Annotations
Coronary artery and therapeutic
spasm-diagnostic implications
The hypothesis of coronary vasospasm as a cause of angina, suggested by accurate clinical observations long ago, began to be reconsidered recently on the basis of some isolated, occasional angiographic observations, made more by chance than by design during attacks of “variant” angina. The role of coronary vasospasm in angina pectoris at rest was confirmed in our institution by three series of studies: 1. Continuous hemodynamic monitoring demonstrated that angina1 attacks at rest characterized by S-T segment elevation or depression, were never preceded by an increase of the hemodynamic variables that control myocardial oxygen consumption.‘-’ Indeed, the hemodynamic pattern observed consistently during these attacks was remarkably similar to t,hat observed during experimental, transient coronary occlusion.? 2. Regional myocardial perfusion studies by Thallium-201 scintigraphy during angina1 attacks showed massive transmural deficit of perfusion in patients with S-T segment elevation? and, in more recent studies, severe diffuse or subendocardial flow reduction in patients with S-T segment depression. 3. Coronary angiography during attacks demonstrated a severe spasm of one or two major coronary vessels in patients with S-T segment elevation and a spasm of a small branch, or presence of collaterals or diffuse lumen reduction of several branches in patients with S-T segment depression.’ The degree of atherosclerotic involvement of the patients with vasospastic angina was extremely variable, from normal coronary angiograms to severe triple vessel disease. The spasm appears to involve the vessel over a long segment and, in the presence of organic stenosis, extends proximally and/or distally to the lesion. Our studies indicate that the electrocardiogram may show S-T segment elevation or depression, depending on the predominantly transmural or subendocardial distribution of myocardial ischemia. Both patterns may be sometimes observed in the same patient during angina at rest depending on the severity of the vasospasm. The objective demonstration of the possible role of coronary vasomotoricity reducing myocardial perfusion, suggests a revision of the traditional notion that angina ensues only when myocardial metabolic demand increases beyond the possibility of coronary reserve (set by the degree of coronary stenosis and of collateral development). Indeed, the concept that the only variable capable of determining an acute inbalance between demand and supply is an excessive increase of myocardial demand,’ has so far conditioned medical and surgical approach to angina. Yet the demonstration that angina at rest is not preceded by a rise of the determinants of oxygen consumption, indicates that it is not secondary to this mechanismF In our experience the borders between “primary” vasospastic angina and traditional, secondary angina are very illdefined because, on the one hand, some patients with “vari-
554
October,
1978, Vol. 96, No. 4
ant” angina (usually a reasonable landmark of vasospastic angina, as suggested by Prinzmetal) may also have effortinduced angina with fixed reduced exercise tolerance; on the other, some others may develop occasionally vasospastic angina on exertion. Finally, alpha tone appears under some circumstances capable of reducing coronary reserve,’ and a severe reduction of myocardial perfusion was demonstrated in patients during angina induced by pacing.” The diagnostic evaluation of patients with angina at rest should aim to demonstrate whether or not onset of S-T segment changes (not of chest pain’ which is always a late phenomenon) is preceded by increased metabolic demands beyond the possibilities of supply. In most cases the determination of the double or triple product at the onset of the attack and at the onset of ischemia during a graduated effort or a pacing test may serve the purpose. The therapeutic approach of these patients is substantially different from that of the patients with angina secondary to excessive increase of demands, for whom beta blockers and coronary surgery represent a rational approach. Since cardiac denervation does not prevent coronary vasospasm,” medical treatment with high doses of nitrates and calcium antagonists such as verapamil, represents in our experience, so far, the most effective form of treatment for patients with vasospastic angina.
Laboratorio
di Fisiologi
a
Attilio Maseri Clinica, C.N.R. Via Savi 8 56100 Pisa Italy A. L’A bbate S. Chierchia 0. Parodi
REFERENCES 1.
2.
3.
4.
5. 6.
