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Muscular ventricular septal defects∗
Clinical
Studies
Muscular Ventricular NICHOLAS
G. SAAB, M.D., HOWARD B. BURCHELL, JACK L. TITUS, Rochester,
S
Septal Defects* M.D.,
JAMES \%‘. DUSHANE, M.D. and
M.D.
Minnesota
muscular ventricular septal defects are said to comprise about 10 per cent of all ventricular septal defects,1*2 a review of the clinical, hetnodynatnic, electrocardiographic and morphologic features associated with musclllar defects of the ventricular septum was tindertaken. In this study we considered a muscular ventricular septal defect to be one that was completely surrounded by muscular tissue of the ventricular septum; thus it did not involve the membranous septum, and no part was immediately related to a valvular ring.
mined from the operative record, it was termed “indeterminate.” Electrocardiographic analysis included determination ot the mean QRS axis and loops in both the frontal and horizontal planes; the presence of Q deflections and the Q to R ratios in one or more of leads the duration aVF, aVL and Vs or Vg, or both; and pattern of the QRS complex in lead VL: and the voltages of R and S waves in leads VI and 1-S 01 Vg, or both. Hemodynamic data, when available, were analyzed. In most of the surgically treated patients, pressures in both ventricles had been recorded at operation prior to the institution of extracorporeal circulation. Some of the 92 patients had had right cardiac catheterization. and systemic arterial pressure, pulmonic and systemic flow and resistance, and magnitude of shunt had been measured.
INCE
MATERIALS AND METHODS The operative records of all patients who had had operations for ventricular septal defect performed in this institution from 1955 through 1964 were reviewed to obtain the surgeons’ descriptions of the morphologic features of the defects. The autopsy protocols of all cases in which a diagnosis of ventricular septal defc,ct had been made at autopsy from 1955 through 1964
RESULTS Autopsy was perfortned in 27 of the 92 castss (operation had been performed in 22 of these The age 27): 65 were purely surgical cases. range of the whole group was from 3 weeks to 60 years, but most patients were between 2 and 20 years. The sex distribution was 30 male and 53 female patients (approximately 0.7 : 1). The 92 cases were divided into three nlain groups (Table I). Group 1 consisted of 23 cases with a single muscular ventricular septal defect without any other significant cardiac anomaly-. Group 2 consisted of 14 cases of mllltiple musclelar septal defects with no other major cardiac anomaly. Group 3 included the 55 C~SCS of one
\vere reviewed, and the hearts were examined when the descriptions of the defects suggested that they might have been the muscular type. From the cases selected by the combined review of surgical records and autopsy specimens, a group was selected for detailed study. The criteriafor thisgroup were: (1) The defect or defects were muscular according to the definition already noted; (2) they were at least 3 mm. in and (3) the patient had had at least one diameter; t=lectrocardiogram, usually 12 leads, which was of good quality, although occasionally a case was included if it had only leads VI, Vs, Vs, and the six limb leads. These three criteria were fulfilled in 92 cases. For morpholo&c clas$ication of the location of the,muscular defects, the muscular ventricular septum, as viewed from the right side, was arbitrarily divided into four areas (Fig. 1): postero(infero)basal, midseptal, apical and outflow. Whenever the location of the muscular defect could not be accurately deter-
or more
other
ular
septal
type,
atria1
septal
coarctation great
cardiac
defect
vessels,
of
anomalies,
of the Ilsual defect,
the
patent
aorta,
tetralogy
such as ventric(“nletnbrano\~s”) ductus
transposition
of Fallot,
or
arterioslls, of
the
siqiiificant
* From the Sections of Medicine, Pediatrics and Experimental and Anatomic Pathology, Mayo Clinic and MAYO Foundation and Mayo Graduate School of Medicine, University of Minnesota, Rochester, Minn.
\‘OLIJME18, NOVEMBER1966
713
714
Saab,
Burchell,
DuShane
and
Titus
FE.
scle of conus Membranous septu
____-----
Tricuspid valve ring
1.
vmtricular
?f the muscular septum as seen from the
Diagram
right after removal of the free wall of the right ventricle. The septum has been arbitrarily divided into outflow (Out), posterobasal (PB), midseptal (MS) and apical (c\p) areas.
Crlsta supraventricularis
vahwlar lesions, associated with the muscular This group was further subdivided into defect. group 3A (single muscular defect) and group 3B (multiple muscular defects). Each of these major groups included autopsy as well as surgical cases, although group 1 was composed almost entirely of surgical cases. Some of the patients had died in the immediate postoperative period, and these were considered as autopsy cases since the morphologic aspects were determined from autopsy specimens. MORPHOLOGIC
FINDINGS
Group 1 (Single Muscular Sepal Defect): Of the 23 cases, 1 was an autopsy case and 22 were surTABLE I Age and Sex Distribution in Gases of Muscular Ventricular Septal Defect (mVSD)
Age (G Sex Distribution
A$< Q-6 mo. 6-12 mo. l-2 yr. 2-5 yr. i-10 yr. IO-20 yr. Over 20 yr. Total Range Sex (male-female)
Total Series
Group 1 (single mVSD)
6 5 6 17 27 25 6 92 3 wk.60 yr.
0 1 1 5 7 9 0 23 7 nlo.182/s yr.
39:53
11:12
* Those with other cardiac anomaly.
Group 2 (multiple mVSD)
1 0 0 5 5 2 1 14 4 mo21
.75yr.
2:12
Group 3*
5 4 5 7 15 14 5 55 3 wk.60 yr. 26~29
gical. In the autopsy case, there was a posterobasal defect 1.5 cm. in diameter, and a suggestion of muscular subaortic stenosis. In the surgical cases, the defect was posterobasal in 11, midseptal in 5, apical in 2, outflow in 1, and indeterminate in 3. Thus, in about half of the cases the defect was situated in the posterobasal part of the muscular septum. The defects ranged from 4 by 2 mm. to 2.2 by 1.4 cm. Group 2 (Multiple Muscular Ventricular Septal Defects): There were 6 autopsy cases and 8 surgical ones. In the autopsy cases the muscular defects were situated in the midseptal region in 5, the posterobasal region in 4, the apical region in 3, and the outflow tract in 1. The defects ranged from 3 mm. to 2.0 cm. in diameter. In some of these cases other minor abnormalities were present, such as slight bulge of the membranous septum, suggesting the earliest state of an aneurysm in 1 case, slight hypoplasia of the aorta in 1, a double orifice of the mitral valve with slight mitral insufficiency in 1, and a slight malformation of the tricuspid valve in 1. In the 8 surgical cases, one or more defects were located in the posterobasal region in 4 cases, in the rnidseptal region in 4, in the apical region in 4, and in the outflow tract in 2. The defects ranged from 3 mm. to 3.5 cm. in diameter. In 1 case there was mild infundibular pulrnonic stenosis. For the whole group, the distribution of the muscular defect was posterobasal in 8 cases, THE AMERICAN
JOURNAL
OF CARDIOLOGY
Muscular
Septal
1Iet’ects
FIN. 2. I&art of 10 month old in/m/ shows fmtovbasal muscular r:untricular srptal dqfcct and an ntrml .sefital clrfert. both wpaiwd. The patient died after surgical treatment in 1956. Three weeks preoperatively the prrssures in the left and the right ventricles and the pulnlonnry artery were, respectively, 86/O, 77/-l, and 79/32 mm. Hg, and the left to right shunt was calculated to br 73 per cent; the relative quantitation at atria1 and vrntricular levels was difficult to assess. ‘The baby weighed 9 pounds, and had a grade 3/6 systolic mururur to the left of the sternum; the heart was huge, and pulmonary vascular shadows were prominent on the roentgenograrn. A, right side of heart with tricuspid valve opened. shows the repaired posterobasal muscular ventricular septnl drfeet and the repaired atria1 septal defect. H, close-up view of the posterobasal defect as seen from the right side with the tricuspid valve reflected toward the atrium. C, left ventricular view of the posterobasal defect with the aortic valve opened.
nlidseptal in 9, apical in 7, and outflow in 3. 7 hers. no area of the muscular septum was 1110rc freq\rcntly involved than another in instances of r~lrtltiple ventricular septal defects; however, defects in the outflow tract of the right ventricle I\ere relatively rare. &VU/I.P (~kluiuscxlnrlPntricular Septal Defect Witfl Otfwr Major Cardiac ilnomaly): Subgroup 3A (sin,gle defect) consisted of 36 cases, 13 autopsy and 23 surgical. Among the autopsy cases, the defect was posterobasal in 9 (Fig. 2 and 3), midseptal in 2 (Fig. 4), apical in 1, and outflow in 1. Thedefects ranged from 3 mm. to 2.5 cm. in diamc,ter. Among the surgical cases, the defect was apical in 9, posterobasal in 8, midseptal in 5, and indeterminate in 1. None was in the outflow tract of the right ventricle. These defects ranged from 3 mm. to 3 cm. in diameter. Among the total subgroup of 36 cases, the \‘Ol.UME
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1966
defect was in the posterobasal region in 17, ill the apical region in 10, in the midseptal regiorl in 1 case in 7, and in the outflow tract in 1; the location was not determined. The associated major anomalies in these 36 cases inaortic valve with aortic cluded : bicuspid stenosis or insufficiency, or both, in different insufficiency; mitral stenosis ; cases ; mitral tricuspid insufficiency or stenosis, or both ; pulmonary stenosis (infundibular or \.alvular, or both) ; pulmonary insufficiency- ; lloIlIl1LlscL1lar septal defect (the usual type of high septal defect partly involving the lnembranorts septum) ; atria1 septal defect ; patent ductrts coarctation of the aorta; tctralogy arteriosus; and complete transposition of the of Fallot; Some hearts had rnore than one great vessels. of these anomalies in addition to a muscular septal defect.
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and
‘ritus
F’IG.3.
