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Left atrial enlargement: An early sign of hypertensive heart disease
Left atrial enlargement: An early sign of hypertensive heart disease Left atrial abnormality on the electrocardiogram (ECG) has been considered an early sign of hypertensive heart disease. In order to determine if echocardiographic left atrial enlargement is an early sign of hypertensive heart disease, we evaluated 10 normal and 14 hypertensive patients undergoing routine diagnostic cardiac catheterization for echocardiographic left atrial enlargement. All patients had normal coronary arteriography, sinus rhythm, normal left ventricular volumes and function, no valvular disease, and no echocardiographic or ECG left ventricular hypertrophy. No patient met ECG criteria for left atrial abnormality. The mean left atrial dimension was 3.46 f 0.3 cm in normal individuals versus 4.04 -+ 0.3 cm In the hypertensive patients (p < 0.01). The left atrial index was also higher in the hypertensive group, 2.16 + 0.45 versus 1.66 k 0.10 cm/m2 (p < 0.05), and the left atrial-to-aortic root dimension ratio was significantly higher in the hypertensive group, 1.36 + 0.20 versus 1.17 + 0.07 (p < 0.01). We conclude that echocardiographic left atrial enlargement may be an early sign of hypertensive heart disease in patients with no other discernible cause of left atrial enlargement. (AM HEART J 1966:116:1046.)
John T. Miller, MD, Robert San Antonio, Texas
A. O’Rourke,
MD, and Michael
Systemic hypertension often leads to left ventricular hypertrophy, congestive heart failure, and death.’ In some patients, concentric left ventricular hypertrophy can occur early in the course of mild to moderate hypertension.* Other patients may present with left ventricular dilatation, asymmetric septal hypertrophy, or eccentric left ventricular hypertrophyP Frohlich et aL4 have suggested that electrocardiographic (ECG) evidence of a left atrial abnormality is an early sign of hypertensive heart disease. However, because of the frequent association of hypertension with coronary atherosclerosis, some5 have questioned whether the structural and functional changes observed in hypertension develop in the absence of coronary artery stenosis. We have observed echocardiographic left atria1 enlargement as the only abnormality in patients with systemic hypertension in the absence of definite left ventricular hypertrophy by ECG or echo-
H. Crawford,
MD.
cardiographic criteria. While Dunn et aL6 have suggested that left atrial enlargement may be an earlier sign of hypertensive heart disease than left ventricular hypertrophy and/or dilatation, other studies3 have suggested that left atria1 enlargement is only an age-related phenomenon and does not reflect a structural change in the heart due to hypertension. Unfortunately, the study by Dunn et al. was not controlled for all other causes of possible left atrial enlargement such as ischemic heart disease. Therefore we sought to test the hypothesis that left atrial enlargement as assessed by echocardiography is the earliest indication of cardiac dysfunction in patients with systemic hypertension alone who have neither quantitative evidence of left ventricular hypertrophy by noninvasive techniques, nor other causes of left atrial enlargement such as coronary attery or valvular heart disease. METHODS
The study population consisted of 24 consecutive patients undergoing routine diagnostic cardiac catheterFrom the Division of Cardiology, Department of Medicine, University of Texas Health Science Center and Audie L. Murphy Memorial Veterans’ Hospital. Supported in part by National Institutes of Health Training Grant No. T32HL07350 and by the Veternas Administration tieceived for publication Feb. 1, 1988; accepted May 25, 1988. Reprint requests: Micahel H. Crawford, MD, Department of Medicine, Division of Cardiology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78284-7872.
