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Morphologic basis for obstruction to right ventricular outflow in hypertrophic cardiomyopathy
CARDlOMYOPATHY
Morphologic Basis for Obstruction to Right Ventricular Outflow in Hypertrophic Cardiomyopathy Barry J. Maron, MD,* Charles L. McIntosh, MD, PhD, Heinrich G. Klues, MD, Richard 0. Cannon III, MD, and William C. Roberts, MDt
The mechanism by which obstruction to right V~IP trlcukw (RV) outWw occurs in patients with hyperbphlc cardiiyopathy (HC) is not well under stood. To clarify this issue, 5 severely symptomaticpatMts(agedlsto55yearqmean3O)with HC and marked subpuhnonic obstruction (basal peak systollk inssure gradients 60 to 118 mm Hg) were studied. Four patSents also had obstru~ tion to left ve~cular outflow (maximal basal or provocable pressure gradient I.3 to 110 mm Hg). 7heRVoutflowobstructionineachpatientre suited fTom greatly hrypertrophied musculature comprised of crlsta supravent&ularis, moderator band or trabeculae. Operative resection of portlons of this muscle resutted in aboliii or sub stantlal reduction of the RV outflow gradient (to 0 tollmmHg)inthe3patientswithbothpand postoperatlve hemodynamlc studii. The kft vem tricular wall and ventticular septum also were masslveiy thickened (32 to 40 mm) in each pa tient. These findlngs support the view that marked RV outtlow tract obstruction in patients with HC is due to greatly hypertrophied RV muscle, and that operative resection will reMeve the outflow gradients and normaliie RV systolic pressure. The rnus cular RV hyperbophy causing obsbuctii ap constitute a primary and excessive hypea=Jb perbophic process involvhqg both ventricles. (Am J Cardiol1993;71:108~1094)
From the Cardiology, Surgery and Pathology Branches, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. Manuscript received July 24, 1992; revised manuscript received November 20, 1992, and accepted November 23. *Present address: Minneapolis Heart Jnstitute Foundation, Division of Cardiovascular Research, 920 East 28th Street, Minneapolis, Minnesota 55407. TPresent address: Baylor Cardiovascular Institute, Baylor University Medical Center, 3701 Junius Street, P.O. Box EOlO, Dallas, Texas 75246. Address for reprints: Barry J. Maron, MD, Cardiology Branch, National Institutes of Health, Building 10, Room 7B-15, Bethesda, Maryland 20892.
any patients with hypertrophic cardiomyopathy (HC) have dynamic obstruction to left ventricular outllow due to systolic anterior motion of the mitral valve, and midsystolic contact between the mitral leaflets and ventricular septum.‘” Substantial right ventricular (RV) outtIow tract pressure gradients also may occur (although infrequently) in Hc6-i9 and am usually associatedwith subaortic ~adients.8-10,12-15,17,19 To determine the mechanismof RV outllow obstruction, we studied at operation or necropsy,or both, 5 patients with HC who had marked obstruction to RV outiow.
M
MnHODS Selection of patients: The caserecords of the Cardiology and Pathology Branches were reviewed. Five adults with HC were identified who fulfilled the following inclusion criteria: (1) RV o&low tract peak systolic pressuregradient >50 mm Hg at catheterization;and (2) RV anatomy assesseddirectly at operation (n = 4) and by gross visual inspection at necropsy (n = 3). Each patient had a hypertrophied, nondilated left ventricle in the absenceof another cardiac or systemic di~ease.2~ EchocardiEchocardiographic studies were performed in 3 patients, using commercially available instruments with 2.25 or 2.50 MHz transducers.Twodimensional imageswere obtained in standardcross-sectional planes21;M-mode echocardiogramswere derived from 2-dimensional images under direct anatomic visualization.
RESULTS vies: The 5 study patients (all men) ranged in age from 18 to 55 years (mean 30) at operation or death. All 5 patients had had substantial symptoms of cardiac dysfunction (Table I). Four patients had evidence of genetic transmission of HC to first-degree relatives,22including 3 with family history of sudden cardiac death; 1 of the latter patients had a brother with HC who had left ventricular outflow tract obstruction.16 Preoperative hemadynamierr (l&e I): In each patient, peak systolic pressure gradients between the RV body and outfIow tract under basal conditions ranged from 60 to 118mm Hg (average 76) (Figure 1). Each gradient was recorded by pullback withdrawal of the catheterfrom the pulmonary trunk to right ventricle. RV systolic pressuresranged from 82 to 135 mm Hg. Four patients also had obstruction to left ventricular outfIow; subaortic gradients were recorded under basal conditions in 3 patients (50, 82 and 110mm Hg) and
RIGHTVENTRICULAROBSTRUCTIONIN HYPERTROPHIC CARDIOMYOPATHY 1089
only after provocation with isoproterenol infusion in 1 (40 mm Hg). The remaining patient had no pressuregradient under basal conditions, but provocative maneuvers were not performed. RigW ventricular anatomy: Morphology of the RV outflow tract was assessedat operation in the 4 patients at the time of right ventriculotomy and muscular resec-
tion (and also at necropsy in 2 of them), and only at necropsy in the 1 who had myotomy-myectomywithout right ventriculototq. Based on direct visual inspection of outflow tract anatomy, greatly hypertrophied myocardium was observed,which decreasedRV cavity size (Figure 2). In 4 patients, the crista supraventricularis muscle (both the septal and parietal limbs) was enor-
TABLE I Clinical and Morphologic Findings in Five Patients with Hypertrophic Cardiomyopathy and Marked Obstruction to Right Ventricular Outflow
Age (year)* NYHA functional class (preop/postop) Syncope Exertional dyspnea Chest pain LV-SA peak systolic gradient (mm Hg) (preop/postop) Basal Provocation Systolic anterior motion, mitral valve (preop/postop)t RV-PA peak systolic gradient (mm Hg) (preop/postop) Basal Provocation Right ventricle (s/d) (mm Hg) Left ventricle (s/d) (mm Hg) LV contractility (angiogram) Cardiac index 1L/min/m2) (preop/postop) Family history of HC Echocardiographic dimensions (mm) LV thickness Anterior septum Posterior septum Lateral free wall Posterior free wall Cavity LV (end-diastole) Left atrium Electrocardiogram RV hypertrophy T-wave inversion LV hypertrophy Q waves & right precordial lead voltage LA/RA enlargement Right BBB/left AFB Operation Myotomy-myectomy (or myotomy) RV resection Age (year) RV muscle resected Moderator band Crista supraventricularis Trabeculations Weight of resected myocardium (g) Ventricular septum Right ventricle RV wall thickness (mm) Outcome Ventricular septal histology Cellular disorganization Abnormal intramural arteries
1 (CW)
2 (FR)
3 (CZ)
4 (DP)
5 (GK)
28 312 + 0 0
28
21
312
4/-
0 + +
+ + +
18 3/l 0 + +
55 3/+ t t