Heart oj a .J rrvrk old znjaut
showing posterobasal muscular sepal dpjcct (moderate narrowzng of thr aortic isthmus and a patent dvctu arteriosus nlsnprewzt). The muscu-
lar defect is more anterior in the posterobasal region of the septum than that shown in Figure 2. ;\, right ventricular view with probe in defect. B, left ventricular virw of the defect.
Subgrou@ 3B (multiple muscular septal deftxts) was found in 19 cases (7 autopsy cases and 12 surAmong the autopsy cases, the Inuscular gical), defects were found, in various colnbinations, ill the midseptal region in 4, the apical region in 4, in the posterobasal region in 2, and in the outflow tract in 1 (Fig. 5 and 6). The defects ranged from 3 mm. to 2 cm. in diameter. .4mong the surgical cases, the muscular defects were, in various combinations, midseptal in 4, apical in 4, posterobasal in 2, outflow in 1, and indeterminate in 2. They ranged from 3 mm. to 1.6 cm. in diameter. Among the combined subgroup of 19 cases, the locations of the multiple muscular septal
FIG. 4. Heart of a 7 month old infant shows midseptal muscular defect and a patent ductus arteriosus. Right ventricular view with probe in the defect.
defects were Inidseptal in 8, apical in 8, posterobasal in 4, outflow in 2, and indeterminate in 7 _. The associated major cardiac anomalies were essentially similar to those associated with the single muscular defects (group 3A). ELECTROCARDIOGRAPHIC
STUDIES
Preoperative electrocardiograms Group I: were available in 22 of the 23 cases. Complete right bundle branch block (rSR’ in lead V1, with a QRS duration of 0.12 sec. or longer) was present in 2 cases, and in both the defect was in the posterobasal region of the septum. “Incomplete right bundle branch block” (rSR’ in lead V1, with a QRS of 0.08 to 0.11 sec.) was present in 9 cases ; among these the defect was posterobasal in 4, midseptal in 2, apical in 2, and indeterminate in 1. In 10 cases a Q wave was greater than 3 mm. in lead V5 or Vg, or in both, and the Q to R ratio varied from 1: 3.8 to 1: 3, with an average of 1 :5.5. In 7 of the 10 cases the muscular septaldefectwas posterobasal, while in 3 it was midseptal (Fig. 7). A Q wave greatel than 3 mm. in lead aVL occurred in 2 cases with Q to R ratios of 1:3.4. In 1 of them the frontal plane axis was + 15’ with a counterclockwise loop when the patient was 2.5 years old. Both cases had posterobasal defects. A Q wave greater than 3 mm. in lead aVF was present in 10 of the 22 cases; the defect was posterobasal in 5, midseptal in 3, and indeterminate in 2. The Q to R ratio ranged from In 6 1 : 3.4 to 1: 6.6 with an average of 1:4.9. of these 10 cases the Q wave was greater than 3 mm. itI the left precordial leads (Fig. 8). Cornplete right bundle branch block occurred postoperatively in 5 of the 19 cases in which both preoperative and postoperative electrocardiograms were available for comparison. Among these 5, the defect was posterobasal in 1, midTHE AMERICAN
JOURNAL
OF CARDlOL.OCY
Muscular-
Septal
1Defects
‘l‘his , sys;md .) thckinod basr: hmd ~fiwS L irw
septal ill I, apical in I, outflow in 1, and indeterminate in 1. Group 2: Atnong the 14 cases, complete right bundlr branch block occurred in 1; this patient had one large posterobasal and several small apical defects of the muscular type. In 4 cases there was “incomplete right bundle branch block“ ; in these the defects were apical and midseptal in 2 cases, posterobasal and apical in 1, and posterobasal and outflow in the fourth. A Q wave greater than 3 mm. in lead V, or Vg, or both, occurred in 5 cases; the Q to R ratio varic*d from 1 : 2.1 to 1 : 7.7, with an average of In these 5, the defects were apical and 1 : 4.2. midseptal in 1, posterobasal and outflow in 1, posterobasal and midseptal in 1, outflow and midseptal in 1 (Fig. 9), and apical only in the fifth. A Q wave greater than 3 mtn. in lead in these the Q to aVF was present in 5 cases; R ratio varied from 1 :4.2 to 1: 5.5 with an average of 1: 4.7. The defects were apical only in 2 cases, apical and posterobasal in I, apical and rnidseptal in I, and posterobasal and outIn 3 of these 5 cases the Q wave also flow in I. was greater than 3 nun. in the left precordial VOI.,TME18,
NOVEMBER
1966
leads. A Q wave greater than 3 111111.irt lcad aVL was found in 2 cases; the Q to ii ratio was 1 :2.6 in 1, 1:0.8 in the other. In 1 of thetn the frontal axis was -30’ with a countcrclockwise loop when the patient was 3 years old. In this case the defects MJere postcrobasal and tiGtlseptal, while in the other thr); \vt’x lllids~ptal and outflow. Complete right btllltlle branch block developed postoperatively ill 5 of the’ 13 cases in which both preoperati\re alld postopctxtive electrocardiograms WWC’ a\-ailablc. ‘l’hr defects \vere midseptal only in 1, postcwhasal and midseptal in 2. posterohasal aild o(ltflow in 1, and posterobasal and apical in the fifth cast. Grouf, .3: No electrocardiographic analysis of group 3 will be presented. Brcar~ of the complexity and Iilultiplicity of the associated lesions which affect the electl.ocaldiogt.alll, no inference as to the influcncc of thr 11111scr11at scptal defect on it seelned jrlstificd. HEMODYNAMIC
CORRELATION
In 18 of the 23 cases, silllrlltancorls measurements of right ventricular and systeltlic systolic pressures and accttrate tneastttwttents of Group
I:
718
Saab,
Burchell,
DuShane
and Titus
aVR
aVL
n
III
FE. 7. El~ctmcardio~ram in a 72 yr,ar old boy &h mdsepta muscular dpfpct which nwasurpd 7.1 by 03 cm. a~ operation The surgeon noted “a powerful systolic thrill over the outflow tract of the right ventricle, which originated low in the ventricle, making us suspect a Inoscular defect. A defect measuring 1.1 by 0.6 cm. in the midportion of the muscular portion of the septum which had a good fibrous ring” was found. Note prominent Q wave in Ve, delayed excitation of the right ventricle (KsK’ in V,), the magnitude of 12’ (2.0 ~nv.) indicating right ventricular hypertrophy, and evidence of left ventricular hypertrophy. l‘he thoracic roentgenogram showed cardiomegaly (cardiothoracic ratio, 0.52) and moderately increased pulmonary vascular markings. Systolic pressures (mm. Hg j at the time of operation were KV, 55 ; systemic, 120. FIG. 6. Heart of 72 year old girl shows multiple muscular septal d&s, a “membranou.c” si;btal dcfmt (narrow patent ductus arteriosus alsopresent). Clinically, the patientwas small and thin with moderate limitation in her exercise tolerance. There was a grade 3/6 systolic murmur of moderate length to the left of the sternum and a grade Z/6 diastolic murmur at the apex. There was marked cardiac enlargement and prominence of the pulmonary vasculature. Cardiac catheterization revealed equivalent pressures in the pulmonary and femoral arteries (103/70 and 101/70 mm. Hg, respectively) and a calculated left to right shunt of 70 per cent. The surgeon had difficulty identifying all of the defects, and reported a “Swiss cheese” structure; heart block occurred, and the patient died 9 days postoperatively. A, right ventricular view showing probes in midseptal defects and a patch over a large apical defect. Sutures close other midseptal defects and the “membranous” septal defect. B, left ventricular view shows a patch over a large apical defect, white probes in midseptal defects, and a usual high septal defect under the aortic valze (black probe at arrow).
the size of the ventricular septal defect were availabfe. The area of the defect was calculated by using the formula for an ellipse, except in those few cases in which the defects were circular or triangular (in which case the appropriate geometric formula was used). The ratio of right ventricular systolic pressure to systemic systolic pressure was plotted against the area of the muscular septal defect per unit body surface area calculated from the patient’s height and weight3 (Fig. 10). This showed an approximately linear relation between the pressure ratios and the defect area up to a defect of 100 n~m.2/M.2; beyond this size there was evidence of a tendency to equalization of pressures in the two ventricles. In group 2, no such measurements were attempted because the multiplicity of the muscular THE
AMERICAN
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CARDIOLOGY
Muscular
Septal
I~l~ct,-ocar~fir,ra~n~ of 5.75 year old boy w/h .~rn,gle FIG. 8. po~lProhnraf nrrr,culnr d$PCl I.3 by 0.9 cm. at operation. Note Ixoluinrnt (2 waves in leads aVF and Vg, with evidrnce of biventricular hypertrophy (V, taken at 0.5 usual starldardiz;ltion). ‘l’he thoracic roentgenogram showed cardionwgaly (cardiothoracic ratio, 0.57), prominent central pulmonary arteries, and prominent peripheral Systolic pressures (mm. Hg) at time vascular Inarkings. of surqrry wrrr K\‘. 70: systemic, 110.
defects made calculation of their total area unreliable. The calculations were considered meaningless in group 3 because complex lesions were present. CLINICAL
18,
NOvEMBKR
of 6 YPC.V oldgirl with two n~~c.rrulor FIG. 9. El~ctroca~diqrm s$tal d+ctJ, one in the outflow region 1.4 by 0.8 city. and Mild the other in the nlidseptal region 0.8 by 0.5 con. I’rollGncnt infundibular pulrnonic strnosis was present. Q waves in aV1, and Vc are present together tvith a counterclockwise rotation of the sequential QRS vectors as prqjected on the frontal plane, indicating left ventricuThere is evidencr of right ventricular lar hypertrophy. ‘Thoracic roentgenogram showed hypertrophy also. cardiomegaly (cardiothoracic ratio, 0.56) and Inodcrate increase in pulmonary vascular markings. Systolic pwssurcs (mm. Hg) were RV, 75; systrmic, 80.
. ..
