Symposium on Therapeutic Problems
The Mitral Valve Prolapse Syndrome Spectrum and Therapy
Charles Z. Naggar, M.D.* With the technical assistance of Lori L. Downing and Debra A. Dumont Reports of serious and, at times, catastrophic events 22 complicating the mitral valve prolapse syndrome have shattered the illusion of innocence often attributed to it. A disorder thought to be obscure and infrequently encountered merely two decades ago, mitral valve prolapse syndrome is currently recognized through auscultation in 17 per cent of asymptomatic women during screening examination. 27 Auscultatory, echocardiographic, or cineangiographic evidence of this syndrome has been found so frequently in asymptomatic persons that the clinical significance of the abnormality has come into question. The true incidence of its complications, which must be small, remains unknown. Nevertheless, some patients with mitral valve prolapse syndrome are indisputably at increased risk of the development of infective endocarditis, 8 malignant ventricular arrhythmias,6, 44, 48 or severe mitral regurgitation requiring replacement of the mitral valve. 10, 20, 29 This paper describes in detail our experience with an ambulatory population of 380 patients with idiopathic. mitral valve prolapse syndrome. The spectrum of the syndrome and its varied clinical presentation will be discussed. Preliminary evidence that certain auscultatory, electrocardiographic, and echocardiographic abnormalities might confer increased risk on the patient with mitral valve prolapse syndrome will be presented. Finally, an approach to the diagnosis, therapy, and follow-up study of patients with mitral valve prolapse syndrome will be put forth.
DEFINITION AND CLASSIFICATION Barlow et al. 5 are credited with having shown the association of a midsystolic click and late systolic murmur to mitral regurgitation re'Cardiovascular Section; Director, Noninvasive Laboratory, Labey Clinic Supported in part by Grant DR-665 from the Division of Research, Labey Clinic Foundation.
Medical Clinics of North America-Vo!. 63, No. 2, March 1979
337
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NAGGAR
sulting from prolapse or herniation of the mitral valve leaflets into the left atrium during systole. They described 90 patients with these acoustic h~arks, a variety of cardiac symptoms, electrocardiographic abnormalities, and mitral valve prolapse. These patients were classified according to coexisting cardiovascular disorder: rheumatic (26 per cent), ischemic (7 per cent), after open heart surgery (3 per cent), traumatic (2 per cent), obstructive cardiomyopathy (1 per cent), and Marfan's syndrome (3 per cent). A full 58 per cent of the total group was labeled either familial (10 per cent) or idiopathic (48 per cent). With greater use of cineangiography and echocardiography, it became increasingly evident that herniation of the mitral leaflets into the left atrium is a nonspecific finding. This abnormal motion can result from a variety of disease states and can be induced artifactually by others. Thus, the original classification fell short of describing the anatomic pathophysiology of the mitral valve prolapse. An etiologic classification has therefore emerged and has proved of greater usefulness to the understanding of mitral valve prolapse syndrome. 9
ETIOLOGIC. CLASSIFICATION Primary Mitral Valve Prolapse Myxomatous degeneration of the mitral leaflets constitutes the basic defect and is characterized histologic ally by loss of normal valvular architecture and replacement by loose, myxomatous tissue riCh in acid mucopolysaccharides. Such loss of normal supporting, dense, collagenous tissue allows stretching of the cusps during systole resulting in ballooning of a segment or all of the leaflet surface into the left atrium. The gross appearance of these leaflets is described as redundant, floppy, or voluminous. 12. 28. 45 This congenital abnormality can be. sporadic, familial, or part of a generalized connective tissue disorder, such as Marfan's syndrome. Secondary Mitral Valve Prolapse The mitral leaflets are ma~roscopiCally and histologic ally no~w., but dysfunction of the mitral valve apparatus prevents proper valvUlar closure. Ischemia, infarction, or fibrosis of papillary muscles or their contiguous myocardium together with left ventricular motion abnormality in human beings3 • 7 or in experimental animals 13 produces prolapsed mitral leaflets. Occlusive coronary artery disease or corona.i-Y artery spasm causes asymmetric, disordered patterns of left ventricuc lar contraction, which in turn results in mitral valve prolapse. Achiev~ ing more synchronous left ventricular contractility patterns through coronary revascularization or ventricular aneurysmectomy results. in resumption of normal motion ofthe mitral leaflets. 3 Pseudo Mitral Valve Prolapse Pseudo mitral valve prolapse is often encountered echocardiographically in patients with pericardial effusion and in those with a small left ventricular cavity.
