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GUEST EDITORS’ PAGE

From the aHypertrophic Cardiomyopathy Institute, Divisio

ogy, Tufts Medical Center, Boston, Massachusetts (forme

apolis Heart Institute Foundation, Hypertrophic Cardiomyo

Minneapolis, Minnesota); and the bBaylor Heart and Vasc

Dallas, Texas. Both authors have reported that they have no

relevant to the contents of this paper to disclose.

The Father of SeptalMyectomy forObstructive HCM,Who Also Had HCM

The Unbelievable Story

Barry J. Maron, MD,a William C. Roberts, MDb

FIGURE 1 Andrew Glenn Morrow, 1963

A ndrew Glenn Morrow, MD, was Chief of theClinic of Surgery at the National Institutesof Health (NIH), Bethesda, Maryland, from

1953 until his death in 1982 (Figure 1). During thattime, he established an international training pro-gram for future cardiac surgeons, and among manyother accomplishments, the ventricular septal myec-tomy operation for obstructive hypertrophic cardio-myopathy (HCM) (1,2).

He was the first surgeon to perform the myectomyoperation to relieve left ventricular (LV) outflowobstruction in patients experiencing inadequatesymptom response to medical treatment, a proce-dure which he designed, which he performed on 299patients, and which bears his name (1,2). A smallamount of muscle is resected from the basal septumto widen the LV outflow tract (3) and abolish systolicanterior motion of the mitral valve, the mechanismresponsible for subaortic obstruction. Dr. Morrowalso was first to report obstruction as due tomuscular hypertrophy sufficient to impede LVoutflow (4).

The Morrow operation (now modified by extendedmuscular resection) was introduced in the early 1960sat the NIH and quickly spread to major institutionsin the United States, including Mayo Clinic, and

n of Cardiol-

rly at Minne-

pathy Center,

ular Institute,

relationships

internationally (5–7). Now, >50 years later, surgicalmyectomy continues to benefit thousands of patientswith HCM, resulting in reversal of heart failuresymptoms and restoration of normal daily activity inalmost 90% (5,8–12), as well as enhanced survivalconsistent with the general population (5). In guide-lines (10) and consensus recommendations (11),myectomy remains the primary treatment option formost patients with severe drug-refractory heartfailure symptoms, becoming the safest open heartprocedure when performed in experienced centers(mortality, 0.3%) (6).

FIGURE 2 Morrow Family Pedigree

? ?

(91) (60)

1 2

(65) (83)

3 4

(83)

1

(63)

2

(52)

3

(66)

1 2 3 4

(23) (21) (20) (16)

I.

II.

III.

Squares indicate men; circles indicate women; arrow indicates

proband (Dr. Morrow, I.1.); solid symbols indicate hypertrophic

cardiomyopathy; and slash indicates deceased.

FIGURE 3 The Heart of Dr. Morrow

Weight, 645 g. (A) The ascending aorta (Ao) is free of atherosclerotic plaque, with a

structurally normal aortic valve, nondilated left ventricular (LV) cavity, and greatly dilated

left atrium (LA). Ventricular septal (VS) thickness is 20 mm, asymmetrically hypertrophied

with respect to LV free wall (FW). Behind posterior mitral leaflet is a large calcific deposit

(arrow), frequent in older patients. Several small scars are evident in the VS and at the

apex (arrowheads). (B) In the subaortic region of the hypertrophied septum is a fibrous

plaque (arrowheads) in apposition to the thickened anterior mitral leaflet (AML), evidence

of prior outflow obstruction. RV ¼ right ventricle.

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HCM AND GLENN MORROW’S ILLNESS

It is not widely known that Dr. Morrow himself hadHCM, with this diagnosis substantiated by anaggressive form of the disease identified in 2 of hischildren (Figure 2). Dr. Eugene Braunwald, Chief ofCardiology, was a close friend and colleague ofDr. Morrow. While collaborating at the NIH on the firstmajor clinical description of HCM (13), Dr. Morrowasked Dr. Braunwald: “Gene, would you examine myheart?” (14). Solely by precordial auscultation, andrecognizing the classic finding of a systolic ejectionmurmur due to LV outflow obstruction, Dr. Braunwaldmade the diagnosis of obstructive HCM at age 40 years(called “IHSS” at that time) (13,14). This diagnosiswas impressive for several reasons: 1) it occurred in1961, in the pre-echocardiographic era; and 2) it wasmade with auscultation when diagnostic criteriafor this complex disease were just being formulated.Dr. Morrow was probably the 25th clinically identifiedHCM patient (13,14).