50/o 70/10 3+/o
82140 1041104 4+/1+
12/40/Ol-
o/-I-/-
110/o 150/-l-
60/O
60/11
77/-
11810 -
95118 148/20 f 2.8fl.7 t
82/l 180/10 Normal 2.613.1 t
115115 140124 t 2.8/0
13517 10814
65/80/8616 230/10 -
35 30 25 12
37 29 19 14
35 35 22 15
42 52
34 40
40 42
0 0 0 t (I, AVL) 0 t/t t/t
0 t (I, AVL, Vs) 0
+t
+
+ t 0
0 t (1, AVL, v5, v6) 0
4.114.1 t
40/I
2.5/t
3211
-
-
19
18
-
+
0
t
0
0 + (II, Ill, AVF) + o/o o/o
0 + (I, AVL) + t/t o/+
+ t 21
0 t 13
+ 0 55
+ 0 0
t + 0
0 t t
0 t 0
3.5 10.2 16 Alive
3.5 2.2 7 Alive
1.2 20.0 18 Dead ( 1 day postop)
0
0 0 10 Dead (7 days postop)
t5 +I
05 05
t +
2:
+ (Vl-V3)
0
0 t/o t/+
0 o/o t/t
2:
Died suddenly (5 years postop) t 0
t +
‘Current or at death. tClassification of mitral valve systohc anterior motion as assessed from M-mode echocardlogram2: 0 = absent: 1+ = present with the mmimum distance between mitral valve and ventricular septum during systole > 10 mm; 2+ = without mitral-septal contact, but with a distance < 10 mm behveen mitral valve and septum during systole; 3+ = brief mitral-septal contact (< 30% of echocardiographic systole); and 4+ = prolonged apposition of mitral valve with septum (> 30% of echocardiographic systole). tUndenvent mitral valve replacement for moderately severe mitral regurgitation 2 years after my&my-myectomy. §Only surgical speomens available; all others based on necropsy observations. 01ed before era of echocardiography; wall thickness measurements were obtained at necropsy. [’ FB -- anteriorfasclcular block; EIBB = bundle branch block: LV = left ventricular; NYHA = New York Heart Association: PA = pulmonary artery; postop = postoperative; prep preoperative; RA = right atrial; RV = right ventricular; SA = systemic artery: s/d = peak systolelend-diastole; - = data not available or not applicable: + = present; 0 = absent; 1’: Increased; J = decreased.
1090
THE AMERICANJOURNALOF CARDIOLOGY VOLUME71
MAY 1.1993
mously thickened, as was the moderator band and other RV trabeculae; the RV free wa1123was thickened in all 5 patients (Figure 2). In 1 patient, RV hypertrophy appeared to preferentially involve the moderator band. Two-dimensional echocardiogram(Figure 3) and RV angiogram showed a small or normal-sized RV cavity. In addition, echo-dense structures (or filling defects) were identified in the mid-cavity or outflow tract regions that were consistent with severely hypertrophied intraventricular trabeculae,muscle bands or crista supraventricularis (Figure 4). Operative procedures In 3 of 4 patients with evidence of obstruction to left ventricular outflow, a standard septal myotomy-myectomyoperation (Morrow prowas performed through an aortotomy; 1.2 to cedure)24,25 3.5 g of muscle was resectedfrom the ventricular septum (Figures 3 and 4). One other patient had septal myotomy alone. In 3 of 4 patients with myotomy-myectomy (or myotomy alone), a right ventriculotomy also was performed at the same operation (Figures 3 and 5). In the remaining patient, only a right ventriculotomy was performed (without prior myotomy-myectomy).Thus, in all 4 study patients with right ventriculotomy, substantial portions of greatly hypertrophied RV muscle (believed by the surgeonto be obstructive to outflow) were resected (2.2 to 20.0 g), including crista and moderator band in 2 patients, crista and greatly hypertrophied trabeculae in 1, and moderator band alone in 1; the removal of muscle substantially enlargedRV outflow tract size (Figures 2 to 5). In patient 1, after surgery, the RV cavity was dilated and showed impaired contractility and decreasedcardiac output (Table I). Postoperative hemodynamics: In 3 patients, a postoperativecardiac catheterization was performed; the basal RV outflow tract gradient was eliminated in 2 patients and was 11 mm Hg in the third (Figure 1). Siilarly, in the same 3 patients, the basal left ventricular outflow gradient was abolished in 2 and reduced to 40 mm Hg in 1 patient. L&t ventricular hyperbmphy: Assessmentby echocardiography and at necropsy showed that all 5 patients had a particularly marked and diffuse pattern of left ventricular hypertrophy (Figures 3 and 5). The thickness of the anterior portion of the ventricular septum ranged from 32 to 40 mm; substantial portions of the posterior ventricular septum and anterolateral free wall also were also greatly thickened. Heart weights (3 specimens) ranged from 660 to 1,070 g (normal 1400). Electmcardiograms (Table I): Electrocardiograms showed several abnormalities, and no single pattern was characteristic.Three patients had combined right bundle branch and left anterior fascicular block, and 1 other had left anterior fascicular block alone; 4 had prominent Q waves. DISCUSSION This study focuses on the mechanism by which marked obstruction to RV outflow occurs in patients with HC. Subpulmonic gradients in HC usually occur in association with left ventricular outflow tract obstruction8~‘o~‘2-1s~17~19~26~27; 4 of 5 patients had biventricular
obstruction. All 5 severely symptomatic patients with HC were selected for study solely because they had marked RV outflow tract gradients. Based on hemodynamic, angiographic, operative and necropsy observations, the RV outllow gradients in these patients appeared to result from the excessive hypertrophy and increasedmass of RV muscular components(most frequently and prominently the crista supraventricularis). Therefore, in contrast to left ventricular outflow obstruction in HC (which is characteristically dynamic and due to mitral valve systolic anterior motion),1-5RV outflow gradients in HC are the result of a static and fixed muscular impediment to outflow. These observations differ from previous speculationsthat RV outtlow obstruction in patients with HC is produced by the projection of the hypertrophied ventricular septum into the RV cavity7.17J9 or by systolic anterior motion of a tricuspid valve leaflet.28 Postoperativehemodynamic studies showed that the subpulmonic gradients were abolished or greatly reduced after portions of the hypertrophied RV muscular structures were resectedat operation. This iinding substantiatesthat these muscular componentswere responsible for the RV outflow gradients measuredbefore op
FIGURE 1. Changes in d&t heart pressure recordings assock ated wlth operative resection of hypehyhied ri@t venttb ular (RV) muscles in a 2Syeerdd sum with hyperbophi wdllyopathy and biventricukv otmtruction (patlent i; Table I). Top, pmopeMlvepuRbackofcatheterfromRv bodytoRvoutfiowtract(RvoT)showsi-larpeak systolicpressuregradientof6Omm~Rotbm,~ tive pullbeck of catheter from the mein pulmonary artery (MPA)toRVbodyshowsthettheRVoutRowtmctpressure gradient has bsen ebohhed. Pulmonary hypertenskn is present pwtoperatively due to elevation in left veebiculaf filling pressures.