1048
ization for chest pain syndromes who met the following criteria: sinus rhythm and no history of atria1 fibrillation; no abnormal narrowing in any coronary artery as interpreted by a hlin&rl observer; no systolic global or regional dysfunction by biplane left ventricular cineangiography; normal left ventricular end-diastolic and end-systolic volumes;no hemodynamic or angiographicevidence of mitral or aortic valve disease;no left atrial abnormality by ECG
Volume Numbor
Table
116 4
Left atria1
enlargement
1049
in hypertension
I. Clinical, echocardiographic, and hemodynamic characteristics
(Yr)
Control (n = 10) (mean* SD) Hypertensive
51
MAP (mm Hd
BSA Cm3
&e (38-65)
1.81
f
0.28
48 (36-68)
1.83
r 0.19
91
107
Ejection fraction (%)
LVEDP (mm Hgl
Fractional shortening (cm)
ESD (cm)
EDD (o/o)
9
14 f
5
68 2 9
38
f
7
4.8
+ 0.5
3.04
* 9
10 f
7
70
42
f
9
4.9
f
2.92&
f
zk 11
0.7
L V mass (km)
k 0.4
147
k 35
0.7
163
k37
(n = 14)
(mean+ SD) p value
NS
NS
BSA = body surface area; MAP = mean arterial systolic dimension; SD = 1 standard deviation.
NS
LVEDP
= left
NS
ventricular
criteria7; and no left ventricular hypertrophy when Estes’ ECG criteria8 or the echocardiographic criteria of enddiastolic left ventricular posterior wall thickness > 1.2 cm were used.g The 24 patients were divided into two groups-10 normotensive and 14 hypertensive patients. The normotensive patients had blood pressuresthat never exceeded 140/90mm Hg on multiple clinic visits. The hypertensive patients had blood pressureconsistently > 140/90 mm Hg on at least twice yearly clinic visits for several years. Although all the patients were reported to be taking various antihypertensive medications, compliance was uncertain in our indigent population who repeatedly demonstrated elevated blood pressure values. The mean duration of clinically documented hypertension was 6.9 years (range 4.2 to 9.9 years). Five of the 10 normotensive patients and 6 of the 14 hypertensive patients were male. Cardiac catheterization was performed from the femoral or brachial approach. Mean arterial blood pressure was determined by electronically averaging the signal from the central aorta during cardiac catheterization. Within 72 hours of cardiac catheterization, patients were studied with M-mode and two-dimensional echocardiography by means of standard techniques. The aortic root and left atrial dimensions were measured with the leading edge technique.g The aortic root dimension was measuredat end-diastole at the level of the aortic valve. The left atria1 dimension was measured at its largest diameter and the exact location of the posterior atrial wall wasconfirmed by two-dimensional echocardiography. The normal values for left atrial size, left atria1 index, and left atrial-to-aortic root dimension ratio are 4.0 cm, 2.0 cm, and 1.17, respectively.g~la Left ventricular cavity dimensionswere measuredfrom two-dimensional echocardiographic-guided M-mode recordingsat the level of the chordae tendineae by meansof a technique we have previously validated.” Left ventricular posterior wall thickness was measuredas the distance between the endocardium of the posterior wall and the origin of the epicardial echo obtained during electrical damping of the ultrasound signaLl The end-diastolic point was measured at the peak of the R wave on a
end-diastolic
NS pressure;
NS EDD
= end-diastolic
NS dimension;
NS ESD
= end-
simultaneousECG recording. Echocardiographic left ventricular cross-sectional area and mass were determined with the end-diastolic posterior wall thickness by the method of Troy et al.,13 and were corrected by the technique of Devereux et al.,” since we used the newer American Society of Echocardiography conventiorP for measuring wall thickness. Those reading the echocardiograms were blinded as to the results of cardiac catheterization and the clinical status of the subjects. The values for hemodynamic and echocardiographic variables were listed as mean f 1 standard deviation. The control values were compared to the hypertensive patient values by meansof an unpaired Student’s t test. RESULTS
Table I lists the clinical, echocardiographic, and hemodynamic characteristics of the two groups. There was no difference in the age, end-diastolic or end-systolic dimensions, percent fractional shortening or ejection fraction, end-diastolic pressure, or left ventricular mass. The hypertensive group had a significantly higher mean arterial pressure at 107 ZL 9 mm Hg compared to 91 + 9 mm Hg for the normotensive group. Fig. 1, A shows the left atrial dimension for each patient in the two groups. Note that most of the normotensive patient values fall below the normal upper limit of 4 cm. The average left atria1 dimension was 3.46 k 0.3 cm for the normotensive group and was significantly higher, at 4.04 + 0.3 cm, in the hypertensive group @ < 0.01). Fig. 1, B shows the left atrial index-left atrial dimension divided by body surface area for the two groups. The hypertensive group had a significantly higher mean value of 2.18 + 0.45 cm/m2 as compared to 1.88 + 0.10 cm/ m2 in the normotensive patients (p < 0.05). Again, most of the normotensive patients fell below the upper limit of normal of 2 cm/m2. The ratio of the left atrial dimension to the aortic root dimension for each patient in the two groups is
oclober
1050
Miller,
O’Rourke,
and Crawford
Amorlcan
3.4 3. 4 SO2.c
T-I-SD
Hmrl
less
Journal
l
. .
