Jimmy Pham
Michigan, United States

“To all the students who listen, look, touch and reflect: may they hear, see, feel and comprehend”
—John Barlow, Perspectives on the Mitral Valve (1986)

Mitral valve prolapse is now recognized as one of the most commonly diagnosed cardiac valvular abnormalities, occurring in 2.4% of the general population using standardized echocardiographic criteria, and having the highest incidence in women.¹ The syndrome of mid-systolic click accompanying a systolic murmur was first mentioned in the medical literature in 1887, but it was not until 1963 that its association with mitral valve and mitral regurgitation was demonstrated by John Barlow and colleagues.^2,3

Originally, the extra midsystolic sound was designated a systolic gallop rhythm and was thought to be benign, extracardiac, and associated with pleuropericardial adhesions.^4-8 This concept was based largely on the work of Gallavardin, who described pleuropericardial adhesions in four autopsied patients in whom systolic clicks had been heard (similar sounds were also described by Potain), and on the observations by Johnston, who found that mid-systolic clicks and murmurs changed markedly with changes in position and respiration.^9-12 John Barlow and colleagues, and later Segal and Likoff, used left ventricular cineangiography and clearly demonstrated that patients with mid to late systolic clicks and late systolic murmurs did in fact have mild mitral incompetence and that the regurgitation occurred during the latter part of systole.¹³

John Barlow was born in Cape Town, South Africa, on October 24, 1924, to Madeline Dicks and Lancelot White Barlow. His father was a South African who had studied medicine in England, where he met Madeline Dicks, and returned to South Africa to work as a medical pathologist.

Barlow began his medical studies at the University of the Witwatersrand in Johannesburg. His first year of medical school was interrupted when South Africa entered World War II and he enlisted in the military, serving with the British Eighth Army forces in North Africa and the American Fifth Army in Italy. He returned to medical school in 1946 and completed his MBBCh (Bachelor in Medicine and Surgery) in November 1951.¹⁴

Barlow trained in medicine, surgery, and pediatrics at Baragwanath Hospital in Soweto and in 1955 when he sailed to England to sit for his examination for the Membership of the Royal Colleges of Physicians. In London he worked as senior house officer for the renowned hepatologist Sheila Sherlock and later as a medical registrar under Sir John McMichael at the Royal Postgraduate Medical School at Hammersmith Hospital in west London. Becoming interested in auscultation and phonocardiography, he investigated under the guidance of McMichael the auscultatory syndrome of non-ejection mid-systolic clicks and late systolic murmurs—challenging the published evidence that these findings were benign and extracardiac.¹⁵

John Barlow entered the international cardiology scene in 1963 with his landmark paper on the mid-systolic click and late systolic murmur.¹⁶ During his time at the Royal Postgraduate Medical School, Barlow attended the postmortem examination of a patient known to have had a mid-systolic click. Barlow noticed that the man had a single fibrosed mitral valve chord but no abnormality outside the heart to account for this click. By further investigation he was able to demonstrate that the cause of this still poorly understood problem was due to an abnormality of the mitral valve. This view was considered controversial at the time and initially was met with skepticism by the cardiology community.

His first paper on the subject was declined by the journal Circulation on the grounds that his assertions were extreme. His friend and former schoolmate Bernard Tabatznik persuaded Barlow to submit a shorter version of the paper to the Maryland State Medical Journal (of which his friend was a sub-editor) where it was published under the title “The Significance of Late Systolic Murmurs and Mid-Late Systolic Clicks.”¹⁶ A second and groundbreaking paper appeared in the American Heart Journal on October 1963.¹⁷ Barlow also worked and published papers on the role of tricuspid regurgitation; the role of a hemodynamic valve load as the origin of refractory heart failure in patients with active carditis; submitral aneurysm; hypertrophic cardiomyopathy; and the time course of a false positive stress electrocardiogram.^18-21

In fact it was Barlow’s efforts to clarify the features of non-ejection systolic click and late systolic murmur that began the “mitral valve prolapse” controversy, which later led to further detailed understanding of this phenomenon. While visiting the John Hopkins Hospital in 1964, Barlow met John Michael Criley, who introduced the term “prolapse” of the mitral valve. Although this is sometimes called Barlow syndrome, he distinctively preferred the term “billowing mitral leaflet.”¹⁴

In South Africa, Barlow worked as a medical registrar, and then consultant physician at the Johannesburg Hospital, and in 1971 became director of the cardiovascular research unit. He was appointed professor of cardiology in the newly created department of cardiology in 1980, continuing as such until he retired in 1990, when he was awarded an honorary doctorate of science in medicine by Witwatersrand. From the three-year stint at Hammersmith (1955–1957) he had developed so much respect for John McMichael that in 1961 he named after him his cardiac catheterization laboratory at Johannesburg Hospital.