RIGHTVENTRICULAROBSTRUCTIONIN HYPERTROPHIC CARDIOMYOPATHY 1091
FIWRE 2. Right ventrkular (RV) anatomy in 2l-yew-old man (patient 3; Table I) wRh hype&ophk cardiomyopathy who had m&edobsbuctiontoRVoutRow(outRow gmdient77mmRg).A,6,4~dE,as vlewedbythesur@onthmu~@#tverr trlculotomy at the time of muscular w tiun (i.e., of hypertrophled crkta suprave* trlculasis and moderator b-0. G ablpam nlaticpltrayadofpreoperativec?udkc anatomy showia asynmdk venttlculer septd (VS) thkkeni* and hypettrophy of RV structures (Indudi~ crista supraventrio ularis, moderaW band and RV free wall) compromioing the effecMve size of the ca* ty. PT = pulmonay tnmk.
FlRURE 3. Preoperative (A and 6) and postoperative (Cl, !dopfmm, 2diechocardiol4ams obtained in a 3lyeaFdd man with hypeWophk cap dkmyopathy and hiventrkubr OlltRow obstnlction (petll3; Table I). A, lamstemal kag-axis view showiw asymmetric thikkeni~ of ventrkular septum (VS)thatappearstobulgelntoboththeleff(LV)and right(Rv)ventricularolltRow~andreducesthe effective size of eech cavity. B, shortads view at ofante&uand chordal level showiN hypeM@y posterkrpurtionsofseptumthatbulgeintoRVoutflowtractandappeiartoobliitheRVcavRyat this level (MOWS]. C, shmt41~is view obtained intta operativelyatsamelevelasinBafterthen#rection -bandandcrktasuprav~ ofportknsof trkularls muscle. The RV cavity at this level appear0 dilated compared with that in 8. lhsre is also evL dence of the ventricular septal myotomymyectomy (arows). Calibration nuults am 1 cm apart. IA q left atrium; PW = poste&w let% ventricular free well.
1092
THE AMERICANJOURNALOF CARDIOLOGY VOLUME71
MAY 1,1993
FlWREARi@tV-lsr~ cml~ebtakedlnthem -pmjbctlonuvdy(AmdB)lmdpoMpsdve
ty(CandD)lna3Syeaddmim mdnmked w”-zF venbla~kwoutllow. (AmdCare dbrtolk;andBasdDatesys tolk).AudB,lar@mdklucent fllllng defects w evirknt in lhe mhkavlty.CandD,afterr8sae tkndpemOnsof~su~ VSllWCUlakrmlmoderatorband
muscuktllre, the flllhlg defects Ilb nok@srevkknt.
FlWRES.~llndhgsin2&yee ddllWlWiUl hnmbopMc~thylmdbiveMalktoulnewtmct obsbwctknwhoalday~ uvely(pstknt3;TabkI).A,extsmal viewoftheheartthatwasgmatly tWnlm&khyperbophyOfVelar
septum(VS)with~tothekltv~ mallmliwwdl(FW),nnsldlyi~ cmassd~ventrkahr(Rv)wdltMdcnewspandmdacedskeofbothRvand kftVOllt~la-~~Of~
epemthreuctkeofmuscleIfomRv @twwads) md k@t ventrkab @luws) olmlow tracts Iw widmlt. Dio cokmtknofvenbkularseptumk~ ablythetesuttofm~ nlyocrdbl kfamtkn. c, abnamal intrs llUldCWOlWY~Wtthth-
wall and m (hamato~n
nawewed lumen stdn XrO; nduced
by37%).D,chaotk -of-
dkcmusckcdkinwhkh~celk --ato#lqwcndltWtM@SStoWBChOlllW(-XyIln-eoain st8k XeO; reduced by 37%).
RIGHTVENTRICULAROBSTRUCTIONIN HYPERTROPHIC CARDIOMYOPATHY 1093
eration and also demonstratesa suitable surgical approach to this abnormality, However, 1 patient had a dilated RV cavity with impaired contractility after operative resection of substantialamounts (10 g) of RV muscle, suggesting that excessive removal of muscle may have deleterious effects on RV function. In all 5 patients, RV hypertrophy was associatedwith massive left ventricular hypertrophy, Left ventricular wall thickening was marked and diffuse, involving most of the ventricular septum and free wall; septal thickness was >30 mm in each patient and ranged up to 40 mm.29 Consequently,the muscular RV hypertrophy causing the outtlow tract obstruction appearedto constitute part of a primary and excessive hypertrophic process involving both ventricles. We made no effort to estimatethe prevalenceof subpuhnonic gradients in the overall population of patients with HC. Relatively small (5 to 25 mm Hg) RV outflow tract gradients occur frequently in patients with HC.5*26*27 Although this study does not examine the etiology of such small gradients, we presume that the underlying mechanismsresponsible are likely to be similar to those for the larger RV outflow tract gradients described in the present report.