Maseri, A. Pesola, A., Mimmo, R., Chierchia, S., and L’Abbate, A.: Pathogenetic mechanisms of angina at rest (Abstr.). Circulation 51 AND 52: (Suoal.) 11:89. 1975. i\ilaseri;’ A., Mimmo, R., Chierchia, ‘s:, Marchesi, C., Pesola, A., and L’Abbate, A.: Coronary artery spasm as a cause of acute myocardial ischemia in man, Chest 68:625, 1975. Maseri, A., Parodi, O., Severi, S., and Pesola, A.: Transient transmural reduction of myocardial blood flow, demonstrated by Thallium-201 scintigraphy, as a cause of variant angina, Circulation 54:2801 1976. Maseri, A., L’Abbate, A., Pesola, A., Ballestra, A. M., Marzilli, M., Maltini, G., Severi, S., De Nes, D. M., Parodi, O., and Biagini, A.: Coronary vasospasm in angina pectoris, Lancet 1:713, 1977. Friedberg, L. K.: Diseases of the heart, 3rd ed., Philadelphia, 1966, W. B. Saunders Company. Maseri, A., Klassen, G. A., and Lesch, M., eds.: Primary
0002-8703/78/100554
+ 0.2$00.20/O
0 1978 The
C. V. Mosby
Co.
7.
8.
angina, pathogenetic mechanisms and therapeutic implications. Proceedings of the Satellite Symposium of the Seventh European Congress of Cardiology, Pisa, June< 15-17, XV6, New York, 1978, Grune & Stratton, Inc. Mudge, G. H., Grossman, W., Millis, R., Lesch, M., and Braunwald, E.: Reflex increase in coronary vascular resistance in patients with ischemic heart disease, N. Engl. J. Med. 295:1333, 1976. Maseri, A., L’Abbate, A., Pesola, A., Michelassi, C.,
lacement c mitral valve
9.
on motion
Mitral valce prolapse is a common condition which often is readily diagnosed by clinical examination, disclosing the typical non-ejection click and/or mid to late systolic murmur. However, such patients may present with unusual or labile auscultatory findings and left ventricular angiography has been required t,o establish the diagnosis in some cases. The discovery that mitral valve prolapse can be accurately diagnosed in many patients using M-mode echocardiography has been a great impetus to the study of this syndrome.‘. ? In patients with angiographically proven mitral valve prolapse, various echocardiographic patterns have been described and are used to establish the diagnosis in patients with or without typical auscultatory features of the prolapse syndrome.3. i In a group of 100 presumably healthy subjects, we performed echocardiograms to study the waveform of the mitral valve relative to other signs of prolapse and to tabulate the systolic mitral waveform specifically.5 In the design of this study we attempted to assess the effect of transducer position on the mitral waveform by trying to record the anterior and posterior mitral leaflets and left atrium (or atrioventricular junction) with the ultrasound transducer located at the second, third, fourth, and fifth intercostal spaces. During systole, a single echo usually could be identified as continuously recorded from the point of leaflet apposition (Cpoint) to the point of leaflet separation at end-systole (Dpoint). This echo was interpreted as representing the mitral valve leafiets in the area of coaptation and was analyzed for absolute anterior or posterior systolic motion. A straight line was drawn from the C-point to the D-point (C-D line) and deviation of the common continllous mitral echo from this line was noted. We found the echocardiographic patterns previously assodated with mitral valve prolapse, i.e., a hammock-like smooth posterior motion beginning early in systole or a late systolic posterior motion, could be obtained from some intercostal space in over 5O per cent of the subjects. We noticed that such patterns were more frequent when the transducer was located in the higher intercostal spaces, but less common in the same patients with the transducer located in the lower intercostal spaces. Further analysis showed the angulation of the transducer on the chest wall was a major determinant of the mitral valve systolic pattern, while the absolute intercostal space in which the transducer was placed was less important. Extensive statistical work demonstrated an excellent correlation
0002~87O;3/78;1OC555
i
02$0020/O
0 1978 The
Marzilli, .%K, and De Nes, 2. M.: Regionai :nyocardiai perfusion in patients with atherosclerotic coronary artery disease, at rest and during angina pectoris induced by tachycardia, Circulation 55423, 1377. Clark, D. A., Quint, R. A., Mitcbel!, R. L., and Angell, W. W.: Coronary artery spasm. Medical management, surgical denervation, and autotracsplantation, J. Thorac. ‘Jardiovasc. Surg 7X332, 1977.
