Pulmonary Pulsus Alternans in Acute Myocardial Infarction
LOPEZ-SENDON, MD ISABEL COMA-CANELLA, MD LUIS MARTIN JADRAQUE, MD ISIDORO GONZALEZ MAQUEDA, MD
JO&
Madrid, Spain
From the Coronary Care Unit, Department of Medicine, Residencia Sanitaria La Paz, Universidad Autbnoma de Madrid, Madrid, Spain. Manuscript received March 16, 1978; revised manuscript received f&y 30, 1978, accepted May 31, 1978. Address for reprints: Jose Lopez-Sendon, MD, C. Juan Ramon Jimenez 2, 4” 8. Madrid 16. Spain.
A total of 100 consecutive patients with acute myocardial infarction were studied with hemodynamic monitoring. Five groups were established: A, all eight patients with pulmonary pulsus alternans; B, the four patients in group A who did not die; C, the four patients in group A who died in the coronary care unit; D, control patients with heart failure, but without pulmonary alternans; and E, patients in group A who underwent hemodynamic studies just before (five patients) the appearance of pulmonary pulsus alternans and six patients studied just after its disappearance. Patients in group A had a smaller cardiac index (2P < O.OOS),stroke index (2P < 0.05), left ventricular stroke work index (2P < 0.01) and higher pulmonary resistance levels (2P < 0.005) than patients in control group D. They also had a smaller cardiac index (2P < 0.005) and higher pulmonary resistance (2P < 0.05) levels than patients in group E. Patients in group B had a higher stroke index (2P < 0.05), left ventricular stroke work index and left ventricular net work index (2P < 0.01) than patients in group C. Appearance of pulmonary pulsus alternans accompanied a decrease in cardiac index and an increase in pulmonary pressure and resistance levels. Its disappearance sometimes followed a drug-induced decrease in pulmonary pressure and resistance levels, and an increase in cardiac index. On other occasions it occurred after the administration of inotropic agents (digoxin or dopamine), without changes in pulmonary pressure. Pulmonary pulsus alternans in acute myocardial infarction may appear under two conditions: (1) right ventricular strain secondary to left heart failure; and (2) impaired right ventricular contractility. Mortality was greater in group A than in group D (2P < 0.05). Patients in group C were in worse condition than those in group B. Therefore, the prognosis depends on the degree of heart failure and not on the pulmonary pulsus alternans itself.
Mechanical (pulsus) alternans is in most cases an index of ventricular failure.i-5 It is a frequent finding in various heart diseases, including aortic stenosis,s,4*e17 cardiomyopathies2T6s and chronic ischemic heart disease.s.8 The alternans in pulmonary pressure is a less frequent finding than systemic alternans.3,s It was first described in detail by Rabago et al.1° in a patient with an interatrial septal defect, and later by Ferrer et all in several cases of mitral stenosis and heart failure. In several studies it was related to pulmonary embolism,g cardiomyopathieslg and other At the same time, it was demcauses of right ventricular strain. 1,g~11~12 onstrated that mechanical alternans does not necessarily occur simultaneously in both the systemic and pulmonary circulations.1,2s8J3 We have not found any reference to pulmonary pulsus alternans in acute mvocardial infarction. In this renort we nresent the clinical and hemodynamic significance of this condition, as well as the cause of its appearance and its prognostic value during acute myocardial infarction.
October 1978
The American Journal of CARDIOLOGY
Volume 42
577
PULMONARY
ALTERNANS
IN MYOCARDIAL
INFARCTION-LOPEZ-SENDON
ET AL
TABLE I Clinical and Hemodynamic Evolution in Eight Patients With Pulmonary Pulsus Alternans Hemodynamic Subset
PPA
PTP
Cl
TPR
Clinical Subset
Yes No
46-32/25- 15 22173
2.7 3.0
a00 427
C-II C-II
H-II H-l
Nitroglycerin
Yes Yes No
44-36127 37-33178 26115
1.9 2.3 3.2
7737 a35 475
C-II C-II C-l
H-IV H-II H-l
Ph&tolamine Phentolamine
Yes Yes Yes No Yes Yes No
63-49136-37 48-42123-20 59-5 1127-23 49122 50-47124 40-36120 43120
2.1 2.5 1.7 2.7 2.1 2.4 2.9
7600 864 7647 978 7226 867 763
C-II C-II C-II C-II C-II C-II C-II
H-IV H-II H-IV H-II H-IV H-II H-II
&;oprusside Nitroprusside Dopamine i- nitroprusside lsosorbide dinitrate lsosorbide dinitrate -k digoxin lsosorbide dinitrate + digoxin
No Yes No
50130 47-43123 40120
2.8 2.3 2.4
1057 7043 900
C-II C-II C-II
H-II H-II H-II
iioiorbide dinitrate lsosorbide dinitrate -I digoxin
5*+
Yes No
67-63135 60130
2.0 2.1
7800 7524
C-II C-II
H-IV H-IV
Dopamine
6*+
No Yes Yes Yes Yes Yes Yes Yes No
45126 49-39130123 3a-32121-79 43-37128-26 58-38137-27 45-35/22- 76 53-47130-26 57-57129 48133
2.5 1.6 2.2 2.3 7.5 7.7 7.6 7.7 7.8
1073 1634 909 1078 7884 1271 1750 1756 7689
C-II C-IV C-IV C-IV C-IV c-iv C-IV C-IV C-IV
H-II H-IV H-II H-II H-IV H-IV H-IV H-IV H-IV
bhentolamine Dopamine i- phentolamine Dopamine + phentolamine Phentolamine Phentolamine Phentolamine + dopamine Dopamine Dopamine (large doses)
7’
No Yes
46127 52-48133
7.8 1.5
7467 2028
C-II C-IV
H-IV H-IV
bbbamine
a*+
No Yes
45130 30-24119-77
2.4 1.9
7767 a84
C-IV C-IV
H-II H-IV
NGoglycerin
Case no. 1 2
3
4
Drugs
Patient died. + Autopsy performed. Cl = cardiac index (literslmin per m*); PPA = pulmonary pulsus alternans; PTP = pulmonary trunk pressure (mm Hg); TPR = total pulmonary resistance (dynes set cmw51m2). l
Materials
and Methods
Patients: Between August 1 and December 23,1977, a total of 120 patients with acute myocardial infarction were admitted to the “La Paz” coronary care unit. Hemodynamic monitoring was performed in 100 of these patients. It was not performed for a variety of reasons in the remaining 20 patients, but none of these showed clinical heart failure or low cardiac output. The diagnosis of acute myocardial infarction was determined using well known clinical, electrocardiographic and laboratory criteria.l* All of the patients were admitted within the first 24 hours of evolution. In each patient we studied the clinical features, classifying the patients according to Forrester’s method’s in the following subsets: C-I: no evidence of pulmonary congestion or peripheral hypoperfusion. C-II: pulmonary congestion only. C-III: hypoperfusion only. C-IV: both pulmonary congestion and hypoperfusion. Hemodynamic data: Right heart catheterization was performed on admission by inserting a Swan-Ganz thermodilution catheter into the pulmonary trunk through the right antecubital vein. Right atrial, pulmonary arterial and pul-
