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Pulmonary Embolism and Heart Disease
Path. Res. Pract. 189, 1058-1062 (1993)
Pulmonary Embolism and Heart Disease An Autopsy Study B. Karwinski and E. Svendsen Department of Pathology, The Gade Institute, University of Bergen, Norway
S. Seim Medical Department, University of Bergen, Norway
SUMMARY
The frequency of pulmonary embolism in patients with myocardial infarction (MI) and chronic rheumatic heart disease (RHE) has been investigated in an autopsy series. The series comprised 21530 hospital autopsies from 1960 to 1984. Altogether 5351 patients with MI and 289 patients with RHE as underlying death cause were selected for this study. Patients with RHE or old myocardial infarction (aMI) had a significantly higher frequency of pulmonary embolism than patients with acute myocardial infarction (AMI) or acute and old myocardial infarction combined (AOMI). This was true irrespective of duration of stay in the hospital during last admission. The frequency of pulmonary embolism decreased in patients with aMI or RHE from 1960 to 1984 suggestive of better therapy of chronic heart failure. A similar trend was seen in patients with AMI during a period with consistent anticoagulation treatment.
Introduction Pulmonary embolism is a life-threatening disorder, which has been underestimated as shown in a number of reports 1,2,5,6. Previously we have shown the frequency of pulmonary embolism to be elevated in patients dying from cancer compared with other death causes lO • The frequency varied among different types of cancer 10 • Previous work has likewise shown that circulatory disturbances of the lower limbs drastically increased the risk of pulmonary embolism ll . We now report the frequency of pulmonary embolism in patients dying due to myocardial infarction (MI) and to rheumatic heart disease (RHE), autopsied from 1960 to 1984 inclusive at Haukeland Hospital. 0344-0338/93/0189-1058$3.50/0
Material and Methods Patients with MI and RHE were selected from our autopsy files from 1960 to 1984 inclusive. During these 25 years 21530 hospital autopsies were performed in the department. Forensic cases are not included. All internal viscera were examined. The pulmonary arteries were routinely opened to the segmental level. The autopsy record of the department has been described in detail previously3. In altogether 5351 patients MI was the underlying death cause, whereas 289 patients died due to RHE. As we were interested to see how various heart diseases had an influence upon the frequency of pulmonary embolism, only patients with the respective diseases as underlying cause of death were selected. This made the material better suitable for grouping and for comparison between and within groups. Patients with MI were subdivided into 3 groups, those with solely acute myocardial infarction © 1993 by Gustav Fischer Verlag, Stuttgart
Pulmonary Embolism· 1059 (AMI), with old myocardial infarction (OMI) or with acute and old myocardial infarction combined (AOMI). In all 3 subdivided groups and in patients with RHE, age, duration of last admission and the significance of cancer were paid attention to with regard to pulmonary embolism. The highest median age within the groups (72 years among OMI patients) was arbitrarily chosen and the frequency of pulmonary embolism below and beyond this age examined. All pulmonary emboli were macroscopical findings. Only exceptionally the diagnosis of pulmonary embolism was established from an incidental microscopical finding in lung sections. In all the examined categories of cardiac diseases, groups of 5 -year intervals were established to see if the frequency of pulmonary embolism had changed during the observation period. CHF was used for statistical evaluation.
25
__ RHE ..... OMI
E
-<>-
Table 1. Heart diseases and pulmonary embolism (PE). Total material
AMI
en
m ::I
15
~
10
'" 0 ::I
.... J
Every fifth patient dying with RHE as underlying death cause had pulmonary embolism, a frequency significantly higher than in any of the subgroups of MI. Patients with AMI and AOMI as underlying death cause had the lowest frequency of pulmonary embolism in this study, significantly lower than OMI or RHE (Tables 1 and 2). Old age seemed to playa significant role with regard to pulmonary embolism. This was true in patients who succumbed due to AMI and AOMI, and patients with OMI showed a similar trend. An inverse trend was seen in patients with RHE, but the figures in the RHE group were small. Also patients with RHE, despite a significantly higher incidence of pulmonary embolism, were on average much younger than patients with MI (Table 3). The frequency of pulmonary embolism in 5-year intervals for each of the four groups is shown in Fig. 1. OMI
...... AOMI
20
::I
:::i 0
Results
Q.
