John B. Barlow

The significance of late systolic murmurs

Abstract 1. 1. Four patients with apical systolic murmurs confined to mid-late systole, and 3 patients with pansystolic murmurs with late accentuation were subjected to left ventricular cineangiocardiography. Regurgitation of dye into the left atrium during ventricular systole occurred in all 7 patients. 2. 2. Inhalation of amyl nitrite, a Valsalva maneuver, and intravenous injection of phenylephrine resulted in a fairly constant alteration in the intensity and the time of maximal accentuation of these murmurs. The conclusion is that the pattern of change is compatible with that of a mitral regurgitant systolic murmur. 3. 3. The common association of late murmurs with mid-late systolic clicks is confirmed, and reasons for suspecting that these clicks are due to fibrosed chordae are discussed. 4. 4. The importance of appreciating that late systolic murmurs are due to mildmitral incompetence is stressed. Although little hemodynamic alteration is present, these patients are presumably potential candidates for subacute bacterial endocarditis, and, in younger patients, prophylaxis against rheumatic activity is indicated.

Late systolic murmurs and non-ejection ("mid-late") systolic clicks. An analysis of 90 patients.

Evidence has previously been produced from this laboratory (Barlow and Pocock, 1963; Barlow et al., 1963; Barlow, 1965) that apical late systolic murmurs denote mitral regurgitation, and that the commonly associated non-ejection systolic clicks also have an intracardiac, and probably chordal, origin. It has also been suggested that the association of these auscultatory features with a distinctive electrocardiographic pattern and a billowing posterior leaflet of the mitral valve constitutes a specific syndrome (Barlow, 1965; Barlow and Bosman, 1966). In this paper we present an analysis of 90 subjects with either a late systolic murmur, a nonejection click, or both. The intracardiac origin of these murmurs and clicks is reaffirmed and their possible mode of production is considered. The abnormal electrocardiogram, the probable structural abnormality of the mitral valve mechanism, the various underlying aetiological factors, and the prognosis are discussed.

Aneurysmal protrusion of the posterior leaflet of the mitral valve: An auscultatory-electrocardiographic syndrome

Abstract In previous communications, evidence has been produced that apical late systolic murmurs are invariably due to mitral regurgitation, and that the commonly associated nonejection systolic clicks result from abnormalities of the mitral chordae tendineae. The present paper describes 5 patients with both of these auscultatory findings who had, in addition, electrocardiographic signs compatible with posteroinferior myocardial ischemia or infarction. Left ventricular cineangiocardiography was performed in 4 of the 5 patients, and an aneurysmal dilatation of the posterior leaflet of the mitral valve was demonstrated. It is postulated that distortion of the circumflex coronary artery by the abnormal mitral valve may be the cause of the electrocardiographic features. The probability is briefly discussed that in some instances the mitral valve anomaly results from a genetically determined defect, or weakness, of the posterior leaflet.

The spectrum of severe rheumatic mitral valve disease in a developing country. Correlations among clinical presentation, surgical pathologic findings, and hemodynamic sequelae.