578
October 1978
The American Journal of CARDIOLOGY
monary capillary wedge pressures were recorded through a Hewlett-Packard 1280 transducer, with a Siemens Elema Mingograph 34, at a paper speed of 25 mm/set. Cardiac output was determined with the thermodilution technique, using an Edwards 9500 computer. In every case, at least three successive determinations were made, and the average value was calculated. We followed Forrester’s method,15 classifying the hemodynamic studies in four subsets: H-I: pulmonary capillary wedge pressure 18 mm Hg or less and cardiac index 2.2 liters/min per m2 or greater. H-II: pulmonary capillary wedge pressure more than 18 mm Hg and cardiac index more than 2.2 liters/min per m ? H-III: pulmonary capillary wedge pressure 18 mm Hg or less and cardiac index 2.2 liters/min per m2 or less. H-IV: pulmonary capillary wedge pressure more than 18 mm Hg and cardiac index 2.2 liters/min per m2 or less. Arterial blood pressure was measured with an arm cuff and expressed in mm Hg. Hemodynamic values were calculated according to the following formulas16J7: CI = CO/BSA, where CI is cardiac index in liters/min per m2, CO is cardiac output in liters/min and BSA is body surface area in m2; SI = CI/HR, where SI is stroke index in ml/beat per m* and HR is heart rate in beats/min; TPR = 80 (PTP/CI), where TPR is total pulmonary resistance in dynes set cm-“/m”, 80 is the conversion
Volume 42
PULMONARY
ALTERNANS
IN MYOCARDIAL
INFARCTION-LOPEZ-SENDON
ET AL.
(mean f standard deviation) for All Hemodynamic Variables in Every Group and Statistical Significance of Differences Between Groups GroupA I1 9 studies) HR I%
85.1 f
17.5
Group B 19 studies)
Group C (10 studies)
80.1 f
90.0 f
17.8
17.1
Group D (30 studies) 86.6 f
16
Group E
t 11 studies) 87.9 f
16.0
Avs. D
2P values Avs. t
Bvs.C
NS
NS
NS
31.5 23.4 11 f 6.4 6.6 4.3
30.3 20.8 8.8 f 5.8 7.0 7.3
32.6 24.9 13.0 f 5.3 4.0 7.0
30.4 23.9 9.6 f 4.0 4.06 7.3
20.7 29.7 8.5 f 5.6 5.1 7.3
/:
NS ;:
NS K
:P SbR
77.8 2.04 f 0.36 16.6 1319 24.8 f 424 5.8
85.1 2.17 f 0.31 13.7 1113 28.2 f 324 6.7
1.92 75 f 0.42 17.8 1505 21.9 f 432 2.5
90.3 2.62 f 0.63 15.9 31.1 927 f 245 10.9
79.5 2.5 f 0.5 15.7 1041 29.2 f 428 8.2
!:25 0.005 0.05 0.005
::05 K5
K5 0.05
LVSWI
31.5 24.7 0.76 9.9
38.6 31.9 0.81 12.2
25.2 18.3 0.71 7.8
45.7 36.0 0.78 13.2
38.1 28.0 0.75 11.6
0.01 0.02 NS NS
NS NS NS NS
Kl 0:01 0.01 NS
LVNWI LVNWIILVSWI RVNWI
f 10.7 f 11 f 0.10 f 3.7
f 11.1 f 11.4 f 0.1 f 2.5
f f f f
5.3 5.5 0.08 3.3
f 18.8 f 16.3 f 0.06 f 4.1
f 13.4 f 13.5 f 0.08 f 3.2
BP = blood pressure (mm Hg); Cl = cardiac index (literslmin per m * &, _ = heart rate (beatsjmin); LVNWI = left ventricular n-work index (g-m/beat . HR per m*); LVSWI = left veaular stroke work index (g-m/beat per m ); PCP = mean pulmonary capillary pressure (mg Hg); PTP = mean pulmonary trunk pressure (mm Hg); RAP = right atrial pressure (mm Hg); RVNWI = right ventricular net work index (g-m/beat per m*); SI = stroke index (ml/beat per m*); SWI = stroke work index (g-m/beat per m*); TPR = total pulmonary resistance (dynes set cme5/m2).
factor to dynes set cmp5 and PTP is rn-ulmonary trunk pressure in mm Hg; LVSWI = SI X ASP X 0.0136, where LVSWI is left ventricular stroke work index in g-m/beat per m2, ASP is mean aortic systolic pressure in mm Hg and 0.0136 the conversion factor from mm Hg/ml to g; ASP = 0.8 (aortic systolic- - aortic - diastolic) + aortic diastolic pressure; LVNWI = SI (ASP - PCP) X 0.0136, where LVNWI is left ventricular net work index in g-m/beat per m2 and pep is mean pulmonary capillary pressure in mm Hg; LVNWI/LVSWI; RVNWI = SI (PSTP - RAP) X 0.0136, where RVNWI is right ventricular net work index in g-m/beat per m2, mis mean right atria1 pressure in mm Hg and PSTP is mean pulmonary systolic trunk pressure. Pulmonary pulsus alternans: This was defined as the alternation of strong and weak peak systolic pulmonary pressure in the presence of regular rhythm and in the absence of respiratory movements. We excluded patients with pulmonary pulsus alternans who also had the following: (1) valve disease (one patient with aortic stenosis); (2) major arrhythmias (two patients with ventricular tachycardia); or (3) false pulmonary pulsus alternans, such as the alternans that may accompany significant variations in rhythm, or is induced by atria1 contractions in cases of external cardiac pacing or atrioventricular dissociation. We found eight patients with pulmonary pulsus alternans. Their age was 62.2 f 10.7 years (mean f standard deviation). None had chronic obstructive lung disease. The following groups were established: Group A: all eight patients with pulmonary pulsus alternans. From their studies we selected 19 different hemodynamic studies in which pulmonary alternans was present. These were separated by a minimal interval of 12 hours and showed significant changes in some of the measured values. Group B: the four patients in group A who did not die in the coronary care unit (nine hemodynamic studies). Group C: the four patients in group A who died while in the coronary care unit (10 hemodynamic studies). Group D: control group of patients with 30 hemodynamic studies chosen at random from all patients without pulmonary alternans but included in subsets H-II and H-IV of Forrester’s classification. Group E: patients in group A who had hemodynamic measurements just before the appearance (five patients) or
just after the disappearance (six patients) of pulmonary pulsus alternans (total of 11 hemodynamic studies). We statistically compared the mean values of each hemodynamic measurement in groups A and D, A and E, and B and C, using Students’ t test (2P values).