2.62.4.
PS.05
2.2.
;
2.0. I.& 1.61.41.2. LO-
Ir 2 .
IrLEF&?IALIND$m,d DIMENSION
J’ ! .
C.LAd/Aod
1. A, Left atrial dimension. 6, Left atrial index. C, Left atrial dimension-to-aortic root dimension ratio for normal (IV) and hypertensive (HT) individuals. Fig.
shown in Fig. 1, C. Note that 13 of the 14 hypertensive patients’ values were above the suggested normal value of 1.17. Also, the mean value in the normotensive group was significantly lower than that in the hypertensive group (1.17 -+ 0.07 versus 1.36 + 0.20, p < 0.01). DISCUSSION
ECG evidence of left atrial enlargement has been shown to occur in hypertensive patients. Frohlich et al.4 compared 25 normotensive patients to 97 untreated hypertensive patients (21 of whom had normal coronary arteriography) to determine the presence of left ventricular dysfunction and left atrial enlargement by ECG criteria. It was found that ECG left atrial abnormality was related to the initial hemodynamic evidence of left ventricular dysfunction, as measured by left ventricular ejection rate, tension time index, and left ventricular stroke work. Furthermore, when left ventricular hypertrophy became apparent, there was further deterioration in hemodynamic indices of left ventricular function. Also, it should be noted that the ECG was used solely for evaluation of left atrial size, and other investigators15 have shown that left atrial enlargement by ECG does not necessarily correlate with echocardiographic left atrial enlargement and may be a manifestation of a conduction delay due to other causes. Savage et a1.3 studied 234 hypertensive patients by echocardiography. They excluded the presence of coronary artery disease on the basis of a negative history and the absence of ECG evidence of myocar&al infarction. Thev found 15% to have increased left atrial dimensions and concluded that left atrial enlargement did not appear to be an early sign of cardiac involvement; however, they did not study left atrial enlargement in relation to left ventricular
hypertrophy and whether they occur independently. Also, the number of patients with subclinical coronary artery disease was unknown but presumably was not zero in a population of middle-aged patients with hypertension. Our results demonstrate that echocardiographicalIy demonstrated left atrial enlargement in patients with hypertension and no other cardiovascular disease occurs in the absence of ECG left atrial abnormality and ECG or echocardiographic manifestations of left ventricular hypertrophy. Of the three methods used to determine left atrial enlargement echocardiographically, the left atrial-to-aortic root dimension ratio provided the best separation between the normotensive and hypertensive subjects. However, with all three methods there is overlap of the hypertensive patients with the normal patients. Nevertheless, few of the normal patients had abnormal values and none of the 10 normotensive patients had left atrial enlargement when all three methods were used. The cause of early left atrial enlargement is unknown, but other studies have suggested that abnormal left ventricular compliance may be an early sign in hypertensive patients. Dreslinski et all6 demonstrated reduced left atrial emptying index as assessed by M-mode echocardiography in hypertensive patients without ECG evidence of left atrial or ventricular enlargement, but their patients did have a significantly higher echocardiographic left ventricular mass compared to a control group. Also, Inouye et al.” noted abnormal radionuclide angiographic measures of diastolic left ventricular filling in patients with mild to moderate hypertension, but there was a correlation between these measures and echocardiographic left atrial dimension and left ventricular mass. In addition, Smith et all8 showed that radionuclide peak diastolic filling rates were
Volume Numbor
116 4