339
THE MITRAL VALVE PROLAPSE SYNDROME
PERICARDIAL EFFUSION. In pericardial effusion, a posterior swing of the heart within the pericardial fluid occurs in late systole and results in posterior displacement of the mitral valve into the left atrium. Echocardiographically, this motion simulates prolapse of the mitral leaflets. After resolution of the effusion, the mitral valve resumes its normal systolic anterior motion. 25 SMALL LEFT VENTRICULAR CAVITY. In adult echocardiography, when left ventricular end-diastolic dimension is less than 23 mm per sq meter of body surface area (personal observation), pseudo mitral valve prolapse is explained in the following way. Motion of the anterior mitral leaflet is restricted, and it abuts the interventricular septurn throughout diastole. During their systolic coaptation, the histologically normal mitral leaflets are displaced posteriorly into the left atrial cavity. Echocardiographically, this simulates the picture of mitral valve prolapse. In such instances, the left ventricular cavity appears to be disproportionately small and unable to accommodate normal motion of the mitral leaflets. This situation is encountered in hypertrophic cardiomyopathy, in instances of severe pulmonary hypertension, and in some instances of secundum interatrial septal defect where the left ventricular cavity is quite small. Hereafter, mitral valve prolapse syndrome refers to the primary idiopathic variety. It is the form that is commonly encountered in clinical practice. 38 The mode of inheritance of this congenital affliction is probably autosomal dominant with reduced male expressivity.18,47 Since mitral valve prolapse syndrome is a common entity, its coincidental association with other forms of heart disease is expected. Furthermore, the echocardiogram should be interpreted within the clinical context while bearing in mind the classification mentioned previously (Fig. 1). This classification will be modified as longer follow-up studETIOLOGICAL CLASSIFICATION OF MITRAL VALVE PROLAPSE Mitral leaflets histologicolly and morpholooicolly
NORMAL
- - - - ------ - - - - - -- -.- -- - - - - --- ---- ------
C~I:~d~rOlopse
Mitral Arlifoctuol
Figure 1. Classification of mitral valve prolapse according to pathophysiologic pathways of different disease entities leading to the echocardiographic or angiographic picture of mitral valve prolapse.
Coronor~~:~::;eDiseose
: ' o r Coronary Spasm
MITRAL VALVE PROLAPSE Echocardiographically
or Angiographically
IDIOPATHIC MVPS Mitral leaflets histological1y ABNORMAL, thin and voluminous
CHARLES Z. NAGGAR
340
ies, coupled with anatomic-echocardiographic correlation, define more clearly the pathophysiology and natural history of the various subgroups.
CLINICAL PRESENTATION The following is a brief description of seven case histories to highlight the myriad of presenting symptoms, the spectrum of clinical manifestation, and the complications encountered in mitral valve prolapse syndrome. CASE 1. MITRAL VALVE PROLAPSE SYNDROME PRESENTING AS CHEST PAINS. A 35 year old woman (gravida 2, para 2, abortions 0) presented with squeezing pains in the chest lasting for hours unrelated to exertion, fatigue, and episodes of light-headedness without syncope. Exertional palpitation had severely limited her activities, and she was normotensive and in regular sinus rhythm interrupted by frequent extrasystoles. A midsystolic click followed by a late systolic murmur was heard at the apex (Fig. 2). Electrocardiography revealed inferolateral T wave flattening and normal PR and QTc intervals. Ambulatory monitoring showed an average of 259 ventricular premature beats an hour. Neurologic evaluation was negative, and echocardiography was diagnostic of mitral valve prolapse (Fig. 3). Cardiac catheterization revealed a prolapsed mitral valve with modest Initral regurgitation and normal coronary arteries. Propranolol given orally, 200 mg daily in divided doses, resulted in dramatic improvement. CASE 2. MITRAL VALVE PROLAPSE SYNDROME MIMICKING CORONARY ARTERY DISEASE. A 47 year old man complained of tightness in the chest aggravated by exertion. A second type of chest pain was described as lancinating and radiating to the left shoulder. He had served in the armed forces without cardiovascular complications and had no known coronary risk factors. He was quite anxious and made several visits to the emergency ward for chest pains in the past two years without documentation of myocardial ischemia. Auscultation revealed an isolated, loud, midsystolic click, but no murmur could be elicited despite provocative maneuvers. Electrocardiography showed flattened T waves in leads V. through V6 , stress electrocardiography gave positive results for ischeInia (Fig. 4), and echocardiography revealed a mitral valve prolapse. Cardiac catheterization demonstrated normal coronary arteries and normal left ventricular contraction and documented the mitral valve prolapse without regurgitation. Chest pain was controlled with propranolol, 160 mg daily. The patient has not required a visit to the emergency ward in more than a year. CASE 3. MITRAL VALVE PROLAPSE SYNDROME AND VENTRICULAR ARRHYTHMIA. A 29 year old woman (gravida 2, para 2, abortions 0) presented with frequent, bothersome palpitations and with discomfort in the chest unrelated to exertion and lasting a few minutes. A late systolic murmur, noted 2 years before admission, was still present; no clicks were heard. Electrocardiography showed T wave inversion in leads 11, Ill, aVF, and V6 ; the rhythm was ventricular bigeminy. Submaximal exercise testing provoked a short burst of ventricular tachycardia; ambulatory monitoring showed an average of 816 ventricular premature beats an hour. Echocardiography revealed mitral valve prolapse ,and a large left ventricular end-diastolic dimension of 58 mm (or 32 mm per m 2). Propranolol had no affect on the frequency of ventricular ectopy. CASE 4. MITRAL VALVE PROLAPSE SYNDROME PRESENTING AS INFECTIVE ENDOCARDITIS. Hematuria and fever developed in a 65 year old man 6 months before admission. Results of extensive urologic investigation were negative,
THE MITRAL VALVE PROLAPSE SYNDROME
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Figure 2 (Case 1). Simultaneous recording of electrocardiogram, phonocardiogram, and mitral valve echocardiogram showing the midsystolic click (C) and late systolic murmur (LSM) characteristic of the mitral valve prolapse. Arrows point to the posterior displacement of the mitral valve leaflet in late systole. SI, first heart sound; S2, second heart sound; MV, m'tral valve.