Results Clinical data: All eight patients with pulmonary pulsus alternans had clinical left heart failure (Table I). Six patients were in clinical subset C-II and two in C-IV. Five patients had clinical right heart failure, and one of them had pulmonary thromboembolism. HemOdynamic data (Tables I and II): All 19 hemodynamic studies in group A (eight patients) showed pulmonary capillary pressure greater than 18 mm Hg; 12 studies were classified in subset H-IV and 7 in subset H-II. Patients in group A had lower values for blood pressure (2P < 0.025), cardiac index (2P < 0.005), stroke index (2P < 0.05), left ventricular stroke work index (2P < 0.01) and left ventricular net work index (2P < 0.02) and higher values for total pulmonary resistance (BP < 0.005) than patients in group D (control). Patients in group A had statistically smaller values for cardiac index (2P < 0.005) and higher values for pulmonary resistance (2P < 0.05) than patients in group E. When comparing group B (nonfatal pulmonary pulsus alternans) with group C (fatal pulmonary pulsus alternans) we observed that group B had higher values for stroke index (2P < 0.05), left ventricular stroke work index (LVSWI) (2P < 0.01) and left ventricular net work index (LVNWI) (2P < 0.01). The ratio LVNWULVSWI was smaller in group C (2P < 0.01). The more interesting data for each hemodynamic study in group A are shown in Table I, as well as the hemodynamic data and clinical classification before the appearance of pulmonary alternans and after its disappearance (Group E), if available. In five patients the pulmonary trunk pressure and cardiac index were known before the pulmonary alternans was present. Note that pulmonary trunk pressure may be increased
October 1978
The American Journal of CARDIOLOGY
Volume 42
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PULMONARY ALTERNANS IN MYOCARDIAL INFARCTION-LOPEZ-SENDON
or decreased when pulmonary alternans appears, but cardiac index always decreases and total pulmonary resistance usually increases (Fig. 1). The disappearance of pulmonary pulsus alternans could be studied in six patients, including four with clinical improvement. The changes associated with the disappearance of pulmonary pulsus alternans were less striking than those that accompanied the appearance of pulmonary alternans but generally included a more or less important decrease in pulmonary trunk pressure and total pulmonary resistance (Fig. 2) or an increase in cardiac index, or both (Fig. 3). In four patients the pulmonary alternans disappeared after the administration of inotropic drugs such as dopamine or digoxin, with or without significant changes in pulmonary trunk pressure and cardiac index (Fig. 1 and 3). In three other patients pulmonary alternans disappeared after treatment with several vasodilators, which produced an
ET AL.
important reduction in total pulmonary resistance values (Fig. 2). Mortality: Four patients with pulmonary pulsus alternans died in the coronary care unit (group C) (Table I)-two with cardiogenic shock (H-IV) and two with pulmonary edema (H-II). Postmortem studies, performed in three of these patients revealed ischemic lesions in both ventricles of all three. The mortality rate was higher in patients with pulmonary alternans than in the patients of control group D with left heart failure (16.7 percent) (2P < 0.05). Discussion Incidence: Mechanical alternans of the lesser circulation simultaneous with or independent of left heart alternans occurs in patients with isolated left heart diseases and heart failure,l or primary right heart diseases such as idiopathic pulmonary hypertensionll or
FIGURE 1. Case 6. Pulmonary alternans appears in B and is maximum in C, after an increase in total pulmonary resistance (TPR) and a decrease in cardiac index, with the same pulmonary trunk pressure (PTP). After administration of dopamine, pulmonary alternans diminishes in D and even disappears with high doses of dopamine (E). The patient had cardiogenic shock after the appearance of pulmonary alternans. Cl = cardiac index (liters/min per m*); PTP = pulmonary trunk pressure in mm Hg; TPR = total pulmonary resistance (dynes set cm-5/m2).
590
October 1979
The American Journal 01 CARDIOLOGY
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PULMONARY ALTERNANS IN MYOCARDIAL INFARCTION-LOPEZ-SENDON
pulmonary embolism.9 Sometimes the underlying disease is common to both ventricles, as in cardiomyopathies.2 Pulmonary pulsus alternans has been reported in patients with chronic ischemic heart diseaseas but not during acute myocardial infarction. The hemodynamic monitoring performed in almost all of our patients with acute myocardial infarction has proved that it is a frequent finding, appearing in at least 8 percent of patients. Clinical and hemodynamic significance: Every patient with pulmonary pulsus alternans showed clinical, radiologic and hemodynamic signs of left heart failure. This failure was more severe than in patients without pulmonary alternans, documented by the lower values for cardiac index, stroke index, stroke work index and net work index. These findings are in agreement with previous data1-5 associating mechanical alternans with heart failure. Even if it is possible to find mechanical alternans in people without heart disease, it occurs only in nonphysiologic conditions such as during arrhythmias or pacing at high rates.4Js,18,20 Significance during acute myocardial infarction: Two main mechanisms have been proposed to explain mechanical alternans: (1) the hemodynamic theory, based on Starling’s principle, which holds that alternation in diastolic volume or pressure or fiber length accounted for the alternating contractile force (increase preload preceding the more powerful beats7Jg,21p22);and (2) the myocardial theory, which holds that primary alternation in contractility of the whole or only part of the heart occurs in the absence of changes in ventricular diastolic vo1ume.6,8Js,2s,25We believe that mechanical alternans of the pulmonary pressure in acute myocardial infarction may appear under certain conditions: 1. Right ventricular strain secondary to left heart failure. A common finding in our patients with pulmonary pulsus alternans was severe left heart failure. It produced an increase in pulmonary resistance levels with corresponding overload to the right ventricle, with or without signs of right ventricular failure. Total pul-
ET AL.
monary resistance levels were higher in these patients than in those without alternans. In many patients, the appearance and disappearance of pulmonary alternans followed significant changes in hemodynamic measurements (pulmonary trunk pressure, cardiac index and total pulmonary resistance values). These changes were due to the intervention of preload- or afterloadreducing agents without direct inotropic action. Pulmonary pulsus alternans has been found in patients with primary pulmonary hypertension,‘i pul-
FIGURE 2. Case 1. Pulmonary pulsus altemans disappears 10 minutes after the sublingual administration of 0.6 mg of nitroglycerin (NG), with striking reduction in pulmonary pressures (PTP) and total pulmonary resistance (TPR). Abbreviations and units as in Figure 1.