prolonged in 20 hypertensive patients without ECG evidence of left ventricular hypertrophy, including 4 of 12 patients with normal echocardiographic left ventricular mass. However, peak filling rate also is determined by left atrial pressure and cannot be ascribed exclusively to changes in left ventricular diastolic function.ls Therefore without knowledge of left atrial pressure, firm conclusions concerning the meaning of changes in noninvasively determined filling rates cannot be made. One limitation of our study was that this was a select group of patients undergoing cardiac catheterization for chest pain syndromes. Although no cardiac disease was found by the usual criteria, we may have selected out patients with subclinical heart disease. Consequently, we cannot estimate the frequency with which left atrial enlargement would be the first manifestation of hypertensive heart disease. Second, we have no invasive or noninvasive measures of left ventricular diastolic function, since these procedures are not routinely performed in our clinical laboratories. However, there was no difference between the control subjects and the hypertensive patients in left ventricular end-diastolic pressure. Thus we cannot determine directly the specific cause of the left atrial enlargement in our patients. Finally, we have insufficient long-term longitudinal data on our patients to ascertain whether overt hypertensive heart disease eventually will develop. Regardless of the mechanism, our data demonstrate that echocardiographic left atria1 enlargement in the absence of evidence for left ventricular hypertrophy can occur in patients with systemic hypertension. This finding may represent an early manifestation of hypertensive heart disease and should not be ignored. Also, patients with ECG evidence of left atria1 abnormality should have an echocardiogram to corroborate that this aberration is due to left atrial enlargement rather than to atrial conduction abnormalities. REFERENCES
1. Kannel WB, Castelli WP, McNamara PM, Mckee PA, Feinlab M. Role of blood pressure in the development of congestive heart failure. N Engl J Med 1972;287:781. 2. Culpepper WS. Cardiac anatomy and function in juvenile hypertension: current understanding and future concerns. Am J Med 1983;75:57.
Left
atria1 enlargement
in hypertension
1051
3. Savage DD, Drayer JIM, Henry WL, et al. Echocardiographic assessment of cardiac anatomy and function in hypertensive subjects. Circulation 1979;59:623. 4. Frohlich ED, Tarazi RC, Dustan HP. Clinical-physiological correlations in the development of hypertensive heart disease. Circulation 1971;44:446. 5. Friedberg CK. Diseases of the heart. Philadelphia: W.B. Saunders Co, 19661474. 6. Dunn FG, Chandraratna P, decarrallo JGR, Basta LL, Frohlich ED. Pathophysiologic assessment of hypertensive heart disease with echocardiography. Am J Cardiol 1977; 39389. 7. Morris JJ, Estes EH, Whalen RE, Thompson HK, McIntosh HD. P-wave analysis in valvular heart disease. Circulation 1964;29:242. 8. E&es EH. Electrocardiography and vectorcardiography. In: Hurst JW, ed. The heart. New York: McGraw-Hill Book Co, Inc, 1974:297. 9. Gardin JM, Henry WL, Savage DD, Ware JH, Burn C, Borer JS. Echocardiographic measurements in normal subjects: evaluation of an adult population without clinically apparent heart disease. J Clin Ultrasound 1979;7:439. 10. Brown OR, Harrison DC, Popp RL. An improved method for echographic detection of left atria1 enlargement. Circulation 1974;50:58. 11. Crawford MH, Grant D, O’Rourke RA, Starling MR, Groves BM. Accuracy and reproducibility of new M-mode echocardiographic recommendations for measuring left ventricular dimensions. Circulation 1980;61:137. 12. Sahn DJ, DeMaria A, Kisslo J, Weiman A: The Committee on M-mode Standardization of the American Society of Echocardiography. Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements. Circulation 1978;58:1072. 13. Troy BL, Pombo J, Rackley CE. Measurements of left ventricular wall thickness and mass by echocardiography. Circulation 1972;45:602. 14. Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Camp0 E, Sachs I, Reichek N. Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol 1986;57:450. 15. Josephson ME, Kastor JA, Morganroth J. Electrocardiographic left atria1 enlargement; electrophysiologic, echocardiographic and hemodynamic correlates. Am J Cardiol 1977;39:969. 16. Dreslinski GR, Frohlich ED, Dunn FG, Messerli FH, Suarez DH, Reisin V. Echocardiographic diastolic ventricular abnormality in hypertensive heart disease: atria1 emptying index. Am J Cardiol 1981;47:108’7. 17. Inouye I, Massie B, Loje D, et al. Abnormal left ventricular filling: an early finding in mild to moderate systemic hypertension. Am J Cardiol 1984;53:120. 18. Smith VE, Schulman P, Karimeddini MK, White WB, Meeran MK, Katz AM. Rapid ventricular tilling in left ventricular hypertrophy. 11. Pathologic hypertrophy. 3 Am Co11 Cardiol 1985;5:869. 19. Ishida Y, Meisner JS, Tsujioka K, Gallo JI, Yoran C, Frater RWM, Yellin EL. Left ventricular filling dynamics: influence of left ventricular relaxation and left atria1 pressure. Circulation 1986;74:187.