Figure 3 (Case 1). Longitudinal scan from the left ventricular cavity (LV) to the base of the heart depicting the mitral valve prolapse (arrow). Ao, aorta; LA, left atrial cavity; IVS, interventricular septum.
CHARLES Z. NAGGAR
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Rest HR- 58 BPM
SXT KI'M-7s0 HR-ISO BPM
-86% of
Recovery 2 Min.
HR-90 BPM
!
i! 1I
!
I'.
lj
jj
l
'iliUii
Recovery 4 Min.
1IR-8s BPM
Figure 4 (Case 2). Submaximal graded exercise test showing ischeIIl;c ST segment depression in lateral lead Vs at peak exercise and during recovery; the inferior lead (Ill) changes are best shown dUring recovery. HR, heart rate (beats per minute) ; SXT, submaximal exercise test.
and three short courses of antibiotics were prescribed for presumed infection of the urinary tract. Fever recurred, and a murmur was heard three days before the patient's transfer to the Lahey Clinic Foundation. On admission, he was normotensive, febrile, and in mild left ventricular failure. The first heart sound was normal in intensity, but a harsh, grade 3/6 holosystolic murmur was heard at the apex and radiated to the axilla. A third heart sound was heard. Echocardiography showed mitral valve prolapse with ruptured chordae tendineae (Fig. 5). Six blood cultures grew Hemophilus aphrophilus. Bacteriologic cure was achieved after 6 weeks of treatment, and one year later, the patient remained in the New York Heart Association functional class 11 taking no cardiac medication. CASE 5. MITRAL VALVE PROLAPSE SYNDROME PRESENTING AS SEVERE CONGESTIVE HEART FAILURE. A 56 year old man had been denied adInission to the Armed Forces because of a heart murmur 26 years earlier. He had remained asymptomatic until 2 years before admission when progressive fatigue, dyspnea on exertion, paroxysmal nocturnal dyspnea, ankle edema, and, finally, jaundice developed. He was treated with digitalis and diuretics. On admission, he was in biventricular failure with a pulsatile liver secondary to significant tricuspid regurgitation, and a left ventricular heave was felt. The first heart sound was faint, and the second heart sound was loud. A harsh pansystolic murmur, grade 4/6, was heard at the lower sternal border associated with a palpable thrill, and marked ankle edema and cyanotic nail beds were observed. Electrocardiography showed left ventricular hypertrophy and delay in left atrial conduction, and echocardiography revealed ruptured chordae tendineae with left ventricular volume overload. Cardiac catheterization showed normal coronary arteries and 4+ mitral regurgitation. After the patient lost 32 pounds with vigorous medical management, operation for replacement of the mitral valve confirmed myxomatous degeneration of and ruptured chordae tendineae to both leaflets; the leaflets were not flail. Three years after operation, the patient is gainfully employed and taking no cardiac medication. Left ventricular end-diastolic di-
THE MITRAL VALVE PROLAPSE SYNDROME
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mension decreased from 68 to 51 mm, and the radiographic cardiothoracic ratio dropped from 20.0/31.0 to 14.0/30.5. Electrocardiography now shows normal P wave morphology. CASE 6. AUSCULTATORILY SILENT MITRAL VALVE PROLAPSE SYNDROME. A 50 year old woman complained of chest pains in the interscapular region radiating to the left shoulder, lasting from minutes to hours, and necessitating three separate hospitalizations. Coronary artery disease was diagnosed with no chemical evidence of myocardial infarction, but the electrocardiographic pattern was consistent with myocardial damage (Fig. 6). The patient's activities were restricted, and nitroglycerin was prescribed but was ineffective. On admission, auscultation was normal; simultaneous echocardiography and phonocardiography showed auscultatorily silent mitral valve prolapse (Fig. 7). Stress electrocardiography to a maximal heart rate of 175 beats a minute failed to reveal any abnormalities. Cardiac catheterization showed normal coronary arteries and mitral valve prolapse. The patient's identical twin also had acoustically silent mitral valve prolapse, which was asymptomatic. Receiving increasing dosages of propranolol, the patient is asymptomatic, gainfully employed, and physically active.
Comment. Auscultatorily silent mitral valve prolapse is encountered in 80 of 380 (21 per cent) of our patients; the diagnosis is suspected from the history, unexplained electrocardiographic abnormalities, or arrhythmias. CASE 7. MITRAL VALVE PROLAPSE SYNDROME AND RUPTURED CHORDAE TENDINEAE. A 75 year old woman (gravida 3, para 2, abortions 1) complained of episodes of paroxysmal atrial tachycardia for 2 years before admission. Cough and progressive dyspnea on exertion and a modest decrease in exercise capacity ensued. On admission, she was normotensive and in congestive heart failure. The first heart sound was preserved. A thrill felt over the cardiac apex was associated with a harsh pansystolic murmur, grade 4/6, which radiated to the back and dorsal spine. A third heart sound was present, and chest radiography showed cardiomegaly and left atrial enlargement. Angiography revealed mitral valve prolapse and ruptured chrodae tendineae to the posterior leaflet (Fig. 8). During operation, the mitral valve was described as redundant and myxomatous. Ruptured chordae tendineae to the posterior mitral leaflet were documented.