Bland and Jones [1], in their benchmark report on rheumatic fever and rheumatic heart disease in 1951, documented a mortality rate of 50% by age 20 years among young patients presenting with rheumatic mitral valve disease before 1920. With the advent of antibiotics, the incidence and severity of rheumatic fever and acute rheumatic carditis have declined markedly in the Western world [2, 3]. In the United States, the decline in rheumatic disease resulting from antimicrobial therapy was so dramatic that several important issues relating to the natural history of this condition have never been resolved. Specifically, the high early mortality rate among young patients with acute rheumatic carditis [1, 4] has not been explained. In this context, Bland and Jones [1] did report a high prevalence of mild mitral regurgitation early in the course of the disease but felt that this lesion was benign. The prevalence and natural history of pure, severe rheumatic mitral regurgitation have not been established, and its unique surgical anatomy has not been well characterized. In developing areas, where predisposing factors to rheumatic fever persist and prophylactic penicillin therapy is often inadequate, acute rheumatic carditis still frequently follows a fulminant course, resulting in death or severe disability at an early age [5-8]. In South Africa, the sociopolitical situation is such that abject poverty and deprivation are often juxtaposed with sophisticated tertiary care services. The availability of the latter, specifically cardiac surgery, for patients with this disease permitted us to analyze clinical, hemodynamic, and surgical pathologic data that had not been previously correlated. Methods We retrospectively studied 748 consecutive patients with rheumatic heart disease who had mitral valve surgery between 1983 and 1986 at Baragwanath Hospital in South Africa. All patients were blacks living either in townships in the environs of the hospital (equivalent to inner-city areas in the metropolitan United States) or in rural areas. Eleven patients in whom concurrent infective endocarditis or primary degenerative leaflet disease (1 patient) confounded evaluation of the hemodynamic severity of the rheumatic lesion itself were excluded from the analysis. Of the remainder, 520 were female and 217, male. Patients ranged in age from 4 to 73 years (mean, 27 13 years [SD]; median, 25 years); 271 (37%) were 20 years of age or younger. All were in New York Heart Association (NYHA) class 3 or 4 and receiving maximal medical treatment. Preoperative Classification of Valve Lesions Before surgery, all patients were examined independently by at least two cardiologists. Mitral valve lesions were classified as purely regurgitant, purely stenotic, or mixed according to recognized clinical, radiologic, and echocardiographic criteria [9]. Mitral regurgitation was considered to be pure when associated with unrestricted valve leaflet excursion and a normal mitral orifice area as assessed by two-dimensional echocardiography. Pure mitral stenosis was diagnosed when no clinical or echocardiographic evidence for regurgitation was found. Mixed mitral valve disease was diagnosed when features of both regurgitation and stenosis were present. Cases in which discordance existed among clinical, hemodynamic, and surgical pathologic assessments were excluded from the analysis. Surgical Evaluation Hemodynamic Assessment The hemodynamic severity of valve lesions was confirmed by measurements of left atrial, left ventricular, and right ventricular pressures using fluid-filled catheters connected through strain gauge transducers (Statham, Oxnard, California) to a multichannel recorder (Honeywell Meddars, Lenexa, Kansas). The transmitral end-diastolic gradient (timed according to the R wave on the electrocardiogram) was determined by analysis of simultaneous left atrial and left ventricular pressure recordings. The ratio of left atrial V wave to mean left atrial pressure was calculated as an index of the hemodynamic severity of mitral regurgitation [10]. In 74 patients (10%), pressure measurements were not obtained for technical reasons or because of hemodynamic instability. Surgical Anatomy After cardiotomy, mitral valves were examined independently by two experienced surgeons according to a standard protocol, implemented in all patients having rheumatic valve surgery at Baragwanath Hospital between 1983 and 1986 at the instigation of one of the surgeons who was then doing research in this area. Valve leaflets were assessed for their pliability as well as for evidence of retraction (scarring) or calcification. Valve commissures were evaluated for evidence of fusion. Mitral valve prolapse was diagnosed at operation if the free edge of one or more scallops of a leaflet, almost invariably the anterior, could be retracted toward the left atrium beyond the free margin of the complementary leaflet and above the plane of the mitral annulus without applying tension