John T. Miller, MD, Robert San Antonio, Texas
A. O’Rourke,
MD, and Michael
Systemic hypertension often leads to left ventricular hypertrophy, congestive heart failure, and death.’ In some patients, concentric left ventricular hypertrophy can occur early in the course of mild to moderate hypertension.* Other patients may present with left ventricular dilatation, asymmetric septal hypertrophy, or eccentric left ventricular hypertrophyP Frohlich et aL4 have suggested that electrocardiographic (ECG) evidence of a left atrial abnormality is an early sign of hypertensive heart disease. However, because of the frequent association of hypertension with coronary atherosclerosis, some5 have questioned whether the structural and functional changes observed in hypertension develop in the absence of coronary artery stenosis. We have observed echocardiographic left atria1 enlargement as the only abnormality in patients with systemic hypertension in the absence of definite left ventricular hypertrophy by ECG or echo-
H. Crawford,
MD.
cardiographic criteria. While Dunn et aL6 have suggested that left atrial enlargement may be an earlier sign of hypertensive heart disease than left ventricular hypertrophy and/or dilatation, other studies3 have suggested that left atria1 enlargement is only an age-related phenomenon and does not reflect a structural change in the heart due to hypertension. Unfortunately, the study by Dunn et al. was not controlled for all other causes of possible left atrial enlargement such as ischemic heart disease. Therefore we sought to test the hypothesis that left atrial enlargement as assessed by echocardiography is the earliest indication of cardiac dysfunction in patients with systemic hypertension alone who have neither quantitative evidence of left ventricular hypertrophy by noninvasive techniques, nor other causes of left atrial enlargement such as coronary attery or valvular heart disease. METHODS
The study population consisted of 24 consecutive patients undergoing routine diagnostic cardiac catheterFrom the Division of Cardiology, Department of Medicine, University of Texas Health Science Center and Audie L. Murphy Memorial Veterans’ Hospital. Supported in part by National Institutes of Health Training Grant No. T32HL07350 and by the Veternas Administration tieceived for publication Feb. 1, 1988; accepted May 25, 1988. Reprint requests: Micahel H. Crawford, MD, Department of Medicine, Division of Cardiology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78284-7872.
1048
ization for chest pain syndromes who met the following criteria: sinus rhythm and no history of atria1 fibrillation; no abnormal narrowing in any coronary artery as interpreted by a hlin&rl observer; no systolic global or regional dysfunction by biplane left ventricular cineangiography; normal left ventricular end-diastolic and end-systolic volumes;no hemodynamic or angiographicevidence of mitral or aortic valve disease;no left atrial abnormality by ECG
Volume Numbor
Table
116 4
Left atria1
enlargement
1049
in hypertension
I. Clinical, echocardiographic, and hemodynamic characteristics
(Yr)
Control (n = 10) (mean* SD) Hypertensive
51
MAP (mm Hd
BSA Cm3
&e (38-65)
1.81
f
0.28
48 (36-68)
1.83
r 0.19
91
107
Ejection fraction (%)
LVEDP (mm Hgl
Fractional shortening (cm)
ESD (cm)
EDD (o/o)
9
14 f
5
68 2 9
38
f
7
4.8
+ 0.5
3.04
* 9
10 f
7
70
42
f
9
4.9
f
2.92&
f
zk 11
0.7
L V mass (km)
k 0.4
147
k 35
0.7
163
k37
(n = 14)
(mean+ SD) p value
NS
NS
BSA = body surface area; MAP = mean arterial systolic dimension; SD = 1 standard deviation.
