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Mitral valve prolapse requiring surgery. Clinical and Pathologic study
Mitral Valve Prolapse Requiring Surgery Clinical and Pathologic Study
DONALD D. TRESCH, M.D. TIMOTHY P. DOYLE, M.D. LAWRENCE I. BONCHECK, M.D. RONALD SIEGEL, M.D. MICHAEL H. KEELAN, Jr., M.D. GORDON N. OLINGER, M.D. HAROLD L. BROOKS, M.D. Milwaukee. Wisconsin
From the Divisions of Cardiology and Cardiovascular Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin. Requests for reprints should be addressed to Dr. Donald D. Tresch, Cardiobgty Dlvislon, Medical Colle@ of Wisconsin, 8700 West Wisconsin Avenue, Milwaukee, Wisconsin 53266. Manuscript accepted July 23, 1984.
The clinical, hemodynamic, surgical, and pathologic flndlngs In 30 patients who required mitral valvular surgery and who had a preoperatlve diagnosis of mitral valve prolapse were reviewed. The mean age of the patients was 59.5 years; 28 patients were over 45 years of age and 10 were over 80 years. 9urprlslngly, 20 were males. A long history of systolic murmur was common, whereas symptoms of heart failure were of abrupt onset. At the time of surgery, a local holosystolic murmur typical of mitral regurgitation was present, although a mid- to late systolic click was not heard in any of the patients. Electrocardkgraphic abnormalities were present In all patients, with 13 patlents demonstratlng atria1 fibrillation. Only four patients had a normal heart size radkgraphkally. Echocardiography conflmM the radlographk flndlngs, in that 27 patients demonstrated left atria1 and ventricular enlargement. All 29 patients undergoing cardiac catheterlxaHon and angkgraphy demonstrated a prolapsing mitral valve with severe regurgltatlon. Surgical and pathologic examination revealed findings characterlstk of a myxomatous valve in all patients, with 19 also demonstrating ruptured chordae tendineae. This study demonstrates that heart failure requiring valvular surgery occurs in a subset of patknts with mitral valve prolapse. In this subset, males predominate and most are over 50 years of age. These patients may be asymptomatk for many years, demonstrating mild to moderate mltral valvular regurgitation, before heart failure develops. In the last 15 years, the mitral valve prolapse syndrome has been recognized as a firmly established clinical entity; it is thought by many to be the most common cardiovascular abnormality [l-4]. The natural history of this disorder, however, is still not fully understood. In the majority of patients, it is thought to be a relatively benign cardiac disorder. Significant cardiac arrhythmias, progressive mitral regurgitation, endocarditis, and neurologic impairment may occur, but the incidence would appear quite small in relation to the large numbers of persons in whom mitral valve prolapse is diagnosed [ 5-81. Mitral valve surgery for progressive mitral regurgitation has been necessary in some patients with mitral valve prolapse, although once again the incidence is thought to be low. Recent studies [9-l 11, however, have reported the increasing recognition of mitral valve prolapse on pathologic examination of surgical specimens from persons who have undergone mitral valve surgery, and some investigators believe that mitral valve prolapse is the most common cause of mitral valve regurgitation that requires surgical intervention.
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Previous studies including case reports [ 12- 161 have described patients with mitral valve prolapse who required surgery, although the numbers have been small and the details concerning the clinical history have been sketchy. Other studies of persons with ruptured chordae tendineae who required mitral valve surgery have been reported [ 17,181. Most of these studies, however, were published before the recognition of mitral valve prolapse as a clinical entity was established. In our present study, we reviewed the clinical, hemcdynamic, surgical, and pathologic findings in a group of patients who required mitral valve surgery and had a preoperative diagnosis of mitral valve prolapse. From these data, we have attempted to provide more insight into the subset of patients with mitral valve prolapse who require valvular surgery. PATIENTS
AND METHODS
Between the years 1977 and 1982, 30 patients with the diagnosis of mitral valve prolapse underwent mitral valve surgery at the Medical College of Wisconsin. The majority of the patients had surgery following January 1981, which was the time that mitral valve repair was starred at our institutlon. One patient in the study was evaluated preoperatively at the Medical College of Wisconsin but underwent surgery in Paris, France. All patients were clinically assessed preoperatively with physical examination, electrocardiography, and chest radiography. Routine preoperative laboratory results were obtained. M-mode echocardiograms were obtained preoperatlvely in all patients, and 22 of the 30 patlents also had twodimensional echocardiographic studies. Chamber sizes and septal wall measurements were obtained from the M-mode findings. Normal left atria1and ventricular diastolic dimensions used were 1.9 to 4.0 cm and 3.0 to 5.6 cm, respectively. Prolapse of the mitral valve was diagnosed by both M-mode and two-dimensional echocardiography. Two M-mode echccardiographic patterns were accepted for the dlagnosls of mitral valve prolapse in this study: (1) late systolic posterior bowing of the mitral apparatus and (2) pansystolic bowing. Mitral valve prolapse was said to be present on twodimensional echocardiography if the full thickness of any part of the leaflet extended through the plane of the mitral annulus into the left atrium during systole. Of the 30 patients, 29 underwent cardiac catheterization and anglography. Coronary angiography was performed by either the Sones or Judkins technique. Stenosis of greater than 50 percent of the vessel diameter was considered significant. Left ventricular angiography was performed in a 3Odegree right anterior oblique projection in all patients, and most patients had biplane angiography. Either early or late systolic bulging of the mitral valvular apparatus into the left atrium was accepted as angiographic evidence of mitral valve prolapse. At the time of surgery, the mitral valve apparatus was examined. Annular size was evaluated, and gross abnormalities of the leaflets and papillary muscles were determined. Chordae tendineae were assessed to determine if
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rupture or elongation was present. Microscopic examination was performed on all valvular specimens obtained at the time of surgery that included the leaflets and papillary muscles or, in some cases, only portions of the leaflet. Data were analyzed using the Student paired t test and are represented as the mean f SEM. Probability (p) values less than 0.05 were considered statistically significant. RESULTS