Figure 5 (Case 4). Echocardiographic scan of the longitudinal axis of the heart showing mitral valve prolapse (large arrows) and a tonguelike structure (small arrows) representing the distal tip of ruptured chordae tendineae prolapsing into the left atrlal cavity (LA) during systole. LV, left ventricular cavity; IVS, interventricular septum; Ao, aorta; AVJ, atrioventricular junction. (From Naggar, CZ: Self-Teaching Atlas of Echocardiography. Bowie, Maryland, Charles Press, 1978, p 209, reproduced with permisSion.)
344
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NAGGAR
AUGUST f, 1974
II
III
AVR
AVL
~VF
AUGUST 1, 1974
AUGUST 12, 1974
AUGUST
13, 1974
AUGUST 15, 1914
Figure 6 (Case 6). Serial electrocardiograms showing T wave changes in the precordial leads that might be confused with myocardial ischemia.
Figure 7 (Case 6). Simultaneous recording of electrocardiogram, phonocardiogram, and mitral valve echocardiogram (middle panel) in a patient with acoustically silent mitral valve prolapse. Note absence of the click and murmur characteristically heard in patients with mitral valve prolapse syndrome. Arrows point to the mitralleafiet abnormality. LV, left ventricle; SI, first heart sound; S2, second heart sound; Ao, aorta; LA, left atrial cavity. (From Naggar, CZ: Self-Teaching Atlas of Echocardiography. Bowie, Maryland, Charles Press, 1978, p. 87, reproduced with permission.)
THE MITRAL VALVE PROLAPSE SYNDROME
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CATHETER
Figure 8 (Case 7). Composite of systolic frame of left ventricular angiogram in the right anterior oblique projection (right panel) and corresponding outline in the left panel. Segmental ballooning or hooding of the redundant mitral valve is clearly visualized (MVP, mitral valve prolapse). Arrow points to the part of the posterior leaflet with ruptured chordae tendineae prolapsing into the left atrium and outlined by the dye. Note the large left atrium filled with dye, indicating severe mitral regurgitation. Ao, aorta; LV, left ventricle.
THE CONTRIBUTION OF ECHOCARDIOGRAPHY TO THE UNDERSTANDING OF MITRAL VALVE PROLAPSE SYNDROME Lack of correlation between symptoms or electrocardiographic abnormalities and severity of mitral valve prolapse led us to search for an echocardiographic explanation for the electrocardiographic abnormalities 35 and to relate the hemodynamic alterations of mitral valve prolapse to the auscultatory findings. Such a correlation might identify subgroups of patients with mitral valve prolapse syndrome at different risks of the development of complications. The subjects were 380 patients treated at the Lahey Clinic Foundation between 1974 and 1977 who had clinical features of mitral valve prolapse syndrome without coexisting cardiovascular disease. The group included 274 women and 106 men whose ages ranged from 7 to 84 years (mean age, 43.9 years). All patients had a complete history and physical examination. Initially, the diagnosis was made on the basis of presenting symptoms, auscultatory findings, or electrocardiographic abnormalities. Echocardiographic documentation of mitral valve prolapse was obtained in all patients. Echocardiograms were analyzed searching for a possible anatomic significance of the murmur and the ST segment and T wave abnormalities (ST-TA) ascribed to mitral valve prolapse syndrome. 4 All electrocardiograms were recorded with patients in the resting, postprandial state in the supine position. Echocardiograms were recorded with patients supine and slightly tilted to the left side. Submaximal exercise tests were carried out in 243 patients using a graded bicycle ergometer, as described by Frishman et al. 15 Patients were segregated according to the presence or absence of a systolic murmur regardless of whether the murmur was elicited with provocation. The two groups were compared using two echocardiographic parameters - left atrial dimension was measured at end-systole and left ventricular end-diastolic dimension was measured at the
346
CHARLES
Z. N AGGAR
height of the electrocardiographic R wave - and both parameters were corrected for the patient's body surface area yielding the left atrial index (LAI) and _left ventricular end-diastolic index (LVDdI) respectively. Figure 9 displays graphically the relationship between the two groups. Patients were then re grouped according to the presence or absence of ST-TA on electrocardiography as described by Barlow et al. 4 (Fig. 10). In the 243 patients who underwent submaximal exercise testing, the severity of ventricular ectopy harvested during the stress test correlated with resting electrocardiographic abnormalities. The ST-TA were associated with more frequent and malignant ventricular ectopy (Fig. 11) confirming an earlier report by Campbell et al. 6 An ischemic response to exercise testing (defined as an ST segment depression of 1 mm for at least 80 msec) developed in 19 per cent of patients. Comparing this group of patients to those who failed to show such a response, we found the left ventricular dimensions to be increased in the ischemic group (Fig. 12). The so-called ischemic response to submaximal exercise testing not uncommonly encountered in the mitral valve proLVDdI