PTP
FIGURE 3. Case 3. Pulmonary pulsus alternans (A) does not disappear after reduction of pulmonary pressure and resistance with nitroprusside (B) until dopamine is administered (C). Alternans appears again when the inotropic drug is discontinued (0) and is no longer present when the patient is given intravenous digoxin. Note that pulmonary trunk pressure is the same in magnitude from B to E. Abbreviations and units as in Figure 1.
October 1978
The American Journal of CARDIOLOGY
Volume 42
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PULMONARY ALTERNANS IN MYOCARDIAL INFARCTION--LOPEZ-SENDON
ET AL.
a complex phenomenon that can be modified by more than one factor, and may depend on hemodynamic as well as on direct inotropic conditions.2,4,1gJf Prognostic significance: Pulmonary pulsus alternans in acute myocardial infarction is associated with a very high mortality rate. Half of the patients died while in the coronary care unit. The mortality rate was higher than in control patients in the same hemodynamic classification but without pulmonary alternans (2P < 0.05). Mechanical alternans has previously been associated believe with a poor prognosis, s7,28 but other author&” that the severity of the underlying disease is what really determines the prognosis. Heart failure was more severe in patients with than in patients without pulmonary alternans; it was also more severe in the four patients with pulmonary alternans who died than in those who survived-another indication that the prognosis depends on the degree of heart failure.
monary thromboembolism,s as well as in patients with valve disease.lJs In every case, there was right ventricular strain (sometimes secondary to left heart failure) which could be the cause of pulmonary alternans. This could not be proved by others.” 2. Impaired right ventricular contractility: Five of the eight patients with pulmonary alternans had clinical right heart failure. This could have been secondary to left heart failure with right ventricular strain, or produced by direct ischemic involvement of the right ventricle. All of our patients with autopsy studies had some degree of right ventricular damage. The imbalance between oxygen supply and demand has already been proposed as one cause of mechanical alternans in aortic stenosis.3 In some of our patients, the pulmonary al,ternans disappeared after the administration of strong inotropic drugs such as dopamine or digoxin, without significant changes in pulmonary pressure, cardiac index or pulmonary resistance levels, but perhaps with improvement in right ventricular contractility. We believe that even in cases without clinical evidence of right heart failure pulmonary alternans may indicate decreased right ventricular contractility. All these findings are in accord with those observed alternans is by others1,2T5,18 and prove that pulmonary
Acknowledgment We gratefully acknowledge the assistance of Dr. J. Calderon Montero from the National School of Chest Diseases, Madrid, Spain in performing the statistical analyses.
References 1.
2.
3.
4. 5.
6.
7. 8. 9. 10.
11.
12. 13. 14.
582
Ferrer I, Harvey RM, Cournand A, et al: Cardiocirculatory stu&es in pulsus alternans of the systemic and pulmonary circulations. Circulation 14:163-174, 1956 Harris LC, Nghiem OX, Schreiber MH, et al: Severe pulsus alternans associated with primary myocardial disease in children. Circulation 34:948-961, 1966 Cooper T, Braunwald E, Morrow AG: Pulsus alternans in aortic stenosis. Hemodynamic observations in 50 patients studied by left heart catheterization. Circulation 18:64-70, 1958 Cohn KE, Sandler H, Hancock EW: Mechanisms of pulsus alternans. Circulation 36:372-379, 1967 Ryan JM, Schieve JF, Hull HB, et al: Experiences with pulsus alternans. Ventricular alternation and the stage of heart failure. Circulation 14:1099-1103, 1956 Swanton RH, Jenkins BS, Brooksby IA, et al: Pulsus alternans: force-velocity and angiographic volume analysis in man (abstr). Br Med J 37: 558, 1975 Gleason WL, Braunwald E: Studies on Starling’s law of the heart. Circulation 25:841-848. 1962 D’Cruz I, Cohen HC, Prabhu R, et al: Echocardiography in mechanical alternans. Circulation 54:97-102, 1976 Calick A, Berger S: Pulmonary artery pulsus alternans associated with pulmonary embolism. Chest 64:663-664, 1973 Rabago P, Kohout FW, Katz LN: An unusual case of pulsus alternans recorded during cardiac catheterization from the pulmonary and systemic blood vessels. Am Heart J 49:472-482, 1955 Meyer BL, Bogart DB, Carley J, et al: Pulmonary arterial pulsus alternans secondary to primary pulmonary hypertension. Chest 701374-377, 1976 Hashiba K. Katavama T. Takahashi A. et al: Pulsus alternans involving the right heart. Jpn Heart J 6:452-457, 1965 Desser KB, Benchimol A: Phasic left ventricular blood velocity alternans in man. Am J Cardiol 36:309-314, 1975 Killip T, Kimball JT: Treatment of myocardial infarction in a coronary care unit. A two year experience with 250 patients. Am J
October 1978
The American Journal of CARDIOLOGY
Cardiol 201457-464, 1967 15. Forrester JS, Diamond GA, Swan HJC: Correlative classification of clinical and hemodynamic function after acute myocardial infarction. Am J Cardiol 39:137-143, 1977 16. Yang SS, Bentivoglio LG, Maranhao V, et al: Cardiac Catheterization Data to Hemodynamic Parameters. Philadelphia, FA Davis, 1972, p 163 17. Russell RO, Rackley CE: Hemodynamic Monitoring in a Coronary Intensive Care Unit. New York, Futura Publishing, 1974, p 65 18. Leighton RF, Zaron SJ, Robinson JL: Left ventricular mechanical alternans in man: effects of atrial pacing and isoproterenol (abstr). Circulation 37. 38: SUDDI VI: VI-125. 1968 19. Mitchell JH, Sarnoff &I; Sonnenblick EH: The dynamics of pulsus alternans: alternating end-diastolic fiber length as a causative factor. J Clin Invest 42:55-63, 1963 20. Gilbert JL, Janse MJ, Lu HH, et al: Production and abolition of alternation in mechanical action of the ventricle. Am J Physiol 209:945-950, 1965 21. Wenckebach KF: Zur Analyze des unregelmassigen Pulsus. IV. Veber den Pulsus alternans. Z Klin Med 44:218-226, 1910 22. Straub H: Dynamik des Herzalternans. Dtsch Arch Klin Med 123:296-305, 1917 23. Wiggers CJ: Circulatory Dynamics. New York, Grune & Stratton, 1952, p 78 24. Hering HE: Zur Erklarung des Herzalternans. Z Exp Path Ther 12:235-242. 1913 25. Elessas A, Ryan TJ: A force-velocity analysis of pulsus alternans. Circulation 41, 42:Suppl Ill: 111-86-111-94,1970 26. Nayler WG, Robertson PGC: Mechanical alternans and the staircase phenomenon in dog papillary muscle. Am Heart J 70:494498, 1965 27. Cecil RL, Loeb RF: A Textbook of Medicine. Philadelphia, WB Saunders, 1959, p 1320 28. Bellett S Clinical Disorders of the Heart Beat, second edition. Philadelphia, Lea & Febiger, 1963, p 552
Volume 42
LOPEZ-SENDON, MD ISABEL COMA-CANELLA, MD LUIS MARTIN JADRAQUE, MD ISIDORO GONZALEZ MAQUEDA, MD
JO&
Madrid, Spain
From the Coronary Care Unit, Department of Medicine, Residencia Sanitaria La Paz, Universidad Autbnoma de Madrid, Madrid, Spain. Manuscript received March 16, 1978; revised manuscript received f&y 30, 1978, accepted May 31, 1978. Address for reprints: Jose Lopez-Sendon, MD, C. Juan Ramon Jimenez 2, 4” 8. Madrid 16. Spain.