Of the 30 patients, 20 were male and 10 were female. The mean age was 59.5 f 12.04 (SD), with a range of 25 to 72 years. Ten patients were over 60 years of age; 28 were over 45 years of age. In the two patients under 30 years of age, typical Marfan’s syndrome had been diagnosed many years prior to surgery. History (Table I). Nine of the 30 patients had a history of rheumatic fever, and nine gave a history of myocardial infarction. In two of the 30 patients, Marfan’s syndrome had been diagnosed on the basis of skeletal and ocular abnormalities. Twenty-eight patients were aware of having a heart murmur prior to the development of symptoms, 25 for longer than 5 years prior to heart surgery, 10 for longer than 10 years, and nine for longer than 20 years. In 24 patients, symptoms of heart failure of less than six months’ duration were noted prior to surgery; eight of these patients had onset of symptoms one month or less before surgery and one patient had acute refractory pulmonary edema requiring immediate surgery. Five patients had symptoms of heart failure for one year or greater, two for two years or greater, and one for five years. Chest pain, not typical of angina pectoris, was present in five patients. None of the patients had typical angina pectoris, and none had undergone coronary angiography prior to their evaluation for valvular surgery. Chest palpitations were reported in 11 patients, with most patients being aware of the palpitations for more than five years. Three patients gave a history of acute endocardiiis, which was thought to be the cause of the heart failure in two. Physical Examinatlon (Table I). All patients had grade III-IV/VI systolic murmurs at the time of surgery. In 26 patients, the murmur was holosystolic, heard best at the apex, and radiating to the axilla. In two persons, the murmur was harsh in quality and heard best at the left sternal border, suggesting aortic valvular stenosis. A gallop rhythm was common, with an S4 being detected in patients without atrial fibrillation. Only three patients had a systolic click, all three in early systole. None of the 30 patients had the typical mid-systolic click frequently associated with mitral valve prolapse. Two of the 30 patients had pulmonary congestion by auscultation at the time of surgery, and one patient’s condition was so critical that cardiac catheterization was not performed prior to surgery. Electrocardiography (Table I). All 30 patients had
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abnormalities on resting electrocardiography. Atrial fibrillation was present in 13 patients (43 percent), premature atrial contractions in five, and premature ventricular contractions in 10. lntraventricular conduction delays were present in five patients, complete right bundle branch block patterns in three, and complete left bundle branch block patterns in two. Left ventricular enlargement was present in 15 patients and left atrial enlargement in nine. Combined left ventricular and left atrial enlargement was demonstrated in seven patients. None of the patients with atrial fibrillation had conversion to sinus rhythm following surgery. Chest Radiography (Table I). Only four patients had a normal heart size radiographically. Both left atrial and ventricular enlargement was present in 26 patients. The degree of enlargement was judged moderate in most patients. Echocardiography (Table I). Echocardiography confirmed left cardiac chamber enlargement in 27 patients. Both atrial and ventricular enlargement was noted in these patients. The mean left atrial dimension was 4.6 cm, with a range of 3.3 to 6.2 cm. Eleven patients had left atria1 diameters of 5.0 cm or greater; only five had an atrial diameter of greater than 5.5 cm. The left ventricular diameter varied from 4.5 to 7.5 cm, with a mean of 5.9 cm. The left ventricular internal diameter was 6.2 to 6.5 cm in 11 patients and greater than 6.5 cm in nine patients. M-mode echocardiography demonstrated prolapse of the mitral valve in 29 of the 30 patients. Two-dimensional echocardiography was performed in 22 patients, and mitral valve prolapse was diagnosed in all 22. Hemodynamics and Angiography (Table ii). Results of cardiac catheterization performed in 29 of the 30 patients are shown in Table II. Pulmonary capillary wedge pressure was elevated in 28 of the 29 patients, with a prominent “V wave” being present. The resting “V wave” ranged from 19 to 66 mm Hg. None of the patients demonstrated an end-diastolic gradient across the mitral valve. Left ventricular enddiastolic pressure was variable in the group, with a range of 12 to 38 mm Hg. Resultant pulmonary hypertension was present in 28 of the 29 patients. Left ventriculography demonstrated mitral valve prolapse with severe mitral regurgitation in all patients. Coronary artery disease was diagnosed by angiography in three patients, although none of the patients demonstrated a totally occluded vessel and none had findings of a previous myocardial infarction. Surgical and Pathologic Findings (Table iii). Gross examination of the mitral valve at the time of surgery revealed findings characteristic of myxomatous valves in all of the 30 patients (Figure 1). The leaflets were yellowish in color, thickened, redundant, and prolapsing. Two patients with the complete Marfan’s syndrome had
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Clinical Findings (30 patients) Data
Mean age (years) Sex (male:female) Mean duration of heart murmur (wars) Mean duration of congestive heart failure (months) Endocarditis (number of patients) Holosystolic murmur (number of patients) Systolic ejection murmur (number of patients) Systolic ejection clicks (number of patients) Atrial fibrillation (number of patients) Normal chest radiographic findings (number of patients) Echocardiographic findings Mitral valve prolpase (number of patients) Mean left atrial size (cm; normal 1.9-4.2) Mean left ventricular size (cm; normal 3.5-5.6)
TABLE ii
59.5 f 12.04 (SD) 2O:lO 15.3 5.7 3 27 3 3 13 4 29 4.98 5.81
Catheterization Data (29 patients) Data
Mean cardiac index (liters/minute/ m*) Mean left ventricular end-diastolic pressure (mm Hg) Mean pulmonary capillary wedge pressure (mm Hg) Mean pulmonary caplllary wedge “V wave” pressure (mm Hg) Mean pulmonary artery systolic pressure (mm Hg) Mitral valve prolapse with severe mitral regurgitation (number of patients) Coronary artery disease (number of patients)
TABLE
III
2.32 15.3 22.2 33 47 29 3 (2 bypassed)
Surgical and Pathologic Findings Numkr ot Patlents
Myxomatous valves (gross) Ruptured chordae Posterlor Anterior Both Mucoid degeneration Endocarditls
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Ff#m 1. Ml&al valve excised during surgery in 67-year4d man with mitral valve prolapse. Note the dilated annular circumference with ruptured chordae.