l. Shah PM, Gmmiak R, Kramer DH. Ultrasound location of left ventricular outflow obstruction in hypertmphic obsrmctive cardiomyopathy. Circulation 1%%40: 3-11. 2 Pollick C, Rakowski H, Wigle DE. Muscular subamtic stenosis: the quantitative relationship between systolic anterior motion and pressure gradient. Circularion
1984;69:43-49. 8. Spirita P, Mamn BJ. Patterns of systolic anterior motion of the mitral valve in hypwtmpbic cardiomyopathy: assessment by two dimensional echocardiography. Am J Cardiol 1984,54:1039-1046. 4. Maron BJ, Bonow RO, Cannon RO, Leon MB, Epstein SE. Hypemophic cardiomyopathy: interrelation of clinical manifestations, pa&physiology, and therapy. N Engl .I Med 1987;316:780-789 and 84&852. 5. Wigle DE, Sasson Z, Henderson MA, Ruddy TD, Fulop J, Rakowski H, Williams WG. Hypertmphic cardiomyopathy. The importance of the site and extent of hypertrophy. A review. frog Cardiovasc Dis 1985;28:1-83. A Asin Cat&l E, Alonso M, Delcan JL, Menarguez L. Echocardiographic sign of right sided hypcrtmphic obstructive cardiomyopathy. Br Heart J 1978;40: 1321-1324. 7. Barr PA, Celetmajer JM, Bowdler JD, Cartmill TB. Idiopathic hypertrophic obstructive cardiomyopathy causing severe right ventricular outflow tract obstruction in infancy. Br Hearr J 1973:35:1109-l 115.
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THE AMERICANJOURNALOF CARDIOLOGY VOLUME71
8. Bevegard S, Jonsson B, Karlof I. Low subvalvular aortic and puhnonic stenosis caused by asymmetrical hypertmphy and derangement of muscle bundles of the ventricular wall. Acra Medica Scand 1973; 172:26%283. @. Botti G, Tagliavini S, Bonatti V, Aurier E. Isolated hypertmphic obstructive cardiomyopathy of the right ventricle. G Ital Cardiol 1979;9:170-181. 10. Cohen J, Effat H, Goodwin JF, Oakley CM, Steiner RE. Hypxtmphic obstmctive cardiomyopathy. Br Heart J 1964:26:1&32. 11. Goodwin JF, Hollman A, Cleland WP, Teare D. Obstructive cardiomyopathy simulating a&c stenosis. Br Heart J 1960;22:403414. 12. Grow-Brcxkhoff F, Loogen F. Infundibular pulmonary stenosis in chronic left venticular cardiopathy. Dtsch Med Wochenschr 1%2;87:52>530. la. Lockhart A, Charpentier A, Bowlarias JP, Ben Ismail M, Outback P, Scebat L. Right ventricular involvement in obstructive canliomyopathies. Hemodynamic studies in 13 cases. Br Heart J 1966;28:122-133. 14. Mamn BJ, Edwards JE, Henry WL, Clark CE, BingIe GJ, Epstein SE. Asymmetric septal hypertrophy (ASH) in infancy. Circulation 1974;50:809-820. 15. Mamn BJ, Tajik AJ, Ruttenberg HD, Graham TP, Atwood GF, Victmica BE, Lie IT, Roberts WC. Hypertmphic cardiomyopathy in infants: clinical features and natural history. Circulation 1982;65:7-17. 16. Morrow AG, Fisher RD. Fogarty TJ. Isolated hypertmphic obstruction to right ventricular outtlow. Am Heart J 1%9;77:814-817. 17. Taylor RR, Bernstein L, Jose AD. Obstructive phenomena in ventricular hypertrophy. Br Heart J 1964;26:193-198, 18. Van Do&off W, Nanda NC. Obstruction within the right ventricular body: hvodimensional echocardiographic features. Am J Cardiol 1983;51:1498-1501. 10. Wigle ED, Heimbecker RO, Gunton RW. Idiopathic ventricular septal hypertrophy causing muscular subsonic stenosis. Circulation 19622632s340. 20. Mamn BJ, Epstein SE. Hypertmphic cardiomyopathy: a discussion of nomenclature. Am J Cardiol 1979;43: 1242-1244. 21. Tajik Al, Seward JB, Ha& DJ, Mair DD. Lie JT. Two-dimensional real-time ultrasonic imaging of the heart and great vessels. Mayo Clin from 1978;53:271-303. 22. Maron BJ, Nichols PF, Pickle. LW, Wesley YE, Mulvihill JJ. Patterns of inheritance in hypertmphic cardiomyopathy: assessment by M-mode and hvodimensional echocardiography. Am J Cordial 1984,53: 1087-1094. 23. McKenna WJ, Kleinebenne A, Nihoyannopoulos P, Foale R. Echocardiographic measurement of right ventricular wall thickness in hypertmphic cardiomyopathy: relation to clinical and prognostic features. J Am Co0 Cardiol 1988:11:351-358. 24. Morrow AG, Reitz BA, Epstein SE, Henry WL, Conkle DM, Itscoitz SB, Redwood DR. Operative treatment in hypertmphic subamtic stenosis: techniques and the results of pre and postoperative assessments in 83 patients. Circulation 1975;52:88-102. 26. Mamn BJ, Epstein SE, Morrow AG. Symptomatic stah~s and prognosis of patients after operation for hypemophic obstructive cardiomyopathy: efficacy of ventricular septal myotomy and myectomy. Eur Hean J 1983;4(suppl F):175-185. 26. Frank S, Braunwald E. Idiopathic hypettmphic subaortic stenosis. Clinical analysis of 126 patients with emphasis on the natural history. Circulation 1968;37:
75'+788. 27. Braunwald E, Lambrew CT, Morrow AG, pierce GE, Rockoff SD, Ross J. Idiopathic hypertmphic subaottic stenosis: 1. A description of the disease based upon an analysis of 64 patients. Circulation 1964;29 and 3O(suppl IV):IV-3-119. 22. Brik H, Meller J, Bahkz AS, Herman MV, Teichholz LE. Systolic anterior motion of the tricuspid valve in idiopathic hypettmphic subaortic stenosis. J C/in film 1978;6:121-124. 29. Louie EK, Mamn BJ. Hypettmphic cardiomyopathy with extreme increase in left ventricular wall thickness: Clinical significance, functional and morphologic feamm. J Am Coil Cardiol 1986;8:57-65.
