limits. The ventricular septal rup-ture was diagnosed by echocardiography (disrupted ven-tricular septum with evidence of left-to-right shunt by colorDoppler) in all cases.

Demographic data, medical history, electrocardio-graphic patterns, Killip class, hemodynamic data, and

epted for publication Jan 2, 2008.

dress correspondence to Dr Munk, Department of Cardiology, Aarhusiversity Hospital, Skejby, Brendstrupgaardsvej 100, 8200 Aarhus N, DK0, Denmark: e-mail: [email protected].

008 by The Society of Thoracic Surgeons 0003-4975/08/$34.00blished by Elsevier Inc doi:10.1016/j.athoracsur.2008.01.010e of thrombolytic agents seems to have reduced theidence from 1% to 2% in the prethromobolytic era to% [1, 2, 4]. In the prethrombolytic era septal ruptureurred most often in the first week of AMI, typicallyee to five days after onset of symptoms [1, 4, 5]. Thetcome after septal rupture in the prethrombolytic eras extremely poor, with an in-hospital mortality rate ofproximately 45% in surgically treated patients and 90%medically managed patients [13]. Predictors of a poore outcome in this population included cardiogenicock, inferior infarction, and poor right ventricular func-ats.ctsnetjournals.orDownloaded from se selected populations indicate that the overall mor-ity rates remain high with 73.8% at 30 days in theSTO trial and 87% in the SHOCK trial [9, 10]. Hence,aim of this paper was, in a contemporary group ofsecutive patients with postinfarction ventricular sep-

defect referred to our tertiary center, to study the patientracteristics, the short and long-term outcomes, and theuence of different treatment strategies on outcome.

tients and Methodsentricular Septal Ruptureyocardial Infarction: Clinontemporary Outcome

een Hvitfeldt Poulsen, MD, DMSci, Michaer Wierup, MD, DMSci, Henrik Egeblad, MD

ns Erik Nielsen-Kudsk, MD, DMScipartments of Cardiology and Cardiothoracic Surgery, Aarhus U

ackground. The objective of this paper was to studypatient characteristics and contemporary short- andg-term outcome in patients with postinfarct ventricu-septal rupture.ethods. Based on patient files and register data we

rformed a review of 64 consecutive patients withntricular septal rupture complicating acute myocardialarction, admitted to our tertiary center.esults. The mean age of the patients was 70 7. Thedian time was five days from onset of symptoms to thegnosis of the ventricular septal rupture. The overallday, one-, and five- year mortalities were 62%, 72%,omplicating Acuteal Characteristics and

rstholm, MD, Kim Munk, MD,MSci, and

rsity Hospital, Skejby, Denmark

d 95%, respectively. Medical treated patients (n 19)d a 30-day mortality of 100%. Among surgically treatedtients (n 45) the survival at one month, one and fivears was 71%, 48%, and 32%, respectively. History ofpertension, complicating congestive heart failure, ande were associated with poor outcome.onclusions. Despite improvements in medical anderventional techniques the early as well as the long-m prognosis remains poor in this contemporary series.

(Ann Thorac Surg 2008;85:15916) 2008 by The Society of Thoracic Surgeons by on September 1, 2009 g

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1592 POULSEN ET AL Ann Thorac SurgPROGNOSIS IN POSTINFARCT VENTRICULAR SEPTAL RUPTURE 2008;85:15916AD

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Cgiographic and echocardiographic findings were ob-ned for each patient. Medical treatment and scheduleding of surgery were noted. Two-dimensional Dopplerocardiography was performed in all patients to assess

t ventricular systolic function, location and character ofventricular septal defect, Doppler pressure gradient,

d systolic pulmonary artery pressure.he overall strategy of the department throughout thedy period was to delay surgical repair for at least 3 todays according to each surgeons preference, in the

pe that the septal muscle would become sturdier overe. All patients were operated with a uniform tech-ue, using a single Dacron patch (Bard Medical,

mpe, AZ).division between early (2 days from diagnosis of

ntricular septal defect) and late (2 days) surgery wased to distinguish those who needed acute-subacuteeration because they were decompensated or wereged to be too unstable at the time of diagnosis fromse who underwent scheduled surgery.

ble 1. Patient Characteristics

mber 64e (yrs) (range) 70 7 (5384)nder M/F 35/29 (55/45)pertension 18 (28)betes mellitus 7 (11)vious angina 17 (27)vious AMI 9 (14)oker 41 (64)D localization (anterior/posterior) 32/32 (50/50)k CKMB (g/L) 242 198k TNT (g/L) 2.75 3.99k CKB (g/L) 79 68

ues are given as mean one standard deviation for continuousiables and for categoric variables as numbers (%).