Dr. Morrow experienced exertional dyspnea andnear-syncope almost daily in the morning, multipleepisodes of syncope, atrial fibrillation, and ulti-mately, embolic stroke. He refused beta-blockertherapy, cardiac catheterization, and considerationfor septal myectomy. Dr. Morrow died suddenly atonly 60 years of age in his home. His heart wasrecovered by Dr. William Roberts with the permissionof Dr. Morrow’s wife. At autopsy, cardiac morphologicfindings were typical of HCM with asymmetricseptal hypertrophy, myocyte disarray, myocardialscarring, and structural microvascular abnormalities(Figure 3).

THE MORROW FAMILY DISEASE

The Morrows were married for 37 years and had3 children, including 2 with an unusually aggressiveform of HCM.

DAUGHTER. One child is a 52-year-old woman whowas diagnosed with HCM at age 21 with a heartmurmur due to mitral valve systolic anterior motionand ventricular septal hypertrophy (Figures 2 and 4).For many years, she experienced symptoms of heartfailure and limited physical activity, refractory topharmacological agents, chronic dual-chamber pacing(15), and also radiofrequency ablations that were un-successful in reducing symptomatic episodes of atrialfibrillation.

Although initially with a subaortic gradient of 70mm Hg, she evolved to a nonobstructive state withend-stage heart failure (New York Heart Associationfunctional class III to IV), associated with both

preserved LV hypertrophy and systolic function(ejection fraction, 67%) (15), nondilated LV, and bia-trial enlargement, characteristic of a novel subgroupof transplant candidates (16). She underwent suc-cessful heart transplant at age 51 years, and has beengenotyped to a pathogenic beta-myosin heavy chainmutation (MYH7) (DNA coding c.485A>G; variantpTyr162Cys [y162c]).

SON. Another of Dr. Morrow’s children is a 63-year-old man who has obstructive HCM (septal thickness,21 mm) (Figure 2). For many years, he has beenencumbered by recurrent episodes of syncope,symptomatic atrial fibrillation (left atrium, 48 mm)

FIGURE 4 The Explanted Heart of Daughter

Weight 510 g. (A) The VS thickness is 23 mm, asymmetrically hypertrophied with respect to LV FW, and with a nondilated LV cavity.

(B) Septal endocardial fibrous plaque (white arrowheads) adjacent to the thickened AML, and prior evidence of mitral valve systolic

anterior motion and obstruction. (C) Typical disorganized myocyte arrangement in septum, and areas of interstitial fibrosis (blue);

myocardial scarring was absent (�400). (D) Intramural coronary artery with disrupted media and intimal fibrous thickening (�100).

Masson trichrome stain. Abbreviations as in Figure 3.

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requiring cardioversion, and 1 transient ischemicattack. At age 57 years, he developed severe pro-gressive heart failure due to LV outflow obstruction(gradient, 55 mm Hg). He underwent successful sur-gical septal myectomy with symptomatic relief,remarkably with the same operation his fatherhad developed and promoted 5 decades earlier (1,2).His 21-year-old daughter has HCM, completing a3-generation disease transmission.

PERSPECTIVES

The saga of Dr. Glenn Morrow, HCM, and the Morrowfamily is of unique interest to cardiovascular medi-cine, and also one which has been largely unknown. It

is reported here to complete the historical record. AsDr. Braunwald reflected (14), should this scenariohave been encountered on television or in themovies, it would be considered impossible or ridicu-lous, that is, one colleague diagnosing the other whilethey are both collaborating on the description of thesame new disease, which was then consideredextraordinarily rare.

In addition, several important facets of HCM areunderscored here, that is, an autosomal dominantdisease with great heterogeneity in expression, theimportance of atrial fibrillation, and contemporarymanagement considerations (17). The particularlyaggressive clinical variants reported here in Dr.Morrow and his offspring are considered somewhat

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unusual within the broad HCM disease spectrum,most often associated with normal life expectancywithout major disability (12,17). Indeed, all 3 in-dividuals were affected by a progressive diseasecourse involving repetitive atrial fibrillation (withthromboembolism in the father), recurrent syncope(both males), heart transplant (the daughter), andsubaortic obstruction causing severe heart failure

symptoms in the son and reversed by the very oper-ation designed by and named for his father.