C. V. Mosby
Co.
between the phonocardiographic findicgs and he echocardiographic patterns when the ultrasound trar&ucer was in a position perpendicular to the chest waii when recording the mitral leaflets and left atrium. This was considered the “perpendicular” position. Regardless of the intercostal space, !.f the transducer was pointed caudally, patterns suggesting mit,ral valve prolapse were observed ifi many subjects without phonocardiographic evidence for this syndrome. Conversely, many patients with phonocardiographic evidence of p&apse did not have the echocardiographic features asc;ociated with this condition if the echocardiogram was recorded with the transducer located low on the chest wall and p&n&g markedly cepbalad. In the latter situation the echocardiograpbic patterns associated with mitrai valve pro&se usually were seen when repeating the study with the trahsdncer located one intercostal space higher and being perpendicr,&r to the chest wall. The sequence of recorded echocardiographic patterns with various transducer angnlations was consister.t with previous studies describing the motion of the base of the heart during the cardiac cycle.’ s During systole the base of the heart moves towards the apex as the annulus fibrosus moves caudally and anteriorly. During systole the normal mitral leaflets close and passively follow the motion of the mitral annulus. With the transducer located high on the chest, the mitral annulus and leaflets move away from the transducer during systole as they descend toward the cardiac apex. Ir, this situation the D-point will be posterior to the C-point, and a hammock-shaped posterior nnotion may be recorded without. regard to the presence of actual mitral v&e prolapse. Conversely, when the transducer is ioca:ed iow on the chest pointing cephalad, the mitral annulus azd closed leaflets will move directly toward the transducer. “In this situation the Dpoint will be markedly anterior to the C-point. The path of valve and annulus creates the smooth curvilinear anteriorly convex C-D segment commonly recorded Gona such a low ‘intercostal space. With such transducer pos,tion and angulation, bul@ng of mitral valve leaflets as they prolapse toward the left atrium may not be apparent. This study has shown the importance of sx-znsducer angulation and position in standardizing the echocardiogram fo‘or assessment of the mitral valve systolic waveform using Mmode echocardiagrzphy. Recording both mitrz+l leaflets and !eft atrium with the transducer perpendictdar to the chest
Coronary artery and therapeutic
spasm-diagnostic implications
The hypothesis of coronary vasospasm as a cause of angina, suggested by accurate clinical observations long ago, began to be reconsidered recently on the basis of some isolated, occasional angiographic observations, made more by chance than by design during attacks of “variant” angina. The role of coronary vasospasm in angina pectoris at rest was confirmed in our institution by three series of studies: 1. Continuous hemodynamic monitoring demonstrated that angina1 attacks at rest characterized by S-T segment elevation or depression, were never preceded by an increase of the hemodynamic variables that control myocardial oxygen consumption.‘-’ Indeed, the hemodynamic pattern observed consistently during these attacks was remarkably similar to t,hat observed during experimental, transient coronary occlusion.? 2. Regional myocardial perfusion studies by Thallium-201 scintigraphy during angina1 attacks showed massive transmural deficit of perfusion in patients with S-T segment elevation? and, in more recent studies, severe diffuse or subendocardial flow reduction in patients with S-T segment depression. 3. Coronary angiography during attacks demonstrated a severe spasm of one or two major coronary vessels in patients with S-T segment elevation and a spasm of a small branch, or presence of collaterals or diffuse lumen reduction of several branches in patients with S-T segment depression.’ The degree of atherosclerotic involvement of the patients with vasospastic angina was extremely variable, from normal coronary angiograms to severe triple vessel disease. The spasm appears to involve the vessel over a long segment and, in the presence of organic stenosis, extends proximally and/or distally to the lesion. Our studies indicate that the electrocardiogram may show S-T segment elevation or depression, depending on the predominantly transmural or subendocardial distribution of myocardial ischemia. Both patterns may be sometimes observed in the same patient during angina at rest depending on the severity of the vasospasm. The objective demonstration of the possible role of coronary vasomotoricity reducing myocardial perfusion, suggests a revision of the traditional notion that angina ensues only when myocardial metabolic demand increases beyond the possibility of coronary reserve (set by the degree of coronary stenosis and of collateral development). Indeed, the concept that the only variable capable of determining an acute inbalance between demand and supply is an excessive increase of myocardial demand,’ has so far conditioned medical and surgical approach to angina. Yet the demonstration that angina at rest is not preceded by a rise of the determinants of oxygen consumption, indicates that it is not secondary to this mechanismF In our experience the borders between “primary” vasospastic angina and traditional, secondary angina are very illdefined because, on the one hand, some patients with “vari-
554
October,
1978, Vol. 96, No. 4
ant” angina (usually a reasonable landmark of vasospastic angina, as suggested by Prinzmetal) may also have effortinduced angina with fixed reduced exercise tolerance; on the other, some others may develop occasionally vasospastic angina on exertion. Finally, alpha tone appears under some circumstances capable of reducing coronary reserve,’ and a severe reduction of myocardial perfusion was demonstrated in patients during angina induced by pacing.” The diagnostic evaluation of patients with angina at rest should aim to demonstrate whether or not onset of S-T segment changes (not of chest pain’ which is always a late phenomenon) is preceded by increased metabolic demands beyond the possibilities of supply. In most cases the determination of the double or triple product at the onset of the attack and at the onset of ischemia during a graduated effort or a pacing test may serve the purpose. The therapeutic approach of these patients is substantially different from that of the patients with angina secondary to excessive increase of demands, for whom beta blockers and coronary surgery represent a rational approach. Since cardiac denervation does not prevent coronary vasospasm,” medical treatment with high doses of nitrates and calcium antagonists such as verapamil, represents in our experience, so far, the most effective form of treatment for patients with vasospastic angina.
Laboratorio
di Fisiologi
a
Attilio Maseri Clinica, C.N.R. Via Savi 8 56100 Pisa Italy A. L’A bbate S. Chierchia 0. Parodi
REFERENCES 1.
2.
3.
4.
5. 6.
Maseri, A. Pesola, A., Mimmo, R., Chierchia, S., and L’Abbate, A.: Pathogenetic mechanisms of angina at rest (Abstr.). Circulation 51 AND 52: (Suoal.) 11:89. 1975. i\ilaseri;’ A., Mimmo, R., Chierchia, ‘s:, Marchesi, C., Pesola, A., and L’Abbate, A.: Coronary artery spasm as a cause of acute myocardial ischemia in man, Chest 68:625, 1975. Maseri, A., Parodi, O., Severi, S., and Pesola, A.: Transient transmural reduction of myocardial blood flow, demonstrated by Thallium-201 scintigraphy, as a cause of variant angina, Circulation 54:2801 1976. Maseri, A., L’Abbate, A., Pesola, A., Ballestra, A. M., Marzilli, M., Maltini, G., Severi, S., De Nes, D. M., Parodi, O., and Biagini, A.: Coronary vasospasm in angina pectoris, Lancet 1:713, 1977. Friedberg, L. K.: Diseases of the heart, 3rd ed., Philadelphia, 1966, W. B. Saunders Company. Maseri, A., Klassen, G. A., and Lesch, M., eds.: Primary
0002-8703/78/100554
+ 0.2$00.20/O
0 1978 The
C. V. Mosby
Co.
7.
8.
angina, pathogenetic mechanisms and therapeutic implications. Proceedings of the Satellite Symposium of the Seventh European Congress of Cardiology, Pisa, June< 15-17, XV6, New York, 1978, Grune & Stratton, Inc. Mudge, G. H., Grossman, W., Millis, R., Lesch, M., and Braunwald, E.: Reflex increase in coronary vascular resistance in patients with ischemic heart disease, N. Engl. J. Med. 295:1333, 1976. Maseri, A., L’Abbate, A., Pesola, A., Michelassi, C.,
lacement c mitral valve
9.