CORREL.ATION
In general, the clinical features of these cases of defects in the muscular septum were not distinctive compared with those of the usual type The susof defect under the aortic valve. picions of one of us (H. B.) that defects in the right ventricular outflow tract above the papillary muscle of the conus might simulate pulmonary stenosis in the location of the murmur and that defects in the apical portion of the septum might more closely simulate mitral incompetence did not gain strong general support in this study. In retrospect, many of the recorded findings are inadequately discussed but items are mentioned which are of interest ; some examples follow. Regrettably, phonocardiogrants were not made of these patients. VOI.UME
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IIefects
1966
.
.
l
l
.
.
. .
FIG. 10. Ratio of right ventricular systolic pressure to systemic systolic pressure plotted against ratio of calculated area of muscular septal defect to body surface area. The 18 patients in this graph had an isolated single muscular defect (group 1 ).
720
Saab,
Burchell,
The clinical diagnosis of ventricular scptal defect was made of an 18 year old girl, and there was a note that “there was good transmission to the left axilla.” The electrocardiogram was normal. Cardiac catheterization revealed pressures and fo\v values as follo\vs : right ventricle. 34/3 mm. Hg; pulmonary artery, 33/14 mm. Hg; pulmonary flow (Qp) 11.6 L.,/min. ; systemic flow (Qs) 5.6 L./min. The surgeon spent considerable time in locating the defect because it was practically hidden by the papillary muscle, but he sutured it successfully. A 16 year old girl had only a faint systolic murmur
at the left upper part of the sternum. The electrocardiogram showed right ventricular hypertrophy and delayed excitation of the right ventricle (RSR’ in VI). Pulmonary artery pressure was reported as 75/30 mm. Hg when systemic arterial pressure was 104/70 mm. Hg and the Qp/Qs ratio was 1.9. At operation the right ventricular, left ventricular and pulmonary artery systolic pressures were equal, and no decrease in pulmonary artery pressure occurred after closure of the defect. The apical communication between the ventricles was 2 by 2 cm. The patient survived the operation and is living and active five years later but has severe pulmonary hypertension. One consultant suspected that the ventricular septal defect in a 12 year old girl was associated with congenital mitral stenosis and incompetence because of a rather prominent (grade 2;‘6) apical diastolic murmur. The electrocardiogram showed right ventricular hypertrophy and right axis deviation. The surgeon reported the mitral valve was normal; the ventricular septal defect, measuring 2.2 by 1.4 cm, was “1OW” in the muscular septum. Preoperative hemodynamic studies were not done; at operation, right and left ventricular pressures were 70/O and 75/O mm. Hg before repair and 40/l and 115/5 mm. Hg afterward. In the records of 3 children, 5, 6 and 12 years old, there was a note that the murmur was heard well toward the apex, but this finding was apparently not unusual (such a finding is present in young patients with ordinary ventricular septai defects). Analysis of the records shows that the apical diastolic murmur has been prominent in some cases, possibly unduly so compared to the usual type of ventricular septal defect. Figure 6 shows the heart in a case in which the apical diastolic murmur had been prominent; the hemodynamic findings are given in the legend. This patient had an unusual electrocardiogram with Qs in VI, and Rs in Vg and Vi, and an RS in leads II and 111-a vectorial loop oriented posteriorly in the horizontal plane and counterclockwise in the frontal plane. One possibility considered clinically as a complication in this case \vas a “corrected transposition” because of absence of Q waves in lead I and in the left precordial leads.
DISCUSSION The definition of muscular ventricular septal defect used in this study was adapted to exclude
DuShane
and
Titus
defects which involved part or all of the tnelnbranous septum (that is, the usual high septal defect posteroinferior to the crista supravcntricularis), atrioventricular canal types of ventricular septal defect4 (which involve the tricuspid or mitral valve rings, or both), and high defects that involve the aortic or pulmonary valve rings, or both, and which often lead to incompetence of these valves. The classification of muscular septal defect by location was similar to Edwards’ classification” of ventricular septal defect in general, within the limitations of the definition of muscular septal defect, except that we have included a midseptal region between the posterobasal and apical regions. The exclusion from this study of muscular defects less than 3 mm. in diameter should not materially affect the data since such small defects probably are hemodynamically and clinically insignificant. Previous studies6-lo of the frequency of location of ventricular septal defects have not specified whether or not the defects were muscular as defined herein, and therefore they are not exactly comparable to this study. In this study, when the muscular defect was single, it was posterobasal in about half of the cases, whether there were associated cardiac anomalies or not. Edwards5 observed that when the muscular defect was single it was usually located in the apical region. With multiple defects there was no selectivity of site, and the presence of associated cardiac lesions did not seem to influence the location. The outflow region of the right ventricle was rarely involved with either single or multiple muscular defects. We confirmed that the muscular ventricular septal defect is uncommonly associated with tetralogy of Fallot;” in only 5 of our 92 cases was this also present. The defect was posterobasal in 2 of these 5 cases, midseptal in 1, and apical in 1; in the fifth case there was a posterobasal and many apical defects. As did Edwards and associates,” we observed that it was less common for a muscular defect to be associated with a nonmuscular defect than for the muscular defect to be the sole malformation of the ventricular septum. Excluding the cases of tetralogy of Fallot, only 19 muscular defects were associated with nonmuscular septal defects. In his description of ventricular septal defect Seizer’ stated that, although 90 per cent of isolated defects are membranous in location, almost all those with associated malformations are membranous. This implied that a muscular defect was more likely to be isolated than to be THE
AMERICAN
JOLJRNAL
OF
CARDIOLOGY
Muscular However, associated with other cardiac lesions. we found that in 55 of the 92 cases the muscular septal defect was associated with other major cardiac anomalies. Whether or not this represents Ilndetected bias in the selection of the This material cannot be stated with certainty. appears unlikely as the sole explanation since all the isolated cases, whether autopsy or surgical, were indexed in our files under the diagnosis of ventricular septal defect, whereas some of those associated with other major cardiac anomalies wrre filed only under the associated diagnosis. C:onsequently, if any cases were missed in this sturdy, they probably would have been among the complex variety, and their inclusion would have further increased the relative incidence of muscular septal defects associated with other cardiac lesions. The incidence of subacute bacterial endocarditis in patients with muscular septal defects is said to be lower than in those with the more common types of ventricular septal defects.12 In none of our 27 autopsy cases was there morphologic evidence of bacterial endocarditis. ICffect of 17entricular Systole on Size of Muscular Defect: Seizer, 1 Downing and Goldberg,‘” and Darnlnann and co-workers14 have expressed the opinion that a muscular septal defect tends to be of lninor physiologic significance because the defect may decrease in size or even close with contraction of the ventricular septal musculature during ventricular systole, at which time the shunt would be at its peak. However, Heath and associates’” reported a case of apical muscular septal defect in a 21 year old woman with ~narked pulmonary hypertension and hemoptysis; at autopsy, severe changes in the pulmonary arterioles were found. They pointed out that a muscular septal defect may not be as innocuous as supposed. Of the 7 autopsy cases of isolated ~nuscular ventricular septal defect in our series, 2 had obstructive pulmonary vascular disease shown by histologic examination of the lungs. There were multiple, large defects in both cases. The area of the defect appeared to be related to the ratio of the right ventricular systolic (RV) to the systemic systolic (S) pressure (Fig. 10) in patients with single, isolated muscular ventricular septal defect. It was found that, with the exception of 1 patient less than 2 years old, the ratio RV/S was less than 0.6 for a defect less than 100 mm.2/M.2 and that the relation was nearly linear with decreasing size of the defect. .4mong defects with areas greater than 100 VOLIJME
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1966
Septal
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‘21
‘;1/1.‘, there \vas no case with an K\’ S ratio less than 0.6, and the scatter indicattd hiqhtar RV,!S ratios than would be cxpectrd fro111 the This relation was calculated sizes of the defects. noted by Savard and co-workers”’ for thr IISIIA type of high (Inembranous) ventriclilar septal defect and is in accord with the obscr\,ation that, for defects with areas greater than 100 IIII~.~, ‘h,1.2, there is a tendency for eqllalization of prcssllrcs in the two ventricles.‘“,‘7 ‘The findings stlggcst that, at least in the 18 cases shown in Figrlrc 10, there did not seem to have been any sig-nificallt decrease of the defect with ventricular systolc. If the latter had been true, one wol11d ha1.e cxpetted a wide scatter in the lower left qlladrallt of the plot, indicating a greater pressure gradient across the defect in relation to its calclllatrcl size. Thus, although the findings in this stncl~. did not disprove the possibility of a dilninished size of defect with ventricular systole in son~e cases, they did not support a concept of systolic closure of the defect as a universal event. Thcsc findings and the fact that pulmonary vascular disease was present in 2 of the 7 autopsy casts indicated that in seine cases a tnuscular septal defect rcsults in syndromes similar to those observed in the usual type of ventricular septal defect. Therefore, a muscular septal defect appears to present a hemodynamic and clinical spectrlllil which ranges from the very small defects with minimal shunts (which were excluded fro111 this study because of size) to large defects associated with pulmonary vascular disease. ?‘he ele~trocardiq~raphic jindings in the cases of isolated muscular septal defect (both single and multiple) were similar to the expected findings in ventricular septal defect in general.1x-‘7 The main determinant of the electrocardiographic pattern seemed to be the hemodynamic status, namely, size of the shunt and degree of the pulmonary vascular disease. Thus, patterns of left, right, or combined ventricular overload Lvere encountered which reflected Inoderate left to right shunting, pulmonary \,ascular disease with minimal, balanced, or reversed shunting, and marked left to right shunting, respcctively. Complete and “incomplete” right brandle branch block also were seen. None of the 37 cases with isolated defects, however, had the atrioventricular canal type of loop4fY‘ which is found in about 15 per cent of cases of ventricular septal defect of the usual type.22 This might be expected since Titus and associates28 found that, of 4 cases of posterobasal muscular defect assoIIIIII.~
722
Saab,
Burchell,
ciated with usual “membranous defect,” in only 1 was the muscular defect related to conduction tissue and the posterobasal defect was large with its anterior rim adjacent to the conduction tissue. Although deep Q waves in leads reflecting left ventricular potentials are known to occur with it was ventricular septal defect, 18,2?,23,26~27,39,3il our clinical impression before this study that perhaps they may be more pronounced in paIf such were the tients with muscular defects. case, one could hypothesize that the excitation of the left ventricular free wall was sufficiently delayed to allow the septal excitation to dominate Accordthe mean vector for a longer period. ingly, we analyzed the initial vector by noting the depth of Q waves in V5 or Vg, or both, and in aVF in the cases of isolated muscular septal defect. The Q waves 3 11~x1. or greater were present in 54 per cent of cases in group 1 and in 57 per cent in group 2. Although this was slightly higher than the 40 per cent incidence reported by Vince and Keith26 for ventricular septal defect in general, our series was not large enough to allow us to draw any firm conclusions. In this study there was no correlation between the location of the defect in the muscular septum and the presence or magnitude of Q waves in V, In 4 of the 22 cases or Vg, or both, or in aVF. in group 1 (none in group 2) there were Q waves 4.5 mm. or greater in both left precordial leads The muscular septal defect was and in aVF. posterobasal in 3 of these cases and midseptal in 1. No correlation between age of the patient The development of and Q waves was found. right bundle branch block postoperatively in a minority of the cases could not be correlated with any specific location of the defect or defects in the muscular septum. Since completion of this study, Friedman and associate?* reported data on 7 patients with multiple muscular septal defects, 6 with autopsy. Their study emphasized the serious nature of Morphomultiple muscular septal defects. logically, the defects were located in various regions of the septum, and in more than half the cases at least one of the defects was greater than 3.0 mm. in diameter. Of the 7 patients, 4 were boys and 3 were girls; their ages ranged from 4 months to 3 years. All manifested congestive heart failure and growth retardation. Combined ventricular hypertrophy and “incomplete” right bundle branch block were demonstrated Right in the electrocardiograms of all patients. heart catheterization showed marked pulmonary hypertension.