to the chordae tendineae [5, 11]. The size of the mitral annulus and the length of the chordae tendineae were assessed. The size of the mitral annulus was graded by inspection using a 4-point scale from 0 (normal size) to 3+ (markedly dilated). In addition, the annular diameter was measured using valve sizers in all patients who had insertion of mechanical prostheses or valve rings (Carpentier, Santa Ana, California). The chordae tendineae were assessed for length (elongated, shortened, or normal), fusion, and evidence of rupture. Among patients who had mitral valvuloplasty, the requirement for chordal shortening procedures was used as ancillary evidence for the presence of chordal elongation. Surgical Classification of Valve Lesions The hemodynamic and anatomic features that were considered diagnostic of pure mitral regurgitation included absent or minimal end-diastolic gradient across the mitral valve; pliable, freely mobile mitral valve leaflets; and absence of commissural fusion or subvalvular disease. Pure mitral stenosis was confirmed at surgery in patients with no clinical or echocardiographic evidence for mitral regurgitation when there was marked commissural fusion and a substantial transmitral end-diastolic gradient. Assessment of Rheumatic Activity Clinical Evaluation Rheumatic activity was diagnosed preoperatively when there was serologic evidence for antecedent group A -hemolytic streptococcal infection in addition to at least two major (or one major plus two minor) criteria of acute rheumatic fever (revised Jones criteria) [12]. Macroscopic Evaluation Valves were examined during surgery for the macroscopic features of active rheumatic carditis that have been described [5, 13]: fibrinous pericarditis with epicardial involvement; pinhead vegetations on the free edges of the valve leaflets in the absence of infective endocarditis; and nonspecific signs of acute inflammation including edema, erythema, and hemorrhage within leaflet tissue. Histologic Evaluation Where sufficient cardiac tissue was available for adequate histologic assessment, the following light microscopic findings were used as criteria of rheumatic activity [13, 14]: fibrinoid necrosis in valve leaflet or annular tissue; polymorphonuclear or histiocyte infiltration; edema; and neovascularization. Analysis of Data For continuous variables, such as pressure data, analysis of variance with the Tukey allowance for multiple comparisons was used to compare three or more groups, and two-sample t-tests were used in instances when only two groups were compared. For categorical data, such as the prevalence of mitral valve prolapse, chi-square tests were used. Three x two contingency tables were constructed to establish the presence of intergroup differences; individual groups were then compared using the Bonferroni correction for multiple comparisons. Statistical differences were recorded using two-tailed P values. Results Correlation between Preoperative and Surgical Classification of Valve Lesions Surgical and preoperative classifications of valve lesions were in agreement in 714 of 737 (97%) cases. The 23 patients in whom discordance existed between the preoperative and surgical assessment of the mitral valve lesion were excluded from the analysis. Relative Prevalence of Valve Lesions When the entire patient population was considered, the three types of mitral valve lesion were documented with similar frequency: Two hundred nineteen patients had pure mitral regurgitation (31%), 275 had pure stenosis (38%), and 220 had mixed lesions (31%). However, 36 of 46 patients (78%) who had surgery in the first 10 years of life had pure mitral regurgitation; pure regurgitation was the most common lesion in patients 20 years of age and younger, accounting for 58% of surgically treated rheumatic mitral valve disease (158 of 271 cases) in this age group. Eighty-nine percent (194 of 219) of patients with pure mitral regurgitation were 30 years of age or younger (Figure 1). In contrast, the prevalence of mitral stenosis increased with age. Only 20% of patients with pure stenosis (55 of 275) were less than 20 years of age. Mixed mitral valve disease also increased in frequency until the fourth decade, after which its prevalence declined slightly. Figure 1. Time-course analysis (by decades) of the relative prevalence of pure mitral regurgitation, mixed mitral valve disease, and pure mitral stenosis. Hemodynamic Data Average values for mean left atrial pressure were similarly increased in all three groups (24 mm Hg for pure regurgitation and pure stenosis and 25 mm Hg for mixed disease). Pure mitral regurgitation was also characterized by a markedly raised left atrial V wave (46 18 mm Hg) and an average V wave:mean left atrial pressure ratio of 1.9:1, indicating severe hemodynamic compromise [10]. In addition, left ventricular end-diastolic pressure was elevated, whereas the end-diastolic gradient across the mitral valve was trivial. Pure mitral stenosis