on motion
Mitral valce prolapse is a common condition which often is readily diagnosed by clinical examination, disclosing the typical non-ejection click and/or mid to late systolic murmur. However, such patients may present with unusual or labile auscultatory findings and left ventricular angiography has been required t,o establish the diagnosis in some cases. The discovery that mitral valve prolapse can be accurately diagnosed in many patients using M-mode echocardiography has been a great impetus to the study of this syndrome.‘. ? In patients with angiographically proven mitral valve prolapse, various echocardiographic patterns have been described and are used to establish the diagnosis in patients with or without typical auscultatory features of the prolapse syndrome.3. i In a group of 100 presumably healthy subjects, we performed echocardiograms to study the waveform of the mitral valve relative to other signs of prolapse and to tabulate the systolic mitral waveform specifically.5 In the design of this study we attempted to assess the effect of transducer position on the mitral waveform by trying to record the anterior and posterior mitral leaflets and left atrium (or atrioventricular junction) with the ultrasound transducer located at the second, third, fourth, and fifth intercostal spaces. During systole, a single echo usually could be identified as continuously recorded from the point of leaflet apposition (Cpoint) to the point of leaflet separation at end-systole (Dpoint). This echo was interpreted as representing the mitral valve leafiets in the area of coaptation and was analyzed for absolute anterior or posterior systolic motion. A straight line was drawn from the C-point to the D-point (C-D line) and deviation of the common continllous mitral echo from this line was noted. We found the echocardiographic patterns previously assodated with mitral valve prolapse, i.e., a hammock-like smooth posterior motion beginning early in systole or a late systolic posterior motion, could be obtained from some intercostal space in over 5O per cent of the subjects. We noticed that such patterns were more frequent when the transducer was located in the higher intercostal spaces, but less common in the same patients with the transducer located in the lower intercostal spaces. Further analysis showed the angulation of the transducer on the chest wall was a major determinant of the mitral valve systolic pattern, while the absolute intercostal space in which the transducer was placed was less important. Extensive statistical work demonstrated an excellent correlation
0002~87O;3/78;1OC555
i
02$0020/O
0 1978 The
Marzilli, .%K, and De Nes, 2. M.: Regionai :nyocardiai perfusion in patients with atherosclerotic coronary artery disease, at rest and during angina pectoris induced by tachycardia, Circulation 55423, 1377. Clark, D. A., Quint, R. A., Mitcbel!, R. L., and Angell, W. W.: Coronary artery spasm. Medical management, surgical denervation, and autotracsplantation, J. Thorac. ‘Jardiovasc. Surg 7X332, 1977.
C. V. Mosby
Co.
between the phonocardiographic findicgs and he echocardiographic patterns when the ultrasound trar&ucer was in a position perpendicular to the chest waii when recording the mitral leaflets and left atrium. This was considered the “perpendicular” position. Regardless of the intercostal space, !.f the transducer was pointed caudally, patterns suggesting mit,ral valve prolapse were observed ifi many subjects without phonocardiographic evidence for this syndrome. Conversely, many patients with phonocardiographic evidence of p&apse did not have the echocardiographic features asc;ociated with this condition if the echocardiogram was recorded with the transducer located low on the chest wall and p&n&g markedly cepbalad. In the latter situation the echocardiograpbic patterns associated with mitrai valve pro&se usually were seen when repeating the study with the trahsdncer located one intercostal space higher and being perpendicr,&r to the chest wall. The sequence of recorded echocardiographic patterns with various transducer angnlations was consister.t with previous studies describing the motion of the base of the heart during the cardiac cycle.’ s During systole the base of the heart moves towards the apex as the annulus fibrosus moves caudally and anteriorly. During systole the normal mitral leaflets close and passively follow the motion of the mitral annulus. With the transducer located high on the chest, the mitral annulus and leaflets move away from the transducer during systole as they descend toward the cardiac apex. Ir, this situation the D-point will be posterior to the C-point, and a hammock-shaped posterior nnotion may be recorded without. regard to the presence of actual mitral v&e prolapse. Conversely, when the transducer is ioca:ed iow on the chest pointing cephalad, the mitral annulus azd closed leaflets will move directly toward the transducer. “In this situation the Dpoint will be markedly anterior to the C-point. The path of valve and annulus creates the smooth curvilinear anteriorly convex C-D segment commonly recorded Gona such a low ‘intercostal space. With such transducer pos,tion and angulation, bul@ng of mitral valve leaflets as they prolapse toward the left atrium may not be apparent. This study has shown the importance of sx-znsducer angulation and position in standardizing the echocardiogram fo‘or assessment of the mitral valve systolic waveform using Mmode echocardiagrzphy. Recording both mitrz+l leaflets and !eft atrium with the transducer perpendictdar to the chest