MAY 1,1993
Morphologic Basis for Obstruction to Right Ventricular Outflow in Hypertrophic Cardiomyopathy Barry J. Maron, MD,* Charles L. McIntosh, MD, PhD, Heinrich G. Klues, MD, Richard 0. Cannon III, MD, and William C. Roberts, MDt
The mechanism by which obstruction to right V~IP trlcukw (RV) outWw occurs in patients with hyperbphlc cardiiyopathy (HC) is not well under stood. To clarify this issue, 5 severely symptomaticpatMts(agedlsto55yearqmean3O)with HC and marked subpuhnonic obstruction (basal peak systollk inssure gradients 60 to 118 mm Hg) were studied. Four patSents also had obstru~ tion to left ve~cular outflow (maximal basal or provocable pressure gradient I.3 to 110 mm Hg). 7heRVoutflowobstructionineachpatientre suited fTom greatly hrypertrophied musculature comprised of crlsta supravent&ularis, moderator band or trabeculae. Operative resection of portlons of this muscle resutted in aboliii or sub stantlal reduction of the RV outflow gradient (to 0 tollmmHg)inthe3patientswithbothpand postoperatlve hemodynamlc studii. The kft vem tricular wall and ventticular septum also were masslveiy thickened (32 to 40 mm) in each pa tient. These findlngs support the view that marked RV outtlow tract obstruction in patients with HC is due to greatly hypertrophied RV muscle, and that operative resection will reMeve the outflow gradients and normaliie RV systolic pressure. The rnus cular RV hyperbophy causing obsbuctii ap constitute a primary and excessive hypea=Jb perbophic process involvhqg both ventricles. (Am J Cardiol1993;71:108~1094)
From the Cardiology, Surgery and Pathology Branches, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. Manuscript received July 24, 1992; revised manuscript received November 20, 1992, and accepted November 23. *Present address: Minneapolis Heart Jnstitute Foundation, Division of Cardiovascular Research, 920 East 28th Street, Minneapolis, Minnesota 55407. TPresent address: Baylor Cardiovascular Institute, Baylor University Medical Center, 3701 Junius Street, P.O. Box EOlO, Dallas, Texas 75246. Address for reprints: Barry J. Maron, MD, Cardiology Branch, National Institutes of Health, Building 10, Room 7B-15, Bethesda, Maryland 20892.
any patients with hypertrophic cardiomyopathy (HC) have dynamic obstruction to left ventricular outllow due to systolic anterior motion of the mitral valve, and midsystolic contact between the mitral leaflets and ventricular septum.‘” Substantial right ventricular (RV) outtIow tract pressure gradients also may occur (although infrequently) in Hc6-i9 and am usually associatedwith subaortic ~adients.8-10,12-15,17,19 To determine the mechanismof RV outllow obstruction, we studied at operation or necropsy,or both, 5 patients with HC who had marked obstruction to RV outiow.
M
MnHODS Selection of patients: The caserecords of the Cardiology and Pathology Branches were reviewed. Five adults with HC were identified who fulfilled the following inclusion criteria: (1) RV o&low tract peak systolic pressuregradient >50 mm Hg at catheterization;and (2) RV anatomy assesseddirectly at operation (n = 4) and by gross visual inspection at necropsy (n = 3). Each patient had a hypertrophied, nondilated left ventricle in the absenceof another cardiac or systemic di~ease.2~ EchocardiEchocardiographic studies were performed in 3 patients, using commercially available instruments with 2.25 or 2.50 MHz transducers.Twodimensional imageswere obtained in standardcross-sectional planes21;M-mode echocardiogramswere derived from 2-dimensional images under direct anatomic visualization.
RESULTS vies: The 5 study patients (all men) ranged in age from 18 to 55 years (mean 30) at operation or death. All 5 patients had had substantial symptoms of cardiac dysfunction (Table I). Four patients had evidence of genetic transmission of HC to first-degree relatives,22including 3 with family history of sudden cardiac death; 1 of the latter patients had a brother with HC who had left ventricular outflow tract obstruction.16 Preoperative hemadynamierr (l&e I): In each patient, peak systolic pressure gradients between the RV body and outfIow tract under basal conditions ranged from 60 to 118mm Hg (average 76) (Figure 1). Each gradient was recorded by pullback withdrawal of the catheterfrom the pulmonary trunk to right ventricle. RV systolic pressuresranged from 82 to 135 mm Hg. Four patients also had obstruction to left ventricular outfIow; subaortic gradients were recorded under basal conditions in 3 patients (50, 82 and 110mm Hg) and
RIGHTVENTRICULAROBSTRUCTIONIN HYPERTROPHIC CARDIOMYOPATHY 1089
only after provocation with isoproterenol infusion in 1 (40 mm Hg). The remaining patient had no pressuregradient under basal conditions, but provocative maneuvers were not performed. RigW ventricular anatomy: Morphology of the RV outflow tract was assessedat operation in the 4 patients at the time of right ventriculotomy and muscular resec-
tion (and also at necropsy in 2 of them), and only at necropsy in the 1 who had myotomy-myectomywithout right ventriculototq. Based on direct visual inspection of outflow tract anatomy, greatly hypertrophied myocardium was observed,which decreasedRV cavity size (Figure 2). In 4 patients, the crista supraventricularis muscle (both the septal and parietal limbs) was enor-
TABLE I Clinical and Morphologic Findings in Five Patients with Hypertrophic Cardiomyopathy and Marked Obstruction to Right Ventricular Outflow
Age (year)* NYHA functional class (preop/postop) Syncope Exertional dyspnea Chest pain LV-SA peak systolic gradient (mm Hg) (preop/postop) Basal Provocation Systolic anterior motion, mitral valve (preop/postop)t RV-PA peak systolic gradient (mm Hg) (preop/postop) Basal Provocation Right ventricle (s/d) (mm Hg) Left ventricle (s/d) (mm Hg) LV contractility (angiogram) Cardiac index 1L/min/m2) (preop/postop) Family history of HC Echocardiographic dimensions (mm) LV thickness Anterior septum Posterior septum Lateral free wall Posterior free wall Cavity LV (end-diastole) Left atrium Electrocardiogram RV hypertrophy T-wave inversion LV hypertrophy Q waves & right precordial lead voltage LA/RA enlargement Right BBB/left AFB Operation Myotomy-myectomy (or myotomy) RV resection Age (year) RV muscle resected Moderator band Crista supraventricularis Trabeculations Weight of resected myocardium (g) Ventricular septum Right ventricle RV wall thickness (mm) Outcome Ventricular septal histology Cellular disorganization Abnormal intramural arteries
1 (CW)
2 (FR)
3 (CZ)
4 (DP)
5 (GK)
28 312 + 0 0
28
21
312
4/-
0 + +
+ + +
18 3/l 0 + +
55 3/+ t t
50/o 70/10 3+/o
82140 1041104 4+/1+
12/40/Ol-
o/-I-/-
110/o 150/-l-
60/O
60/11
77/-