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

Abstract The etiology of the mitral valve pathology in 130 patients with either a late systolic murmur (twenty-six), a nonejection systolic click (sixty-three) or both (forty-one) is analyzed. In the majority (eighty patients) no cause could be found, but in twenty-three of these a familial factor was present, and in eighteen others (including two sisters) there was association with congenital heart disease, in particular a secundum atrial septal defect. Other etiologic factors included the Marfan syndrome, rheumatic endocarditis, hypertrophic obstructive cardiomyopathy and ischemic heart disease. In eight patients the appearance of the nonejection click followed a mitral commissurotomy. Twelve patients had the characteristic electrocardiographic pattern of posteroinferior myocardial “ischemia,” which is not infrequently encountered in the billowing posterior mitral leaflet syndrome, and six others had nonspecific abnormalities, including S-T segment and T wave changes and prolongation of the P-R interval. Ventricular or supraventricular premature contractions occurred at rest in nine patients. Multifocal ventricular premature contractions occurred after effort in six of the fifty patients subjected to strenuous exercise, particularly in those with the electrocardiographic pattern of posteroinferior myocardial ischemia. The mechanism of production of the myocardial pathology in patients with the billowing posterior mitral leaflet remains unknown, but the view is favored that the pathology of the leaflet precedes that of the papillary muscles in the majority of patients.

Sotalol, hypokalaemia, syncope, and torsade de pointes.

Thirteen patients developed syncope and a prolonged QTc interval while taking therapeutic doses of sotalol. Polymorphous ventricular tachycardia was observed in 12 patients, and criteria typical of torsade de pointes were present in 10. In 12 patients sotalol had been given with hydrochlorothiazide in a combined preparation, Sotazide, but with inadequate or no potassium supplementation. Serum potassium concentrations were reduced in eight patients. Four patients were taking other drugs known to prolong the QT interval, including disopyramide (three patients) and tricyclic antidepressants (two patients). The QT interval returned to normal in all patients after withdrawal of the drugs and correction of the hypokalaemia. Thus even in low dosage sotalol may be hazardous in the presence of hypokalaemia or when combined with drugs that also prolong the QT interval. The use of sotalol concurrently with potassium losing diuretics, such as the combined preparation Sotazide, may expose the patient to unnecessary risk and should be avoided unless the class III antiarrhythmic action of this unique beta adrenoreceptor blocking agent is also required.

Management of tricuspid valve regurgitation

Management of tricuspid regurgitation (TR) is becoming an increasingly difficult decision-making problem. TR occurs in 8–35% of patients, especially in association with acquired left heart valve disease of rheumatic origin, primary isolated TR being very rare. It is more frequently found in association with mitral rather than with aortic valve disease, and is much rarer in degenerative disease. In the majority of patients (70–85%), the TR is said to be “functional”, caused by dilatation of the annulus as a result of increased pulmonary and right ventricular pressure; in the remaining 15–30% of the cases it may be organic and related to direct involvement of the tricuspid valve by the rheumatic disease.1,2 Whichever type, TR has a significant impact on the clinical condition and the medium and long-term prognosis of the patients. Hence, it requires special consideration during mitral and/or aortic valve surgery and thereafter. In 1967, Brawnwald et al 3 advised a conservative (no touch) approach to TR. Indeed, it was thought that appropriate correction of the left-sided valve disease would most probably result in a decrease or even abolition of the so-called functional TR. However, experience has shown that TR does not always disappear, and may increase, especially when the mitral and/or aortic valve disease is not completely or adequately resolved during surgery, as happens sometimes in cases with less than perfect correction of mitral regurgitation or stenosis. Furthermore, isolated severe TR is now increasingly observed in patients with normal left heart valve function after either mitral valve annuloplasty or replacement. The true incidence of secondary TR is not well known, but it has led some to question the functional nature of TR, accompanying left-sided valve disease. Even moderate TR observed during surgery of left heart valves may not regress spontaneously, especially when there is already a …

