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Coumarin in pregnancy
Letters to the Editor
Coumarin in Pregnancy The report of Palacios-Macedo, Diaz-Devis and Escudero in the December 1969 issue of the Journal 1 should be balanced against the following case. A 35 year old woman, in her fifth month of pregnancy, experienced acute pulmonary edema while at bed rest 5 days after her admission for the treatment of congestive heart failure. A prosthetic mitral valve had been inserted 19 months before, and she had a history of 4 previous pregnancies with living children, the youngest of whom was 5 years old. The pulmonary edema responded to diuretic and digitalis therapy, and hospitalization was continued. Two attempts to record a fetal electrocardiogram were negative. The patient responded to the initial therapy, the heart failure cleared, and hospitalization with continued bed rest was uneventful until the twenty-fifth day when recurrent pulmonary edema responded to morphine and diuretics. On the thirty-first day she again became very dyspneic. Cyanosis and a very definite change in the valve sounds with distinct muffling were noted. There was no response to intravenous heparin and an idioventricular rhythm which preceded cardiac standstill did not respond to external cardiac massage.
The most significant finding at autopsy examination was a clot at the base of the valve which obstructed the movement of the ball and limited it to approximately 2 mm. Microscopically this organizing thrombus had some areas of calcification. This patient had received no anticoagulant therapy, except for the terminal administration of heparin, for about 1 year preceding admission. Anticoagulant therapy was not used because of the presence of some pain in the right lower quadrant, the pregnancy and the apparent tolerance to normal blood clotting. It was evident from the autopsy examination that the clot had been present for sufficient time that the therapy would have been valueless in any event. The results in this patient contrast markedly with those reported by Palacios-Macedo et al., but this single patient does balance their single patient who did not have anticoagulant therapy. RICHARD J. GREENWOOD, MD Westchester, Pennsylvania January 26, 1970 Reference 1. Pabcios-Mace& X, DiazSevis C. Escudwu _I: Fetal risk wth the use of cownar~~ antwagulant agents in pregnant patents with intracardiac ball valve prosthews. Amer J Cardiol 25853~856. 1969
Reply to Greenwood 1. We fully believe that coumarin anticoagulant agents can be of benefit to patients with an intracardiac ball valve prosthesis. In July 1968 we reported in Archivos o!el Instituto de Cardiokgiu de Mexico a comparative study of 40 patients with a Starr-Edwards prosthesis, half of whom received coumarin anticoagulant treatment. After a year of observation, we found that embolism occurred in 55 percent of the control group but in only 10 percent of those receiving anticoagulant therapy. This difference was highly significant (P = 0.001). The higher incidence of embolism occurred in the patients who had a mitral valve prosthesis; the mortality rate was the same in both groups. 2. Although anticoagulant therapy tends to improve the prospects of patients with an intracardiac prosthesis, it does not entirely prevent thromboembolic phenomena. We have observed some patients who had several episodes of cerebral microembolism and others who.had had formation of thrombus at the site of the prosthesis. Pulmonary edema
and death occurred in these patients though they were receiving full anticoagulant treatment and their prothrombin time was within therapeutic levels. 3. On the other hand, coumarin anticoagulant agents have been shown to be of potential risk to the fetus when administered to pregnant women, as in the cases we reported. Thus, the physician is faced with a difficult decision in such cases: the withdrawal of coumarin increases the possibility of thromboembolism in the mother, but continued administration may cause death of the fetus. Our view is given on page 855 in the Clinical Implications section of our paper. JORGE ESCUDERO, MD Servicio de Cardiologia Hospital General del Centro Medico National del I. H. S. S. Mexico 7, D. F., Mexico January 29, 1970
Isolated Tricuspid Valvular Stenosis In their article, “Isolated Tricuspid Valvular Stenosis”,’ Keefe et al. seem to attach great diagnostic significance to the inspiratory increase in amplitude of the “prominent presystolic a waves” which they observed in their patient. They further state that “In other conditions associated with prominent jugular venous a waves in the absence of tricuspid valvular obstruction (that is, right ventricular hypertension and an intact interventricular septum), this phenomenon is not observed.” This statement is contrary to my obsewationsz and those
VOLUME 26. OCTOBER
1970
of others:’ It is the normal and usual effect of inspiration to increase the amplitude of all of the jugular waves (except the c wave due to carotid interference), whereas the mean venous pressure falls to a lower level. These changes have been explained on the basis of a greater difference, with inspiration, in the degree of fullness of the cervical versus the thoracic veins (increased filling of the central veins as the neck veins are emptied), and a lesser differential filling with expiration, so that there is less fluctuation in the volume of blood in the jugular veins.