5
Disorder
n
% PE
AMI OMI AOMI RHE
1823 1245 2283 289
5.9 13.9 6.3
21.1
AMI = acute myocardial infarction; OMI = old myocardial infarction; AOMI = acute and old myocardial infarction combined; RHE = rheumatic heart disease.
01+-19-6+0--6-4--19-6-+5--6-9--1-97--10---74--1-9-751---79--19:-::-:'80-84 YEARS
Fig. 1. Pulmonary embolism in 5-year intervals in patients with heart diseases. AMI, OMI, AOMI and RHE as in Table 1. Apart from AMI there is a significant drop in the frequency of pulmonary embolism from 1960 to 1984. In patients with AMI a significant transient drop is seen during 1970-1974. OMI + RHE: 1960-1964 versus 1980-1984 X2 = 6.72 P < 0.01 1960-1964 versus AOMI: 1980-1984 X2 = 5.77 P < 0.025 AMI: 1960-1964 versus 1980-1984 X2 = 0.05 NS AMI: 1970-1974 versus 1960-1969/1975-1984 X2 = 6.38 P < 0.025
Table 2. Comparison between different heart diseases with regard to pulmonary embolism (CH2)
RHE
AMI
OMI
AOMI
X2 = 61.31 p < 0.0005
X2 = 6.68 p < 0.01
X2 = 59.12 p < 0.0005
X2 = 47.26 p < 0.0005
X2 = 0.30 NS
AMI
X2 = 46.47 p < 0.0005
OMI AMI, OMI, AOMI and RHE as in Table 1.
Table 3. Median age with range and pulmonary embolism (PE)
All (years) With PE ca (years) < 72 years (n) < 72 years % PE > 72 years (n) > 72 years % PE
AMI (n = 1823)
OMI (n = 1245)
AOMI (n = 2283)
RHE (n = 289)
71 (25-97) 74 (49-92) 983 3.7 (36) 840 8.5 (71)
72 (16-96) 75 (46-96) 627 12.1 618 15.7
70 (34-99) 73 (39-94) 1338 5.3 (71) 945 7.7 (73)
64 (24-94) 62 (37-85) 216 23.0 73 15.3
AMI < 72 years versus> 72 years: X2 = 16.67 = P < 0.0005, AOMI < 72 years versus> 72 years: X2 = 4.81 = P < 0.05, AMI, OMI, AOMI and RHE as in Table 1.
1060 . B. Karwinski, S. Seim and E. Svendsen Table 4. Stay in Hospital during last admission, all patients and those with pulmonary embolism (PE) AMI (n = 1823)
OMI
(n = 1245)
AOMI (n = 2283)
RHE
(n = 289)
All (days)
2 (1-365)
2 (1-365)
2 (1-365)
5 (1- 94)
With PE (days)
8 (1-120)
10 (1-365)
10 (1-365)
8 (1-174)
AMI, OMI, AOMI and RHE as in Table 1.
and RHE showed a significant decrease in frequency over the years. The same was also seen in patients with AMI from 1970 to 1974, but this lowered frequency was not persistent. In patients with AOMI a steady decrease in frequency was observed. Patients with MI stayed on average only 2 days in the hospital during last admission. Patients with RHE stayed longer, on average 5 days. Patients with MI and pulmonary embolism stayed 8 to 10 days, similar to the RHE patients with pulmonary embolism (Table 4). When patients were grouped according to equal duration of last admission a clearly higher frequency was nevertheless seen among patients with RHE and OMI compared with AMI and AOMI. A significant increase of pulmonary embolism ensued with increased duration of last admission in all groups (Fig. 2). Cancer occurred in approximately 7% of all patients, evenly distributed among groups. Cancer did not seem to affect frequency of pulmonary embolism if MI or RHE were the underlying cause of death. Figures were small and are not given.