A total of 100 consecutive patients with acute myocardial infarction were studied with hemodynamic monitoring. Five groups were established: A, all eight patients with pulmonary pulsus alternans; B, the four patients in group A who did not die; C, the four patients in group A who died in the coronary care unit; D, control patients with heart failure, but without pulmonary alternans; and E, patients in group A who underwent hemodynamic studies just before (five patients) the appearance of pulmonary pulsus alternans and six patients studied just after its disappearance. Patients in group A had a smaller cardiac index (2P < O.OOS),stroke index (2P < 0.05), left ventricular stroke work index (2P < 0.01) and higher pulmonary resistance levels (2P < 0.005) than patients in control group D. They also had a smaller cardiac index (2P < 0.005) and higher pulmonary resistance (2P < 0.05) levels than patients in group E. Patients in group B had a higher stroke index (2P < 0.05), left ventricular stroke work index and left ventricular net work index (2P < 0.01) than patients in group C. Appearance of pulmonary pulsus alternans accompanied a decrease in cardiac index and an increase in pulmonary pressure and resistance levels. Its disappearance sometimes followed a drug-induced decrease in pulmonary pressure and resistance levels, and an increase in cardiac index. On other occasions it occurred after the administration of inotropic agents (digoxin or dopamine), without changes in pulmonary pressure. Pulmonary pulsus alternans in acute myocardial infarction may appear under two conditions: (1) right ventricular strain secondary to left heart failure; and (2) impaired right ventricular contractility. Mortality was greater in group A than in group D (2P < 0.05). Patients in group C were in worse condition than those in group B. Therefore, the prognosis depends on the degree of heart failure and not on the pulmonary pulsus alternans itself.
Mechanical (pulsus) alternans is in most cases an index of ventricular failure.i-5 It is a frequent finding in various heart diseases, including aortic stenosis,s,4*e17 cardiomyopathies2T6s and chronic ischemic heart disease.s.8 The alternans in pulmonary pressure is a less frequent finding than systemic alternans.3,s It was first described in detail by Rabago et al.1° in a patient with an interatrial septal defect, and later by Ferrer et all in several cases of mitral stenosis and heart failure. In several studies it was related to pulmonary embolism,g cardiomyopathieslg and other At the same time, it was demcauses of right ventricular strain. 1,g~11~12 onstrated that mechanical alternans does not necessarily occur simultaneously in both the systemic and pulmonary circulations.1,2s8J3 We have not found any reference to pulmonary pulsus alternans in acute mvocardial infarction. In this renort we nresent the clinical and hemodynamic significance of this condition, as well as the cause of its appearance and its prognostic value during acute myocardial infarction.
October 1978
The American Journal of CARDIOLOGY
Volume 42
577
PULMONARY
ALTERNANS
IN MYOCARDIAL
INFARCTION-LOPEZ-SENDON
ET AL
TABLE I Clinical and Hemodynamic Evolution in Eight Patients With Pulmonary Pulsus Alternans Hemodynamic Subset
PPA
PTP
Cl
TPR
Clinical Subset
Yes No
46-32/25- 15 22173
2.7 3.0
a00 427
C-II C-II
H-II H-l
Nitroglycerin
Yes Yes No
44-36127 37-33178 26115
1.9 2.3 3.2
7737 a35 475
C-II C-II C-l
H-IV H-II H-l
Ph&tolamine Phentolamine
Yes Yes Yes No Yes Yes No
63-49136-37 48-42123-20 59-5 1127-23 49122 50-47124 40-36120 43120
2.1 2.5 1.7 2.7 2.1 2.4 2.9
7600 864 7647 978 7226 867 763
C-II C-II C-II C-II C-II C-II C-II
H-IV H-II H-IV H-II H-IV H-II H-II
&;oprusside Nitroprusside Dopamine i- nitroprusside lsosorbide dinitrate lsosorbide dinitrate -k digoxin lsosorbide dinitrate + digoxin
No Yes No
50130 47-43123 40120
2.8 2.3 2.4
1057 7043 900
C-II C-II C-II
H-II H-II H-II
iioiorbide dinitrate lsosorbide dinitrate -I digoxin
5*+
Yes No
67-63135 60130
2.0 2.1
7800 7524
C-II C-II
H-IV H-IV
Dopamine
6*+
No Yes Yes Yes Yes Yes Yes Yes No
45126 49-39130123 3a-32121-79 43-37128-26 58-38137-27 45-35/22- 76 53-47130-26 57-57129 48133
2.5 1.6 2.2 2.3 7.5 7.7 7.6 7.7 7.8
1073 1634 909 1078 7884 1271 1750 1756 7689
C-II C-IV C-IV C-IV C-IV c-iv C-IV C-IV C-IV
H-II H-IV H-II H-II H-IV H-IV H-IV H-IV H-IV
bhentolamine Dopamine i- phentolamine Dopamine + phentolamine Phentolamine Phentolamine Phentolamine + dopamine Dopamine Dopamine (large doses)
7’
No Yes
46127 52-48133
7.8 1.5
7467 2028
C-II C-IV
H-IV H-IV
bbbamine
a*+
No Yes
45130 30-24119-77
2.4 1.9
7767 a84
C-IV C-IV
H-II H-IV
NGoglycerin
Case no. 1 2
3
4
Drugs
Patient died. + Autopsy performed. Cl = cardiac index (literslmin per m*); PPA = pulmonary pulsus alternans; PTP = pulmonary trunk pressure (mm Hg); TPR = total pulmonary resistance (dynes set cmw51m2). l
Materials
and Methods
Patients: Between August 1 and December 23,1977, a total of 120 patients with acute myocardial infarction were admitted to the “La Paz” coronary care unit. Hemodynamic monitoring was performed in 100 of these patients. It was not performed for a variety of reasons in the remaining 20 patients, but none of these showed clinical heart failure or low cardiac output. The diagnosis of acute myocardial infarction was determined using well known clinical, electrocardiographic and laboratory criteria.l* All of the patients were admitted within the first 24 hours of evolution. In each patient we studied the clinical features, classifying the patients according to Forrester’s method’s in the following subsets: C-I: no evidence of pulmonary congestion or peripheral hypoperfusion. C-II: pulmonary congestion only. C-III: hypoperfusion only. C-IV: both pulmonary congestion and hypoperfusion. Hemodynamic data: Right heart catheterization was performed on admission by inserting a Swan-Ganz thermodilution catheter into the pulmonary trunk through the right antecubital vein. Right atrial, pulmonary arterial and pul-