Sudden death in primary mitral valve prolapse

Sudden unexpected death is a recognized complication of mitral valve prolapse (MVP), but well-documented cases are rare and either clinical details or necropsy findings are absent or scanty. One of our patients, a young woman with MVP who had been fully investigated’e2 and followed since childhood, died suddenly at the age of 24 years, and we were able to obtain detailed pathologic findings. At the age of 8 years a grade 216 late systolic murmur and a nonejection click were heard (see Fig. 10 of Ref. 1). Occasional ectopic beats were present, but she was asymptomatic. Chest x-ray examination was normal. The ECG (see Fig. 11 of Ref. 1) showed slight ST segment elevation with T wave inversion in leads 2, 3, and AVF. Left ventricular cineangiography (see Fig. 12 of Ref. 1) demonstrated mild mitral regurgitation and marked prolapse of the posterior leaflet. Her father had an isolated nonejection click. A diagnosis of MVP on a familial basis was made, and no treatment was given. She attended the clinic at B-month intervals and remained asymptomatic. At 13 years of age numerous multifocal ventricular premature contractions were recorded after a strenuous exercise test (See Fig. 2, a of Ref. 2). On propranolol, 80 mg daily, and diphenylhydantoin, 300 mg daily, the arrhythmia was suppressed. She was thereafter assessed at yearly intervals

Thrombosed Björk-Shiley mitral prostheses.

During a 4.5-year period ending in January 1978, 224 patients were discharged from the hospital after Bjork-Shiley mitral valve replacement. Follow-up records for all patients were available until the last date of inquiry on March 31, 1978.Twelve patients presented to us 3–43 months (mean 17 months) after surgery with thrombosis of their mitral prostheses. A clinical syndrome consisting of acute onset of ischemic or pleuritic chest pain, dyspnea and rightsided cardiac failure is described. The prosthetic sounds, especially the opening click, are invariably absent or markedly muffled, but definitely abnormal mitral murmurs are infrequently detected. The echocardiogram is a useful adjunct in confirming the diagnosis. Total thrombotic encapsulation of the prosthesis may supervene within hours or days and is invariably fatal unless there is surgical intervention. Our first patient died because we failed to make an immediate correct diagnosis. Thereafter, the early recognition of the clinical features resulted in successful valve replacement.In addition to the first patient, there were 18 deaths among the 224 patients. Although none of these 18 patients was examined by us, hospital records, telephone inquiries or necropsy reports revealed that six of them died because of thrombotic occlusion of their mitral prostheses.We conclude that poor anticoagulant control was the principal factor predisposing to prothetic thrombosis in our experience. Eighteen patients (8%) sustained this complication during the study. Neither the original mitral valve lesion nor the size of the Bj6rk-Shiley prosthesis was relevant. We have discontinued using the Bj8rk-Shiley prosthesis for mitral valve replacement when we cannot be certain of ideal control of anticoagulant therapy.

Epidemiology of rheumatic heart disease in black shcoolchildren of Soweto, Johannesburg.

A survey to determine the prevalence of rheumatic heart disease (R.H.D.) in Black children was conducted in the creeches and primary schools of the South Western Townships of Johannesburg (Soweto). A total of 12 050 Black children were examined by 10 cardiologists in May to October 1972. The overal prevalence rate of R.H.D. was 6.9 per 1000, with a peak rate of 19.2 per 1000 in children of the seventh school grade. The maximal age incidence was 15-18 years and there was a female preponderance of 1 6:1. A rise in prevalence occurred with increasing family size. Most children (92%) were asymptomatic, and in 82.5% R.H.D. was diagnosed for the first time during the school survey. The commonest valve lesion was mitral regurgitation, which was present in 93% and occurred as an isolated lesion in 47.5%. Lancefields group A beta-haemolytic streptococcus was isolated from the throats of 52 per 1000 Soweto children. The auscultatory features of a non-ejection systolic click and late systolic murmur were prevalent (13.9 per 1000) and had several epidemiological factors in common with R.H.D. A comprehensive preventative campaign is urgently needed in South Africa, directed at both primary and secondary prophylaxis of R.H.D. The socioeconomic status of the community must be improved if optimal prevention is to be achieved.