an exaggerated version of these abnormalities, with an extremely dilated annulus circumference of more than 20 cm. One patient had thin translucent leaflets of the type described by Carpentier et al [ 191 as having fibrocollagenous deficiency. Seventeen of the patients had ruptured chordae: 11 to the posterior leaflet, four to the anterior leaflet, and two to both. Seven patients had elongated chordae; in three of these, rupture of chordae was associated with the elongation. In 19 of the patients, mitral valve reconstruction as described by Carpentier et al [ 191 was performed. The other 11 patients had valve replacement with insertion of Bjork-Shiley prostheses. Histologic examination of the surgical specimen (portion of the valve leaflets or complete valve and papillary muscles) revealed myxomatous degenerative changes in 17 of the 30 patients (Table Ill). Nonspecific fibrotic changes were noted in the remaining valves. Two valves displayed changes consistent with endocarditis, with posterior leaflet perforations. Comparison of Patients with and without Ruptured Chordae (Table IV). The mean age of the patients demonstrating ruptured chordae at the time of surgery was 61.8 years compared with a mean age of 56.4 in the group with intact chordae. Seven of the 17 patients (41 percent) with ruptured chordae demonstrated atrial fibrillation, whereas atrial fibrillation was found in six of the 13 patients (46 percent) without ruptured chordae. Left cardiac chamber enlargements as demonstrated by echocardiography were similar in both groups. The group with ruptured chordae had a mean atrial size of 4.7 cm, and the group without rupture had a mean atrial
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size of 4.82 cm. In both groups, the mean left ventricular internal diameter was 5.9 cm. Hemodynamic measurements demonstrated elevated pulmonary artery pressures in both groups; mean resting pulmonary systolic pressure was 51 mm Hg in the group with ruptured chordae and 40.3 mm Hg in the group with nonruptured chordae. Prominent “V waves” in the pulmonary artery wedge pressure tracing during rest were present in both groups. The mean “V wave” was 33 mm Hg in the group with chordae rupture and 26 mm Hg in the group without chordae rupture. In assessment of the onset of symptoms of congestive heart failure, we found that duration of symptoms before surgery was usually six months or less in both groups. Fourteen of the 17 patients with ruptured chordae had onset of symptoms six months or less before surgery in comparison to 11 of the 13 patients with intact chordae. None of the differences between the two groups was statistically significant. COMMENTS The present study demonstrates that some persons with mitral valve prolapse will require valve surgery as a result of significant valvular incompetence. With the large number of patients in whom mitral valve prolapse is diagnosed, we presume that the number requiring surgery is quite small. However, recent studies have shown that mitral valve prolapse may now be the most common cause of mitral regurgitation in patients requiring mitral valve surgery. Waller and his associates [9] reported autopsy findings in 97 patients more than 30 years of age who required mitral valve surgery for pure mitral insufficiency; 60 were found to have mitral valve prolapse without coronary artery disease or other associated primary cardiac abnormalities. Furthermore, pathologic studies prior to the mid 1960s most likely underestimated mitral valve prolapse as the cause of mitral regurgitation, since most prolapsing floppy valves were incorrectly called “rheumatic.” A striking finding in this study was the predominance of men older than 50 years since this is a disease more common in young women. The two patients younger than 30 years had Marfan’s syndrome with the typical ocular and skeletal abnormalities associated with the syndrome. This predominance of older men among patients with mitral valve prolapse requiring valve surgery is consistent with previous reports of patients requiring mitral valve surgery because of ruptured chordae tendineae. In 1967, Seizer et al [ 181 reported on 22 patients who required mitral valve surgery and demonstrated ruptured chordae tendineae at operation. They divided the patients into two groups: one group had ruptured chordae tendineae in association with other disease of the mitral valve apparatus and the other group was thought to have isolated rupture. Among the
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20 patients with isolated rupture, 18 were males and were between 40 and 60 years of age. Few clues to the specific cause of the rupture were obtained from gross or microscopic examinations of the valvular apparatus. In 1966, Marchand et al [20] reported on a series of six patients with pure mitral regurgitation who required valve surgery and who demonstrated ruptured chordae at the time of surgery. Five were males; the ages ranged from 36 to 68 years of age. All valves demonstrated annular dilatation, free commissures, and mobile voluminous leaflets. In 1972, Singh et al [?l] described seven patients with ruptured chordae requiring mitral valve surgery. Five of the seven were male, and their average age was 60 years. Pathologic examination of the valves did demonstrate mucoid degeneration. In Waller et al’s [9] recent report, there were 13 patients with mitral valve prolapse who demonstrated ruptured chordae; seven were male, six were female, and the mean age was 57 years. From our data, it would appear that most persons with mitral valve prolapse who require valve surgery have long-standing mitral regurgitation. In most cases, radiographic and echocardiographic findings demonstrate mild to moderate left-sided cardiac chamber enlargement. Atrial fibrillation, another finding of long-standing mitral regurgitation, was present.in 43 percent of the patients. Most patients related a long history of a heart murmur, although symptoms of heart failure were usually of recent onset prior to surgery. This clinical picture of long-standing mitral regurgitation with sudden onset of heart failure would be compatible with the superimposition of acute regurgitation. Similar findings have recently been reported by Kolibash et al [ 131 in which they reported on 76 patients with mitral valve prolapse who presented with severe mitral regurgitation. The mean duration of symptoms was less than one year, although a murmur had been present for a mean of 25 years. Atrial fibrillation was present in four patients. Mitral valve surgery was necessary in 69 patients, and ruptured chordae were noted in 38 of these patients. No mention was made of the sex preponderance in the study. In two of our patients, endocarditis was documented approximately one month prior to the development of heart failure, and we would assume that the endocarditis was the cause of the acute regurgitation. Neither of these two patients demonstrated ruptured chordae at the time of surgery. Seventeen patients in our series did demonstrate chordae tendineae rupture, which may have been the cause of acute regurgitation. However, reports by Chandraratna and Aronow [22] and Grenadier et al [23] have shown that rupture of chordae tendineae in patients with mitral valve prolapse is not always associated with cardiac decompensation. In both of these reports, only a few patients who demonstrated