I acute myocardial infarction; CKB creatine kinase B;MB creatine kinase MB; VSD ventricular septal defect.(861. The time course from onset of symptoms to diagnosis of theventricular septal rupture.

ats.ctsnetjournals.orDownloaded from ortalityuses of death and survival information for the entirepulation were obtained from medical records andough the Danish Central Personnel Register, where allaths in the country are recorded within two weeks. Thervival information was obtained in February 2003.

tistical Analysisntinuous variables were summarized as mean SDd the rank sum test was used for comparisons. Categoriciables were compared by the 2 test. Survival rates weretted according to the Kaplan-Meier method and com-

rison of survival rates between subgroups were testedth the log-rank test. A multivariate Cox proportionalzard analysis was performed to identify independentdictors of cardiac death. Variables included were age,

art rate, a history of hypertension, diabetes mellitus,lip class, infarct location, systolic blood pressure, ejectionction, and previous myocardial infarction. A p value ofs than 0.05 was considered significant. SPSS version 10.0SS Inc, Chicago, IL) was used for calculations.

sults

inical Characteristicsble 1 displays the baseline characteristics for the 64tients. Median time from debut of AMI symptoms tognosis of the ventricular septal rupture was five daysnge, 0 to 195 days). Twenty-seven percent and 64% ofcases were diagnosed within two days, respectively, one

ek after the reported onset of AMI symptoms (Fig 1).ased on electrocardiographic (ECG) findings, the in-

x myocardial infarction was inferior in 29 patients,terior in 30 patients, and combined anterior and infe-r in 3. The index myocardial infarction was character-d by ST-segment elevation and (or) Q-waves in 97% ofes. Two patients presented with left bundle branchck. Based on echocardiography, the location of thetal rupture was equally distributed between an ante-

r and inferior-posterior location.

giographic and Hemodynamic Dataronary angiography was performed in 55 patients

ble 2. Hemodynamic Profile of Patients

art rate (beats/minute) 101 20tolic blood pressure (mm Hg) 98 18stolic blood pressure (mm Hg) 61 13

lip class (I-IV) 25/34/5/0EF 0.44 0.1ntricular septal defect Doppler gradientmm Hg)

52 18

cuspid valve regurgitation Doppler gradientmm Hg)

44 15

tral valve regurgitation (none, mild, moderate,evere)

44/16/4/0

ues are given as mean SD for continuous variables and for categorica as numbers.

EF left ventricular ejection fraction.%). The majority had single-vessel or double-vessel

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1593Ann Thorac Surg POULSEN ET AL2008;85:15916 PROGNOSIS IN POSTINFARCT VENTRICULAR SEPTAL RUPTURE

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Conary artery disease (51% and 31%, respectively)ile the remaining 18% had triple-vessel disease. The

t anterior descending artery was identified as thearct-related artery in 23 patients (42%), the right cor-ary artery in 29 patients (53%), and the left circumflexery in only 3 patients (5%).

emodynamic characteristics are shown in Table 2. Atmission, 32% and 59% of the patients demonstrated atolic blood pressure less than 90 mm Hg and less thanmm Hg, respectively. A heart rate greater than 100

ats per minute was noted in 41% of all cases. The meant ventricular ejection fraction was mildly reducedean, 0.44 0.1; range, 0.25 to 0.65) and was signifi-tly higher in inferior infarcts compared with anterior

arcts (0.47 0.09 vs 0.41 0.09, p 0.02). None of thetients demonstrated severe mitral valve regurgitation.nsistent with the presence of a left-to-right shunt, thelmonary systolic pressure was elevated as assessed byppler measurements of tricuspid valve regurgitations (Table 2).

eatmentrombolytic therapy had been administrated in 28 pa-nts (44%) while seven of the patients (11%) underwent

ble 3. Profile of Medical or Surgically Treated Patients

aracteristics Nonoperated Operated p Value

mber 19 45e (yrs) 73 6 68 7 0.03pertension 10 (53) 7 (16) 0.002betes mellitus 3 (16) 4 (9) 0.42

or myocardial infarction 4 (21) 5 (11) 0.43art rate (beats per min) 99 32 102 14 0.35tolic BP (mm Hg) 94 26 100 14 0.38terior infarction 10 (52) 22 (49) 0.78lip class I 15 (79) 24 (53) 0.09EF 0.44 0.10 0.45 0.10 0.91


blood pressure; LVEF left ventricular ejection fraction.an2. Short-term cumulative survival in medically and surgicallyted patients.