NS
LVEDP
= left
NS
ventricular
criteria7; and no left ventricular hypertrophy when Estes’ ECG criteria8 or the echocardiographic criteria of enddiastolic left ventricular posterior wall thickness > 1.2 cm were used.g The 24 patients were divided into two groups-10 normotensive and 14 hypertensive patients. The normotensive patients had blood pressuresthat never exceeded 140/90mm Hg on multiple clinic visits. The hypertensive patients had blood pressureconsistently > 140/90 mm Hg on at least twice yearly clinic visits for several years. Although all the patients were reported to be taking various antihypertensive medications, compliance was uncertain in our indigent population who repeatedly demonstrated elevated blood pressure values. The mean duration of clinically documented hypertension was 6.9 years (range 4.2 to 9.9 years). Five of the 10 normotensive patients and 6 of the 14 hypertensive patients were male. Cardiac catheterization was performed from the femoral or brachial approach. Mean arterial blood pressure was determined by electronically averaging the signal from the central aorta during cardiac catheterization. Within 72 hours of cardiac catheterization, patients were studied with M-mode and two-dimensional echocardiography by means of standard techniques. The aortic root and left atrial dimensions were measured with the leading edge technique.g The aortic root dimension was measuredat end-diastole at the level of the aortic valve. The left atria1 dimension was measured at its largest diameter and the exact location of the posterior atrial wall wasconfirmed by two-dimensional echocardiography. The normal values for left atrial size, left atria1 index, and left atrial-to-aortic root dimension ratio are 4.0 cm, 2.0 cm, and 1.17, respectively.g~la Left ventricular cavity dimensionswere measuredfrom two-dimensional echocardiographic-guided M-mode recordingsat the level of the chordae tendineae by meansof a technique we have previously validated.” Left ventricular posterior wall thickness was measuredas the distance between the endocardium of the posterior wall and the origin of the epicardial echo obtained during electrical damping of the ultrasound signaLl The end-diastolic point was measured at the peak of the R wave on a
end-diastolic
NS pressure;
NS EDD
= end-diastolic
NS dimension;
NS ESD
= end-
simultaneousECG recording. Echocardiographic left ventricular cross-sectional area and mass were determined with the end-diastolic posterior wall thickness by the method of Troy et al.,13 and were corrected by the technique of Devereux et al.,” since we used the newer American Society of Echocardiography conventiorP for measuring wall thickness. Those reading the echocardiograms were blinded as to the results of cardiac catheterization and the clinical status of the subjects. The values for hemodynamic and echocardiographic variables were listed as mean f 1 standard deviation. The control values were compared to the hypertensive patient values by meansof an unpaired Student’s t test. RESULTS
Table I lists the clinical, echocardiographic, and hemodynamic characteristics of the two groups. There was no difference in the age, end-diastolic or end-systolic dimensions, percent fractional shortening or ejection fraction, end-diastolic pressure, or left ventricular mass. The hypertensive group had a significantly higher mean arterial pressure at 107 ZL 9 mm Hg compared to 91 + 9 mm Hg for the normotensive group. Fig. 1, A shows the left atrial dimension for each patient in the two groups. Note that most of the normotensive patient values fall below the normal upper limit of 4 cm. The average left atria1 dimension was 3.46 k 0.3 cm for the normotensive group and was significantly higher, at 4.04 + 0.3 cm, in the hypertensive group @ < 0.01). Fig. 1, B shows the left atrial index-left atrial dimension divided by body surface area for the two groups. The hypertensive group had a significantly higher mean value of 2.18 + 0.45 cm/m2 as compared to 1.88 + 0.10 cm/ m2 in the normotensive patients (p < 0.05). Again, most of the normotensive patients fell below the upper limit of normal of 2 cm/m2. The ratio of the left atrial dimension to the aortic root dimension for each patient in the two groups is
oclober
1050
Miller,
O’Rourke,
and Crawford
Amorlcan
3.4 3. 4 SO2.c
T-I-SD
Hmrl
less
Journal
l
. .
2.62.4.
PS.05
2.2.
;
2.0. I.& 1.61.41.2. LO-
Ir 2 .