DuShane
and
Titus SUMMARI~
Ninety-two cases of muscular ventricular These defects were septal defect were reviewed. defined as completely surrounded by muscular septurrl and consequently did not involve the membranous septum or any valvular ring. They were classified, according to their location in the right side of the muscular ventricular septum, as posterobasal, midseptal, apical, or outflow. Of the 92 cases, 23 were isolated single defects, 14 were isolated multiple defects, and 55 were associated with other major cardiac anomalies. In these 55 cases, the defect was single in 36 cases and muItiple in 19. Regardiess of the presence or absence of associated cardiac anomalies, when the defect was single, it was posterobasal in about half of the cases. No specific location of multiple defects was apparent. Muscular defects in the outflow tract of the right ventricle were rare. The evidence suggests that muscular ventricular septal defects may cause hemodynamic and clinical syndromes similar to those caused by the usual type of ventricular septal defect. The electrocardiographic features in the 37 cases of isolated defects were analyzed. A possible increased incidence of prominent Q waves in leads reflecting left ventricular potential occurred but, as a generalization, the electrocardiogratns were similar to those observed in cases of the usual type of defect. ACKNOWLEDGMENT The authors wish to thank Dr. John W. Kirklin and Dr. Dwight C. McGoon for their permission to use the reports of the surgical observations. REFERENCES 1. SELZER, A. Defects of the cardiac septums. J.A. M.A., 154: 129, 1954. 2. SHERMAN, F. E. An Atlas of Congenital Heart Disease, pp. 167-174. Philadelphia, 1963. Lea PC Febiger. 3. DUBOIS, E. F. Basal Metabolism in Health and Disease, ed. 3, pp. 131 and 135. Philadelphia, 1936. Lea & Febiger. 4. NEUFELD, H. N., TITUS, J. L., DUSHANE, J. W., BURCHELL, H. B. and EDWARDS, J. E. Isolated ventricular septal defect of the persistent common atrioventricular canal type. Circulation, 23: 685, 1961. 5. EDWARDS, J. E. Congenital malformations of the heart and great vessels. B. Malformations of the ventricular septal complex. In: Pathology of the Heart, ed. 2, pp. 294-317. Edited by GOULD, S. E. Springfield, Ill., 1960. Charles C Thomas. 6. BECU, L. M. et al. Anatomic and pathologic studies in ventricular septal defect. Circulation, 14: 349, 1956. 7. KIRKLIN, J. W., HARSHBARGER, H. G., DONALD, THE AMERICANJOURNAL OF CARDIOLOGY
Muscular
Septal
E. and EDWARDS, .I. E. Surgical correction of ventricular septal defect: Anatomic and technical considerations. .I. ‘Thoracic Sq., 33: 45, 1957. WARDEN, H. E., DEWALL, R. A., COHEN, M., VARCO, R. L. and LILLEHEI, C. W. A surgicalpathologic classification for isolated ventricular septal defects and for those in Fallot’s tetralogy based on observations made on 120 patients during repair under direct vision. J. Thoracic Surq., 33: 21,1957. CLELAND, W. P. Ventricular septal defects. Pm. Roy. Sac. Med., 54: 785, 1961. COOLEY, D. A., GARRETT, H. E. and HOWARD, H. S. ‘l’he surgical treatment of ventricular septal defect: ,413analysis of 300 consecutive surgical cases. Prog. Cardionas. Us., 4: 312, 1962. EDWARDS, .I. E., CAREY, L. S., NEUFELD, H. N. and LW~ER. R. G. Congenital Heart Disease: Correlation of Pathologic Anatomy and Angiocardiography, Vol. 1, p. 95. Philadelphia, 1965. W. B. Saunders Company. VBASY, L. G. Clinical findings in ventricular septal defects. Am. J. Cardiol., 5: 185, 1960. DOWNINCI,D. F. and GOLDBERG,H. Cardiac septal dffects. I. Ventricular septal defect: Analysis of one hundred cases studied during life. Dis. Chest, 29: 475, 1956. DAMMANN,J. F., JR., THOMPSON,W. M., JR., SOSA, OMAR, and CHRISTLIEB,I. Anatomy, physiology and natural history of simple ventricular septal defects. .4m. J. Cardiol., 5 : 136, 1960. HEA.I.H,D., BROWN, J. W. and WHITAKER, W. Muscular defects in the ventricular septum. Brit. Heart J., 18: 1, 1956. S~VARD, M., SWAN, 1-I. J. C., KIRKLIN, J. W. and WOOD. E. H. Hemodynamic alterations associated with ventricular septal defects. In: Congenital Heart Disease. A Symposium Presented at the Washington Meeting of the American Association for the Advancement of Science, pp. 141-164. Edited by BASE, A. D. and MOE, G. K. Washington, D. C., 1960. BURGHELL, H. B. Studies in pulmonary hypertension in congenital heart disease. Brit. Heart J., 21: 255, 1959. MARSICO, F., PE~~ALOZA,D., TRANCHESI,J., LIM~N, Ii. and SODI-PALLARES, D. The electrocardiogram in ventricular septal defect: Scalar and vectorial analysis of thirty-two cases. Am. Heart J., 49: 188,1955. BLOUN.L.,S. G., JR., MUELLER, H. and MCCORD, M. C. Ventricular septal defect: Clinical and I).
8.
9. 10.
11.
12. 13.
14.
15.
16.
17.
18.
19.
VOLUME 18, NOVEMBER1966
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
Defects
723
hemodynamic patterns. :lm. .I. .+fpd.. 18: 871, 1955. IIUBBARD, T. F. and ANGLE, W. D. The rlectrocardiogram in ventricular septal defect: A correlative study of fifty cases. .4m. J. Z)is. Chi/d.. 04: 20, 1957. FYLER, D. C., RUDOLPH, A. M., WITTENBORG,M. H. and NADAS, A. S. Ventricular septal defect in infants and children: A correlation of clinical, physiologic, and autopsy data. Clrcitlation, 18 : 833, 1958. TOSCANO-BARBOZA,E. and DUSHANE, .J. \V. Ventricular septal defect: Correlation of electrocardiographic and hemodynamic findings in 60 proved cases. .4m. J. Cardiol., 3: 721, 1959. CHAR, F., ADAMS, P., JR. and ANDERSON, R. C. Electrocardiographic findings in one hundred verified cases of ventricular septal defect. Am. .1. Dis. Chzld., 97: 48, 1959. BRISTOW, J. D., KASSEBAUM,D. G., STARR, A. and GRISWOLD, H. E. Observation on the occurrence of right bundle-branch block following open repair of ventricular septal defects. C’irrulation, 22: 896, 1960. BEREGOVICH,J., BLEIFER,S., DONOSO,E. and GRISHMAN, A. The vectorcardiogram and electrocardiogram in ventricular septal defect: With special reference to the diagnosis of combined ventricular hypertrophy. Brit. Heart .I., 22: 205, 1960. VINC~, D. J. and KEITH, J. D. The electrocardiogram in ventricular septal defect. Circulation, 23: 225, 1961. SODI-PALLARES,D. and TESTELLI, M. R. Electrocardiography in the diagnosis of congenital heart disease. Hmrt Bull., 13: 24, 1964. Torus, J. L., DAUGHERTY,G. W. and EDWARDS,J. E. AnatoIny of the atrioventricular conduction system in ventricular septal defect. Circulation, 28: 72, 1903. DUSHANE, J. IV., WEIDMAN, W. II. and BRANDENBURG, R. 0. The electrocardiogram in children with ventricular septal defect and severe pulmonary hypertension: Correlation with response of pulmonary arterial pressure to surgical repair (.4bstr.). rim. J. Dis. Child., 98: 464. 1759. DU~HANE, J. 1%‘. and KIRKLIN, J. W. Selection for surgery of patients with ventricular septal defect and pulmonary hypertension. Circulation, 21 :13, 1960. FRIEDMAN,W. F., MEIXRIZI, A. and PUSCI~ A. L. Multiple muscular ventricular septal defects. Cmlution, 32: 35, 1965.