ats.ctsnetjournals.orDownloaded from mary angioplasty. Vasopressor therapy was given inpatients (59%) combined with intraaortic balloonnter pulsation therapy (IABP) in 35 patients (55%).

ute severe renal failure developed during the first 24urs in 6 patients. They were treated with hemodialysis.

entricular septal rupture repair was performed in 45tients (70%) and patients with more than one-vesselease had concomitant coronary artery bypass grafting%). Patients treated medically were significantly older,d a history of hypertension and advanced heart failurere more frequently present compared with patientso underwent surgery (Table 3). The median time fromdiagnosis of ventricular septal rupture to surgery

s six days (interquartile range, 1.5 to 12 days).rgery was performed within 48 hours in 14 patients.e patients who were scheduled for surgery after two toee days had to be operated on an earlier basis due torsening of the clinical and hemodynamic status. Base-e characteristics in patients who had early surgeryre comparable to patients with late surgery exceptm a significantly lower blood pressure (Table 4).

ort- and Long-Term Outcomee overall 30-day, 1-, and 5-year mortality rates were

, 72%, and 95%, respectively. The median survivale was 32 days (interquartile range, 6 to 649 days).ne of the medically treated patients survived 30 daysile patients treated surgically had a 30-day survivale of 71% (Fig 2). The long-term survival rate in thergically treated group was 48% after one year and 32%er five years. In the surgically treated patients with ane 75 years or greater (n 7) the one-year survival rates 0% compared with 52% in patients with an age lessn 75 years. The highest one-year survival rate amongsurgically treated group was found in patients with

ble 4. Comparison of Patients Managed With Early orte Surgical Repair

aracteristicsEarly

OperationLate

Operation

mber 14 31e (yrs) 69 6 68 8 0.67nder (M/F) 6/8 19/12 0.25pertension 3 (21) 5 (16) 0.67betes mellitus 0 (0) 4 (13) 0.29vious AMI 1 (7) 4 (13) 0.96terior AMI 6 (43) 14 (45) 0.89tolic BP (mm Hg) 89 14 105 11 0.0001stolic BP (mm Hg) 59 14 67 12 0.05

art rate (beats/min) 102 14 102 14 0.97lip class 1 8 (57) 16 (52) 0.73EF 0.42 0.09 0.46 0.10 0.23


ly operation: day 12; Late operation day 3.

I acute myocardial infarction; BP blood pressure; LVEF ventricular ejection fraction.age less than 65 years (n 12) as compared with


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Ctients with an age of 65 to 74 years (n 26) (83% and, respectively, p 0.05) (Fig 4). Patients who under-

nt late (2 days) or early (2 days) surgical repair hade-year survival rates of 64% and 38%, respectively (p5) (Fig 3). In patients who underwent late surgery (2ys after the diagnosis), no statistical difference between

AMI treatment strategies (fast revascularization, con-vative treatment) and mortality were found (p 0.62).wever, there was a tendency toward better one-year

rvival among patients treated with percutaneous an-plasty or thrombolysis (71%) compared with patients

thout revascularization (59%).multivariate regression analysis was performed to

ntify factors associated with one-year mortality (Table 5).story of hypertension, high Killip class at admission,d heart rate were identified as independent predictorsmortality.

mment

a relatively large consecutive and contemporary series oftients with AMI complicated with ventricular septal rup-

ble 5. Multivariate Cox Regression Analysis for PredictorsAll Cause Mortality After One Year

dictors Wald 2 p Value

pertension 7.46 0.006lip class 1 4.02 0.04art rate (beats/min) 3.69 0.05betes mellitus 1.17 0.28tolic BP (mm Hg) 0.99 0.32EF (5) 0.87 0.35e (yrs) 0.08 0.78arct location 0.01 0.98vious AMI 0.01 0.98

I acute myocardial infarction; BP blood pressure; LVEF ventricular ejection fraction.wi3. Long-term survival in patients treated with early (2 days)late surgery (2 days).

ats.ctsnetjournals.orDownloaded from e, the present study demonstrates that the overall short-d long-term mortality remains high in the reperfusion. It is notable that, due to the Danish socialized medicinectice, this material represents unselected patients from a

fined geographic area within a defined time period.