IrLEF&?IALIND$m,d DIMENSION
J’ ! .
C.LAd/Aod
1. A, Left atrial dimension. 6, Left atrial index. C, Left atrial dimension-to-aortic root dimension ratio for normal (IV) and hypertensive (HT) individuals. Fig.
shown in Fig. 1, C. Note that 13 of the 14 hypertensive patients’ values were above the suggested normal value of 1.17. Also, the mean value in the normotensive group was significantly lower than that in the hypertensive group (1.17 -+ 0.07 versus 1.36 + 0.20, p < 0.01). DISCUSSION
ECG evidence of left atrial enlargement has been shown to occur in hypertensive patients. Frohlich et al.4 compared 25 normotensive patients to 97 untreated hypertensive patients (21 of whom had normal coronary arteriography) to determine the presence of left ventricular dysfunction and left atrial enlargement by ECG criteria. It was found that ECG left atrial abnormality was related to the initial hemodynamic evidence of left ventricular dysfunction, as measured by left ventricular ejection rate, tension time index, and left ventricular stroke work. Furthermore, when left ventricular hypertrophy became apparent, there was further deterioration in hemodynamic indices of left ventricular function. Also, it should be noted that the ECG was used solely for evaluation of left atrial size, and other investigators15 have shown that left atrial enlargement by ECG does not necessarily correlate with echocardiographic left atrial enlargement and may be a manifestation of a conduction delay due to other causes. Savage et a1.3 studied 234 hypertensive patients by echocardiography. They excluded the presence of coronary artery disease on the basis of a negative history and the absence of ECG evidence of myocar&al infarction. Thev found 15% to have increased left atrial dimensions and concluded that left atrial enlargement did not appear to be an early sign of cardiac involvement; however, they did not study left atrial enlargement in relation to left ventricular
hypertrophy and whether they occur independently. Also, the number of patients with subclinical coronary artery disease was unknown but presumably was not zero in a population of middle-aged patients with hypertension. Our results demonstrate that echocardiographicalIy demonstrated left atrial enlargement in patients with hypertension and no other cardiovascular disease occurs in the absence of ECG left atrial abnormality and ECG or echocardiographic manifestations of left ventricular hypertrophy. Of the three methods used to determine left atrial enlargement echocardiographically, the left atrial-to-aortic root dimension ratio provided the best separation between the normotensive and hypertensive subjects. However, with all three methods there is overlap of the hypertensive patients with the normal patients. Nevertheless, few of the normal patients had abnormal values and none of the 10 normotensive patients had left atrial enlargement when all three methods were used. The cause of early left atrial enlargement is unknown, but other studies have suggested that abnormal left ventricular compliance may be an early sign in hypertensive patients. Dreslinski et all6 demonstrated reduced left atrial emptying index as assessed by M-mode echocardiography in hypertensive patients without ECG evidence of left atrial or ventricular enlargement, but their patients did have a significantly higher echocardiographic left ventricular mass compared to a control group. Also, Inouye et al.” noted abnormal radionuclide angiographic measures of diastolic left ventricular filling in patients with mild to moderate hypertension, but there was a correlation between these measures and echocardiographic left atrial dimension and left ventricular mass. In addition, Smith et all8 showed that radionuclide peak diastolic filling rates were
Volume Numbor
116 4
prolonged in 20 hypertensive patients without ECG evidence of left ventricular hypertrophy, including 4 of 12 patients with normal echocardiographic left ventricular mass. However, peak filling rate also is determined by left atrial pressure and cannot be ascribed exclusively to changes in left ventricular diastolic function.ls Therefore without knowledge of left atrial pressure, firm conclusions concerning the meaning of changes in noninvasively determined filling rates cannot be made. One limitation of our study was that this was a select group of patients undergoing cardiac catheterization for chest pain syndromes. Although no cardiac disease was found by the usual criteria, we may have selected out patients with subclinical heart disease. Consequently, we cannot estimate the frequency with which left atrial enlargement would be the first manifestation of hypertensive heart disease. Second, we have no invasive or noninvasive measures of left ventricular diastolic function, since these procedures are not routinely performed in our clinical laboratories. However, there was no difference between the control subjects and the hypertensive patients in left ventricular end-diastolic pressure. Thus we cannot determine directly the specific cause of the left atrial enlargement in our patients. Finally, we have insufficient long-term longitudinal data on our patients to ascertain whether overt hypertensive heart disease eventually will develop. Regardless of the mechanism, our data demonstrate that echocardiographic left atria1 enlargement in the absence of evidence for left ventricular hypertrophy can occur in patients with systemic hypertension. This finding may represent an early manifestation of hypertensive heart disease and should not be ignored. Also, patients with ECG evidence of left atria1 abnormality should have an echocardiogram to corroborate that this aberration is due to left atrial enlargement rather than to atrial conduction abnormalities. REFERENCES
1. Kannel WB, Castelli WP, McNamara PM, Mckee PA, Feinlab M. Role of blood pressure in the development of congestive heart failure. N Engl J Med 1972;287:781. 2. Culpepper WS. Cardiac anatomy and function in juvenile hypertension: current understanding and future concerns. Am J Med 1983;75:57.
