Wendy A. Pocock

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.

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.

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

Postexercise arrhythmias in the billowing posterior mitral leaflet syndrome.

Abstract The syndrome of late systolic murmur, nonejection click, billowing posterior leaflet, and mild mitral regurgitation is well documented. Electrocardiographic abnormalities consisting of S-T and T-wave changes suggestive of posteroinferior myocardial ischemia are not uncommon. Sudden death, sometimes related to effort, has occasionally occurred. Twelve patients with a late systolic murmur, a nonejection click or both, 5 of whom had an abnormal resting ECG, were subjected to strenuous exercise and the ECG recorded immediately and at intervals thereafter. A striking feature in 3 patients was the appearance, 1 to 2 minutes after cessation of exercise, of numerous multifocal ventricular extrasystoles. Postexercise ECGs after oral propranolol in 2 patients and propranolol plus diphenylhydantoin in the third patient showed disappearance of the ectopic beats. It is suggested that sudden death in this syndrome may be due to ventricular fibrillation preceded by multifocal ventricular extrasystoles. We recommend that a postexercise electrocardiogram be done in all patients with a late systolic murmur or nonejection click. Although papillary muscle dysfunction, secondary to ischemia, may be the cause of billowing of the mitral leaflet in some instances, we believe that leaflet or chordal pathology is the primary abnormality in the majority of cases of this syndrome. The nature of the myocardial pathology remains unknown.

Billowing, floppy, prolapsed or flail mitral valves?

More than 2 decades ago the auscultatory features of a late systolic murmur and non-ejection systolic click were shown to originate at the mitral va1ve.i Left ventricular cineangiocardiography confirmed that late systolic murmurs were indicative of mild mitral regurgitation and demonstrated “massive dilatation,” “aneurysmal protrusion,” “billowing” or “ballooning” of the posterior mitral leaflet.2g3 Later studies showed that the anterior leaflet was also involved. In 1966, Criley et al4 clarified the cineangiocardiographic appearances and introduced the term prolapse. Mitral valve prolapse (MVP) is now a widely used term regardless of whether the valve anomaly is anatomically mild, echocardiographically demonstrable, functionally normal or clinically silent. This has contributed to the general confusion, and it is now crucial for the terms billowing, floppy, prolapse and flail to be defined. Such definitions should be based essentially on the functional anatomic, or pathologic, characteristics of the mitral valve mechanism. Auscultatory, echocardiographic, cineangiocardiographic and other clinical features should then be correlated with the probable functional anatomy. It is, after all, the functional anatomy of the mitral valve mechanism that we attempt to assess by all invasive or noninvasive investigations. We recently expressed the view5 that the concept propounded by the French cardiac surgeon, Alain Carpentier, defines the essential differences between prolapse and billowing. In this context Carpentier restricts the use of the term prolapse to failure of the leaflet edges to appose normally. Such partial loss of apposition may occur with or without abnormal billowing of the bellies of the leaflets, and mitral regurgitation, albeit mild or even minimal, will inevitably result. This concept of prolapse implies that the valve function is abnormal which is, in fact, both appropriate and correct. Any cardiac valve, provided there is not a hole or a cleft in a leaflet, remains competent while there is sustained coaptation of the leaflet edges. Prevention of apposition may occur if 1 or more leaflets are fibrosed or retracted. If leaflets are normal in size or larger, failure of sustained apposition will result in prolapse. Based on Carpentier’s understanding of MVP, we consider that the following terms, which reflect normal and abnormal mitral valve functional anatomy, should clarify much of the current confusion. The normal mitral leaflets billow slightly, after closure, into the left atria1 cavity (Fig. 1A). Exaggeration

Non-ejection systolic clicks and mitral systolic murmurs in black schoolchildren of Soweto, Johannesburg.

A survey was conducted on 12 050 Black schoolchildren, aged 2 to 18 years, in the South Western Townships of Johannesburg (Soweto), and the prevalence of non-ejection systolic clicks and late systolic murmurs was determined. One or both of these auscultatory findings were detected in 168 children, yielding a prevalence rate of 13-99 per 1000 in the school population. A female preponderance of 1-9:1 was present and there was a strong linear increase in prevalence with age, with a peak rate of 29-41 per 1000 in 17-year-old children. A non-ejection click was the only abnormal auscultatory finding in 123 children (73%) and a mitral systolic murmur in 8 (5%), whereas in 37 (22%) both these findings were present. Of the latter 37 children, the murmur was late systolic in 32; in 5 it was early systolic. Auscultation in different postures was important in the detection of both non-ejection clicks and mitral systolic murmurs. Experience in the detection of these auscultatory findings influenced the frequency with which they were heard. Electrocardiographic abnormalities compatible with those previously described in the billowing mitral leaflet syndrome were present in 11 of 158 children. The aetiology of these auscultatory findings in this community remains unknown. In the same survey, a high prevalence rate of rheumatic heart disease was recorded and the epidemiology of the non-ejection clicks and these mitral systolic murmurs showed similarties to that of rheumatic heart disease. Though the specific billowing mitral leaflet syndrome almost certainly accounts for some of these auscultatory findings, a significant proportion may have early rheumatic heart disease. Further elucidation of this problem is necessary.

Contribution of echocardiography and immediate surgery to the management of severe aortic regurgitation from active infective endocarditis

The timing of surgery in patients with severe aortic regurgitation and left ventricular (LV) failure, particularly when associated with active infective endocarditis (IE), is of the utmost importance. From July 1982 to May 1984, 34 patients, aged 15 to 60 years, with severe aortic regurgitation underwent immediate (within 24 hours of diagnosis) aortic valve surgery. All patients were in New York Heart Association class IV for LV failure. Eighteen patients had right-sided heart failure. Decision for immediate surgery was based on the echocardiographic demonstration of diastolic closure of the mitral valve or of vegetations on the aortic valve. Premature closure of the mitral valve was demonstrated echocardiographically in 17 patients, 13 of whom had diastolic crossover of LV and left atrial pressure tracings recorded at surgery. IE of the aortic valve was confirmed at surgery in 29 patients, 27 of whom had vegetations on echocardiography. Seven patients required replacement of both aortic and mitral valves. Antibiotic therapy for IE was started immediately after blood cultures were taken and continued for 4 to 6 weeks postoperatively. The mortality rate within 30 days of surgery was 6% for the group as a whole and 7% for those with IE. Mean follow-up period for the 32 survivors was 10.6 months. There were 2 late deaths. No patient had periprosthetic regurgitation or persistence of endocarditis. Procrastination in referral for surgery of these extremely ill patients is not justified and is likely to be associated with higher risks of morbidity and mortality.