11810 -
95118 148/20 f 2.8fl.7 t
82/l 180/10 Normal 2.613.1 t
115115 140124 t 2.8/0
13517 10814
65/80/8616 230/10 -
35 30 25 12
37 29 19 14
35 35 22 15
42 52
34 40
40 42
0 0 0 t (I, AVL) 0 t/t t/t
0 t (I, AVL, Vs) 0
+t
+
+ t 0
0 t (1, AVL, v5, v6) 0
4.114.1 t
40/I
2.5/t
3211
-
-
19
18
-
+
0
t
0
0 + (II, Ill, AVF) + o/o o/o
0 + (I, AVL) + t/t o/+
+ t 21
0 t 13
+ 0 55
+ 0 0
t + 0
0 t t
0 t 0
3.5 10.2 16 Alive
3.5 2.2 7 Alive
1.2 20.0 18 Dead ( 1 day postop)
0
0 0 10 Dead (7 days postop)
t5 +I
05 05
t +
2:
+ (Vl-V3)
0
0 t/o t/+
0 o/o t/t
2:
Died suddenly (5 years postop) t 0
t +
‘Current or at death. tClassification of mitral valve systohc anterior motion as assessed from M-mode echocardlogram2: 0 = absent: 1+ = present with the mmimum distance between mitral valve and ventricular septum during systole > 10 mm; 2+ = without mitral-septal contact, but with a distance < 10 mm behveen mitral valve and septum during systole; 3+ = brief mitral-septal contact (< 30% of echocardiographic systole); and 4+ = prolonged apposition of mitral valve with septum (> 30% of echocardiographic systole). tUndenvent mitral valve replacement for moderately severe mitral regurgitation 2 years after my&my-myectomy. §Only surgical speomens available; all others based on necropsy observations. 01ed before era of echocardiography; wall thickness measurements were obtained at necropsy. [’ FB -- anteriorfasclcular block; EIBB = bundle branch block: LV = left ventricular; NYHA = New York Heart Association: PA = pulmonary artery; postop = postoperative; prep preoperative; RA = right atrial; RV = right ventricular; SA = systemic artery: s/d = peak systolelend-diastole; - = data not available or not applicable: + = present; 0 = absent; 1’: Increased; J = decreased.
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MAY 1.1993
mously thickened, as was the moderator band and other RV trabeculae; the RV free wa1123was thickened in all 5 patients (Figure 2). In 1 patient, RV hypertrophy appeared to preferentially involve the moderator band. Two-dimensional echocardiogram(Figure 3) and RV angiogram showed a small or normal-sized RV cavity. In addition, echo-dense structures (or filling defects) were identified in the mid-cavity or outflow tract regions that were consistent with severely hypertrophied intraventricular trabeculae,muscle bands or crista supraventricularis (Figure 4). Operative procedures In 3 of 4 patients with evidence of obstruction to left ventricular outflow, a standard septal myotomy-myectomyoperation (Morrow prowas performed through an aortotomy; 1.2 to cedure)24,25 3.5 g of muscle was resectedfrom the ventricular septum (Figures 3 and 4). One other patient had septal myotomy alone. In 3 of 4 patients with myotomy-myectomy (or myotomy alone), a right ventriculotomy also was performed at the same operation (Figures 3 and 5). In the remaining patient, only a right ventriculotomy was performed (without prior myotomy-myectomy).Thus, in all 4 study patients with right ventriculotomy, substantial portions of greatly hypertrophied RV muscle (believed by the surgeonto be obstructive to outflow) were resected (2.2 to 20.0 g), including crista and moderator band in 2 patients, crista and greatly hypertrophied trabeculae in 1, and moderator band alone in 1; the removal of muscle substantially enlargedRV outflow tract size (Figures 2 to 5). In patient 1, after surgery, the RV cavity was dilated and showed impaired contractility and decreasedcardiac output (Table I). Postoperative hemodynamics: In 3 patients, a postoperativecardiac catheterization was performed; the basal RV outflow tract gradient was eliminated in 2 patients and was 11 mm Hg in the third (Figure 1). Siilarly, in the same 3 patients, the basal left ventricular outflow gradient was abolished in 2 and reduced to 40 mm Hg in 1 patient. L&t ventricular hyperbmphy: Assessmentby echocardiography and at necropsy showed that all 5 patients had a particularly marked and diffuse pattern of left ventricular hypertrophy (Figures 3 and 5). The thickness of the anterior portion of the ventricular septum ranged from 32 to 40 mm; substantial portions of the posterior ventricular septum and anterolateral free wall also were also greatly thickened. Heart weights (3 specimens) ranged from 660 to 1,070 g (normal 1400). Electmcardiograms (Table I): Electrocardiograms showed several abnormalities, and no single pattern was characteristic.Three patients had combined right bundle branch and left anterior fascicular block, and 1 other had left anterior fascicular block alone; 4 had prominent Q waves. DISCUSSION This study focuses on the mechanism by which marked obstruction to RV outflow occurs in patients with HC. Subpulmonic gradients in HC usually occur in association with left ventricular outflow tract obstruction8~‘o~‘2-1s~17~19~26~27; 4 of 5 patients had biventricular
obstruction. All 5 severely symptomatic patients with HC were selected for study solely because they had marked RV outflow tract gradients. Based on hemodynamic, angiographic, operative and necropsy observations, the RV outllow gradients in these patients appeared to result from the excessive hypertrophy and increasedmass of RV muscular components(most frequently and prominently the crista supraventricularis). Therefore, in contrast to left ventricular outflow obstruction in HC (which is characteristically dynamic and due to mitral valve systolic anterior motion),1-5RV outflow gradients in HC are the result of a static and fixed muscular impediment to outflow. These observations differ from previous speculationsthat RV outtlow obstruction in patients with HC is produced by the projection of the hypertrophied ventricular septum into the RV cavity7.17J9 or by systolic anterior motion of a tricuspid valve leaflet.28 Postoperativehemodynamic studies showed that the subpulmonic gradients were abolished or greatly reduced after portions of the hypertrophied RV muscular structures were resectedat operation. This iinding substantiatesthat these muscular componentswere responsible for the RV outflow gradients measuredbefore op
FIGURE 1. Changes in d&t heart pressure recordings assock ated wlth operative resection of hypehyhied ri@t venttb ular (RV) muscles in a 2Syeerdd sum with hyperbophi wdllyopathy and biventricukv otmtruction (patlent i; Table I). Top, pmopeMlvepuRbackofcatheterfromRv bodytoRvoutfiowtract(RvoT)showsi-larpeak systolicpressuregradientof6Omm~Rotbm,~ tive pullbeck of catheter from the mein pulmonary artery (MPA)toRVbodyshowsthettheRVoutRowtmctpressure gradient has bsen ebohhed. Pulmonary hypertenskn is present pwtoperatively due to elevation in left veebiculaf filling pressures.