February
TABLE IV
Comparison ot Patients with Ruptured and Nonruptured Chordae’ Ruptured
Mean age (years) Sex (maie:femaie) Mean duration of heart murmur (year.4 Endocarditis (number of patients) Mean duration of congestive heart failure (months) Hoiosystoiic murmur (number of patients) Systolic ejection murmur (number of patients) Electrocardiographic results Atrial fibrillation (number of patients) Chest radiographic findings Abnormal heart size (number of patients) Echocardiographic findings Mitral valve prolapse (number of patients) Mean left atriai size (cm; normal 1.9-4.0) Mean left ventricular size (cm; normal 3.5-5.6) Catheterization data Mean pulmonary artery systolic pressure (mm Hg) Mean pulmonary capillary wedge pressure (mm Hg) Mean pulmonary capillary wedge “V wave” (mm Hg) Mean left ventricular enddiastolic pressure (mm Hg) Mean cardiac index (liters/ minute/m2) Coronary artery disease (number of patients)
Nonruptured
(n = 17)
(n = 13)
61.6 f 8.5 (SD) 6:11 18
56.4 f 15.7 (SD) 419 15.3
0 7
3 4
15
13
2
0
7
6
13
13
16
13
4.79
4.82
5.9
5.9
51
40.3
23
21.3
33
28
14.4
16.3
2.28
2.38
2
1
None of the parameters was statistically significantly different (p
ruptured chordae by echocardiography had clinical evidence of heart failure, and rarely was valve surgery necessary. Recently, DePace et al [24] also reported on a group of 29 patients with echocardiographic findings of flail mitral valve leaflets. Fifteen patients were treated medically and followed with serial echocardiography. Only four of these patients ultimately required mitral valve surgery. The .authors concluded that a subset of patients with a flail mitral leaflet ‘may be followed clinically without deterioration in left yentricular function. Unlike Cooley et al’s [ 151 series in which they were able to clinically classify patients with mitral valve prolapse into groups on the basis of ‘surgical and pathologic findings, we could not differentiate between
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our two groups bf patients (those with ruptured chordae and those with intact valves). The clinical history was simiiar in both groups, with the majority of patierits having a long history of a heart murmur, although symptoms were of shot-t duration before surgery. Physical exdmination prior to surgerv demonstrated loud hdlosystolic murmurs typical of mitral valvular insufficiency without mid-systolic clicks in most patients in both groups. Two patients with ruptured chordae did show ejection-type murmurs that w&e heard best at the base and could have been confused with ihe mtirmur or aortic valvular stenosis. Electrocardiographic and echocardiographic findings were similar in both groups. Hemodynamic measurerhents were not statistically different, although the group with ruptured chdrdae generally had a higher resting pulmonary syStolic pressure and a more prominent pulmonary capillary wedge “V wave.” The implications of this study are important to physicians caring for patients with mitral valve prolapse.
Even though most patients with mitral valve prolapse have a benign course, heart failure requiring valvular surgery does develop in a small but important group of patients. We are unable to identify the patients in whom this complication will deuelop although, surprisingly, males predominate and most are over 50 years df age. In some patients, the clinical picture will be compatible with chronic, indolent, progressive mitral valve insufficiency. However, the majority of patients may be asymptdmatic for many yearsi demonstrating mild to moderate mitral regurgitation, before the symptoms of heart failure abruptly develop. Auscultatory findings at the time will usually reveal a holosystolic muimur without a mid-systolic click. Pathologically, niost patients will show the typical findings of a myxomatous valve and a percentage will demonstiate ruptured chordtie or endocarditis, which may play a role in producing the acute deterioration. In patients without endocarditis oi ruptured chordae, the cause of the acute Cardiac deterioration remaitis unknown.
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Barlow JB. Bosman CK, Pocock WA, Marchand P: Late systolic murrhur and nonejection (mid-late) systolic clicks: an analysis of 90 patients. Br Heart J 1966; 30: 203-218. Jeresaty FM: Mitral valve prolapse-click syndrome. Prog CardiovasC Dis 1974; 15: 623-651. Devereux RB, Perloff JK, Reicher N, Josephson ME: Mitral valve prolapse. Circulation 1976; 54: 3-14. Markiewicz W, Stoner J, London E, Hunt S, Popp RL: Mitral valve prolapse in 100 presumably healthy young females. Circulation 1976; 53: 464-473. Swartz MH, Teichholz LE, Poroso E: Mitral valve prolapse: a review of associated arrhythmias. Am J Med 1977; 62: 377-389. Mills P, Rose J, Hollingsworth J, Anvan J, Craige E: Long-term prognosis of mitral valve prolapse. N Engl J Med 1977; 297: 13-18. Clemens JD, Horowitz RI, Jaffe CC, Feinstein AR, Stanton BF: A controlled evaluation of the risk of bacterial endocarditis in persons with mitral vaive prolapse. N Engl J Med 1982; 307: 776-781. Kostuk WJ, Boughner DR: Strokes: a complication of mitral leaflet prolapse? Lancet 1977; I: 313-316. Waller BF, Morrow A%. Maron BJ, et al: Etiology of clinically isolated, here, chronic, pure mitral regurgitation: analysis of 97 patients over 30 years of age having mitral valve replacement. Am Heart J 1982; 104: 276-288. Salomon NW, Stinston EB, Griepp RB, Shumway NE: Surgical treatment of degenerative mitral regurgitation. Am J Cardiol 1976; 38: 463-468. Guy FC, MacDonald RPR, Fraser DB, Smith ER: Mitral valve prolapse as a cause of hemodynamically important initral regurgitation. Can J Surg 1980; 23: 166-170. Tresch DD, Siegel R, Keelan MH Jr, Gross CM, Brooks HL: Mitral valve prolapse in the elderly. J Am Geriatr Sot 1979; 27: 421-424. Kolibash AJ Jr, Bush CA, Fontana MB, Ryan JM, Kilman J, Wooley CF: Mitral valve prolapse syndrome: analysis of 62 patients aged 60 years or older. Am J Cardiol 1983; 52:
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534-539. Davies MJ, Moore BP, Braimbridge MV: The floppy mitral valve. Study of incidence, pathology, and complications in surgical, necropsy, and forensic material. Br Heart J 1978; 40: 468-481. Cboley DA, Gerami S, Hallman GL, Wukasch DC, Hall RJ: Mitral insufficiency due to myxomatous transformations: “floppy valve syndrome.” J Cardllvasc Surg (Torino) 1972; 13: 346-349. Kolibash AJ Jr, Bush CA, Kilman J, Ryan JM, Wooley CF: Myxorn&ous mltral valves, mitrcil valve proldpse, and progressive mitral regurgitation (abstr). JACC 1984; 3: 559. Osmunddn P<, Callahan JA, Edward JE: Ruptured mitral chordae tendineae. Circulation 1961; 23: 42-54. Selzer A, Kelly JJ. Vannltamby M, Walker P, Gerbode F, Kerth WJ: The syndrome of mitral insufficiency due to isolated rupture of the chordae tendlneae. Am J Med 1967; 43: 822-836. Carpentier A, Chauvaud S, Fabiani JN, et al: Reconstructive surgery of mitral valve incompetence. J Thorac Cardiiase Surg 1980; 79: 338-348.