tient Characteristicse average age in our study was 70 years, which appearssistent with the GUSTO-I trial and SHOCK trial buther than observed in the prethrombolytic studies10]. The increased age seems to be consistent with thereased age of the general population but may alsoect enhanced confidence to surgical treatment in the

erring hospitals, even in elderly patients. The majorityour patients were men. This is in accordance with

rlier studies but in contrast to the findings in theSTO-I and SHOCK trials, where a predominance ofales was noted [913]. The median time from debut ofI to ventricular septal rupture diagnosis was five days

our study and more than one-fourth of the patientsveloped the rupture within two days. This observationd data from the GUSTO-I trial may indicate thatture might occur sooner than described in prethrom-

lytic studies [1, 5, 9, 13]. Although thrombolytic therapyuces infarct size, reperfusion may potentially promote

morrhage and dissection in the myocardium, thuselerating the risk of rupture. Rupture was also seen

thin one to two days in the smaller group of patientsated with primary angioplasty. It should be noted,wever, that the early recognition of septal rupturerely may reflect that access to echocardiography in themary hospitals is facilitated nowadays.s shown by others we found a predominance of

e-vessel disease with a total occlusion of the infarct-ated coronary artery in approximately 50% of patients.terior infarcts have in some studies been associated

4. Long-term survival in surgically treated patients accordingge.th a more frequent development of septal rupture than


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1595Ann Thorac Surg POULSEN ET AL2008;85:15916 PROGNOSIS IN POSTINFARCT VENTRICULAR SEPTAL RUPTURE

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Cerior-posterior infarcts [5, 1315]. In the present study,ECG location of the AMI and the location of the

tal rupture by echocardiography were equally distrib-d between anterior and inferior-posterior locations inordance with other patient series [16].

eatment and Prognosisngestive heart failure was noted in 61% of the patientsadmission with approximately one-third being in

diogenic shock. Nearly two-thirds received inotropicpport and diuretics and preoperative IABP was used in% of cases, which is in accordance with other reports15]. Although no definite documentation exists that

BP improves survival the use is widely accepted as aorable support in the treatment of myocardial septalture. The IABP decreases left ventricular afterload,uces the magnitude of the left-to-right shunt, andreases the coronary perfusion. Thus, IABP may stabi-

e and improve the clinical and hemodynamic conditiona number of patients. Severe hemodynamic deteriora-n developed in five initially stable patients. In thesetients, who were scheduled for later operation, urgented for surgical closure of the defect suddenly occurred.terioration before surgery and cardiogenic shock atmission are known strong predictors of early mortalityd in accordance with these observations none of thee patients survived for 30 days [9, 15]. In accordanceth previous reports we have demonstrated that clinicalns of heart failure, such as increased Killip class andreased heart rate, were independent predictors ofg-term mortality [9, 12, 15].ospital survival in the United Kingdom during the

riod 1988 to 1999 was 31% to 47% in patients withntricular septal rupture and for surgically treated pa-nts in the SHOCK trial and GUSTO-I trial it was 19%d 53%, respectively. In the present study, the 30-dayrvival in surgically treated patients was as high as 76%.r patients who survive surgery, the long-term progno-

is relatively good. In the GUSTO-I trial, one-yearrvival was 47% in surgically treated patients. Similar tose results, we found a one-year survival of 48%.

rthermore, the five-year survival was 32% in our study,ich is reasonably comparable with the 41% found byja and colleagues [15]. However, the mean age wasly 65 years in the study by Deja and colleagues

pared with a mean age in the present study of 70ars. This difference might indeed affect survival withunger patients displaying a more favorable prognosisn elderly as also illustrated in the present study. As in

prethrombolytic era, the prognosis in medicallyated patients remains extremely poor with an in-spital mortality of 94% in the GUSTO-I trial, 96% in theOCK Registry, and 100% in the present study [9, 10].the present report, the medically treated patients werenificantly older compared with the surgically treatedtients, otherwise they seemed comparable. As shownviously and emphasized by the present study, ad-

nced age is associated with poor outcome. In thisard, it is also noteworthy that none of our surgically

ated patients with an age of 75 years or more survived cor

ats.ctsnetjournals.orDownloaded from first four months after surgery. However, the stron-st predictor of long-term outcome was a history ofpertension. Hypertension is a recognized predictor fortal rupture in AMI but has not previously beenociated with long-term prognosis [17, 18].