RIGHTVENTRICULAROBSTRUCTIONIN HYPERTROPHIC CARDIOMYOPATHY 1091
FIWRE 2. Right ventrkular (RV) anatomy in 2l-yew-old man (patient 3; Table I) wRh hype&ophk cardiomyopathy who had m&edobsbuctiontoRVoutRow(outRow gmdient77mmRg).A,6,4~dE,as vlewedbythesur@onthmu~@#tverr trlculotomy at the time of muscular w tiun (i.e., of hypertrophled crkta suprave* trlculasis and moderator b-0. G ablpam nlaticpltrayadofpreoperativec?udkc anatomy showia asynmdk venttlculer septd (VS) thkkeni* and hypettrophy of RV structures (Indudi~ crista supraventrio ularis, moderaW band and RV free wall) compromioing the effecMve size of the ca* ty. PT = pulmonay tnmk.
FlRURE 3. Preoperative (A and 6) and postoperative (Cl, !dopfmm, 2diechocardiol4ams obtained in a 3lyeaFdd man with hypeWophk cap dkmyopathy and hiventrkubr OlltRow obstnlction (petll3; Table I). A, lamstemal kag-axis view showiw asymmetric thikkeni~ of ventrkular septum (VS)thatappearstobulgelntoboththeleff(LV)and right(Rv)ventricularolltRow~andreducesthe effective size of eech cavity. B, shortads view at ofante&uand chordal level showiN hypeM@y posterkrpurtionsofseptumthatbulgeintoRVoutflowtractandappeiartoobliitheRVcavRyat this level (MOWS]. C, shmt41~is view obtained intta operativelyatsamelevelasinBafterthen#rection -bandandcrktasuprav~ ofportknsof trkularls muscle. The RV cavity at this level appear0 dilated compared with that in 8. lhsre is also evL dence of the ventricular septal myotomymyectomy (arows). Calibration nuults am 1 cm apart. IA q left atrium; PW = poste&w let% ventricular free well.
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THE AMERICANJOURNALOF CARDIOLOGY VOLUME71
MAY 1,1993
FlWREARi@tV-lsr~ cml~ebtakedlnthem -pmjbctlonuvdy(AmdB)lmdpoMpsdve
ty(CandD)lna3Syeaddmim mdnmked w”-zF venbla~kwoutllow. (AmdCare dbrtolk;andBasdDatesys tolk).AudB,lar@mdklucent fllllng defects w evirknt in lhe mhkavlty.CandD,afterr8sae tkndpemOnsof~su~ VSllWCUlakrmlmoderatorband
muscuktllre, the flllhlg defects Ilb nok@srevkknt.
FlWRES.~llndhgsin2&yee ddllWlWiUl hnmbopMc~thylmdbiveMalktoulnewtmct obsbwctknwhoalday~ uvely(pstknt3;TabkI).A,extsmal viewoftheheartthatwasgmatly tWnlm&khyperbophyOfVelar
septum(VS)with~tothekltv~ mallmliwwdl(FW),nnsldlyi~ cmassd~ventrkahr(Rv)wdltMdcnewspandmdacedskeofbothRvand kftVOllt~la-~~Of~
epemthreuctkeofmuscleIfomRv @twwads) md k@t ventrkab @luws) olmlow tracts Iw widmlt. Dio cokmtknofvenbkularseptumk~ ablythetesuttofm~ nlyocrdbl kfamtkn. c, abnamal intrs llUldCWOlWY~Wtthth-
wall and m (hamato~n
nawewed lumen stdn XrO; nduced
by37%).D,chaotk -of-
dkcmusckcdkinwhkh~celk --ato#lqwcndltWtM@SStoWBChOlllW(-XyIln-eoain st8k XeO; reduced by 37%).
RIGHTVENTRICULAROBSTRUCTIONIN HYPERTROPHIC CARDIOMYOPATHY 1093
eration and also demonstratesa suitable surgical approach to this abnormality, However, 1 patient had a dilated RV cavity with impaired contractility after operative resection of substantialamounts (10 g) of RV muscle, suggesting that excessive removal of muscle may have deleterious effects on RV function. In all 5 patients, RV hypertrophy was associatedwith massive left ventricular hypertrophy, Left ventricular wall thickening was marked and diffuse, involving most of the ventricular septum and free wall; septal thickness was >30 mm in each patient and ranged up to 40 mm.29 Consequently,the muscular RV hypertrophy causing the outtlow tract obstruction appearedto constitute part of a primary and excessive hypertrophic process involving both ventricles. We made no effort to estimatethe prevalenceof subpuhnonic gradients in the overall population of patients with HC. Relatively small (5 to 25 mm Hg) RV outflow tract gradients occur frequently in patients with HC.5*26*27 Although this study does not examine the etiology of such small gradients, we presume that the underlying mechanismsresponsible are likely to be similar to those for the larger RV outflow tract gradients described in the present report.