30
...... RH£ ...... OMI .... AOMI
.... AMI
O~--<~1---------->-1~<-5~------~>5 DAYS IN HOSPITAL
Fig. 2. Pulmonary embolism according to duration of last admission. The chronic heart diseases (OMI, RHE) showed a significantly higher frequency in pulmonary embolism compared with AMI and AOMI irrespective of duration of last admission. < 1 day: AMI + AOMI versus OMI + RHE X2 = 14.85 P < 0.0005 AMI + AOMI versus 1-5 days: X2 = 36.06 p < 0.0005 OMI + RHE AMI + AOMI versus > 5 days: X2 = 35.16 p < 0.0005 OMI + RHE
Discussion Deep calf vein thrombosis is the most frequent origin of pulmonary embolism4 . Stasis in the veins of the lower limbs is presumed to facilitate deep calf vein thrombosis 12,13. Chronic heart diseases like OMI and RHE are often accompanied by heart failure, resulting in slowed blood flow, venous stasis and edema in the lower limbs. It is therefore plausible to suggest that these factors including venous stasis are to a large extent responsible for the high frequency of pulmonary embolism in the two chronic disorders. Havig4 found no association between chronic cardiovascular disease and pulmonary embolism, but his series with this patient category was limited to 44 cases. The frequency of pulmonary embolism was high in the early sixties (23 %). However, there has been a substantial decrease in frequency since then. The decline in frequency could be due to better treatment of heart failure. From about 1955 onwards the medical treatment of cardiovascular disease was changed in many ways in the hospital. The changes were threefold: Improved formulations of well-known drugs, introduction of drugs offering new ways of treatment and, last but not least, profoundly altered principles of general care and rules of living for cardiac patients. These developments have continued until now and new diagnostic methods have made therapy more differentiated. The time periods in which major changes in diagnostic procedures, training and medication took place, are roughly indicated in Figs. 3 and 4. The gradual replacement of the old standard preparation of dried digitalis leaves with the chemically welldefined drug components digitoxin and digoxin allowed for a more precise dosage. Measurements of blood concentration of these drugs became practically possible as routine from about 1975 onwards. These achievements along with better application of nitroglycerol and the use of diuretics significantly improved treatment of cardiac failure. The introduction of new classes of drugs like the beta-blocking and the calcium-blocking agents led to an improved control of many forms of cardiac arrhythmias as has the improvement of pacemakers. As a result of introducing Marevan (dicumarol) as the preferred anticoagulant in place of Trombantin (phenylindandion), the stability of anticoagulant effect at defined therapeutic levels became more secure. Also the introduction around 1960 of a new test to control dosage safe-guarded the efficacy of this treatment. The use of anticoagulant drugs in the treatment of AMI has, however, never been quite consistent, though routinely employed in
Pulmonary Embolism· 1061
-----------------------------------------------------------------------------1955
immobilization invasive diagnostic procedures ECG mobilization scintigraphy permanent pacemaker active training information on risk factors drug concentration blood ultra sound
1970
1965
1960
--- ---
1975
1980
1984
-------------------------------------
-- --
---
------
becoming routine going out of routine
1955
1960
1965
folia digitalis digitoxin/digoxin nitroglycerol sublingual nitroglysecerol durettes nitroglycerol infusion thiazides mercury diuretics ~-blockers
--
Ca blocking agents phenylindandion dicumarol heparin streptokinase
(?)
1970
--
---
1975
1980
1984
-------------------------
- - - - - - - - - - -----------------------------
becoming routine going out of routine Fig. 3. Introduction of diagnostic procedures and treatment at Haukeland hospital 1955 to 1984. - Fig. 4. Introduction and termination of drug treatment at Haukeland hospital 1955 to 1984.