Marchand P, Barlow JB, DuPlessisLA, Webster I: Mitral regurgitation with rupture of normal chordae tendineae. Br Heart J 1966; 28: 746-758. Singh R, Schrank JP, Nblan SP, McGuire LB: Spontaneous rupture of mitral chordae teridineae. JAMA 1972; 219: 189-193. Chandraratna PAN, Aronow WS: Incidence of ruptured chordae tendineae in the mitral valvular prolapse syndrome. An echocardlographic study. Chest 1979; 75: 334-339. Grenadier E, Alpan G, Keklar S. Palant A: The prevalence of ruptured chordae tendineae in the mitral valve prolapse syndrome. Am Heart J 1983; 105: 603-610. DePace NL, Mintz GS, Ren J-F, et al: Natural histc+y of the flail mitral leaflet syndrome: a serial two-dimensional echocardiographic study. Am J Cardiol 1983: 52: 789-795.
DONALD D. TRESCH, M.D. TIMOTHY P. DOYLE, M.D. LAWRENCE I. BONCHECK, M.D. RONALD SIEGEL, M.D. MICHAEL H. KEELAN, Jr., M.D. GORDON N. OLINGER, M.D. HAROLD L. BROOKS, M.D. Milwaukee. Wisconsin
From the Divisions of Cardiology and Cardiovascular Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin. Requests for reprints should be addressed to Dr. Donald D. Tresch, Cardiobgty Dlvislon, Medical Colle@ of Wisconsin, 8700 West Wisconsin Avenue, Milwaukee, Wisconsin 53266. Manuscript accepted July 23, 1984.
The clinical, hemodynamic, surgical, and pathologic flndlngs In 30 patients who required mitral valvular surgery and who had a preoperatlve diagnosis of mitral valve prolapse were reviewed. The mean age of the patients was 59.5 years; 28 patients were over 45 years of age and 10 were over 80 years. 9urprlslngly, 20 were males. A long history of systolic murmur was common, whereas symptoms of heart failure were of abrupt onset. At the time of surgery, a local holosystolic murmur typical of mitral regurgitation was present, although a mid- to late systolic click was not heard in any of the patients. Electrocardkgraphic abnormalities were present In all patients, with 13 patlents demonstratlng atria1 fibrillation. Only four patients had a normal heart size radkgraphkally. Echocardiography conflmM the radlographk flndlngs, in that 27 patients demonstrated left atria1 and ventricular enlargement. All 29 patients undergoing cardiac catheterlxaHon and angkgraphy demonstrated a prolapsing mitral valve with severe regurgltatlon. Surgical and pathologic examination revealed findings characterlstk of a myxomatous valve in all patients, with 19 also demonstrating ruptured chordae tendineae. This study demonstrates that heart failure requiring valvular surgery occurs in a subset of patknts with mitral valve prolapse. In this subset, males predominate and most are over 50 years of age. These patients may be asymptomatk for many years, demonstrating mild to moderate mltral valvular regurgitation, before heart failure develops. In the last 15 years, the mitral valve prolapse syndrome has been recognized as a firmly established clinical entity; it is thought by many to be the most common cardiovascular abnormality [l-4]. The natural history of this disorder, however, is still not fully understood. In the majority of patients, it is thought to be a relatively benign cardiac disorder. Significant cardiac arrhythmias, progressive mitral regurgitation, endocarditis, and neurologic impairment may occur, but the incidence would appear quite small in relation to the large numbers of persons in whom mitral valve prolapse is diagnosed [ 5-81. Mitral valve surgery for progressive mitral regurgitation has been necessary in some patients with mitral valve prolapse, although once again the incidence is thought to be low. Recent studies [9-l 11, however, have reported the increasing recognition of mitral valve prolapse on pathologic examination of surgical specimens from persons who have undergone mitral valve surgery, and some investigators believe that mitral valve prolapse is the most common cause of mitral valve regurgitation that requires surgical intervention.