Studies
Muscular Ventricular NICHOLAS
G. SAAB, M.D., HOWARD B. BURCHELL, JACK L. TITUS, Rochester,
S
Septal Defects* M.D.,
JAMES \%‘. DUSHANE, M.D. and
M.D.
Minnesota
muscular ventricular septal defects are said to comprise about 10 per cent of all ventricular septal defects,1*2 a review of the clinical, hetnodynatnic, electrocardiographic and morphologic features associated with musclllar defects of the ventricular septum was tindertaken. In this study we considered a muscular ventricular septal defect to be one that was completely surrounded by muscular tissue of the ventricular septum; thus it did not involve the membranous septum, and no part was immediately related to a valvular ring.
mined from the operative record, it was termed “indeterminate.” Electrocardiographic analysis included determination ot the mean QRS axis and loops in both the frontal and horizontal planes; the presence of Q deflections and the Q to R ratios in one or more of leads the duration aVF, aVL and Vs or Vg, or both; and pattern of the QRS complex in lead VL: and the voltages of R and S waves in leads VI and 1-S 01 Vg, or both. Hemodynamic data, when available, were analyzed. In most of the surgically treated patients, pressures in both ventricles had been recorded at operation prior to the institution of extracorporeal circulation. Some of the 92 patients had had right cardiac catheterization. and systemic arterial pressure, pulmonic and systemic flow and resistance, and magnitude of shunt had been measured.
INCE
MATERIALS AND METHODS The operative records of all patients who had had operations for ventricular septal defect performed in this institution from 1955 through 1964 were reviewed to obtain the surgeons’ descriptions of the morphologic features of the defects. The autopsy protocols of all cases in which a diagnosis of ventricular septal defc,ct had been made at autopsy from 1955 through 1964
RESULTS Autopsy was perfortned in 27 of the 92 castss (operation had been performed in 22 of these The age 27): 65 were purely surgical cases. range of the whole group was from 3 weeks to 60 years, but most patients were between 2 and 20 years. The sex distribution was 30 male and 53 female patients (approximately 0.7 : 1). The 92 cases were divided into three nlain groups (Table I). Group 1 consisted of 23 cases with a single muscular ventricular septal defect without any other significant cardiac anomaly-. Group 2 consisted of 14 cases of mllltiple musclelar septal defects with no other major cardiac anomaly. Group 3 included the 55 C~SCS of one
\vere reviewed, and the hearts were examined when the descriptions of the defects suggested that they might have been the muscular type. From the cases selected by the combined review of surgical records and autopsy specimens, a group was selected for detailed study. The criteriafor thisgroup were: (1) The defect or defects were muscular according to the definition already noted; (2) they were at least 3 mm. in and (3) the patient had had at least one diameter; t=lectrocardiogram, usually 12 leads, which was of good quality, although occasionally a case was included if it had only leads VI, Vs, Vs, and the six limb leads. These three criteria were fulfilled in 92 cases. For morpholo&c clas$ication of the location of the,muscular defects, the muscular ventricular septum, as viewed from the right side, was arbitrarily divided into four areas (Fig. 1): postero(infero)basal, midseptal, apical and outflow. Whenever the location of the muscular defect could not be accurately deter-
or more
other
ular
septal
type,
atria1
septal
coarctation great
cardiac
defect
vessels,
of
anomalies,
of the Ilsual defect,
the
patent
aorta,
tetralogy
such as ventric(“nletnbrano\~s”) ductus
transposition
of Fallot,
or
arterioslls, of
the
siqiiificant
* From the Sections of Medicine, Pediatrics and Experimental and Anatomic Pathology, Mayo Clinic and MAYO Foundation and Mayo Graduate School of Medicine, University of Minnesota, Rochester, Minn.
\‘OLIJME18, NOVEMBER1966
713
714
Saab,
Burchell,
DuShane
and
Titus
FE.
scle of conus Membranous septu
____-----
Tricuspid valve ring
1.
vmtricular
?f the muscular septum as seen from the
Diagram
right after removal of the free wall of the right ventricle. The septum has been arbitrarily divided into outflow (Out), posterobasal (PB), midseptal (MS) and apical (c\p) areas.
Crlsta supraventricularis
vahwlar lesions, associated with the muscular This group was further subdivided into defect. group 3A (single muscular defect) and group 3B (multiple muscular defects). Each of these major groups included autopsy as well as surgical cases, although group 1 was composed almost entirely of surgical cases. Some of the patients had died in the immediate postoperative period, and these were considered as autopsy cases since the morphologic aspects were determined from autopsy specimens. MORPHOLOGIC
FINDINGS
Group 1 (Single Muscular Sepal Defect): Of the 23 cases, 1 was an autopsy case and 22 were surTABLE I Age and Sex Distribution in Gases of Muscular Ventricular Septal Defect (mVSD)
Age (G Sex Distribution
A$< Q-6 mo. 6-12 mo. l-2 yr. 2-5 yr. i-10 yr. IO-20 yr. Over 20 yr. Total Range Sex (male-female)
Total Series
Group 1 (single mVSD)
6 5 6 17 27 25 6 92 3 wk.60 yr.
0 1 1 5 7 9 0 23 7 nlo.182/s yr.
39:53
11:12
* Those with other cardiac anomaly.
Group 2 (multiple mVSD)
1 0 0 5 5 2 1 14 4 mo21
.75yr.
2:12
Group 3*
5 4 5 7 15 14 5 55 3 wk.60 yr. 26~29
gical. In the autopsy case, there was a posterobasal defect 1.5 cm. in diameter, and a suggestion of muscular subaortic stenosis. In the surgical cases, the defect was posterobasal in 11, midseptal in 5, apical in 2, outflow in 1, and indeterminate in 3. Thus, in about half of the cases the defect was situated in the posterobasal part of the muscular septum. The defects ranged from 4 by 2 mm. to 2.2 by 1.4 cm. Group 2 (Multiple Muscular Ventricular Septal Defects): There were 6 autopsy cases and 8 surgical ones. In the autopsy cases the muscular defects were situated in the midseptal region in 5, the posterobasal region in 4, the apical region in 3, and the outflow tract in 1. The defects ranged from 3 mm. to 2.0 cm. in diameter. In some of these cases other minor abnormalities were present, such as slight bulge of the membranous septum, suggesting the earliest state of an aneurysm in 1 case, slight hypoplasia of the aorta in 1, a double orifice of the mitral valve with slight mitral insufficiency in 1, and a slight malformation of the tricuspid valve in 1. In the 8 surgical cases, one or more defects were located in the posterobasal region in 4 cases, in the rnidseptal region in 4, in the apical region in 4, and in the outflow tract in 2. The defects ranged from 3 mm. to 3.5 cm. in diameter. In 1 case there was mild infundibular pulrnonic stenosis. For the whole group, the distribution of the muscular defect was posterobasal in 8 cases, THE AMERICAN
JOURNAL
OF CARDIOLOGY
Muscular
Septal
1Iet’ects
FIN. 2. I&art of 10 month old in/m/ shows fmtovbasal muscular r:untricular srptal dqfcct and an ntrml .sefital clrfert. both wpaiwd. The patient died after surgical treatment in 1956. Three weeks preoperatively the prrssures in the left and the right ventricles and the pulnlonnry artery were, respectively, 86/O, 77/-l, and 79/32 mm. Hg, and the left to right shunt was calculated to br 73 per cent; the relative quantitation at atria1 and vrntricular levels was difficult to assess. ‘The baby weighed 9 pounds, and had a grade 3/6 systolic mururur to the left of the sternum; the heart was huge, and pulmonary vascular shadows were prominent on the roentgenograrn. A, right side of heart with tricuspid valve opened. shows the repaired posterobasal muscular ventricular septnl drfeet and the repaired atria1 septal defect. H, close-up view of the posterobasal defect as seen from the right side with the tricuspid valve reflected toward the atrium. C, left ventricular view of the posterobasal defect with the aortic valve opened.
nlidseptal in 9, apical in 7, and outflow in 3. 7 hers. no area of the muscular septum was 1110rc freq\rcntly involved than another in instances of r~lrtltiple ventricular septal defects; however, defects in the outflow tract of the right ventricle I\ere relatively rare. &VU/I.P (~kluiuscxlnrlPntricular Septal Defect Witfl Otfwr Major Cardiac ilnomaly): Subgroup 3A (sin,gle defect) consisted of 36 cases, 13 autopsy and 23 surgical. Among the autopsy cases, the defect was posterobasal in 9 (Fig. 2 and 3), midseptal in 2 (Fig. 4), apical in 1, and outflow in 1. Thedefects ranged from 3 mm. to 2.5 cm. in diamc,ter. Among the surgical cases, the defect was apical in 9, posterobasal in 8, midseptal in 5, and indeterminate in 1. None was in the outflow tract of the right ventricle. These defects ranged from 3 mm. to 3 cm. in diameter. Among the total subgroup of 36 cases, the \‘Ol.UME
18.
NOVEMBER
1966
defect was in the posterobasal region in 17, ill the apical region in 10, in the midseptal regiorl in 1 case in 7, and in the outflow tract in 1; the location was not determined. The associated major anomalies in these 36 cases inaortic valve with aortic cluded : bicuspid stenosis or insufficiency, or both, in different insufficiency; mitral stenosis ; cases ; mitral tricuspid insufficiency or stenosis, or both ; pulmonary stenosis (infundibular or \.alvular, or both) ; pulmonary insufficiency- ; lloIlIl1LlscL1lar septal defect (the usual type of high septal defect partly involving the lnembranorts septum) ; atria1 septal defect ; patent ductrts coarctation of the aorta; tctralogy arteriosus; and complete transposition of the of Fallot; Some hearts had rnore than one great vessels. of these anomalies in addition to a muscular septal defect.