cases complicated with cardiac arrhythmias. The use of heparin as an anticoagulant was standard in the treatment of deep vein thrombosis throughout most of the period, but the i.v. drip infusion method only became employed routinely in the later part. Presumably as important to consider in relation to thromboembolic risk is the influence of fundamental changes in the standard therapeutic regimen in myocardial infarction, both in the acute phase and in the longer run. Until about 1955 patients with acute myocardial infarction were confined to bed for weeks, and resumption of physical activity was very guarded and slow. In stark contrast, 20 years later these patients were mobilized as soon as the acute event had passed, often only after a few days according to judgment of individual cardiovascular
risk. The development of this drastic change in general treatment took place gradually and cautiously from about 1960 to 1970. Since then most of these patients have been individually advised on an active training program and have been given detailed information as to future lifestyle and risks. Almost simultaneously a popular campaign to influence peoples' lifestyles gained momentum, including advice to stop smoking, to reduce fat and salt intake and enjoy a proper measure of regular physical activity. To sum up we think it is fair to assume that most of the changes in the medical treatment of cardiovascular disease reduced the risk of thromboembolic complications, among them pulmonary embolism. To point out any single factor as the most important in this respect is difficult, though the prolonged bed rest practised as the best cure in acute
1062 . B. Karwinski, S. Seim and E. Svendsen
myocardial infarction at the beginning of the observation period probably represented an increased risk of thromboembolic complications. Early mobilization and introduction of anticoagulant treatment between 1955 and 1975 may explain the significant drop in pulmonary embolism during this period among patients with AMI. The increase in pulmonary embolism in AMI from 1975 onwards is difficult to explain and may be only apparent. But doubts as to the usefulness of anticoagulant therapy in this condition were increasing in this period. Advanced age has been put forward as an important risk factor for pulmonary embolism4, 7. This work supports this view, although patients with RHE indicate a trend to the opposite. RHE seems to represent a strong risk factor for pulmonary embolism, which may overshadow the age factor. However, number in the RHE group is small. Why a low frequency of pulmonary embolism in patients with AMI? On average the duration of last admission was similar in these and in patients with OMI, but somewhat shorter than for RHE patients. AMI represents a state with increased risk of thrombosis 8,9 which could affect deep calf vein thrombosis. However, the endurance of heart failure is short in AMI patients who succumb, whereas in patients with OMI and RHE heart failure may have lasted for a long time prior to hospitalization. This may have significance for onset of deep calf vein thrombosis and pulmonary embolism. Conceivably the improved treatment of cardiac failure is mainly responsible for the decrease in pulmonary embolism during the period studied. A similar decrease has not been observed among cancer patients 6, 10. All other patients in this autopsy series with underlying death causes other than cardiovascular ones, had pulmonary embolism in 8.5% in 1960-1964 and exactly the same percentage in 1980-1984. In conclusion this work demonstrates the frequency of pulmonary embolism in patients dying of the most common heart diseases. Chronic heart diseases like RHE and OMI imply an increased risk of pulmonary embolism, compared with AMI and AOMI, irrespective of duration of last admission. Since 1960 pulmonary embolism has
significantly decreased in patients dying of chronic heart disease. This coincides with major progress in the treatment of cardiac failure.
References 1 Coon WW, Coller FA (1969) Clinicopathologic correlation in thromboembolism. Surg Gynecol Obstet 109: 259-269 2 DalenJE, Dexter L (1969) Pulmonary embolism. JAMA 207: 1505-1507 3 Hartveit F (1979) Autopsy findings in cases with clinically uncertain cancer diagnosis. J Pathol129: 111-119 4 Havig 0 (1977) Deep vein thrombosis and pulmonary embolism. Chapter IV: Pulmonary embolism. Acta Chir Scand (supp!. 478): 24-76 5 Israel HL, Goldstein F (1957) The varied clinical manifestation of pulmonary embolism. Ann Intern Med 47: 202-226 6 Karwinski B, Svendsen E (1989) Comparison of clinical and post-mortem diagnosis of pulmonary embolism. J Clin Pathol42: 135-139 7 Linder F, Schmitz W, Encke A, Trede M, Storch HH (1967) A study of 605 fatal pulmonary embolism and two successful embolectomies. Surg Gynec Obstet 