mm/m2
30 29
P
The Mitral Valve Prolapse Syndrome Spectrum and Therapy
Charles Z. Naggar, M.D.* With the technical assistance of Lori L. Downing and Debra A. Dumont Reports of serious and, at times, catastrophic events 22 complicating the mitral valve prolapse syndrome have shattered the illusion of innocence often attributed to it. A disorder thought to be obscure and infrequently encountered merely two decades ago, mitral valve prolapse syndrome is currently recognized through auscultation in 17 per cent of asymptomatic women during screening examination. 27 Auscultatory, echocardiographic, or cineangiographic evidence of this syndrome has been found so frequently in asymptomatic persons that the clinical significance of the abnormality has come into question. The true incidence of its complications, which must be small, remains unknown. Nevertheless, some patients with mitral valve prolapse syndrome are indisputably at increased risk of the development of infective endocarditis, 8 malignant ventricular arrhythmias,6, 44, 48 or severe mitral regurgitation requiring replacement of the mitral valve. 10, 20, 29 This paper describes in detail our experience with an ambulatory population of 380 patients with idiopathic. mitral valve prolapse syndrome. The spectrum of the syndrome and its varied clinical presentation will be discussed. Preliminary evidence that certain auscultatory, electrocardiographic, and echocardiographic abnormalities might confer increased risk on the patient with mitral valve prolapse syndrome will be presented. Finally, an approach to the diagnosis, therapy, and follow-up study of patients with mitral valve prolapse syndrome will be put forth.
DEFINITION AND CLASSIFICATION Barlow et al. 5 are credited with having shown the association of a midsystolic click and late systolic murmur to mitral regurgitation re'Cardiovascular Section; Director, Noninvasive Laboratory, Labey Clinic Supported in part by Grant DR-665 from the Division of Research, Labey Clinic Foundation.
Medical Clinics of North America-Vo!. 63, No. 2, March 1979
337
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CHARLES
Z.
NAGGAR
sulting from prolapse or herniation of the mitral valve leaflets into the left atrium during systole. They described 90 patients with these acoustic h~arks, a variety of cardiac symptoms, electrocardiographic abnormalities, and mitral valve prolapse. These patients were classified according to coexisting cardiovascular disorder: rheumatic (26 per cent), ischemic (7 per cent), after open heart surgery (3 per cent), traumatic (2 per cent), obstructive cardiomyopathy (1 per cent), and Marfan's syndrome (3 per cent). A full 58 per cent of the total group was labeled either familial (10 per cent) or idiopathic (48 per cent). With greater use of cineangiography and echocardiography, it became increasingly evident that herniation of the mitral leaflets into the left atrium is a nonspecific finding. This abnormal motion can result from a variety of disease states and can be induced artifactually by others. Thus, the original classification fell short of describing the anatomic pathophysiology of the mitral valve prolapse. An etiologic classification has therefore emerged and has proved of greater usefulness to the understanding of mitral valve prolapse syndrome. 9
ETIOLOGIC. CLASSIFICATION Primary Mitral Valve Prolapse Myxomatous degeneration of the mitral leaflets constitutes the basic defect and is characterized histologic ally by loss of normal valvular architecture and replacement by loose, myxomatous tissue riCh in acid mucopolysaccharides. Such loss of normal supporting, dense, collagenous tissue allows stretching of the cusps during systole resulting in ballooning of a segment or all of the leaflet surface into the left atrium. The gross appearance of these leaflets is described as redundant, floppy, or voluminous. 12. 28. 45 This congenital abnormality can be. sporadic, familial, or part of a generalized connective tissue disorder, such as Marfan's syndrome. Secondary Mitral Valve Prolapse The mitral leaflets are ma~roscopiCally and histologic ally no~w., but dysfunction of the mitral valve apparatus prevents proper valvUlar closure. Ischemia, infarction, or fibrosis of papillary muscles or their contiguous myocardium together with left ventricular motion abnormality in human beings3 • 7 or in experimental animals 13 produces prolapsed mitral leaflets. Occlusive coronary artery disease or corona.i-Y artery spasm causes asymmetric, disordered patterns of left ventricuc lar contraction, which in turn results in mitral valve prolapse. Achiev~ ing more synchronous left ventricular contractility patterns through coronary revascularization or ventricular aneurysmectomy results. in resumption of normal motion ofthe mitral leaflets. 3 Pseudo Mitral Valve Prolapse Pseudo mitral valve prolapse is often encountered echocardiographically in patients with pericardial effusion and in those with a small left ventricular cavity.