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monary capillary wedge pressures were recorded through a Hewlett-Packard 1280 transducer, with a Siemens Elema Mingograph 34, at a paper speed of 25 mm/set. Cardiac output was determined with the thermodilution technique, using an Edwards 9500 computer. In every case, at least three successive determinations were made, and the average value was calculated. We followed Forrester’s method,15 classifying the hemodynamic studies in four subsets: H-I: pulmonary capillary wedge pressure 18 mm Hg or less and cardiac index 2.2 liters/min per m2 or greater. H-II: pulmonary capillary wedge pressure more than 18 mm Hg and cardiac index more than 2.2 liters/min per m ? H-III: pulmonary capillary wedge pressure 18 mm Hg or less and cardiac index 2.2 liters/min per m2 or less. H-IV: pulmonary capillary wedge pressure more than 18 mm Hg and cardiac index 2.2 liters/min per m2 or less. Arterial blood pressure was measured with an arm cuff and expressed in mm Hg. Hemodynamic values were calculated according to the following formulas16J7: CI = CO/BSA, where CI is cardiac index in liters/min per m2, CO is cardiac output in liters/min and BSA is body surface area in m2; SI = CI/HR, where SI is stroke index in ml/beat per m* and HR is heart rate in beats/min; TPR = 80 (PTP/CI), where TPR is total pulmonary resistance in dynes set cm-“/m”, 80 is the conversion
Volume 42
PULMONARY
ALTERNANS
IN MYOCARDIAL
INFARCTION-LOPEZ-SENDON
ET AL.
(mean f standard deviation) for All Hemodynamic Variables in Every Group and Statistical Significance of Differences Between Groups GroupA I1 9 studies) HR I%
85.1 f
17.5
Group B 19 studies)
Group C (10 studies)
80.1 f
90.0 f
17.8
17.1
Group D (30 studies) 86.6 f
16
Group E
t 11 studies) 87.9 f
16.0
Avs. D
2P values Avs. t
Bvs.C
NS
NS
NS
31.5 23.4 11 f 6.4 6.6 4.3
30.3 20.8 8.8 f 5.8 7.0 7.3
32.6 24.9 13.0 f 5.3 4.0 7.0
30.4 23.9 9.6 f 4.0 4.06 7.3
20.7 29.7 8.5 f 5.6 5.1 7.3
/:
NS ;:
NS K
:P SbR
77.8 2.04 f 0.36 16.6 1319 24.8 f 424 5.8
85.1 2.17 f 0.31 13.7 1113 28.2 f 324 6.7
1.92 75 f 0.42 17.8 1505 21.9 f 432 2.5
90.3 2.62 f 0.63 15.9 31.1 927 f 245 10.9
79.5 2.5 f 0.5 15.7 1041 29.2 f 428 8.2
!:25 0.005 0.05 0.005
::05 K5
K5 0.05
LVSWI
31.5 24.7 0.76 9.9
38.6 31.9 0.81 12.2
25.2 18.3 0.71 7.8
45.7 36.0 0.78 13.2
38.1 28.0 0.75 11.6
0.01 0.02 NS NS
NS NS NS NS
Kl 0:01 0.01 NS
LVNWI LVNWIILVSWI RVNWI
f 10.7 f 11 f 0.10 f 3.7
f 11.1 f 11.4 f 0.1 f 2.5
f f f f
5.3 5.5 0.08 3.3
f 18.8 f 16.3 f 0.06 f 4.1
f 13.4 f 13.5 f 0.08 f 3.2
BP = blood pressure (mm Hg); Cl = cardiac index (literslmin per m * &, _ = heart rate (beatsjmin); LVNWI = left ventricular n-work index (g-m/beat . HR per m*); LVSWI = left veaular stroke work index (g-m/beat per m ); PCP = mean pulmonary capillary pressure (mg Hg); PTP = mean pulmonary trunk pressure (mm Hg); RAP = right atrial pressure (mm Hg); RVNWI = right ventricular net work index (g-m/beat per m*); SI = stroke index (ml/beat per m*); SWI = stroke work index (g-m/beat per m*); TPR = total pulmonary resistance (dynes set cme5/m2).
factor to dynes set cmp5 and PTP is rn-ulmonary trunk pressure in mm Hg; LVSWI = SI X ASP X 0.0136, where LVSWI is left ventricular stroke work index in g-m/beat per m2, ASP is mean aortic systolic pressure in mm Hg and 0.0136 the conversion factor from mm Hg/ml to g; ASP = 0.8 (aortic systolic- - aortic - diastolic) + aortic diastolic pressure; LVNWI = SI (ASP - PCP) X 0.0136, where LVNWI is left ventricular net work index in g-m/beat per m2 and pep is mean pulmonary capillary pressure in mm Hg; LVNWI/LVSWI; RVNWI = SI (PSTP - RAP) X 0.0136, where RVNWI is right ventricular net work index in g-m/beat per m2, mis mean right atria1 pressure in mm Hg and PSTP is mean pulmonary systolic trunk pressure. Pulmonary pulsus alternans: This was defined as the alternation of strong and weak peak systolic pulmonary pressure in the presence of regular rhythm and in the absence of respiratory movements. We excluded patients with pulmonary pulsus alternans who also had the following: (1) valve disease (one patient with aortic stenosis); (2) major arrhythmias (two patients with ventricular tachycardia); or (3) false pulmonary pulsus alternans, such as the alternans that may accompany significant variations in rhythm, or is induced by atria1 contractions in cases of external cardiac pacing or atrioventricular dissociation. We found eight patients with pulmonary pulsus alternans. Their age was 62.2 f 10.7 years (mean f standard deviation). None had chronic obstructive lung disease. The following groups were established: Group A: all eight patients with pulmonary pulsus alternans. From their studies we selected 19 different hemodynamic studies in which pulmonary alternans was present. These were separated by a minimal interval of 12 hours and showed significant changes in some of the measured values. Group B: the four patients in group A who did not die in the coronary care unit (nine hemodynamic studies). Group C: the four patients in group A who died while in the coronary care unit (10 hemodynamic studies). Group D: control group of patients with 30 hemodynamic studies chosen at random from all patients without pulmonary alternans but included in subsets H-II and H-IV of Forrester’s classification. Group E: patients in group A who had hemodynamic measurements just before the appearance (five patients) or
just after the disappearance (six patients) of pulmonary pulsus alternans (total of 11 hemodynamic studies). We statistically compared the mean values of each hemodynamic measurement in groups A and D, A and E, and B and C, using Students’ t test (2P values).