125: 82-86 8 Meade TW, North WRS, Chakrabarti R, Haines AP, Stirling Y (1977) Population-based distributions of hemostatic variables. Br Med Bull 33: 283-288 9 Meade TW, Mellows S, Brozovic M, Miller GJ, Chakrabarti RR, North WRS, Haines AP, Stirling Y, Imeson JD, Thompson SG (1986) Haemostatic function and ischemic heart disease: Principal results of the Northwick Park heart study. Lancet I: 533-537 10 Svendsen E, Karwinski B (1989) Prevalence of pulmonary embolism at necropsy in patients with cancer. J Clin Pathol 42: 805-809 11 Svendsen E, Karwinski B, Aardal E (1991) Frequency of pulmonary embolism in patients with circulatory disturbances of the lower limb or intestine. An autopsy study. Path Res Pract 187: 267-327 12 Wessler S, Yin ET (1969) On the mechanism of thrombosis. In: Brown EB, More CV (Eds) Progress Haematology. New York, Grune and Stratton 6: 201-231 13 Wessler S (1962) Thrombosis in the presence of vascular stasis. Amer J Med 33: 648-666
Received December 21, 1992 . Accepted February 25, 1993
Key words: Pulmonary embolism - Myocard infarction - Rheumatic disease Dr. Einar Svendsen, Department of Pathology, The Gade Institute, 5021 Bergen, Norway
Pulmonary Embolism and Heart Disease An Autopsy Study B. Karwinski and E. Svendsen Department of Pathology, The Gade Institute, University of Bergen, Norway
S. Seim Medical Department, University of Bergen, Norway
SUMMARY
The frequency of pulmonary embolism in patients with myocardial infarction (MI) and chronic rheumatic heart disease (RHE) has been investigated in an autopsy series. The series comprised 21530 hospital autopsies from 1960 to 1984. Altogether 5351 patients with MI and 289 patients with RHE as underlying death cause were selected for this study. Patients with RHE or old myocardial infarction (aMI) had a significantly higher frequency of pulmonary embolism than patients with acute myocardial infarction (AMI) or acute and old myocardial infarction combined (AOMI). This was true irrespective of duration of stay in the hospital during last admission. The frequency of pulmonary embolism decreased in patients with aMI or RHE from 1960 to 1984 suggestive of better therapy of chronic heart failure. A similar trend was seen in patients with AMI during a period with consistent anticoagulation treatment.
Introduction Pulmonary embolism is a life-threatening disorder, which has been underestimated as shown in a number of reports 1,2,5,6. Previously we have shown the frequency of pulmonary embolism to be elevated in patients dying from cancer compared with other death causes lO • The frequency varied among different types of cancer 10 • Previous work has likewise shown that circulatory disturbances of the lower limbs drastically increased the risk of pulmonary embolism ll . We now report the frequency of pulmonary embolism in patients dying due to myocardial infarction (MI) and to rheumatic heart disease (RHE), autopsied from 1960 to 1984 inclusive at Haukeland Hospital. 0344-0338/93/0189-1058$3.50/0
Material and Methods Patients with MI and RHE were selected from our autopsy files from 1960 to 1984 inclusive. During these 25 years 21530 hospital autopsies were performed in the department. Forensic cases are not included. All internal viscera were examined. The pulmonary arteries were routinely opened to the segmental level. The autopsy record of the department has been described in detail previously3. In altogether 5351 patients MI was the underlying death cause, whereas 289 patients died due to RHE. As we were interested to see how various heart diseases had an influence upon the frequency of pulmonary embolism, only patients with the respective diseases as underlying cause of death were selected. This made the material better suitable for grouping and for comparison between and within groups. Patients with MI were subdivided into 3 groups, those with solely acute myocardial infarction © 1993 by Gustav Fischer Verlag, Stuttgart
Pulmonary Embolism· 1059 (AMI), with old myocardial infarction (OMI) or with acute and old myocardial infarction combined (AOMI). In all 3 subdivided groups and in patients with RHE, age, duration of last admission and the significance of cancer were paid attention to with regard to pulmonary embolism. The highest median age within the groups (72 years among OMI patients) was arbitrarily chosen and the frequency of pulmonary embolism below and beyond this age examined. All pulmonary emboli were macroscopical findings. Only exceptionally the diagnosis of pulmonary embolism was established from an incidental microscopical finding in lung sections. In all the examined categories of cardiac diseases, groups of 5 -year intervals were established to see if the frequency of pulmonary embolism had changed during the observation period. CHF was used for statistical evaluation.