716
Saab,
Burchell,
I>uYhane
and
‘ritus
F’IG.3.
Heart oj a .J rrvrk old znjaut
showing posterobasal muscular sepal dpjcct (moderate narrowzng of thr aortic isthmus and a patent dvctu arteriosus nlsnprewzt). The muscu-
lar defect is more anterior in the posterobasal region of the septum than that shown in Figure 2. ;\, right ventricular view with probe in defect. B, left ventricular virw of the defect.
Subgrou@ 3B (multiple muscular septal deftxts) was found in 19 cases (7 autopsy cases and 12 surAmong the autopsy cases, the Inuscular gical), defects were found, in various colnbinations, ill the midseptal region in 4, the apical region in 4, in the posterobasal region in 2, and in the outflow tract in 1 (Fig. 5 and 6). The defects ranged from 3 mm. to 2 cm. in diameter. .4mong the surgical cases, the muscular defects were, in various combinations, midseptal in 4, apical in 4, posterobasal in 2, outflow in 1, and indeterminate in 2. They ranged from 3 mm. to 1.6 cm. in diameter. Among the combined subgroup of 19 cases, the locations of the multiple muscular septal
FIG. 4. Heart of a 7 month old infant shows midseptal muscular defect and a patent ductus arteriosus. Right ventricular view with probe in the defect.
defects were Inidseptal in 8, apical in 8, posterobasal in 4, outflow in 2, and indeterminate in 7 _. The associated major cardiac anomalies were essentially similar to those associated with the single muscular defects (group 3A). ELECTROCARDIOGRAPHIC
STUDIES
Preoperative electrocardiograms Group I: were available in 22 of the 23 cases. Complete right bundle branch block (rSR’ in lead V1, with a QRS duration of 0.12 sec. or longer) was present in 2 cases, and in both the defect was in the posterobasal region of the septum. “Incomplete right bundle branch block” (rSR’ in lead V1, with a QRS of 0.08 to 0.11 sec.) was present in 9 cases ; among these the defect was posterobasal in 4, midseptal in 2, apical in 2, and indeterminate in 1. In 10 cases a Q wave was greater than 3 mm. in lead V5 or Vg, or in both, and the Q to R ratio varied from 1: 3.8 to 1: 3, with an average of 1 :5.5. In 7 of the 10 cases the muscular septaldefectwas posterobasal, while in 3 it was midseptal (Fig. 7). A Q wave greatel than 3 mm. in lead aVL occurred in 2 cases with Q to R ratios of 1:3.4. In 1 of them the frontal plane axis was + 15’ with a counterclockwise loop when the patient was 2.5 years old. Both cases had posterobasal defects. A Q wave greater than 3 mm. in lead aVF was present in 10 of the 22 cases; the defect was posterobasal in 5, midseptal in 3, and indeterminate in 2. The Q to R ratio ranged from In 6 1 : 3.4 to 1: 6.6 with an average of 1:4.9. of these 10 cases the Q wave was greater than 3 mm. itI the left precordial leads (Fig. 8). Cornplete right bundle branch block occurred postoperatively in 5 of the 19 cases in which both preoperative and postoperative electrocardiograms were available for comparison. Among these 5, the defect was posterobasal in 1, midTHE AMERICAN
JOURNAL
OF CARDlOL.OCY
Muscular-
Septal
1Defects
‘l‘his , sys;md .) thckinod basr: hmd ~fiwS L irw
septal ill I, apical in I, outflow in 1, and indeterminate in 1. Group 2: Atnong the 14 cases, complete right bundlr branch block occurred in 1; this patient had one large posterobasal and several small apical defects of the muscular type. In 4 cases there was “incomplete right bundle branch block“ ; in these the defects were apical and midseptal in 2 cases, posterobasal and apical in 1, and posterobasal and outflow in the fourth. A Q wave greater than 3 mm. in lead V, or Vg, or both, occurred in 5 cases; the Q to R ratio varic*d from 1 : 2.1 to 1 : 7.7, with an average of In these 5, the defects were apical and 1 : 4.2. midseptal in 1, posterobasal and outflow in 1, posterobasal and midseptal in 1, outflow and midseptal in 1 (Fig. 9), and apical only in the fifth. A Q wave greater than 3 mtn. in lead in these the Q to aVF was present in 5 cases; R ratio varied from 1 :4.2 to 1: 5.5 with an average of 1: 4.7. The defects were apical only in 2 cases, apical and posterobasal in I, apical and rnidseptal in I, and posterobasal and outIn 3 of these 5 cases the Q wave also flow in I. was greater than 3 nun. in the left precordial VOI.,TME18,
NOVEMBER
1966
leads. A Q wave greater than 3 111111.irt lcad aVL was found in 2 cases; the Q to ii ratio was 1 :2.6 in 1, 1:0.8 in the other. In 1 of thetn the frontal axis was -30’ with a countcrclockwise loop when the patient was 3 years old. In this case the defects MJere postcrobasal and tiGtlseptal, while in the other thr); \vt’x lllids~ptal and outflow. Complete right btllltlle branch block developed postoperatively ill 5 of the’ 13 cases in which both preoperati\re alld postopctxtive electrocardiograms WWC’ a\-ailablc. ‘l’hr defects \vere midseptal only in 1, postcwhasal and midseptal in 2. posterohasal aild o(ltflow in 1, and posterobasal and apical in the fifth cast. Grouf, .3: No electrocardiographic analysis of group 3 will be presented. Brcar~ of the complexity and Iilultiplicity of the associated lesions which affect the electl.ocaldiogt.alll, no inference as to the influcncc of thr 11111scr11at scptal defect on it seelned jrlstificd. HEMODYNAMIC
CORRELATION
In 18 of the 23 cases, silllrlltancorls measurements of right ventricular and systeltlic systolic pressures and accttrate tneastttwttents of Group
I:
718
Saab,
Burchell,
DuShane
and Titus
aVR
aVL
n
III
FE. 7. El~ctmcardio~ram in a 72 yr,ar old boy &h mdsepta muscular dpfpct which nwasurpd 7.1 by 03 cm. a~ operation The surgeon noted “a powerful systolic thrill over the outflow tract of the right ventricle, which originated low in the ventricle, making us suspect a Inoscular defect. A defect measuring 1.1 by 0.6 cm. in the midportion of the muscular portion of the septum which had a good fibrous ring” was found. Note prominent Q wave in Ve, delayed excitation of the right ventricle (KsK’ in V,), the magnitude of 12’ (2.0 ~nv.) indicating right ventricular hypertrophy, and evidence of left ventricular hypertrophy. l‘he thoracic roentgenogram showed cardiomegaly (cardiothoracic ratio, 0.52) and moderately increased pulmonary vascular markings. Systolic pressures (mm. Hg j at the time of operation were KV, 55 ; systemic, 120. FIG. 6. Heart of 72 year old girl shows multiple muscular septal d&s, a “membranou.c” si;btal dcfmt (narrow patent ductus arteriosus alsopresent). Clinically, the patientwas small and thin with moderate limitation in her exercise tolerance. There was a grade 3/6 systolic murmur of moderate length to the left of the sternum and a grade Z/6 diastolic murmur at the apex. There was marked cardiac enlargement and prominence of the pulmonary vasculature. Cardiac catheterization revealed equivalent pressures in the pulmonary and femoral arteries (103/70 and 101/70 mm. Hg, respectively) and a calculated left to right shunt of 70 per cent. The surgeon had difficulty identifying all of the defects, and reported a “Swiss cheese” structure; heart block occurred, and the patient died 9 days postoperatively. A, right ventricular view showing probes in midseptal defects and a patch over a large apical defect. Sutures close other midseptal defects and the “membranous” septal defect. B, left ventricular view shows a patch over a large apical defect, white probes in midseptal defects, and a usual high septal defect under the aortic valze (black probe at arrow).
the size of the ventricular septal defect were availabfe. The area of the defect was calculated by using the formula for an ellipse, except in those few cases in which the defects were circular or triangular (in which case the appropriate geometric formula was used). The ratio of right ventricular systolic pressure to systemic systolic pressure was plotted against the area of the muscular septal defect per unit body surface area calculated from the patient’s height and weight3 (Fig. 10). This showed an approximately linear relation between the pressure ratios and the defect area up to a defect of 100 n~m.2/M.2; beyond this size there was evidence of a tendency to equalization of pressures in the two ventricles. In group 2, no such measurements were attempted because the multiplicity of the muscular THE
AMERICAN
JOURNAL
OF
CARDIOLOGY
Muscular
Septal
I~l~ct,-ocar~fir,ra~n~ of 5.75 year old boy w/h .~rn,gle FIG. 8. po~lProhnraf nrrr,culnr d$PCl I.3 by 0.9 cm. at operation. Note Ixoluinrnt (2 waves in leads aVF and Vg, with evidrnce of biventricular hypertrophy (V, taken at 0.5 usual starldardiz;ltion). ‘l’he thoracic roentgenogram showed cardionwgaly (cardiothoracic ratio, 0.57), prominent central pulmonary arteries, and prominent peripheral Systolic pressures (mm. Hg) at time vascular Inarkings. of surqrry wrrr K\‘. 70: systemic, 110.
defects made calculation of their total area unreliable. The calculations were considered meaningless in group 3 because complex lesions were present. CLINICAL
18,
NOvEMBKR
of 6 YPC.V oldgirl with two n~~c.rrulor FIG. 9. El~ctroca~diqrm s$tal d+ctJ, one in the outflow region 1.4 by 0.8 city. and Mild the other in the nlidseptal region 0.8 by 0.5 con. I’rollGncnt infundibular pulrnonic strnosis was present. Q waves in aV1, and Vc are present together tvith a counterclockwise rotation of the sequential QRS vectors as prqjected on the frontal plane, indicating left ventricuThere is evidencr of right ventricular lar hypertrophy. ‘Thoracic roentgenogram showed hypertrophy also. cardiomegaly (cardiothoracic ratio, 0.56) and Inodcrate increase in pulmonary vascular markings. Systolic pwssurcs (mm. Hg) were RV, 75; systrmic, 80.