Results Clinical data: All eight patients with pulmonary pulsus alternans had clinical left heart failure (Table I). Six patients were in clinical subset C-II and two in C-IV. Five patients had clinical right heart failure, and one of them had pulmonary thromboembolism. HemOdynamic data (Tables I and II): All 19 hemodynamic studies in group A (eight patients) showed pulmonary capillary pressure greater than 18 mm Hg; 12 studies were classified in subset H-IV and 7 in subset H-II. Patients in group A had lower values for blood pressure (2P < 0.025), cardiac index (2P < 0.005), stroke index (2P < 0.05), left ventricular stroke work index (2P < 0.01) and left ventricular net work index (2P < 0.02) and higher values for total pulmonary resistance (BP < 0.005) than patients in group D (control). Patients in group A had statistically smaller values for cardiac index (2P < 0.005) and higher values for pulmonary resistance (2P < 0.05) than patients in group E. When comparing group B (nonfatal pulmonary pulsus alternans) with group C (fatal pulmonary pulsus alternans) we observed that group B had higher values for stroke index (2P < 0.05), left ventricular stroke work index (LVSWI) (2P < 0.01) and left ventricular net work index (LVNWI) (2P < 0.01). The ratio LVNWULVSWI was smaller in group C (2P < 0.01). The more interesting data for each hemodynamic study in group A are shown in Table I, as well as the hemodynamic data and clinical classification before the appearance of pulmonary alternans and after its disappearance (Group E), if available. In five patients the pulmonary trunk pressure and cardiac index were known before the pulmonary alternans was present. Note that pulmonary trunk pressure may be increased
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or decreased when pulmonary alternans appears, but cardiac index always decreases and total pulmonary resistance usually increases (Fig. 1). The disappearance of pulmonary pulsus alternans could be studied in six patients, including four with clinical improvement. The changes associated with the disappearance of pulmonary pulsus alternans were less striking than those that accompanied the appearance of pulmonary alternans but generally included a more or less important decrease in pulmonary trunk pressure and total pulmonary resistance (Fig. 2) or an increase in cardiac index, or both (Fig. 3). In four patients the pulmonary alternans disappeared after the administration of inotropic drugs such as dopamine or digoxin, with or without significant changes in pulmonary trunk pressure and cardiac index (Fig. 1 and 3). In three other patients pulmonary alternans disappeared after treatment with several vasodilators, which produced an
ET AL.
important reduction in total pulmonary resistance values (Fig. 2). Mortality: Four patients with pulmonary pulsus alternans died in the coronary care unit (group C) (Table I)-two with cardiogenic shock (H-IV) and two with pulmonary edema (H-II). Postmortem studies, performed in three of these patients revealed ischemic lesions in both ventricles of all three. The mortality rate was higher in patients with pulmonary alternans than in the patients of control group D with left heart failure (16.7 percent) (2P < 0.05). Discussion Incidence: Mechanical alternans of the lesser circulation simultaneous with or independent of left heart alternans occurs in patients with isolated left heart diseases and heart failure,l or primary right heart diseases such as idiopathic pulmonary hypertensionll or
FIGURE 1. Case 6. Pulmonary alternans appears in B and is maximum in C, after an increase in total pulmonary resistance (TPR) and a decrease in cardiac index, with the same pulmonary trunk pressure (PTP). After administration of dopamine, pulmonary alternans diminishes in D and even disappears with high doses of dopamine (E). The patient had cardiogenic shock after the appearance of pulmonary alternans. Cl = cardiac index (liters/min per m*); PTP = pulmonary trunk pressure in mm Hg; TPR = total pulmonary resistance (dynes set cm-5/m2).
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PULMONARY ALTERNANS IN MYOCARDIAL INFARCTION-LOPEZ-SENDON
pulmonary embolism.9 Sometimes the underlying disease is common to both ventricles, as in cardiomyopathies.2 Pulmonary pulsus alternans has been reported in patients with chronic ischemic heart diseaseas but not during acute myocardial infarction. The hemodynamic monitoring performed in almost all of our patients with acute myocardial infarction has proved that it is a frequent finding, appearing in at least 8 percent of patients. Clinical and hemodynamic significance: Every patient with pulmonary pulsus alternans showed clinical, radiologic and hemodynamic signs of left heart failure. This failure was more severe than in patients without pulmonary alternans, documented by the lower values for cardiac index, stroke index, stroke work index and net work index. These findings are in agreement with previous data1-5 associating mechanical alternans with heart failure. Even if it is possible to find mechanical alternans in people without heart disease, it occurs only in nonphysiologic conditions such as during arrhythmias or pacing at high rates.4Js,18,20 Significance during acute myocardial infarction: Two main mechanisms have been proposed to explain mechanical alternans: (1) the hemodynamic theory, based on Starling’s principle, which holds that alternation in diastolic volume or pressure or fiber length accounted for the alternating contractile force (increase preload preceding the more powerful beats7Jg,21p22);and (2) the myocardial theory, which holds that primary alternation in contractility of the whole or only part of the heart occurs in the absence of changes in ventricular diastolic vo1ume.6,8Js,2s,25We believe that mechanical alternans of the pulmonary pressure in acute myocardial infarction may appear under certain conditions: 1. Right ventricular strain secondary to left heart failure. A common finding in our patients with pulmonary pulsus alternans was severe left heart failure. It produced an increase in pulmonary resistance levels with corresponding overload to the right ventricle, with or without signs of right ventricular failure. Total pul-
ET AL.
monary resistance levels were higher in these patients than in those without alternans. In many patients, the appearance and disappearance of pulmonary alternans followed significant changes in hemodynamic measurements (pulmonary trunk pressure, cardiac index and total pulmonary resistance values). These changes were due to the intervention of preload- or afterloadreducing agents without direct inotropic action. Pulmonary pulsus alternans has been found in patients with primary pulmonary hypertension,‘i pul-
FIGURE 2. Case 1. Pulmonary pulsus altemans disappears 10 minutes after the sublingual administration of 0.6 mg of nitroglycerin (NG), with striking reduction in pulmonary pressures (PTP) and total pulmonary resistance (TPR). Abbreviations and units as in Figure 1.