25
__ RHE ..... OMI
E
-<>-
Table 1. Heart diseases and pulmonary embolism (PE). Total material
AMI
en
m ::I
15
~
10
'" 0 ::I
.... J
Every fifth patient dying with RHE as underlying death cause had pulmonary embolism, a frequency significantly higher than in any of the subgroups of MI. Patients with AMI and AOMI as underlying death cause had the lowest frequency of pulmonary embolism in this study, significantly lower than OMI or RHE (Tables 1 and 2). Old age seemed to playa significant role with regard to pulmonary embolism. This was true in patients who succumbed due to AMI and AOMI, and patients with OMI showed a similar trend. An inverse trend was seen in patients with RHE, but the figures in the RHE group were small. Also patients with RHE, despite a significantly higher incidence of pulmonary embolism, were on average much younger than patients with MI (Table 3). The frequency of pulmonary embolism in 5-year intervals for each of the four groups is shown in Fig. 1. OMI
...... AOMI
20
::I
:::i 0
Results
Q.
5
Disorder
n
% PE
AMI OMI AOMI RHE
1823 1245 2283 289
5.9 13.9 6.3
21.1
AMI = acute myocardial infarction; OMI = old myocardial infarction; AOMI = acute and old myocardial infarction combined; RHE = rheumatic heart disease.
01+-19-6+0--6-4--19-6-+5--6-9--1-97--10---74--1-9-751---79--19:-::-:'80-84 YEARS
Fig. 1. Pulmonary embolism in 5-year intervals in patients with heart diseases. AMI, OMI, AOMI and RHE as in Table 1. Apart from AMI there is a significant drop in the frequency of pulmonary embolism from 1960 to 1984. In patients with AMI a significant transient drop is seen during 1970-1974. OMI + RHE: 1960-1964 versus 1980-1984 X2 = 6.72 P < 0.01 1960-1964 versus AOMI: 1980-1984 X2 = 5.77 P < 0.025 AMI: 1960-1964 versus 1980-1984 X2 = 0.05 NS AMI: 1970-1974 versus 1960-1969/1975-1984 X2 = 6.38 P < 0.025
Table 2. Comparison between different heart diseases with regard to pulmonary embolism (CH2)
RHE
AMI
OMI
AOMI
X2 = 61.31 p < 0.0005
X2 = 6.68 p < 0.01
X2 = 59.12 p < 0.0005
X2 = 47.26 p < 0.0005
X2 = 0.30 NS
AMI
X2 = 46.47 p < 0.0005
OMI AMI, OMI, AOMI and RHE as in Table 1.
Table 3. Median age with range and pulmonary embolism (PE)
All (years) With PE ca (years) < 72 years (n) < 72 years % PE > 72 years (n) > 72 years % PE
AMI (n = 1823)
OMI (n = 1245)
AOMI (n = 2283)
RHE (n = 289)
71 (25-97) 74 (49-92) 983 3.7 (36) 840 8.5 (71)
72 (16-96) 75 (46-96) 627 12.1 618 15.7
70 (34-99) 73 (39-94) 1338 5.3 (71) 945 7.7 (73)
64 (24-94) 62 (37-85) 216 23.0 73 15.3
AMI < 72 years versus> 72 years: X2 = 16.67 = P < 0.0005, AOMI < 72 years versus> 72 years: X2 = 4.81 = P < 0.05, AMI, OMI, AOMI and RHE as in Table 1.