Barlow spent over thirty-five years working and conducting research in Johannesburg. He treated patients from all walks of life, ranging from underprivileged black children from Soweto to the President Mandela, to whom Barlow was a personal physician. He received during his lifetime numerous awards, including being the first recipient of the Award for Distinguished Contributions to National and International Cardiology in 1990 by the South Africa Cardiac Society, and the “President’s Medal for Distinguished Contributions to International Cardiology” as one of his most honorable awards given by the National Counsel of the South Africa Cardiac Society.

Barlow married Shelagh Cox in 1949 and was predeceased by her. They had two sons: Richard John Barlow, who became a consultant at St John’s Institute of Dermatology, and Clifford William Barlow, consultant cardiac surgeon at Southampton General Hospital. He died on December 10, 2008, at age of eighty-four, remembered fondly by his peers and staff as

“. . . one of the greatest clinical cardiologists in the world, famous for naming Barlow’s Syndrome which is a form of congenital heart disease in which one or both leaflets of the mitral valve protrude into the left atrium during the systolic phase of ventricular contraction.”

His colleagues regarded him as “the ultimate, compleat clinical cardiologist in the elicitation and interpretation of cardiac signs in the classical British style.”²²

References

1. Mann DL, Zipes DP, Libby P, Bonow RP. Braunwald’s Heart Disease, 10^th Edition. 2015:1494.
2. Cuffer and Barbillion, Nouvelles recherches sur le bruit de gallop cardiaque. Archives Generales de Medecine (7^th Series) 1887;1:129 & 301
3. Barlow JB, Pocock WA, Marchand P, Denny M. The significance of late systolic murmurs. Am Heart J. 1963;66:443
4. McKusick VA. Cardiovascular Sound in Health and Disease, Baltimore, Williams & Wilkins Co., 1958:179.
5. Fowler NO. Physical Diagnosis of Heart Disease. New York, Macmillan Co. 1962:34.
6. Leatham A. Auscultation of the heart. Lancet 2:703;758, 1959.
7. Caceres CA and Perry LW. The Innocent Murmur. Boston, Little Brown & Co. 1967:225.
8. Deuchar, DC. Clinical Phonocardiography. Princeton, D. Van Nostrand Co., 1965:34.
9. Gallavardin L. Pseudo-dedoublement du deuxieme bruit du coeur simulant le dedoublement mitral: Part bruit extra-cardiaque telesystolique surajoute. Lyon Med. 1913;121:409.
10. Potain C. Les bruits de galop. Semaine des Hopitaux de Paris. 1900;20:175.
11. Gallavardin L. Nouvelle observation avec autopsie d’un pseudo-dedoublement mitral par bruit extracardiaque telesystolique. Prat Med Franc. 1932;13:19.
12. Johnston FD. Extra sounds occurring in cardiac systole. Am Heart J. 1938;15:221.
13. Segal BL, Likoff W. Late systolic murmur of mitral regurgitation. Am Heart J. 1964;67:757-63.
14. Cheng TO. JohnB.Barlow: the man and his syndrome. Int J Cardiol. 2014; 177(2):311-6.
15. Cheng TO. JohnB.Barlow: master clinician and compleat cardiologist. Clin Cardiol. 2000; 23(1):66-7.
16. Barlow JB, Pocock WA. The significance of late systolic murmurs and mid-late systolic clicks. Maryland State Med J. 1963;12:76–77.
17. Barlow JB, Pocock WA, Marchand P, Denny M. The significance of late systolic murmurs. Am Heart J. 1963;66:443.
18. Lakier JB, Bloom KR, Pocock WA, Barlow JB. Tricuspid component of first heart sound. Br Heart J. 1973; 35(12):1275-9.
19. Barlow JB, Marcus RH, Pocock WA, Barlow CW, Essop R, Sareli P. Mechanisms and management of heart failure in active rheumatic carditis. S Afr Med J. 1990;78(4):181-6
20. Kanarek KS, Bloom KR, Lakier JB, Pocock WA, Barlow JB. Clinical aspects of submitral left ventricular aneurysms. S Afr Med J. 1973 Jul 21;47(28):1225-9
21. Neutel JM, Barlow CW, Barlow JB, King J, Myburgh DP. Evaluation of the post-exercise time-course behaviour of ST-segment and T-wave changes in the elimination of the false-positive stress ECG. S Afr Med J. 1990;78(11):637-41
22. Jankelow D. A Tribute to Professor John Barlow”.Adler Museum Bulletin.2012;38(1):18