l. Shah PM, Gmmiak R, Kramer DH. Ultrasound location of left ventricular outflow obstruction in hypertmphic obsrmctive cardiomyopathy. Circulation 1%%40: 3-11. 2 Pollick C, Rakowski H, Wigle DE. Muscular subamtic stenosis: the quantitative relationship between systolic anterior motion and pressure gradient. Circularion
1984;69:43-49. 8. Spirita P, Mamn BJ. Patterns of systolic anterior motion of the mitral valve in hypwtmpbic cardiomyopathy: assessment by two dimensional echocardiography. Am J Cardiol 1984,54:1039-1046. 4. Maron BJ, Bonow RO, Cannon RO, Leon MB, Epstein SE. Hypemophic cardiomyopathy: interrelation of clinical manifestations, pa&physiology, and therapy. N Engl .I Med 1987;316:780-789 and 84&852. 5. Wigle DE, Sasson Z, Henderson MA, Ruddy TD, Fulop J, Rakowski H, Williams WG. Hypertmphic cardiomyopathy. The importance of the site and extent of hypertrophy. A review. frog Cardiovasc Dis 1985;28:1-83. A Asin Cat&l E, Alonso M, Delcan JL, Menarguez L. Echocardiographic sign of right sided hypcrtmphic obstructive cardiomyopathy. Br Heart J 1978;40: 1321-1324. 7. Barr PA, Celetmajer JM, Bowdler JD, Cartmill TB. Idiopathic hypertrophic obstructive cardiomyopathy causing severe right ventricular outflow tract obstruction in infancy. Br Hearr J 1973:35:1109-l 115.
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8. Bevegard S, Jonsson B, Karlof I. Low subvalvular aortic and puhnonic stenosis caused by asymmetrical hypertmphy and derangement of muscle bundles of the ventricular wall. Acra Medica Scand 1973; 172:26%283. @. Botti G, Tagliavini S, Bonatti V, Aurier E. Isolated hypertmphic obstructive cardiomyopathy of the right ventricle. G Ital Cardiol 1979;9:170-181. 10. Cohen J, Effat H, Goodwin JF, Oakley CM, Steiner RE. Hypxtmphic obstmctive cardiomyopathy. Br Heart J 1964:26:1&32. 11. Goodwin JF, Hollman A, Cleland WP, Teare D. Obstructive cardiomyopathy simulating a&c stenosis. Br Heart J 1960;22:403414. 12. Grow-Brcxkhoff F, Loogen F. Infundibular pulmonary stenosis in chronic left venticular cardiopathy. Dtsch Med Wochenschr 1%2;87:52>530. la. Lockhart A, Charpentier A, Bowlarias JP, Ben Ismail M, Outback P, Scebat L. Right ventricular involvement in obstructive canliomyopathies. Hemodynamic studies in 13 cases. Br Heart J 1966;28:122-133. 14. Mamn BJ, Edwards JE, Henry WL, Clark CE, BingIe GJ, Epstein SE. Asymmetric septal hypertrophy (ASH) in infancy. Circulation 1974;50:809-820. 15. Mamn BJ, Tajik AJ, Ruttenberg HD, Graham TP, Atwood GF, Victmica BE, Lie IT, Roberts WC. Hypertmphic cardiomyopathy in infants: clinical features and natural history. Circulation 1982;65:7-17. 16. Morrow AG, Fisher RD. Fogarty TJ. Isolated hypertmphic obstruction to right ventricular outtlow. Am Heart J 1%9;77:814-817. 17. Taylor RR, Bernstein L, Jose AD. Obstructive phenomena in ventricular hypertrophy. Br Heart J 1964;26:193-198, 18. Van Do&off W, Nanda NC. Obstruction within the right ventricular body: hvodimensional echocardiographic features. Am J Cardiol 1983;51:1498-1501. 10. Wigle ED, Heimbecker RO, Gunton RW. Idiopathic ventricular septal hypertrophy causing muscular subsonic stenosis. Circulation 19622632s340. 20. Mamn BJ, Epstein SE. Hypertmphic cardiomyopathy: a discussion of nomenclature. Am J Cardiol 1979;43: 1242-1244. 21. Tajik Al, Seward JB, Ha& DJ, Mair DD. Lie JT. Two-dimensional real-time ultrasonic imaging of the heart and great vessels. Mayo Clin from 1978;53:271-303. 22. Maron BJ, Nichols PF, Pickle. LW, Wesley YE, Mulvihill JJ. Patterns of inheritance in hypertmphic cardiomyopathy: assessment by M-mode and hvodimensional echocardiography. Am J Cordial 1984,53: 1087-1094. 23. McKenna WJ, Kleinebenne A, Nihoyannopoulos P, Foale R. Echocardiographic measurement of right ventricular wall thickness in hypertmphic cardiomyopathy: relation to clinical and prognostic features. J Am Co0 Cardiol 1988:11:351-358. 24. Morrow AG, Reitz BA, Epstein SE, Henry WL, Conkle DM, Itscoitz SB, Redwood DR. Operative treatment in hypertmphic subamtic stenosis: techniques and the results of pre and postoperative assessments in 83 patients. Circulation 1975;52:88-102. 26. Mamn BJ, Epstein SE, Morrow AG. Symptomatic stah~s and prognosis of patients after operation for hypemophic obstructive cardiomyopathy: efficacy of ventricular septal myotomy and myectomy. Eur Hean J 1983;4(suppl F):175-185. 26. Frank S, Braunwald E. Idiopathic hypettmphic subaortic stenosis. Clinical analysis of 126 patients with emphasis on the natural history. Circulation 1968;37:
75'+788. 27. Braunwald E, Lambrew CT, Morrow AG, pierce GE, Rockoff SD, Ross J. Idiopathic hypertmphic subaottic stenosis: 1. A description of the disease based upon an analysis of 64 patients. Circulation 1964;29 and 3O(suppl IV):IV-3-119. 22. Brik H, Meller J, Bahkz AS, Herman MV, Teichholz LE. Systolic anterior motion of the tricuspid valve in idiopathic hypettmphic subaortic stenosis. J C/in film 1978;6:121-124. 29. Louie EK, Mamn BJ. Hypettmphic cardiomyopathy with extreme increase in left ventricular wall thickness: Clinical significance, functional and morphologic feamm. J Am Coil Cardiol 1986;8:57-65.
MAY 1,1993