339
THE MITRAL VALVE PROLAPSE SYNDROME
PERICARDIAL EFFUSION. In pericardial effusion, a posterior swing of the heart within the pericardial fluid occurs in late systole and results in posterior displacement of the mitral valve into the left atrium. Echocardiographically, this motion simulates prolapse of the mitral leaflets. After resolution of the effusion, the mitral valve resumes its normal systolic anterior motion. 25 SMALL LEFT VENTRICULAR CAVITY. In adult echocardiography, when left ventricular end-diastolic dimension is less than 23 mm per sq meter of body surface area (personal observation), pseudo mitral valve prolapse is explained in the following way. Motion of the anterior mitral leaflet is restricted, and it abuts the interventricular septurn throughout diastole. During their systolic coaptation, the histologically normal mitral leaflets are displaced posteriorly into the left atrial cavity. Echocardiographically, this simulates the picture of mitral valve prolapse. In such instances, the left ventricular cavity appears to be disproportionately small and unable to accommodate normal motion of the mitral leaflets. This situation is encountered in hypertrophic cardiomyopathy, in instances of severe pulmonary hypertension, and in some instances of secundum interatrial septal defect where the left ventricular cavity is quite small. Hereafter, mitral valve prolapse syndrome refers to the primary idiopathic variety. It is the form that is commonly encountered in clinical practice. 38 The mode of inheritance of this congenital affliction is probably autosomal dominant with reduced male expressivity.18,47 Since mitral valve prolapse syndrome is a common entity, its coincidental association with other forms of heart disease is expected. Furthermore, the echocardiogram should be interpreted within the clinical context while bearing in mind the classification mentioned previously (Fig. 1). This classification will be modified as longer follow-up studETIOLOGICAL CLASSIFICATION OF MITRAL VALVE PROLAPSE Mitral leaflets histologicolly and morpholooicolly
NORMAL
- - - - ------ - - - - - -- -.- -- - - - - --- ---- ------
C~I:~d~rOlopse
Mitral Arlifoctuol
Figure 1. Classification of mitral valve prolapse according to pathophysiologic pathways of different disease entities leading to the echocardiographic or angiographic picture of mitral valve prolapse.
Coronor~~:~::;eDiseose
: ' o r Coronary Spasm
MITRAL VALVE PROLAPSE Echocardiographically
or Angiographically
IDIOPATHIC MVPS Mitral leaflets histological1y ABNORMAL, thin and voluminous
CHARLES Z. NAGGAR
340
ies, coupled with anatomic-echocardiographic correlation, define more clearly the pathophysiology and natural history of the various subgroups.
CLINICAL PRESENTATION The following is a brief description of seven case histories to highlight the myriad of presenting symptoms, the spectrum of clinical manifestation, and the complications encountered in mitral valve prolapse syndrome. CASE 1. MITRAL VALVE PROLAPSE SYNDROME PRESENTING AS CHEST PAINS. A 35 year old woman (gravida 2, para 2, abortions 0) presented with squeezing pains in the chest lasting for hours unrelated to exertion, fatigue, and episodes of light-headedness without syncope. Exertional palpitation had severely limited her activities, and she was normotensive and in regular sinus rhythm interrupted by frequent extrasystoles. A midsystolic click followed by a late systolic murmur was heard at the apex (Fig. 2). Electrocardiography revealed inferolateral T wave flattening and normal PR and QTc intervals. Ambulatory monitoring showed an average of 259 ventricular premature beats an hour. Neurologic evaluation was negative, and echocardiography was diagnostic of mitral valve prolapse (Fig. 3). Cardiac catheterization revealed a prolapsed mitral valve with modest Initral regurgitation and normal coronary arteries. Propranolol given orally, 200 mg daily in divided doses, resulted in dramatic improvement. CASE 2. MITRAL VALVE PROLAPSE SYNDROME MIMICKING CORONARY ARTERY DISEASE. A 47 year old man complained of tightness in the chest aggravated by exertion. A second type of chest pain was described as lancinating and radiating to the left shoulder. He had served in the armed forces without cardiovascular complications and had no known coronary risk factors. He was quite anxious and made several visits to the emergency ward for chest pains in the past two years without documentation of myocardial ischemia. Auscultation revealed an isolated, loud, midsystolic click, but no murmur could be elicited despite provocative maneuvers. Electrocardiography showed flattened T waves in leads V. through V6 , stress electrocardiography gave positive results for ischeInia (Fig. 4), and echocardiography revealed a mitral valve prolapse. Cardiac catheterization demonstrated normal coronary arteries and normal left ventricular contraction and documented the mitral valve prolapse without regurgitation. Chest pain was controlled with propranolol, 160 mg daily. The patient has not required a visit to the emergency ward in more than a year. CASE 3. MITRAL VALVE PROLAPSE SYNDROME AND VENTRICULAR ARRHYTHMIA. A 29 year old woman (gravida 2, para 2, abortions 0) presented with frequent, bothersome palpitations and with discomfort in the chest unrelated to exertion and lasting a few minutes. A late systolic murmur, noted 2 years before admission, was still present; no clicks were heard. Electrocardiography showed T wave inversion in leads 11, Ill, aVF, and V6 ; the rhythm was ventricular bigeminy. Submaximal exercise testing provoked a short burst of ventricular tachycardia; ambulatory monitoring showed an average of 816 ventricular premature beats an hour. Echocardiography revealed mitral valve prolapse ,and a large left ventricular end-diastolic dimension of 58 mm (or 32 mm per m 2). Propranolol had no affect on the frequency of ventricular ectopy. CASE 4. MITRAL VALVE PROLAPSE SYNDROME PRESENTING AS INFECTIVE ENDOCARDITIS. Hematuria and fever developed in a 65 year old man 6 months before admission. Results of extensive urologic investigation were negative,
THE MITRAL VALVE PROLAPSE SYNDROME
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Figure 2 (Case 1). Simultaneous recording of electrocardiogram, phonocardiogram, and mitral valve echocardiogram showing the midsystolic click (C) and late systolic murmur (LSM) characteristic of the mitral valve prolapse. Arrows point to the posterior displacement of the mitral valve leaflet in late systole. SI, first heart sound; S2, second heart sound; MV, m'tral valve.