February
1995
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PROLAPSE
REQUIRING
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Previous studies including case reports [ 12- 161 have described patients with mitral valve prolapse who required surgery, although the numbers have been small and the details concerning the clinical history have been sketchy. Other studies of persons with ruptured chordae tendineae who required mitral valve surgery have been reported [ 17,181. Most of these studies, however, were published before the recognition of mitral valve prolapse as a clinical entity was established. In our present study, we reviewed the clinical, hemcdynamic, surgical, and pathologic findings in a group of patients who required mitral valve surgery and had a preoperative diagnosis of mitral valve prolapse. From these data, we have attempted to provide more insight into the subset of patients with mitral valve prolapse who require valvular surgery. PATIENTS
AND METHODS
Between the years 1977 and 1982, 30 patients with the diagnosis of mitral valve prolapse underwent mitral valve surgery at the Medical College of Wisconsin. The majority of the patients had surgery following January 1981, which was the time that mitral valve repair was starred at our institutlon. One patient in the study was evaluated preoperatively at the Medical College of Wisconsin but underwent surgery in Paris, France. All patients were clinically assessed preoperatively with physical examination, electrocardiography, and chest radiography. Routine preoperative laboratory results were obtained. M-mode echocardiograms were obtained preoperatlvely in all patients, and 22 of the 30 patlents also had twodimensional echocardiographic studies. Chamber sizes and septal wall measurements were obtained from the M-mode findings. Normal left atria1and ventricular diastolic dimensions used were 1.9 to 4.0 cm and 3.0 to 5.6 cm, respectively. Prolapse of the mitral valve was diagnosed by both M-mode and two-dimensional echocardiography. Two M-mode echccardiographic patterns were accepted for the dlagnosls of mitral valve prolapse in this study: (1) late systolic posterior bowing of the mitral apparatus and (2) pansystolic bowing. Mitral valve prolapse was said to be present on twodimensional echocardiography if the full thickness of any part of the leaflet extended through the plane of the mitral annulus into the left atrium during systole. Of the 30 patients, 29 underwent cardiac catheterization and anglography. Coronary angiography was performed by either the Sones or Judkins technique. Stenosis of greater than 50 percent of the vessel diameter was considered significant. Left ventricular angiography was performed in a 3Odegree right anterior oblique projection in all patients, and most patients had biplane angiography. Either early or late systolic bulging of the mitral valvular apparatus into the left atrium was accepted as angiographic evidence of mitral valve prolapse. At the time of surgery, the mitral valve apparatus was examined. Annular size was evaluated, and gross abnormalities of the leaflets and papillary muscles were determined. Chordae tendineae were assessed to determine if
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rupture or elongation was present. Microscopic examination was performed on all valvular specimens obtained at the time of surgery that included the leaflets and papillary muscles or, in some cases, only portions of the leaflet. Data were analyzed using the Student paired t test and are represented as the mean f SEM. Probability (p) values less than 0.05 were considered statistically significant. RESULTS
Of the 30 patients, 20 were male and 10 were female. The mean age was 59.5 f 12.04 (SD), with a range of 25 to 72 years. Ten patients were over 60 years of age; 28 were over 45 years of age. In the two patients under 30 years of age, typical Marfan’s syndrome had been diagnosed many years prior to surgery. History (Table I). Nine of the 30 patients had a history of rheumatic fever, and nine gave a history of myocardial infarction. In two of the 30 patients, Marfan’s syndrome had been diagnosed on the basis of skeletal and ocular abnormalities. Twenty-eight patients were aware of having a heart murmur prior to the development of symptoms, 25 for longer than 5 years prior to heart surgery, 10 for longer than 10 years, and nine for longer than 20 years. In 24 patients, symptoms of heart failure of less than six months’ duration were noted prior to surgery; eight of these patients had onset of symptoms one month or less before surgery and one patient had acute refractory pulmonary edema requiring immediate surgery. Five patients had symptoms of heart failure for one year or greater, two for two years or greater, and one for five years. Chest pain, not typical of angina pectoris, was present in five patients. None of the patients had typical angina pectoris, and none had undergone coronary angiography prior to their evaluation for valvular surgery. Chest palpitations were reported in 11 patients, with most patients being aware of the palpitations for more than five years. Three patients gave a history of acute endocardiiis, which was thought to be the cause of the heart failure in two. Physical Examinatlon (Table I). All patients had grade III-IV/VI systolic murmurs at the time of surgery. In 26 patients, the murmur was holosystolic, heard best at the apex, and radiating to the axilla. In two persons, the murmur was harsh in quality and heard best at the left sternal border, suggesting aortic valvular stenosis. A gallop rhythm was common, with an S4 being detected in patients without atrial fibrillation. Only three patients had a systolic click, all three in early systole. None of the 30 patients had the typical mid-systolic click frequently associated with mitral valve prolapse. Two of the 30 patients had pulmonary congestion by auscultation at the time of surgery, and one patient’s condition was so critical that cardiac catheterization was not performed prior to surgery. Electrocardiography (Table I). All 30 patients had
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abnormalities on resting electrocardiography. Atrial fibrillation was present in 13 patients (43 percent), premature atrial contractions in five, and premature ventricular contractions in 10. lntraventricular conduction delays were present in five patients, complete right bundle branch block patterns in three, and complete left bundle branch block patterns in two. Left ventricular enlargement was present in 15 patients and left atrial enlargement in nine. Combined left ventricular and left atrial enlargement was demonstrated in seven patients. None of the patients with atrial fibrillation had conversion to sinus rhythm following surgery. Chest Radiography (Table I). Only four patients had a normal heart size radiographically. Both left atrial and ventricular enlargement was present in 26 patients. The degree of enlargement was judged moderate in most patients. Echocardiography (Table I). Echocardiography confirmed left cardiac chamber enlargement in 27 patients. Both atrial and ventricular enlargement was noted in these patients. The mean left atrial dimension was 4.6 cm, with a range of 3.3 to 6.2 cm. Eleven patients had left atria1 diameters of 5.0 cm or greater; only five had an atrial diameter of greater than 5.5 cm. The left ventricular diameter varied from 4.5 to 7.5 cm, with a mean of 5.9 cm. The left ventricular internal diameter was 6.2 to 6.5 cm in 11 patients and greater than 6.5 cm in nine patients. M-mode echocardiography demonstrated prolapse of the mitral valve in 29 of the 30 patients. Two-dimensional echocardiography was performed in 22 patients, and mitral valve prolapse was diagnosed in all 22. Hemodynamics and Angiography (Table ii). Results of cardiac catheterization performed in 29 of the 30 patients are shown in Table II. Pulmonary capillary wedge pressure was elevated in 28 of the 29 patients, with a prominent “V wave” being present. The resting “V wave” ranged from 19 to 66 mm Hg. None of the patients demonstrated an end-diastolic gradient across the mitral valve. Left ventricular enddiastolic pressure was variable in the group, with a range of 12 to 38 mm Hg. Resultant pulmonary hypertension was present in 28 of the 29 patients. Left ventriculography demonstrated mitral valve prolapse with severe mitral regurgitation in all patients. Coronary artery disease was diagnosed by angiography in three patients, although none of the patients demonstrated a totally occluded vessel and none had findings of a previous myocardial infarction. Surgical and Pathologic Findings (Table iii). Gross examination of the mitral valve at the time of surgery revealed findings characteristic of myxomatous valves in all of the 30 patients (Figure 1). The leaflets were yellowish in color, thickened, redundant, and prolapsing. Two patients with the complete Marfan’s syndrome had
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Clinical Findings (30 patients) Data
Mean age (years) Sex (male:female) Mean duration of heart murmur (wars) Mean duration of congestive heart failure (months) Endocarditis (number of patients) Holosystolic murmur (number of patients) Systolic ejection murmur (number of patients) Systolic ejection clicks (number of patients) Atrial fibrillation (number of patients) Normal chest radiographic findings (number of patients) Echocardiographic findings Mitral valve prolpase (number of patients) Mean left atrial size (cm; normal 1.9-4.2) Mean left ventricular size (cm; normal 3.5-5.6)
TABLE ii
59.5 f 12.04 (SD) 2O:lO 15.3 5.7 3 27 3 3 13 4 29 4.98 5.81
Catheterization Data (29 patients) Data
Mean cardiac index (liters/minute/ m*) Mean left ventricular end-diastolic pressure (mm Hg) Mean pulmonary capillary wedge pressure (mm Hg) Mean pulmonary caplllary wedge “V wave” pressure (mm Hg) Mean pulmonary artery systolic pressure (mm Hg) Mitral valve prolapse with severe mitral regurgitation (number of patients) Coronary artery disease (number of patients)
TABLE
III
2.32 15.3 22.2 33 47 29 3 (2 bypassed)
Surgical and Pathologic Findings Numkr ot Patlents
Myxomatous valves (gross) Ruptured chordae Posterlor Anterior Both Mucoid degeneration Endocarditls
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Ff#m 1. Ml&al valve excised during surgery in 67-year4d man with mitral valve prolapse. Note the dilated annular circumference with ruptured chordae.