REPRINT REQUESTS AND CORRESPONDENCE: Dr.Barry J. Maron, HCM Institute, Division of Cardiology,Tufts Medical Center, 800 Washington Street #70,Boston, Massachusetts 02111. E-mail: barrymaron1@gmail.com.

RE F E RENCE S

1. Morrow AG, Lambrew CT, Braunwald E.Idiopathic hypertrophic subaortic stenosis. II.Operative treatment and the results of pre- andpostoperative hemodynamic evaluations. Circula-tion 1964;30 Suppl 4:120–51.

2. Morrow AG, Reitz BA, Epstein SE, et al. Opera-tive treatment in hypertrophic subaortic stenosis.Techniques, and the results of pre and post-operative assessments in 83 patients. Circulation1975;52:88–102.

3. Spirito P, Maron BJ, Rosing DR. Morphologicdeterminants of hemodynamic state after ven-tricular septal myotomy-myectomy in patientswith obstructive hypertrophic cardiomyopathy: Mmode and two-dimensional echocardiographicassessment. Circulation 1984;70:984–5.

4. Morrow AG, Braunwald E. Functional aorticstenosis; a malformation characterized by resis-tance to left ventricular outflow without anatomicobstruction. Circulation 1959;20:181–9.

5. Ommen SR,Maron BJ, Olivotto I, et al. Long-termeffects of surgical septal myectomy on survival inpatients with obstructive hypertrophic cardiomy-opathy. J Am Coll Cardiol 2005;46:470–6.

6. Maron BJ, Dearani JA, Ommen SR, et al.Low operative mortality achieved with surgicalseptal myectomy: role of dedicated hypertrophic

cardiomyopathy centers in the management ofdynamic subaortic obstruction. J Am Coll Cardiol2015;66:1307–8.

7. Dearani JA. Septal myectomy remains the goldstandard. Eur Heart J 2012;33:1999–2000.

8. Woo A, Williams WG, Choi R, et al. Clinical andechocardiographic determinants of long-termsurvival after surgical myectomy in obstructivehypertrophic cardiomyopathy. Circulation 2005;111:2033–41.

9. Smedira NG, Lytle BW, Lever HM, et al. Currenteffectiveness and risks of isolated septal myec-tomy for hypertrophic obstructive cardiomyopa-thy. Ann Thorac Surg 2008;85:127–33.

10. Gersh BJ, Maron BJ, Bonow RO, et al. 2011ACC/AHA guideline for the diagnosis and treat-ment of hypertrophic cardiomyopathy: AmericanCollege of Cardiology Foundation/American HeartAssociation task force on practice guidelines. J AmColl Cardiol 2016;58:2703–38.

11. Maron BJ, McKenna WJ, Danielson GK, et al.American College of Cardiology/European Societyof Cardiology clinical expert consensus documenton hypertrophic cardiomyopathy. J Am Coll Car-diol 2003;42:1687–713.

12. Maron BJ, Ommen SR, Semsarian C, et al.Hypertrophic cardiomyopathy: present and future,

with translation into contemporary cardiovascularmedicine. J Am Coll Cardiol 2014;64:83–99.

13. Braunwald E, Lambrew CT, Rockoff SD, et al.Idiopathic hypertrophic subaortic stenosis. 1. Adescription of the disease based upon an analysisof 64 patients. Circulation 1964;30 Suppl 4:3–119.

14. Maron BJ, Braunwald E. Eugene Braunwald,MD and the early years of hypertrophic cardio-myopathy: a conversation with Dr. Barry J. Maron.Am J Cardiol 2012;109:1539–47.

15. Maron BJ, Josephson ME. Long-term conse-quences of the right ventricular pacing mania ofthe 1990s for obstructive hypertrophic cardiomy-opathy. Am J Cardiol 2014;113:191–2.

16. Rowin EJ, Maron BJ, Kiernan MS, et al.Advanced heart failure with preserved systolicfunction in nonobstructive hypertrophic cardio-myopathy: under-recognized subset of candidatesfor heart transplant. Circ Heart Fail 2014;7:967–75.

17. Maron BJ, Rowin EJ, Casey SA, Maron MS.How hypertrophic cardiomyopathy became acontemporary treatable genetic disease with lowmortality: shaped by 50 years of clinical researchand practice. JAMA Cardiol 2016 Mar 2 [E-pubahead of print].