Figure 3 (Case 1). Longitudinal scan from the left ventricular cavity (LV) to the base of the heart depicting the mitral valve prolapse (arrow). Ao, aorta; LA, left atrial cavity; IVS, interventricular septum.
CHARLES Z. NAGGAR
342
Rest HR- 58 BPM
SXT KI'M-7s0 HR-ISO BPM
-86% of
Recovery 2 Min.
HR-90 BPM
!
i! 1I
!
I'.
lj
jj
l
'iliUii
Recovery 4 Min.
1IR-8s BPM
Figure 4 (Case 2). Submaximal graded exercise test showing ischeIIl;c ST segment depression in lateral lead Vs at peak exercise and during recovery; the inferior lead (Ill) changes are best shown dUring recovery. HR, heart rate (beats per minute) ; SXT, submaximal exercise test.
and three short courses of antibiotics were prescribed for presumed infection of the urinary tract. Fever recurred, and a murmur was heard three days before the patient's transfer to the Lahey Clinic Foundation. On admission, he was normotensive, febrile, and in mild left ventricular failure. The first heart sound was normal in intensity, but a harsh, grade 3/6 holosystolic murmur was heard at the apex and radiated to the axilla. A third heart sound was heard. Echocardiography showed mitral valve prolapse with ruptured chordae tendineae (Fig. 5). Six blood cultures grew Hemophilus aphrophilus. Bacteriologic cure was achieved after 6 weeks of treatment, and one year later, the patient remained in the New York Heart Association functional class 11 taking no cardiac medication. CASE 5. MITRAL VALVE PROLAPSE SYNDROME PRESENTING AS SEVERE CONGESTIVE HEART FAILURE. A 56 year old man had been denied adInission to the Armed Forces because of a heart murmur 26 years earlier. He had remained asymptomatic until 2 years before admission when progressive fatigue, dyspnea on exertion, paroxysmal nocturnal dyspnea, ankle edema, and, finally, jaundice developed. He was treated with digitalis and diuretics. On admission, he was in biventricular failure with a pulsatile liver secondary to significant tricuspid regurgitation, and a left ventricular heave was felt. The first heart sound was faint, and the second heart sound was loud. A harsh pansystolic murmur, grade 4/6, was heard at the lower sternal border associated with a palpable thrill, and marked ankle edema and cyanotic nail beds were observed. Electrocardiography showed left ventricular hypertrophy and delay in left atrial conduction, and echocardiography revealed ruptured chordae tendineae with left ventricular volume overload. Cardiac catheterization showed normal coronary arteries and 4+ mitral regurgitation. After the patient lost 32 pounds with vigorous medical management, operation for replacement of the mitral valve confirmed myxomatous degeneration of and ruptured chordae tendineae to both leaflets; the leaflets were not flail. Three years after operation, the patient is gainfully employed and taking no cardiac medication. Left ventricular end-diastolic di-
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mension decreased from 68 to 51 mm, and the radiographic cardiothoracic ratio dropped from 20.0/31.0 to 14.0/30.5. Electrocardiography now shows normal P wave morphology. CASE 6. AUSCULTATORILY SILENT MITRAL VALVE PROLAPSE SYNDROME. A 50 year old woman complained of chest pains in the interscapular region radiating to the left shoulder, lasting from minutes to hours, and necessitating three separate hospitalizations. Coronary artery disease was diagnosed with no chemical evidence of myocardial infarction, but the electrocardiographic pattern was consistent with myocardial damage (Fig. 6). The patient's activities were restricted, and nitroglycerin was prescribed but was ineffective. On admission, auscultation was normal; simultaneous echocardiography and phonocardiography showed auscultatorily silent mitral valve prolapse (Fig. 7). Stress electrocardiography to a maximal heart rate of 175 beats a minute failed to reveal any abnormalities. Cardiac catheterization showed normal coronary arteries and mitral valve prolapse. The patient's identical twin also had acoustically silent mitral valve prolapse, which was asymptomatic. Receiving increasing dosages of propranolol, the patient is asymptomatic, gainfully employed, and physically active.
