Barlow JB, Pocock WA, Marchand P, Denny M. The significance of late systolic murmurs. Am Heart J 1963;66:443
Barlow JB, Bosman CK. Aneurysmal protrusion of the posterior leaflet of the mitral valve; An auscultatory-electrocardiographic syndrome. Am Heart J 1966;71:166-78
Barlow JB, Bosman CK, Pocock WA, Marchand P. Late systolic murmurs and non-ejection("mid-late") systolic clicks. An analysis of 90 patients. Br Heart J 1968;30:203-18
Pocock WA, Barlow JB. Etiology and electrocardiographic features of the billowing posterior mitral leaflet syndrome. Analysis of a further 130 patients with a late systolic murmur or nonejection systolic click. Am J Med 1971;51:731-39
Shortly after Reid, Barlow and his colleagues reported their observations on seven patients with apical systolic murmur who underwent left ventricular cineangiography. In three patients a mid-late systolic click was also noted.
In all seven patients, the regurgitation of the dye into the left atrium occurred during ventricular systole. Furthermore, the inhalational of Amyl Nitrate was associated with a significant decrease in systemic blood pressure and the intensity of the systolic murmur on phonocardiography. Similarly, Valsalva maneuver decreasing the venous return resulted in a significant reduction of the intensity of the murmur. In contrast, intravenous administration of Phenylephrine caused an increase in the intensity of the systolic murmur during the hypertensive phase.
In this pioneering work, Barlow and his colleagues showed for the first time with objective evidence that the late systolic murmur was from cardiac origin and due to mitral valve regurgitation.
In 1966, Barlow and Bosman described several cases of late systolic murmur and mid-systolic click that underwent left ventricular cineangiocardiography.
Two patients were adult female of 56 and 48 years of age whereas the two remaining patients were children of 6 and 8 years of age. In the adult, the presenting symptoms were chest pain, dyspnea, and intermittent palpitation.On EKG,nonspecific T-wave abnormality and ST elevation in inferior leads were noted.
Left ventricular cineangicardiography showed "during left ventricular systole a massive protrusion of the posterior (mural) leaflet of the mitral valve into the left atrial cavity, in addition to mild mitral regurgitation."
In the discussion of their article, these authors remarked:
"...It is probable that left ventriculography in patients with late systolic murmurs...would in many instances also reveal some billowing of that leaflet. Mobile and billowing posterior leaflets were certainly apparent in the 9 such patients so examined by us."
Barlow coined the term billowing to describe the abnormal aspect of the posterior leaflet of the mitral valve on ventriculography.
In 1968, Barlow and his colleagues reported their experience with a larger series including 90 patients from the age of 4 to 63 years. The analysis of the data confirmed their early findings indicating the valvular origin of the late systolic murmur. Furthermore, their investigations demonstrated that the vasoactive maneuvers affected the duration and the intensity of late systolic murmurs in a constant manner dependent on alterations of the end diastolic left ventricular volume, the left ventricular systolic pressure, and the strength of myocardial contractility.
In their conclusion, they affirmed: "The combination of a late systolic murmur of mild mitral incompetence, a non-ejection click, and billowing of the posterior leaflet, together with a characteristic electrocardiographic pattern, constitutes a specific syndrome."
Regarding the structural pathology of the mitral valve, they postulated:
"...with late systolic murmurs, we believe that chordae are invariably lengthened, functionally lengthened, or ruptured. In either instance the leaflet to which such chordae attach probably always billows abnormally to a greater or lesser degree. This billowing is accompanied by an increase in surface area of the leaflet and, though this may affect the anterior leaflet, the available evidence suggests that it is the posterior leaflet which is chiefly involved...elongation or rupture of these chordae [posterior leaflet] could allow the central portion of the leaflet to billow, in the same way as the anterior leaflet billows naturally...Once the prolapse has started, the process, following Laplace's law, should be progressive and the leaflet would stretch and become more voluminous."
Finally, in 1971, Barlow and Pocock published their classic paper in which they summarized their findings in a series of 130 patients and introduced the term "Billowing posterior mitral leaflet syndrome". The familial form of the disease was reported in 17% of patients. As previously mentioned, most these patients presented with late systolic murmur, a mid-late systolic click, abnormal aspect of the mitral valve on ventriculography with billowing and excess tissue, and EKG changes. Today we define this type of pathology as degenerative mitral valve disease in general, and this specific subgroup is named Barlow's disease by respect to his seminal contributions.