443
LETTERS
TO THE
EDITOR
Reference 23 (to Wood’) does not seem to bear on the point under discussion but merely states that prominent a waves are usually seen in tricuspid stenosis with sinus rhythm, without mentioning the effect of respiration. ARNOLD L. COLMAN, MD San Francisco, California March 12, 1970
References 1. Keefe JF, Walk MJ, Levine JH: Isolated tricuspid valvular stenosis. Amer J Cardlol 25:252-257, 1970 2. Colman A: Clinical Examination of the Jugular Venous Pulse. Springfield. Ill., Charles C Thomas. 1966, p 20, 116 3. Fe&r W, Cherry RA: External jugular phlebogram as reflecting venous and right atrial hemodynamlcs. Amer J Cardlol. 12:383. 1963 4.
Wood PW: L~pp~ncott
Diseases of the Heart 1956, p 593
and Circulation,
second
edihon.
Philadelphia.
J. B
Reply to Colman Colman is correct in his inference that we attach importance to the evaluation of the jugular venous pulse. However, it was not our intent that this isolated facet of the clinical examination should assume “great diagnostic significance”. It is well known that the mean pressure level of the jugular venous pulse normally falls during inspiration, while the amplitudes of its transients increase. However, with inspiration the top-or absolute-levels of pulsation drop so that the heightened waveforms are due in large part to lower nadirs of the x: and y troughs.’ We regard as significant the fact that in the case reported, not only did the relative height of the a wave increase (as would be normally expected) but so also did its absolute height and the mean cervical venous pressure. This is quite clearly illustrated in Figure 3 of our communication. This truly “paradoxical” response of the jugular venous pulse to respiration may be explained by augmented intrathoracic
venous return encountering a fixed obstruction to rjght atria1 emptying. Finally, we believe that Reference 23 is pertinent to the points mentioned. Wood’s discussion of the venous pulse in tricuspid stenosis begins on page 593. It continues, however, onto the following page, where again is graphically demonstrated inspiratory augmentation of the relative and absolute heights of the a wave (Fig.10.49).’ JOHN F. KEEFE, MD MICHAEL J. WOLK, MD HERBERT J. LEVINE, MD Tufts University School Boston, Massachusetts April 3, 1970
of Medicine
References
1. Wood Pw: Diseasesof plncott, 1956, p 44 2. Ibid.: pages 593-594.
the Heart
and Circulation,
second
edItIon.
Philadelphia.
J.B.Lip
Rebuttal The purpose of my letter was to point out the fact that the amplitude of the venous waves normally increases with inspiration. That this represents an actual augmentation of the positive waves as well as a fall in the z and y troughs is well shown in Figure 4 of Feder and Cherry’s article1 and in several jugular tracings of my own (Fig, 1). Figure 10.49 of Wood’s book’ shows inspiratory changes in the venous pulse which do not appear to differ from those shown here, and in his discussion Wood does not state that such changes are peculiar to tricuspid stenosis. The inspiratory rise in mean venous pressure demonstrated by Keefe et al. seems to be an example of Kussmaul’s sign, which may be present with congestion of the right side of the heart of various causes, such as massive pulmonary embolism” (Fig. Z), also a condition which may be associated with prominent jugular venous a waves. ARNOLD L. COLMAN, MD April 27, 1970
1. Feder W, Cherry RA: External jugular phlebogram as reflecting venous and “ght atrial hemodynamics. Amer J Cardiol 12:363, 1963 2. Wood I%: Diseases of the Heart and Circulation. second edition. Philadelphia, J.B. Lippincott. 1956, p 593 3. Burdina JA, Wallace JM: Pulsus paradoxus and Kussmaul’s sign in masswe pulmonary embolism. Amer J Cardiol 151413-415. 1965
Figure 1. Representative normal lug&r Photoelectric Pulse Recorder). Horizontal
444
venous pulse tracings (made with Concept bar above the tracing marks inspirabon.
Figure
2.