Comment. Auscultatorily silent mitral valve prolapse is encountered in 80 of 380 (21 per cent) of our patients; the diagnosis is suspected from the history, unexplained electrocardiographic abnormalities, or arrhythmias. CASE 7. MITRAL VALVE PROLAPSE SYNDROME AND RUPTURED CHORDAE TENDINEAE. A 75 year old woman (gravida 3, para 2, abortions 1) complained of episodes of paroxysmal atrial tachycardia for 2 years before admission. Cough and progressive dyspnea on exertion and a modest decrease in exercise capacity ensued. On admission, she was normotensive and in congestive heart failure. The first heart sound was preserved. A thrill felt over the cardiac apex was associated with a harsh pansystolic murmur, grade 4/6, which radiated to the back and dorsal spine. A third heart sound was present, and chest radiography showed cardiomegaly and left atrial enlargement. Angiography revealed mitral valve prolapse and ruptured chrodae tendineae to the posterior leaflet (Fig. 8). During operation, the mitral valve was described as redundant and myxomatous. Ruptured chordae tendineae to the posterior mitral leaflet were documented.
Figure 5 (Case 4). Echocardiographic scan of the longitudinal axis of the heart showing mitral valve prolapse (large arrows) and a tonguelike structure (small arrows) representing the distal tip of ruptured chordae tendineae prolapsing into the left atrlal cavity (LA) during systole. LV, left ventricular cavity; IVS, interventricular septum; Ao, aorta; AVJ, atrioventricular junction. (From Naggar, CZ: Self-Teaching Atlas of Echocardiography. Bowie, Maryland, Charles Press, 1978, p 209, reproduced with permisSion.)
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Figure 6 (Case 6). Serial electrocardiograms showing T wave changes in the precordial leads that might be confused with myocardial ischemia.
Figure 7 (Case 6). Simultaneous recording of electrocardiogram, phonocardiogram, and mitral valve echocardiogram (middle panel) in a patient with acoustically silent mitral valve prolapse. Note absence of the click and murmur characteristically heard in patients with mitral valve prolapse syndrome. Arrows point to the mitralleafiet abnormality. LV, left ventricle; SI, first heart sound; S2, second heart sound; Ao, aorta; LA, left atrial cavity. (From Naggar, CZ: Self-Teaching Atlas of Echocardiography. Bowie, Maryland, Charles Press, 1978, p. 87, reproduced with permission.)
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CATHETER
Figure 8 (Case 7). Composite of systolic frame of left ventricular angiogram in the right anterior oblique projection (right panel) and corresponding outline in the left panel. Segmental ballooning or hooding of the redundant mitral valve is clearly visualized (MVP, mitral valve prolapse). Arrow points to the part of the posterior leaflet with ruptured chordae tendineae prolapsing into the left atrium and outlined by the dye. Note the large left atrium filled with dye, indicating severe mitral regurgitation. Ao, aorta; LV, left ventricle.
THE CONTRIBUTION OF ECHOCARDIOGRAPHY TO THE UNDERSTANDING OF MITRAL VALVE PROLAPSE SYNDROME Lack of correlation between symptoms or electrocardiographic abnormalities and severity of mitral valve prolapse led us to search for an echocardiographic explanation for the electrocardiographic abnormalities 35 and to relate the hemodynamic alterations of mitral valve prolapse to the auscultatory findings. Such a correlation might identify subgroups of patients with mitral valve prolapse syndrome at different risks of the development of complications. The subjects were 380 patients treated at the Lahey Clinic Foundation between 1974 and 1977 who had clinical features of mitral valve prolapse syndrome without coexisting cardiovascular disease. The group included 274 women and 106 men whose ages ranged from 7 to 84 years (mean age, 43.9 years). All patients had a complete history and physical examination. Initially, the diagnosis was made on the basis of presenting symptoms, auscultatory findings, or electrocardiographic abnormalities. Echocardiographic documentation of mitral valve prolapse was obtained in all patients. Echocardiograms were analyzed searching for a possible anatomic significance of the murmur and the ST segment and T wave abnormalities (ST-TA) ascribed to mitral valve prolapse syndrome. 4 All electrocardiograms were recorded with patients in the resting, postprandial state in the supine position. Echocardiograms were recorded with patients supine and slightly tilted to the left side. Submaximal exercise tests were carried out in 243 patients using a graded bicycle ergometer, as described by Frishman et al. 15 Patients were segregated according to the presence or absence of a systolic murmur regardless of whether the murmur was elicited with provocation. The two groups were compared using two echocardiographic parameters - left atrial dimension was measured at end-systole and left ventricular end-diastolic dimension was measured at the
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height of the electrocardiographic R wave - and both parameters were corrected for the patient's body surface area yielding the left atrial index (LAI) and _left ventricular end-diastolic index (LVDdI) respectively. Figure 9 displays graphically the relationship between the two groups. Patients were then re grouped according to the presence or absence of ST-TA on electrocardiography as described by Barlow et al. 4 (Fig. 10). In the 243 patients who underwent submaximal exercise testing, the severity of ventricular ectopy harvested during the stress test correlated with resting electrocardiographic abnormalities. The ST-TA were associated with more frequent and malignant ventricular ectopy (Fig. 11) confirming an earlier report by Campbell et al. 6 An ischemic response to exercise testing (defined as an ST segment depression of 1 mm for at least 80 msec) developed in 19 per cent of patients. Comparing this group of patients to those who failed to show such a response, we found the left ventricular dimensions to be increased in the ischemic group (Fig. 12). The so-called ischemic response to submaximal exercise testing not uncommonly encountered in the mitral valve proLVDdI
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