. ..
CORREL.ATION
In general, the clinical features of these cases of defects in the muscular septum were not distinctive compared with those of the usual type The susof defect under the aortic valve. picions of one of us (H. B.) that defects in the right ventricular outflow tract above the papillary muscle of the conus might simulate pulmonary stenosis in the location of the murmur and that defects in the apical portion of the septum might more closely simulate mitral incompetence did not gain strong general support in this study. In retrospect, many of the recorded findings are inadequately discussed but items are mentioned which are of interest ; some examples follow. Regrettably, phonocardiogrants were not made of these patients. VOI.UME
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FIG. 10. Ratio of right ventricular systolic pressure to systemic systolic pressure plotted against ratio of calculated area of muscular septal defect to body surface area. The 18 patients in this graph had an isolated single muscular defect (group 1 ).
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The clinical diagnosis of ventricular scptal defect was made of an 18 year old girl, and there was a note that “there was good transmission to the left axilla.” The electrocardiogram was normal. Cardiac catheterization revealed pressures and fo\v values as follo\vs : right ventricle. 34/3 mm. Hg; pulmonary artery, 33/14 mm. Hg; pulmonary flow (Qp) 11.6 L.,/min. ; systemic flow (Qs) 5.6 L./min. The surgeon spent considerable time in locating the defect because it was practically hidden by the papillary muscle, but he sutured it successfully. A 16 year old girl had only a faint systolic murmur
at the left upper part of the sternum. The electrocardiogram showed right ventricular hypertrophy and delayed excitation of the right ventricle (RSR’ in VI). Pulmonary artery pressure was reported as 75/30 mm. Hg when systemic arterial pressure was 104/70 mm. Hg and the Qp/Qs ratio was 1.9. At operation the right ventricular, left ventricular and pulmonary artery systolic pressures were equal, and no decrease in pulmonary artery pressure occurred after closure of the defect. The apical communication between the ventricles was 2 by 2 cm. The patient survived the operation and is living and active five years later but has severe pulmonary hypertension. One consultant suspected that the ventricular septal defect in a 12 year old girl was associated with congenital mitral stenosis and incompetence because of a rather prominent (grade 2;‘6) apical diastolic murmur. The electrocardiogram showed right ventricular hypertrophy and right axis deviation. The surgeon reported the mitral valve was normal; the ventricular septal defect, measuring 2.2 by 1.4 cm, was “1OW” in the muscular septum. Preoperative hemodynamic studies were not done; at operation, right and left ventricular pressures were 70/O and 75/O mm. Hg before repair and 40/l and 115/5 mm. Hg afterward. In the records of 3 children, 5, 6 and 12 years old, there was a note that the murmur was heard well toward the apex, but this finding was apparently not unusual (such a finding is present in young patients with ordinary ventricular septai defects). Analysis of the records shows that the apical diastolic murmur has been prominent in some cases, possibly unduly so compared to the usual type of ventricular septal defect. Figure 6 shows the heart in a case in which the apical diastolic murmur had been prominent; the hemodynamic findings are given in the legend. This patient had an unusual electrocardiogram with Qs in VI, and Rs in Vg and Vi, and an RS in leads II and 111-a vectorial loop oriented posteriorly in the horizontal plane and counterclockwise in the frontal plane. One possibility considered clinically as a complication in this case \vas a “corrected transposition” because of absence of Q waves in lead I and in the left precordial leads.
DISCUSSION The definition of muscular ventricular septal defect used in this study was adapted to exclude
DuShane
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defects which involved part or all of the tnelnbranous septum (that is, the usual high septal defect posteroinferior to the crista supravcntricularis), atrioventricular canal types of ventricular septal defect4 (which involve the tricuspid or mitral valve rings, or both), and high defects that involve the aortic or pulmonary valve rings, or both, and which often lead to incompetence of these valves. The classification of muscular septal defect by location was similar to Edwards’ classification” of ventricular septal defect in general, within the limitations of the definition of muscular septal defect, except that we have included a midseptal region between the posterobasal and apical regions. The exclusion from this study of muscular defects less than 3 mm. in diameter should not materially affect the data since such small defects probably are hemodynamically and clinically insignificant. Previous studies6-lo of the frequency of location of ventricular septal defects have not specified whether or not the defects were muscular as defined herein, and therefore they are not exactly comparable to this study. In this study, when the muscular defect was single, it was posterobasal in about half of the cases, whether there were associated cardiac anomalies or not. Edwards5 observed that when the muscular defect was single it was usually located in the apical region. With multiple defects there was no selectivity of site, and the presence of associated cardiac lesions did not seem to influence the location. The outflow region of the right ventricle was rarely involved with either single or multiple muscular defects. We confirmed that the muscular ventricular septal defect is uncommonly associated with tetralogy of Fallot;” in only 5 of our 92 cases was this also present. The defect was posterobasal in 2 of these 5 cases, midseptal in 1, and apical in 1; in the fifth case there was a posterobasal and many apical defects. As did Edwards and associates,” we observed that it was less common for a muscular defect to be associated with a nonmuscular defect than for the muscular defect to be the sole malformation of the ventricular septum. Excluding the cases of tetralogy of Fallot, only 19 muscular defects were associated with nonmuscular septal defects. In his description of ventricular septal defect Seizer’ stated that, although 90 per cent of isolated defects are membranous in location, almost all those with associated malformations are membranous. This implied that a muscular defect was more likely to be isolated than to be THE
AMERICAN
JOLJRNAL
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CARDIOLOGY
Muscular However, associated with other cardiac lesions. we found that in 55 of the 92 cases the muscular septal defect was associated with other major cardiac anomalies. Whether or not this represents Ilndetected bias in the selection of the This material cannot be stated with certainty. appears unlikely as the sole explanation since all the isolated cases, whether autopsy or surgical, were indexed in our files under the diagnosis of ventricular septal defect, whereas some of those associated with other major cardiac anomalies wrre filed only under the associated diagnosis. C:onsequently, if any cases were missed in this sturdy, they probably would have been among the complex variety, and their inclusion would have further increased the relative incidence of muscular septal defects associated with other cardiac lesions. The incidence of subacute bacterial endocarditis in patients with muscular septal defects is said to be lower than in those with the more common types of ventricular septal defects.12 In none of our 27 autopsy cases was there morphologic evidence of bacterial endocarditis. ICffect of 17entricular Systole on Size of Muscular Defect: Seizer, 1 Downing and Goldberg,‘” and Darnlnann and co-workers14 have expressed the opinion that a muscular septal defect tends to be of lninor physiologic significance because the defect may decrease in size or even close with contraction of the ventricular septal musculature during ventricular systole, at which time the shunt would be at its peak. However, Heath and associates’” reported a case of apical muscular septal defect in a 21 year old woman with ~narked pulmonary hypertension and hemoptysis; at autopsy, severe changes in the pulmonary arterioles were found. They pointed out that a muscular septal defect may not be as innocuous as supposed. Of the 7 autopsy cases of isolated ~nuscular ventricular septal defect in our series, 2 had obstructive pulmonary vascular disease shown by histologic examination of the lungs. There were multiple, large defects in both cases. The area of the defect appeared to be related to the ratio of the right ventricular systolic (RV) to the systemic systolic (S) pressure (Fig. 10) in patients with single, isolated muscular ventricular septal defect. It was found that, with the exception of 1 patient less than 2 years old, the ratio RV/S was less than 0.6 for a defect less than 100 mm.2/M.2 and that the relation was nearly linear with decreasing size of the defect. .4mong defects with areas greater than 100 VOLIJME
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‘;1/1.‘, there \vas no case with an K\’ S ratio less than 0.6, and the scatter indicattd hiqhtar RV,!S ratios than would be cxpectrd fro111 the This relation was calculated sizes of the defects. noted by Savard and co-workers”’ for thr IISIIA type of high (Inembranous) ventriclilar septal defect and is in accord with the obscr\,ation that, for defects with areas greater than 100 IIII~.~, ‘h,1.2, there is a tendency for eqllalization of prcssllrcs in the two ventricles.‘“,‘7 ‘The findings stlggcst that, at least in the 18 cases shown in Figrlrc 10, there did not seem to have been any sig-nificallt decrease of the defect with ventricular systolc. If the latter had been true, one wol11d ha1.e cxpetted a wide scatter in the lower left qlladrallt of the plot, indicating a greater pressure gradient across the defect in relation to its calclllatrcl size. Thus, although the findings in this stncl~. did not disprove the possibility of a dilninished size of defect with ventricular systole in son~e cases, they did not support a concept of systolic closure of the defect as a universal event. Thcsc findings and the fact that pulmonary vascular disease was present in 2 of the 7 autopsy casts indicated that in seine cases a tnuscular septal defect rcsults in syndromes similar to those observed in the usual type of ventricular septal defect. Therefore, a muscular septal defect appears to present a hemodynamic and clinical spectrlllil which ranges from the very small defects with minimal shunts (which were excluded fro111 this study because of size) to large defects associated with pulmonary vascular disease. ?‘he ele~trocardiq~raphic jindings in the cases of isolated muscular septal defect (both single and multiple) were similar to the expected findings in ventricular septal defect in general.1x-‘7 The main determinant of the electrocardiographic pattern seemed to be the hemodynamic status, namely, size of the shunt and degree of the pulmonary vascular disease. Thus, patterns of left, right, or combined ventricular overload Lvere encountered which reflected Inoderate left to right shunting, pulmonary \,ascular disease with minimal, balanced, or reversed shunting, and marked left to right shunting, respcctively. Complete and “incomplete” right brandle branch block also were seen. None of the 37 cases with isolated defects, however, had the atrioventricular canal type of loop4fY‘ which is found in about 15 per cent of cases of ventricular septal defect of the usual type.22 This might be expected since Titus and associates28 found that, of 4 cases of posterobasal muscular defect assoIIIIII.~
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ciated with usual “membranous defect,” in only 1 was the muscular defect related to conduction tissue and the posterobasal defect was large with its anterior rim adjacent to the conduction tissue. Although deep Q waves in leads reflecting left ventricular potentials are known to occur with it was ventricular septal defect, 18,2?,23,26~27,39,3il our clinical impression before this study that perhaps they may be more pronounced in paIf such were the tients with muscular defects. case, one could hypothesize that the excitation of the left ventricular free wall was sufficiently delayed to allow the septal excitation to dominate Accordthe mean vector for a longer period. ingly, we analyzed the initial vector by noting the depth of Q waves in V5 or Vg, or both, and in aVF in the cases of isolated muscular septal defect. The Q waves 3 11~x1. or greater were present in 54 per cent of cases in group 1 and in 57 per cent in group 2. Although this was slightly higher than the 40 per cent incidence reported by Vince and Keith26 for ventricular septal defect in general, our series was not large enough to allow us to draw any firm conclusions. In this study there was no correlation between the location of the defect in the muscular septum and the presence or magnitude of Q waves in V, In 4 of the 22 cases or Vg, or both, or in aVF. in group 1 (none in group 2) there were Q waves 4.5 mm. or greater in both left precordial leads The muscular septal defect was and in aVF. posterobasal in 3 of these cases and midseptal in 1. No correlation between age of the patient The development of and Q waves was found. right bundle branch block postoperatively in a minority of the cases could not be correlated with any specific location of the defect or defects in the muscular septum. Since completion of this study, Friedman and associate?* reported data on 7 patients with multiple muscular septal defects, 6 with autopsy. Their study emphasized the serious nature of Morphomultiple muscular septal defects. logically, the defects were located in various regions of the septum, and in more than half the cases at least one of the defects was greater than 3.0 mm. in diameter. Of the 7 patients, 4 were boys and 3 were girls; their ages ranged from 4 months to 3 years. All manifested congestive heart failure and growth retardation. Combined ventricular hypertrophy and “incomplete” right bundle branch block were demonstrated Right in the electrocardiograms of all patients. heart catheterization showed marked pulmonary hypertension.