Left
atria1 enlargement
in hypertension
1051
3. Savage DD, Drayer JIM, Henry WL, et al. Echocardiographic assessment of cardiac anatomy and function in hypertensive subjects. Circulation 1979;59:623. 4. Frohlich ED, Tarazi RC, Dustan HP. Clinical-physiological correlations in the development of hypertensive heart disease. Circulation 1971;44:446. 5. Friedberg CK. Diseases of the heart. Philadelphia: W.B. Saunders Co, 19661474. 6. Dunn FG, Chandraratna P, decarrallo JGR, Basta LL, Frohlich ED. Pathophysiologic assessment of hypertensive heart disease with echocardiography. Am J Cardiol 1977; 39389. 7. Morris JJ, Estes EH, Whalen RE, Thompson HK, McIntosh HD. P-wave analysis in valvular heart disease. Circulation 1964;29:242. 8. E&es EH. Electrocardiography and vectorcardiography. In: Hurst JW, ed. The heart. New York: McGraw-Hill Book Co, Inc, 1974:297. 9. Gardin JM, Henry WL, Savage DD, Ware JH, Burn C, Borer JS. Echocardiographic measurements in normal subjects: evaluation of an adult population without clinically apparent heart disease. J Clin Ultrasound 1979;7:439. 10. Brown OR, Harrison DC, Popp RL. An improved method for echographic detection of left atria1 enlargement. Circulation 1974;50:58. 11. Crawford MH, Grant D, O’Rourke RA, Starling MR, Groves BM. Accuracy and reproducibility of new M-mode echocardiographic recommendations for measuring left ventricular dimensions. Circulation 1980;61:137. 12. Sahn DJ, DeMaria A, Kisslo J, Weiman A: The Committee on M-mode Standardization of the American Society of Echocardiography. Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements. Circulation 1978;58:1072. 13. Troy BL, Pombo J, Rackley CE. Measurements of left ventricular wall thickness and mass by echocardiography. Circulation 1972;45:602. 14. Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Camp0 E, Sachs I, Reichek N. Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol 1986;57:450. 15. Josephson ME, Kastor JA, Morganroth J. Electrocardiographic left atria1 enlargement; electrophysiologic, echocardiographic and hemodynamic correlates. Am J Cardiol 1977;39:969. 16. Dreslinski GR, Frohlich ED, Dunn FG, Messerli FH, Suarez DH, Reisin V. Echocardiographic diastolic ventricular abnormality in hypertensive heart disease: atria1 emptying index. Am J Cardiol 1981;47:108’7. 17. Inouye I, Massie B, Loje D, et al. Abnormal left ventricular filling: an early finding in mild to moderate systemic hypertension. Am J Cardiol 1984;53:120. 18. Smith VE, Schulman P, Karimeddini MK, White WB, Meeran MK, Katz AM. Rapid ventricular tilling in left ventricular hypertrophy. 11. Pathologic hypertrophy. 3 Am Co11 Cardiol 1985;5:869. 19. Ishida Y, Meisner JS, Tsujioka K, Gallo JI, Yoran C, Frater RWM, Yellin EL. Left ventricular filling dynamics: influence of left ventricular relaxation and left atria1 pressure. Circulation 1986;74:187.