PTP
FIGURE 3. Case 3. Pulmonary pulsus alternans (A) does not disappear after reduction of pulmonary pressure and resistance with nitroprusside (B) until dopamine is administered (C). Alternans appears again when the inotropic drug is discontinued (0) and is no longer present when the patient is given intravenous digoxin. Note that pulmonary trunk pressure is the same in magnitude from B to E. Abbreviations and units as in Figure 1.
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PULMONARY ALTERNANS IN MYOCARDIAL INFARCTION--LOPEZ-SENDON
ET AL.
a complex phenomenon that can be modified by more than one factor, and may depend on hemodynamic as well as on direct inotropic conditions.2,4,1gJf Prognostic significance: Pulmonary pulsus alternans in acute myocardial infarction is associated with a very high mortality rate. Half of the patients died while in the coronary care unit. The mortality rate was higher than in control patients in the same hemodynamic classification but without pulmonary alternans (2P < 0.05). Mechanical alternans has previously been associated believe with a poor prognosis, s7,28 but other author&” that the severity of the underlying disease is what really determines the prognosis. Heart failure was more severe in patients with than in patients without pulmonary alternans; it was also more severe in the four patients with pulmonary alternans who died than in those who survived-another indication that the prognosis depends on the degree of heart failure.
monary thromboembolism,s as well as in patients with valve disease.lJs In every case, there was right ventricular strain (sometimes secondary to left heart failure) which could be the cause of pulmonary alternans. This could not be proved by others.” 2. Impaired right ventricular contractility: Five of the eight patients with pulmonary alternans had clinical right heart failure. This could have been secondary to left heart failure with right ventricular strain, or produced by direct ischemic involvement of the right ventricle. All of our patients with autopsy studies had some degree of right ventricular damage. The imbalance between oxygen supply and demand has already been proposed as one cause of mechanical alternans in aortic stenosis.3 In some of our patients, the pulmonary al,ternans disappeared after the administration of strong inotropic drugs such as dopamine or digoxin, without significant changes in pulmonary pressure, cardiac index or pulmonary resistance levels, but perhaps with improvement in right ventricular contractility. We believe that even in cases without clinical evidence of right heart failure pulmonary alternans may indicate decreased right ventricular contractility. All these findings are in accord with those observed alternans is by others1,2T5,18 and prove that pulmonary
Acknowledgment We gratefully acknowledge the assistance of Dr. J. Calderon Montero from the National School of Chest Diseases, Madrid, Spain in performing the statistical analyses.
References 1.
2.
3.
4. 5.
6.
7. 8. 9. 10.
11.
12. 13. 14.
582
Ferrer I, Harvey RM, Cournand A, et al: Cardiocirculatory stu&es in pulsus alternans of the systemic and pulmonary circulations. Circulation 14:163-174, 1956 Harris LC, Nghiem OX, Schreiber MH, et al: Severe pulsus alternans associated with primary myocardial disease in children. Circulation 34:948-961, 1966 Cooper T, Braunwald E, Morrow AG: Pulsus alternans in aortic stenosis. Hemodynamic observations in 50 patients studied by left heart catheterization. Circulation 18:64-70, 1958 Cohn KE, Sandler H, Hancock EW: Mechanisms of pulsus alternans. Circulation 36:372-379, 1967 Ryan JM, Schieve JF, Hull HB, et al: Experiences with pulsus alternans. Ventricular alternation and the stage of heart failure. Circulation 14:1099-1103, 1956 Swanton RH, Jenkins BS, Brooksby IA, et al: Pulsus alternans: force-velocity and angiographic volume analysis in man (abstr). Br Med J 37: 558, 1975 Gleason WL, Braunwald E: Studies on Starling’s law of the heart. Circulation 25:841-848. 1962 D’Cruz I, Cohen HC, Prabhu R, et al: Echocardiography in mechanical alternans. Circulation 54:97-102, 1976 Calick A, Berger S: Pulmonary artery pulsus alternans associated with pulmonary embolism. Chest 64:663-664, 1973 Rabago P, Kohout FW, Katz LN: An unusual case of pulsus alternans recorded during cardiac catheterization from the pulmonary and systemic blood vessels. Am Heart J 49:472-482, 1955 Meyer BL, Bogart DB, Carley J, et al: Pulmonary arterial pulsus alternans secondary to primary pulmonary hypertension. Chest 701374-377, 1976 Hashiba K. Katavama T. Takahashi A. et al: Pulsus alternans involving the right heart. Jpn Heart J 6:452-457, 1965 Desser KB, Benchimol A: Phasic left ventricular blood velocity alternans in man. Am J Cardiol 36:309-314, 1975 Killip T, Kimball JT: Treatment of myocardial infarction in a coronary care unit. A two year experience with 250 patients. Am J
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Cardiol 201457-464, 1967 15. Forrester JS, Diamond GA, Swan HJC: Correlative classification of clinical and hemodynamic function after acute myocardial infarction. Am J Cardiol 39:137-143, 1977 16. Yang SS, Bentivoglio LG, Maranhao V, et al: Cardiac Catheterization Data to Hemodynamic Parameters. Philadelphia, FA Davis, 1972, p 163 17. Russell RO, Rackley CE: Hemodynamic Monitoring in a Coronary Intensive Care Unit. New York, Futura Publishing, 1974, p 65 18. Leighton RF, Zaron SJ, Robinson JL: Left ventricular mechanical alternans in man: effects of atrial pacing and isoproterenol (abstr). Circulation 37. 38: SUDDI VI: VI-125. 1968 19. Mitchell JH, Sarnoff &I; Sonnenblick EH: The dynamics of pulsus alternans: alternating end-diastolic fiber length as a causative factor. J Clin Invest 42:55-63, 1963 20. Gilbert JL, Janse MJ, Lu HH, et al: Production and abolition of alternation in mechanical action of the ventricle. Am J Physiol 209:945-950, 1965 21. Wenckebach KF: Zur Analyze des unregelmassigen Pulsus. IV. Veber den Pulsus alternans. Z Klin Med 44:218-226, 1910 22. Straub H: Dynamik des Herzalternans. Dtsch Arch Klin Med 123:296-305, 1917 23. Wiggers CJ: Circulatory Dynamics. New York, Grune & Stratton, 1952, p 78 24. Hering HE: Zur Erklarung des Herzalternans. Z Exp Path Ther 12:235-242. 1913 25. Elessas A, Ryan TJ: A force-velocity analysis of pulsus alternans. Circulation 41, 42:Suppl Ill: 111-86-111-94,1970 26. Nayler WG, Robertson PGC: Mechanical alternans and the staircase phenomenon in dog papillary muscle. Am Heart J 70:494498, 1965 27. Cecil RL, Loeb RF: A Textbook of Medicine. Philadelphia, WB Saunders, 1959, p 1320 28. Bellett S Clinical Disorders of the Heart Beat, second edition. Philadelphia, Lea & Febiger, 1963, p 552
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