DuShane
and
Titus SUMMARI~
Ninety-two cases of muscular ventricular These defects were septal defect were reviewed. defined as completely surrounded by muscular septurrl and consequently did not involve the membranous septum or any valvular ring. They were classified, according to their location in the right side of the muscular ventricular septum, as posterobasal, midseptal, apical, or outflow. Of the 92 cases, 23 were isolated single defects, 14 were isolated multiple defects, and 55 were associated with other major cardiac anomalies. In these 55 cases, the defect was single in 36 cases and muItiple in 19. Regardiess of the presence or absence of associated cardiac anomalies, when the defect was single, it was posterobasal in about half of the cases. No specific location of multiple defects was apparent. Muscular defects in the outflow tract of the right ventricle were rare. The evidence suggests that muscular ventricular septal defects may cause hemodynamic and clinical syndromes similar to those caused by the usual type of ventricular septal defect. The electrocardiographic features in the 37 cases of isolated defects were analyzed. A possible increased incidence of prominent Q waves in leads reflecting left ventricular potential occurred but, as a generalization, the electrocardiogratns were similar to those observed in cases of the usual type of defect. ACKNOWLEDGMENT The authors wish to thank Dr. John W. Kirklin and Dr. Dwight C. McGoon for their permission to use the reports of the surgical observations. REFERENCES 1. SELZER, A. Defects of the cardiac septums. J.A. M.A., 154: 129, 1954. 2. SHERMAN, F. E. An Atlas of Congenital Heart Disease, pp. 167-174. Philadelphia, 1963. Lea PC Febiger. 3. DUBOIS, E. F. Basal Metabolism in Health and Disease, ed. 3, pp. 131 and 135. Philadelphia, 1936. Lea & Febiger. 4. NEUFELD, H. N., TITUS, J. L., DUSHANE, J. W., BURCHELL, H. B. and EDWARDS, J. E. Isolated ventricular septal defect of the persistent common atrioventricular canal type. Circulation, 23: 685, 1961. 5. EDWARDS, J. E. Congenital malformations of the heart and great vessels. B. Malformations of the ventricular septal complex. In: Pathology of the Heart, ed. 2, pp. 294-317. Edited by GOULD, S. E. Springfield, Ill., 1960. Charles C Thomas. 6. BECU, L. M. et al. Anatomic and pathologic studies in ventricular septal defect. Circulation, 14: 349, 1956. 7. KIRKLIN, J. W., HARSHBARGER, H. G., DONALD, THE AMERICANJOURNAL OF CARDIOLOGY
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E. and EDWARDS, .I. E. Surgical correction of ventricular septal defect: Anatomic and technical considerations. .I. ‘Thoracic Sq., 33: 45, 1957. WARDEN, H. E., DEWALL, R. A., COHEN, M., VARCO, R. L. and LILLEHEI, C. W. A surgicalpathologic classification for isolated ventricular septal defects and for those in Fallot’s tetralogy based on observations made on 120 patients during repair under direct vision. J. Thoracic Surq., 33: 21,1957. CLELAND, W. P. Ventricular septal defects. Pm. Roy. Sac. Med., 54: 785, 1961. COOLEY, D. A., GARRETT, H. E. and HOWARD, H. S. ‘l’he surgical treatment of ventricular septal defect: ,413analysis of 300 consecutive surgical cases. Prog. Cardionas. Us., 4: 312, 1962. EDWARDS, .I. E., CAREY, L. S., NEUFELD, H. N. and LW~ER. R. G. Congenital Heart Disease: Correlation of Pathologic Anatomy and Angiocardiography, Vol. 1, p. 95. Philadelphia, 1965. W. B. Saunders Company. VBASY, L. G. Clinical findings in ventricular septal defects. Am. J. Cardiol., 5: 185, 1960. DOWNINCI,D. F. and GOLDBERG,H. Cardiac septal dffects. I. Ventricular septal defect: Analysis of one hundred cases studied during life. Dis. Chest, 29: 475, 1956. DAMMANN,J. F., JR., THOMPSON,W. M., JR., SOSA, OMAR, and CHRISTLIEB,I. Anatomy, physiology and natural history of simple ventricular septal defects. .4m. J. Cardiol., 5 : 136, 1960. HEA.I.H,D., BROWN, J. W. and WHITAKER, W. Muscular defects in the ventricular septum. Brit. Heart J., 18: 1, 1956. S~VARD, M., SWAN, 1-I. J. C., KIRKLIN, J. W. and WOOD. E. H. Hemodynamic alterations associated with ventricular septal defects. In: Congenital Heart Disease. A Symposium Presented at the Washington Meeting of the American Association for the Advancement of Science, pp. 141-164. Edited by BASE, A. D. and MOE, G. K. Washington, D. C., 1960. BURGHELL, H. B. Studies in pulmonary hypertension in congenital heart disease. Brit. Heart J., 21: 255, 1959. MARSICO, F., PE~~ALOZA,D., TRANCHESI,J., LIM~N, Ii. and SODI-PALLARES, D. The electrocardiogram in ventricular septal defect: Scalar and vectorial analysis of thirty-two cases. Am. Heart J., 49: 188,1955. BLOUN.L.,S. G., JR., MUELLER, H. and MCCORD, M. C. Ventricular septal defect: Clinical and I).
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hemodynamic patterns. :lm. .I. .+fpd.. 18: 871, 1955. IIUBBARD, T. F. and ANGLE, W. D. The rlectrocardiogram in ventricular septal defect: A correlative study of fifty cases. .4m. J. Z)is. Chi/d.. 04: 20, 1957. FYLER, D. C., RUDOLPH, A. M., WITTENBORG,M. H. and NADAS, A. S. Ventricular septal defect in infants and children: A correlation of clinical, physiologic, and autopsy data. Clrcitlation, 18 : 833, 1958. TOSCANO-BARBOZA,E. and DUSHANE, .J. \V. Ventricular septal defect: Correlation of electrocardiographic and hemodynamic findings in 60 proved cases. .4m. J. Cardiol., 3: 721, 1959. CHAR, F., ADAMS, P., JR. and ANDERSON, R. C. Electrocardiographic findings in one hundred verified cases of ventricular septal defect. Am. .1. Dis. Chzld., 97: 48, 1959. BRISTOW, J. D., KASSEBAUM,D. G., STARR, A. and GRISWOLD, H. E. Observation on the occurrence of right bundle-branch block following open repair of ventricular septal defects. C’irrulation, 22: 896, 1960. BEREGOVICH,J., BLEIFER,S., DONOSO,E. and GRISHMAN, A. The vectorcardiogram and electrocardiogram in ventricular septal defect: With special reference to the diagnosis of combined ventricular hypertrophy. Brit. Heart .I., 22: 205, 1960. VINC~, D. J. and KEITH, J. D. The electrocardiogram in ventricular septal defect. Circulation, 23: 225, 1961. SODI-PALLARES,D. and TESTELLI, M. R. Electrocardiography in the diagnosis of congenital heart disease. Hmrt Bull., 13: 24, 1964. Torus, J. L., DAUGHERTY,G. W. and EDWARDS,J. E. AnatoIny of the atrioventricular conduction system in ventricular septal defect. Circulation, 28: 72, 1903. DUSHANE, J. IV., WEIDMAN, W. II. and BRANDENBURG, R. 0. The electrocardiogram in children with ventricular septal defect and severe pulmonary hypertension: Correlation with response of pulmonary arterial pressure to surgical repair (.4bstr.). rim. J. Dis. Child., 98: 464. 1759. DU~HANE, J. 1%‘. and KIRKLIN, J. W. Selection for surgery of patients with ventricular septal defect and pulmonary hypertension. Circulation, 21 :13, 1960. FRIEDMAN,W. F., MEIXRIZI, A. and PUSCI~ A. L. Multiple muscular ventricular septal defects. Cmlution, 32: 35, 1965.