From
Burdine
and
Wallace.*
The American Journal of CARDIOLOGY
Coumarin in Pregnancy The report of Palacios-Macedo, Diaz-Devis and Escudero in the December 1969 issue of the Journal 1 should be balanced against the following case. A 35 year old woman, in her fifth month of pregnancy, experienced acute pulmonary edema while at bed rest 5 days after her admission for the treatment of congestive heart failure. A prosthetic mitral valve had been inserted 19 months before, and she had a history of 4 previous pregnancies with living children, the youngest of whom was 5 years old. The pulmonary edema responded to diuretic and digitalis therapy, and hospitalization was continued. Two attempts to record a fetal electrocardiogram were negative. The patient responded to the initial therapy, the heart failure cleared, and hospitalization with continued bed rest was uneventful until the twenty-fifth day when recurrent pulmonary edema responded to morphine and diuretics. On the thirty-first day she again became very dyspneic. Cyanosis and a very definite change in the valve sounds with distinct muffling were noted. There was no response to intravenous heparin and an idioventricular rhythm which preceded cardiac standstill did not respond to external cardiac massage.
The most significant finding at autopsy examination was a clot at the base of the valve which obstructed the movement of the ball and limited it to approximately 2 mm. Microscopically this organizing thrombus had some areas of calcification. This patient had received no anticoagulant therapy, except for the terminal administration of heparin, for about 1 year preceding admission. Anticoagulant therapy was not used because of the presence of some pain in the right lower quadrant, the pregnancy and the apparent tolerance to normal blood clotting. It was evident from the autopsy examination that the clot had been present for sufficient time that the therapy would have been valueless in any event. The results in this patient contrast markedly with those reported by Palacios-Macedo et al., but this single patient does balance their single patient who did not have anticoagulant therapy. RICHARD J. GREENWOOD, MD Westchester, Pennsylvania January 26, 1970 Reference 1. Pabcios-Mace& X, DiazSevis C. Escudwu _I: Fetal risk wth the use of cownar~~ antwagulant agents in pregnant patents with intracardiac ball valve prosthews. Amer J Cardiol 25853~856. 1969
Reply to Greenwood 1. We fully believe that coumarin anticoagulant agents can be of benefit to patients with an intracardiac ball valve prosthesis. In July 1968 we reported in Archivos o!el Instituto de Cardiokgiu de Mexico a comparative study of 40 patients with a Starr-Edwards prosthesis, half of whom received coumarin anticoagulant treatment. After a year of observation, we found that embolism occurred in 55 percent of the control group but in only 10 percent of those receiving anticoagulant therapy. This difference was highly significant (P = 0.001). The higher incidence of embolism occurred in the patients who had a mitral valve prosthesis; the mortality rate was the same in both groups. 2. Although anticoagulant therapy tends to improve the prospects of patients with an intracardiac prosthesis, it does not entirely prevent thromboembolic phenomena. We have observed some patients who had several episodes of cerebral microembolism and others who.had had formation of thrombus at the site of the prosthesis. Pulmonary edema
and death occurred in these patients though they were receiving full anticoagulant treatment and their prothrombin time was within therapeutic levels. 3. On the other hand, coumarin anticoagulant agents have been shown to be of potential risk to the fetus when administered to pregnant women, as in the cases we reported. Thus, the physician is faced with a difficult decision in such cases: the withdrawal of coumarin increases the possibility of thromboembolism in the mother, but continued administration may cause death of the fetus. Our view is given on page 855 in the Clinical Implications section of our paper. JORGE ESCUDERO, MD Servicio de Cardiologia Hospital General del Centro Medico National del I. H. S. S. Mexico 7, D. F., Mexico January 29, 1970
Isolated Tricuspid Valvular Stenosis In their article, “Isolated Tricuspid Valvular Stenosis”,’ Keefe et al. seem to attach great diagnostic significance to the inspiratory increase in amplitude of the “prominent presystolic a waves” which they observed in their patient. They further state that “In other conditions associated with prominent jugular venous a waves in the absence of tricuspid valvular obstruction (that is, right ventricular hypertension and an intact interventricular septum), this phenomenon is not observed.” This statement is contrary to my obsewationsz and those
VOLUME 26. OCTOBER
1970
of others:’ It is the normal and usual effect of inspiration to increase the amplitude of all of the jugular waves (except the c wave due to carotid interference), whereas the mean venous pressure falls to a lower level. These changes have been explained on the basis of a greater difference, with inspiration, in the degree of fullness of the cervical versus the thoracic veins (increased filling of the central veins as the neck veins are emptied), and a lesser differential filling with expiration, so that there is less fluctuation in the volume of blood in the jugular veins.