an exaggerated version of these abnormalities, with an extremely dilated annulus circumference of more than 20 cm. One patient had thin translucent leaflets of the type described by Carpentier et al [ 191 as having fibrocollagenous deficiency. Seventeen of the patients had ruptured chordae: 11 to the posterior leaflet, four to the anterior leaflet, and two to both. Seven patients had elongated chordae; in three of these, rupture of chordae was associated with the elongation. In 19 of the patients, mitral valve reconstruction as described by Carpentier et al [ 191 was performed. The other 11 patients had valve replacement with insertion of Bjork-Shiley prostheses. Histologic examination of the surgical specimen (portion of the valve leaflets or complete valve and papillary muscles) revealed myxomatous degenerative changes in 17 of the 30 patients (Table Ill). Nonspecific fibrotic changes were noted in the remaining valves. Two valves displayed changes consistent with endocarditis, with posterior leaflet perforations. Comparison of Patients with and without Ruptured Chordae (Table IV). The mean age of the patients demonstrating ruptured chordae at the time of surgery was 61.8 years compared with a mean age of 56.4 in the group with intact chordae. Seven of the 17 patients (41 percent) with ruptured chordae demonstrated atrial fibrillation, whereas atrial fibrillation was found in six of the 13 patients (46 percent) without ruptured chordae. Left cardiac chamber enlargements as demonstrated by echocardiography were similar in both groups. The group with ruptured chordae had a mean atrial size of 4.7 cm, and the group without rupture had a mean atrial
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size of 4.82 cm. In both groups, the mean left ventricular internal diameter was 5.9 cm. Hemodynamic measurements demonstrated elevated pulmonary artery pressures in both groups; mean resting pulmonary systolic pressure was 51 mm Hg in the group with ruptured chordae and 40.3 mm Hg in the group with nonruptured chordae. Prominent “V waves” in the pulmonary artery wedge pressure tracing during rest were present in both groups. The mean “V wave” was 33 mm Hg in the group with chordae rupture and 26 mm Hg in the group without chordae rupture. In assessment of the onset of symptoms of congestive heart failure, we found that duration of symptoms before surgery was usually six months or less in both groups. Fourteen of the 17 patients with ruptured chordae had onset of symptoms six months or less before surgery in comparison to 11 of the 13 patients with intact chordae. None of the differences between the two groups was statistically significant. COMMENTS The present study demonstrates that some persons with mitral valve prolapse will require valve surgery as a result of significant valvular incompetence. With the large number of patients in whom mitral valve prolapse is diagnosed, we presume that the number requiring surgery is quite small. However, recent studies have shown that mitral valve prolapse may now be the most common cause of mitral regurgitation in patients requiring mitral valve surgery. Waller and his associates [9] reported autopsy findings in 97 patients more than 30 years of age who required mitral valve surgery for pure mitral insufficiency; 60 were found to have mitral valve prolapse without coronary artery disease or other associated primary cardiac abnormalities. Furthermore, pathologic studies prior to the mid 1960s most likely underestimated mitral valve prolapse as the cause of mitral regurgitation, since most prolapsing floppy valves were incorrectly called “rheumatic.” A striking finding in this study was the predominance of men older than 50 years since this is a disease more common in young women. The two patients younger than 30 years had Marfan’s syndrome with the typical ocular and skeletal abnormalities associated with the syndrome. This predominance of older men among patients with mitral valve prolapse requiring valve surgery is consistent with previous reports of patients requiring mitral valve surgery because of ruptured chordae tendineae. In 1967, Seizer et al [ 181 reported on 22 patients who required mitral valve surgery and demonstrated ruptured chordae tendineae at operation. They divided the patients into two groups: one group had ruptured chordae tendineae in association with other disease of the mitral valve apparatus and the other group was thought to have isolated rupture. Among the
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20 patients with isolated rupture, 18 were males and were between 40 and 60 years of age. Few clues to the specific cause of the rupture were obtained from gross or microscopic examinations of the valvular apparatus. In 1966, Marchand et al [20] reported on a series of six patients with pure mitral regurgitation who required valve surgery and who demonstrated ruptured chordae at the time of surgery. Five were males; the ages ranged from 36 to 68 years of age. All valves demonstrated annular dilatation, free commissures, and mobile voluminous leaflets. In 1972, Singh et al [?l] described seven patients with ruptured chordae requiring mitral valve surgery. Five of the seven were male, and their average age was 60 years. Pathologic examination of the valves did demonstrate mucoid degeneration. In Waller et al’s [9] recent report, there were 13 patients with mitral valve prolapse who demonstrated ruptured chordae; seven were male, six were female, and the mean age was 57 years. From our data, it would appear that most persons with mitral valve prolapse who require valve surgery have long-standing mitral regurgitation. In most cases, radiographic and echocardiographic findings demonstrate mild to moderate left-sided cardiac chamber enlargement. Atrial fibrillation, another finding of long-standing mitral regurgitation, was present.in 43 percent of the patients. Most patients related a long history of a heart murmur, although symptoms of heart failure were usually of recent onset prior to surgery. This clinical picture of long-standing mitral regurgitation with sudden onset of heart failure