1060 . B. Karwinski, S. Seim and E. Svendsen Table 4. Stay in Hospital during last admission, all patients and those with pulmonary embolism (PE) AMI (n = 1823)
OMI
(n = 1245)
AOMI (n = 2283)
RHE
(n = 289)
All (days)
2 (1-365)
2 (1-365)
2 (1-365)
5 (1- 94)
With PE (days)
8 (1-120)
10 (1-365)
10 (1-365)
8 (1-174)
AMI, OMI, AOMI and RHE as in Table 1.
and RHE showed a significant decrease in frequency over the years. The same was also seen in patients with AMI from 1970 to 1974, but this lowered frequency was not persistent. In patients with AOMI a steady decrease in frequency was observed. Patients with MI stayed on average only 2 days in the hospital during last admission. Patients with RHE stayed longer, on average 5 days. Patients with MI and pulmonary embolism stayed 8 to 10 days, similar to the RHE patients with pulmonary embolism (Table 4). When patients were grouped according to equal duration of last admission a clearly higher frequency was nevertheless seen among patients with RHE and OMI compared with AMI and AOMI. A significant increase of pulmonary embolism ensued with increased duration of last admission in all groups (Fig. 2). Cancer occurred in approximately 7% of all patients, evenly distributed among groups. Cancer did not seem to affect frequency of pulmonary embolism if MI or RHE were the underlying cause of death. Figures were small and are not given.
30
...... RH£ ...... OMI .... AOMI
.... AMI
O~--<~1---------->-1~<-5~------~>5 DAYS IN HOSPITAL
Fig. 2. Pulmonary embolism according to duration of last admission. The chronic heart diseases (OMI, RHE) showed a significantly higher frequency in pulmonary embolism compared with AMI and AOMI irrespective of duration of last admission. < 1 day: AMI + AOMI versus OMI + RHE X2 = 14.85 P < 0.0005 AMI + AOMI versus 1-5 days: X2 = 36.06 p < 0.0005 OMI + RHE AMI + AOMI versus > 5 days: X2 = 35.16 p < 0.0005 OMI + RHE
Discussion Deep calf vein thrombosis is the most frequent origin of pulmonary embolism4 . Stasis in the veins of the lower limbs is presumed to facilitate deep calf vein thrombosis 12,13. Chronic heart diseases like OMI and RHE are often accompanied by heart failure, resulting in slowed blood flow, venous stasis and edema in the lower limbs. It is therefore plausible to suggest that these factors including venous stasis are to a large extent responsible for the high frequency of pulmonary embolism in the two chronic disorders. Havig4 found no association between chronic cardiovascular disease and pulmonary embolism, but his series with this patient category was limited to 44 cases. The frequency of pulmonary embolism was high in the early sixties (23 %). However, there has been a substantial decrease in frequency since then. The decline in frequency could be due to better treatment of heart failure. From about 1955 onwards the medical treatment of cardiovascular disease was changed in many ways in the hospital. The changes were threefold: Improved formulations of well-known drugs, introduction of drugs offering new ways of treatment and, last but not least, profoundly altered principles of general care and rules of living for cardiac patients. These developments have continued until now and new diagnostic methods have made therapy more differentiated. The time periods in which major changes in diagnostic procedures, training and medication took place, are roughly indicated in Figs. 3 and 4. The gradual replacement of the old standard preparation of dried digitalis leaves with the chemically welldefined drug components digitoxin and digoxin allowed for a more precise dosage. Measurements of blood concentration of these drugs became practically possible as routine from about 1975 onwards. These achievements along with better application of nitroglycerol and the use of diuretics significantly improved treatment of cardiac failure. The introduction of new classes of drugs like the beta-blocking and the calcium-blocking agents led to an improved control of many forms of cardiac arrhythmias as has the improvement of pacemakers. As a result of introducing Marevan (dicumarol) as the preferred anticoagulant in place of Trombantin (phenylindandion), the stability of anticoagulant effect at defined therapeutic levels became more secure. Also the introduction around 1960 of a new test to control dosage safe-guarded the efficacy of this treatment. The use of anticoagulant drugs in the treatment of AMI has, however, never been quite consistent, though routinely employed in
Pulmonary Embolism· 1061
-----------------------------------------------------------------------------1955
immobilization invasive diagnostic procedures ECG mobilization scintigraphy permanent pacemaker active training information on risk factors drug concentration blood ultra sound
1970
1965
1960
--- ---
1975
1980
1984
-------------------------------------
-- --
---
------
becoming routine going out of routine
1955
1960
1965
folia digitalis digitoxin/digoxin nitroglycerol sublingual nitroglysecerol durettes nitroglycerol infusion thiazides mercury diuretics ~-blockers
--
Ca blocking agents phenylindandion dicumarol heparin streptokinase
(?)