ategy for Managementsides a surgical strategy, the predominant medicalategy prior to surgery is to reduce left ventricular (LV)ing pressures and afterload. This involves the follow-: (1) IABP treatment- inotropics (or both in combina-

n) in cases with signs of heart failure or cardiogenicock (blood pressure below 90 mm Hg); (2) diuretics;d (3) dialysis in cases with an oliguria. After surgery,

medical strategy is based on standard cardiac careolving diuretics to decrease LV filling pressures, an-tensin-converting enzyme inhibitors, and beta block-to diminish LV wall stress and afterload. The treat-

nt strategy in this study has provided resultsparable with the majority of previously published

pers. Still, our 30-day mortality is 24%! How can weprove outcome? In accordance with our expectations

found in the present study that patients who wereerated early (2 days after diagnosis) had a moreverse outcome compared with patients who under-nt late surgery. This observation is likely to be ex-ined by selection bias with more advanced stages of

art failure with significant lower baseline blood pres-res (Table 4). The fragile necrotic myocardium is ajor concern while operating on an urgent basis. There-e, from a technical perspective the best time to per-m surgery is after fibrotic healing of the necroticscle. However, in a histologic study it was demon-

ated that proliferation of connective tissue was notsent until the third week after infarction [19]. Further-re, in a large proportion of patients it is not possible to

stpone surgery because they develop severe heartlure and multiorgan dysfunction. A sudden hemody-mic deterioration between admission and scheduleder operation carried 100% mortality in our population,esult similar to findings of other reports [15]. A logicalasure to avoid further hemodynamic deterioration

ould be to operate upon the patients immediately afterablishment of the diagnosis when a coronary angiog-hy has been performed. A surgical technique with

arct exclusion by means of a large endocardial patchs permitted early operation. This technique was de-ibed by Deja and colleagues [15] and by David andleagues [20] who reported a 30-day mortality of 14%.eir strategy was to operate all patients expeditiously.sently, we have adopted this technique and are oper-

ng the vast majority emergently.n patients who are severely hemodynamically compro-sed, it may be considered to use a ventricular assistvice to bridge the patient to surgery with closure of thetal defect or to heart transplantation. The latter strategy

s recently been reported with excellent outcome [21].n this study, medically treated patients showed 100%rtality after 30 days. Therefore, the overall strategy is to

rect the ventricular septal defect. In the elderly patients


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C75 years), the prognosis with surgery is extremely graved surgical treatment should probably only be offeredselected cases. In this particular group it may also bepropriate to consider the use of a transcatheter closurevice; particularly if the patient is not considered forcomitant coronary artery bypass surgery, if the ven-ular septal defect has a simple structure (predomi-

ntly anterior located), and if it is not located close to thetral valve apparatus. Only case reports and smallies have documented the yield of these devices thaty change into significant future treatment options24]. In this context, an 83-year-old patient with septalture was recently treated in our department with anplatz occluder and the outcome was successful.nother controversial question is the need for concom-

nt coronary bypass surgery. Some series indicate thatcomitant revascularization may improve late survival

, 26], whereas others have failed to show any definitivenefit of concomitant bypass surgery [27, 28]. In thesent study coronary grafting was only performed in

tients with multivessel disease to ensure optimal con-ions for the left and right ventricular performance in

postoperative phase.n summary, the mean age of the patient with ventriculartal defects is higher than described in prethrombolyticies. Clinical signs of congestive heart failure on admis-n, advanced age, and a history of hypertension wereociated with poor long-term outcome. Despite improve-nts in medical and interventional techniques the early asll as the long-term overall prognosis remained poor ins contemporary series. However, a more favorable prog-sis was found in surgically treated patients who wereunger than 75 years. The potential benefit of early trans-heter intervention in selected patients or by modifiedgical techniques needs further exploration.

ferences

Topaz O, Taylor AL. Interventricular septal rupture compli-cating acute myocardial infarction: from pathophysiologicfeatures to the role of invasive and noninvasive diagnosticmodalities in current management. Am J Med 1992;93:6838.Heitmiller R, Jacobs ML, Daggett WM. Surgical manage-ment of postinfarction ventricular septal rupture. Ann Tho-rac Surg 1986;41:68391.Davies RH, Dawkins KD, Skillington PD, et al. Late func-tional results after surgical closure of acquired ventricularseptal defect. J Thorac Cardiovasc Surg 1993;106:5928.Moore CA, Nygaard TW, Kaiser DL, Cooper AA, Gibson RS.Postinfarction ventricular septal rupture: the importance oflocation of infarction and right ventricular function in deter-mining survival. Circulation 1986;74:4555.Edwards BS, Edwards WD, Edwards JE. 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DOI: 10.1016/j.athoracsur.2008.01.010 2008;85:1591-1596 Ann Thorac Surg

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Characteristics and Contemporary OutcomeVentricular Septal Rupture Complicating Acute Myocardial Infarction: Clinical

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Ventricular Septal Rupture Complicating Acute Myocardial Infarction: Clinical Characteristics and Contemporary OutcomePatients and MethodsMortalityStatistical Analysis

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