would be compatible with the superimposition of acute regurgitation. Similar findings have recently been reported by Kolibash et al [ 131 in which they reported on 76 patients with mitral valve prolapse who presented with severe mitral regurgitation. The mean duration of symptoms was less than one year, although a murmur had been present for a mean of 25 years. Atrial fibrillation was present in four patients. Mitral valve surgery was necessary in 69 patients, and ruptured chordae were noted in 38 of these patients. No mention was made of the sex preponderance in the study. In two of our patients, endocarditis was documented approximately one month prior to the development of heart failure, and we would assume that the endocarditis was the cause of the acute regurgitation. Neither of these two patients demonstrated ruptured chordae at the time of surgery. Seventeen patients in our series did demonstrate chordae tendineae rupture, which may have been the cause of acute regurgitation. However, reports by Chandraratna and Aronow [22] and Grenadier et al [23] have shown that rupture of chordae tendineae in patients with mitral valve prolapse is not always associated with cardiac decompensation. In both of these reports, only a few patients who demonstrated
February
TABLE IV
Comparison ot Patients with Ruptured and Nonruptured Chordae’ Ruptured
Mean age (years) Sex (maie:femaie) Mean duration of heart murmur (year.4 Endocarditis (number of patients) Mean duration of congestive heart failure (months) Hoiosystoiic murmur (number of patients) Systolic ejection murmur (number of patients) Electrocardiographic results Atrial fibrillation (number of patients) Chest radiographic findings Abnormal heart size (number of patients) Echocardiographic findings Mitral valve prolapse (number of patients) Mean left atriai size (cm; normal 1.9-4.0) Mean left ventricular size (cm; normal 3.5-5.6) Catheterization data Mean pulmonary artery systolic pressure (mm Hg) Mean pulmonary capillary wedge pressure (mm Hg) Mean pulmonary capillary wedge “V wave” (mm Hg) Mean left ventricular enddiastolic pressure (mm Hg) Mean cardiac index (liters/ minute/m2) Coronary artery disease (number of patients)
Nonruptured
(n = 17)
(n = 13)
61.6 f 8.5 (SD) 6:11 18
56.4 f 15.7 (SD) 419 15.3
0 7
3 4
15
13
2
0
7
6
13
13
16
13
4.79
4.82
5.9
5.9
51
40.3
23
21.3
33
28
14.4
16.3
2.28
2.38
2
1
None of the parameters was statistically significantly different (p
ruptured chordae by echocardiography had clinical evidence of heart failure, and rarely was valve surgery necessary. Recently, DePace et al [24] also reported on a group of 29 patients with echocardiographic findings of flail mitral valve leaflets. Fifteen patients were treated medically and followed with serial echocardiography. Only four of these patients ultimately required mitral valve surgery. The .authors concluded that a subset of patients with a flail mitral leaflet ‘may be followed clinically without deterioration in left yentricular function. Unlike Cooley et al’s [ 151 series in which they were able to clinically classify patients with mitral valve prolapse into groups on the basis of ‘surgical and pathologic findings, we could not differentiate between
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our two groups bf patients (those with ruptured chordae and those with intact valves). The clinical history was simiiar in both groups, with the majority of patierits having a long history of a heart murmur, although symptoms were of shot-t duration before surgery. Physical exdmination prior to surgerv demonstrated loud hdlosystolic murmurs typical of mitral valvular insufficiency without mid-systolic clicks in most patients in both groups. Two patients with ruptured chordae did show ejection-type murmurs that w&e heard best at the base and could have been confused with ihe mtirmur or aortic valvular stenosis. Electrocardiographic and echocardiographic findings were similar in both groups. Hemodynamic measurerhents were not statistically different, although the group with ruptured chdrdae generally had a higher resting pulmonary syStolic pressure and a more prominent pulmonary capillary wedge “V wave.” The implications of this study are important to physicians caring for patients with mitral valve prolapse.
Even though most patients with mitral valve prolapse have a benign course, heart failure requiring valvular surgery does develop in a small but important group of patients. We are unable to identify the patients in whom this complication will deuelop although, surprisingly, males predominate and most are over 50 years df age. In some patients, the clinical picture will be compatible with chronic, indolent, progressive mitral valve insufficiency. However, the majority of patients may be asymptdmatic for many yearsi demonstrating mild to moderate mitral regurgitation, before the symptoms of heart failure abruptly develop. Auscultatory findings at the time will usually reveal a holosystolic muimur without a mid-systolic click. Pathologically, niost patients will show the typical findings of a myxomatous valve and a percentage will demonstiate ruptured chordtie or endocarditis, which may play a role in producing the acute deterioration. In patients without endocarditis oi ruptured chordae, the cause of the acute Cardiac deterioration remaitis unknown.
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Marchand P, Barlow JB, DuPlessisLA, Webster I: Mitral regurgitation with rupture of normal chordae tendineae. Br Heart J 1966; 28: 746-758. Singh R, Schrank JP, Nblan SP, McGuire LB: Spontaneous rupture of mitral chordae teridineae. JAMA 1972; 219: 189-193. Chandraratna PAN, Aronow WS: Incidence of ruptured chordae tendineae in the mitral valvular prolapse syndrome. An echocardlographic study. Chest 1979; 75: 334-339. Grenadier E, Alpan G, Keklar S. Palant A: The prevalence of ruptured chordae tendineae in the mitral valve prolapse syndrome. Am Heart J 1983; 105: 603-610. DePace NL, Mintz GS, Ren J-F, et al: Natural histc+y of the flail mitral leaflet syndrome: a serial two-dimensional echocardiographic study. Am J Cardiol 1983: 52: 789-795.