443
LETTERS
TO THE
EDITOR
Reference 23 (to Wood’) does not seem to bear on the point under discussion but merely states that prominent a waves are usually seen in tricuspid stenosis with sinus rhythm, without mentioning the effect of respiration. ARNOLD L. COLMAN, MD San Francisco, California March 12, 1970
References 1. Keefe JF, Walk MJ, Levine JH: Isolated tricuspid valvular stenosis. Amer J Cardlol 25:252-257, 1970 2. Colman A: Clinical Examination of the Jugular Venous Pulse. Springfield. Ill., Charles C Thomas. 1966, p 20, 116 3. Fe&r W, Cherry RA: External jugular phlebogram as reflecting venous and right atrial hemodynamlcs. Amer J Cardlol. 12:383. 1963 4.
Wood PW: L~pp~ncott
Diseases of the Heart 1956, p 593
and Circulation,
second
edihon.
Philadelphia.
J. B
Reply to Colman Colman is correct in his inference that we attach importance to the evaluation of the jugular venous pulse. However, it was not our intent that this isolated facet of the clinical examination should assume “great diagnostic significance”. It is well known that the mean pressure level of the jugular venous pulse normally falls during inspiration, while the amplitudes of its transients increase. However, with inspiration the top-or absolute-levels of pulsation drop so that the heightened waveforms are due in large part to lower nadirs of the x: and y troughs.’ We regard as significant the fact that in the case reported, not only did the relative height of the a wave increase (as would be normally expected) but so also did its absolute height and the mean cervical venous pressure. This is quite clearly illustrated in Figure 3 of our communication. This truly “paradoxical” response of the jugular venous pulse to respiration may be explained by augmented intrathoracic
venous return encountering a fixed obstruction to rjght atria1 emptying. Finally, we believe that Reference 23 is pertinent to the points mentioned. Wood’s discussion of the venous pulse in tricuspid stenosis begins on page 593. It continues, however, onto the following page, where again is graphically demonstrated inspiratory augmentation of the relative and absolute heights of the a wave (Fig.10.49).’ JOHN F. KEEFE, MD MICHAEL J. WOLK, MD HERBERT J. LEVINE, MD Tufts University School Boston, Massachusetts April 3, 1970
of Medicine
References
1. Wood Pw: Diseasesof plncott, 1956, p 44 2. Ibid.: pages 593-594.
the Heart
and Circulation,
second
edItIon.
Philadelphia.
J.B.Lip
Rebuttal The purpose of my letter was to point out the fact that the amplitude of the venous waves normally increases with inspiration. That this represents an actual augmentation of the positive waves as well as a fall in the z and y troughs is well shown in Figure 4 of Feder and Cherry’s article1 and in several jugular tracings of my own (Fig, 1). Figure 10.49 of Wood’s book’ shows inspiratory changes in the venous pulse which do not appear to differ from those shown here, and in his discussion Wood does not state that such changes are peculiar to tricuspid stenosis. The inspiratory rise in mean venous pressure demonstrated by Keefe et al. seems to be an example of Kussmaul’s sign, which may be present with congestion of the right side of the heart of various causes, such as massive pulmonary embolism” (Fig. Z), also a condition which may be associated with prominent jugular venous a waves. ARNOLD L. COLMAN, MD April 27, 1970
1. Feder W, Cherry RA: External jugular phlebogram as reflecting venous and “ght atrial hemodynamics. Amer J Cardiol 12:363, 1963 2. Wood I%: Diseases of the Heart and Circulation. second edition. Philadelphia, J.B. Lippincott. 1956, p 593 3. Burdina JA, Wallace JM: Pulsus paradoxus and Kussmaul’s sign in masswe pulmonary embolism. Amer J Cardiol 151413-415. 1965
Figure 1. Representative normal lug&r Photoelectric Pulse Recorder). Horizontal
444
venous pulse tracings (made with Concept bar above the tracing marks inspirabon.
Figure
2.
From
Burdine
and
Wallace.*
The American Journal of CARDIOLOGY