1970
--
---
1975
1980
1984
-------------------------
- - - - - - - - - - -----------------------------
becoming routine going out of routine Fig. 3. Introduction of diagnostic procedures and treatment at Haukeland hospital 1955 to 1984. - Fig. 4. Introduction and termination of drug treatment at Haukeland hospital 1955 to 1984.
cases complicated with cardiac arrhythmias. The use of heparin as an anticoagulant was standard in the treatment of deep vein thrombosis throughout most of the period, but the i.v. drip infusion method only became employed routinely in the later part. Presumably as important to consider in relation to thromboembolic risk is the influence of fundamental changes in the standard therapeutic regimen in myocardial infarction, both in the acute phase and in the longer run. Until about 1955 patients with acute myocardial infarction were confined to bed for weeks, and resumption of physical activity was very guarded and slow. In stark contrast, 20 years later these patients were mobilized as soon as the acute event had passed, often only after a few days according to judgment of individual cardiovascular
risk. The development of this drastic change in general treatment took place gradually and cautiously from about 1960 to 1970. Since then most of these patients have been individually advised on an active training program and have been given detailed information as to future lifestyle and risks. Almost simultaneously a popular campaign to influence peoples' lifestyles gained momentum, including advice to stop smoking, to reduce fat and salt intake and enjoy a proper measure of regular physical activity. To sum up we think it is fair to assume that most of the changes in the medical treatment of cardiovascular disease reduced the risk of thromboembolic complications, among them pulmonary embolism. To point out any single factor as the most important in this respect is difficult, though the prolonged bed rest practised as the best cure in acute
1062 . B. Karwinski, S. Seim and E. Svendsen
myocardial infarction at the beginning of the observation period probably represented an increased risk of thromboembolic complications. Early mobilization and introduction of anticoagulant treatment between 1955 and 1975 may explain the significant drop in pulmonary embolism during this period among patients with AMI. The increase in pulmonary embolism in AMI from 1975 onwards is difficult to explain and may be only apparent. But doubts as to the usefulness of anticoagulant therapy in this condition were increasing in this period. Advanced age has been put forward as an important risk factor for pulmonary embolism4, 7. This work supports this view, although patients with RHE indicate a trend to the opposite. RHE seems to represent a strong risk factor for pulmonary embolism, which may overshadow the age factor. However, number in the RHE group is small. Why a low frequency of pulmonary embolism in patients with AMI? On average the duration of last admission was similar in these and in patients with OMI, but somewhat shorter than for RHE patients. AMI represents a state with increased risk of thrombosis 8,9 which could affect deep calf vein thrombosis. However, the endurance of heart failure is short in AMI patients who succumb, whereas in patients with OMI and RHE heart failure may have lasted for a long time prior to hospitalization. This may have significance for onset of deep calf vein thrombosis and pulmonary embolism. Conceivably the improved treatment of cardiac failure is mainly responsible for the decrease in pulmonary embolism during the period studied. A similar decrease has not been observed among cancer patients 6, 10. All other patients in this autopsy series with underlying death causes other than cardiovascular ones, had pulmonary embolism in 8.5% in 1960-1964 and exactly the same percentage in 1980-1984. In conclusion this work demonstrates the frequency of pulmonary embolism in patients dying of the most common heart diseases. Chronic heart diseases like RHE and OMI imply an increased risk of pulmonary embolism, compared with AMI and AOMI, irrespective of duration of last admission. Since 1960 pulmonary embolism has
significantly decreased in patients dying of chronic heart disease. This coincides with major progress in the treatment of cardiac failure.
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Received December 21, 1992 . Accepted February 25, 1993
Key words: Pulmonary embolism - Myocard infarction - Rheumatic disease Dr. Einar Svendsen, Department of Pathology, The Gade Institute, 5021 Bergen, Norway