JOURNAL OF ELECTROCARDIOLOGY, 21 (1), 1988, 31-38

Aortic Valve Disease and the ST Segment/Heart Rate Relationship: A Longitudinal Study Before and After

Aortic Valve Replacement BY NICHOLAS BISHOP, M.R.C.P. (U.K.),* ROGER M. BOYLE, M.R.C.P. (U.K.),$ DAVID A.W. WATSON,

F.R.C.S.,** JOHN B. STOKER, F.R.C.P.,~'~" DAVID A.S.G. MARY, PH.D., F.R.C.P.,***

SUMMARY The ST segment/heart rate relationship or maximal ST/HR slope has been validated

as an index of myocardial ischemia in selected populations of patients with angina pec- toris. The present s tudy involved patients selected as having aortic valve disease unac- companied by angiographic coronary artery narrowing.

In each of seven patients, so far examined, a slope value and ST segment depression of >1 mm were obtained which, according to previous experience, indicated myocardial ischemia equivalent to coronary heart disease.

After aortic valve replacement, there was a significant reduction in heart size as assessed using the cardiothoracic ratio, and the amplitude of QRS complex on the electrocardio- gram. The slope was abolished (two patients) or markedly reduced (five patients), and the decrease in the seven patients was statistically significant. ST segment depression could be obtained in one patient.

This s tudy has shown the occurrence of maximal ST/HR slope in patients without large coronary artery disease who have aortic valve disease and cardiac enlargement.

The maximal rate of depression of the ST seg- ment with increases in heart rate (maximal ST/HR slope} has been proposed as an index of myocardial ischemia. 1 In selected hospital populations of pa- t ients with angina in Leeds this slope was found to be reliable in the detection of myocardial ische- mia solely assessed by coronary arteriographyY -~ In general, however, indices of myocardial ischemia during exercise have been found to be sensitive to other cardiac lesions; for instance, in groups of pa- tients with aortic valve disease and cardiac enlarge- ment unaccompanied by narrowing of the coronary

*Research Fellow, University of Leeds $Consultant Cardiologist, York District Hospital, York, U.K. **Consultant Cardiothoracic Surgeon, Killingbeck Hospital ~tConsultant Cardiologist, Killingbeck Hospital ***Senior Lecturer, University of Leeds

From the Department of Cardiovascular Studies, University of Leeds, Leeds LS2 9JT and Killingbeck Hospital, York Road, Leeds LS14 6UQ. U.K.

Reprint requests to: Dr. D.A.S.G. Mary, Department of Cardio- vascular Studies, The University, Leeds LS2 9JT, U.K.

artery, changes in the level of the ST segment have been reported during exercise and at t r ibuted to myocardial ischemia. 1,5

The present s t u d y was planned to f ind out whether the maximal ST/HR slope can be obtained in a selected group of patients with aortic valve dis- ease unaccompanied by angiographic evidence of coronary artery narrowing. In each of seven con- secutive pat ients so far examined, a slope was ob- t a ined which decreased a f t e r aor t ic valve replacement; the details of the s tudy are reported.

MATERIALS AND METHODS Consecutive patients with evidence of left ventricular

hypertrophy and/or dilatation, as well as aortic valve disease but without narrowing of the coronary artery or angina, in whom aortic valve replacement had been recommended, were included in the trial. Patients were not included if they had pre-syncopal symptoms which could be attributed to aortic stenosis. Other exclusion criteria were cardiac arrhythmia, heart failure, digoxin therapy and inability to exercise.

The trial was designed to find out firstly if significant values of the maximal ST/HR slope could be obtained in the absence of coronary artery disease, and secondly to find out, with each patient acting as his own control, whether the expected reduction in cardiac size or hyper-

31

32 BISHOP ET AL

trophy following aortic valve replacement was associated with a reduction in the maximal ST/HR slope. Cardiac size was assessed using the cardiothoracic rati(~ and echo- cardiographic dimensions of the left ventricle and car- diac hypertrophy were assessed electrocardiographicaUy.

A resting electrocardiogram, chest X-ray, echocardi- ography and the exercise test to derive the maximal ST/HR slope were obtained within the week prior to the operation. These procedures were repeated at least three months post-operatively. Details of the two sets of data, the maximal ST/HR slope and the other estimates, were independently obtained to enable a blind comparison between the two sets. Exercise test

The exercise test was performed in the week prior to operation and at least three months postoperatively. The details of the exercise test have been described elsewhere. 6 Briefly, the exercise test was performed on an electrically braked bicycle ergometer with the patient in the upright position. Each test was preceded by a short preliminary exercise in order to familiarize the patient with the procedure, check the adequacy of ECG record- ings from all 13 leads used and replace them if necessary and to determine the step increases in workload required to obtain step increases in heart rate of approximately 10 beats/min. During the test the workload was increased at three-minute intervals, the test being terminated for the following reasons: anginal pain, ST segment depres- sion >0.3mV, arrhythmia, a decrease in blood pressure, or exhaustion of the patient.

The ECG was recorded from 13 leads, 12 conventional leads and a bipolar lead (CM5) using an ink jet Mingo- graph recorder (Siemens type 62). The leads were cali- brated in the usual way by setting the amplifier gain so tha t a lmV signal caused a displacement of 10mm on the ECG. Records from the 13 ECG leads were obtained at rest, and at the steady state (heart rate value within 5% of the mean which usually occurred during the last minute of each exercise step}; monitoring was continued for at least five minutes after the cessation of exercise. The ECG was monitored throughout the test and recov- ery period. Systemic blood pressure was measured before, during the third minute of each exercise step and dur- ing the recovery period.

The ST segment level was measured at a point 80 msecs after the end of the QRS complex, with a line drawn between consecutive P-R segments being taken as the zero reference. This measurement was made using a magnifying glass fitted with a graticule marked in 0.1mm divisions. The heart rate (beats/min) was calcu- lated by measuring he R-R interval on the ECG. The value of the heart rate and ST segment level used in the calculation were taken as the average value measured in at least ten consecutive cardiac cycles obtained from records of all 13 ECG leads.

The maximal ST/HR slope was derived by perform- ing regression analysis in the relationship between the ST segment level and heart rate in each of the 13 ECG leads. In each lead the steepest slope of the computed regression lines which showed a linear regression was

noted from amongst the lines resulting from analysing the final three stages of exercise and progressively includ- ing further submaximal stages of exercise. The maximal ST/HR slope, representing the steepest slope of all the linear regressions in all 13 ECG leads, was used as an index of myocardial ischemia, and has units of mm/beats.min.10-3.1

The level of the ST segment, at rest and at the end of exercise in each ECG lead, was noted and their differ- ence used to obtain the net maximal ST segment depres- sion in any lead. Assessment of changes in cardiac size and hypertrophy

Hear t size was assessed radiologically by measur- ing the cardiothoracic ratio from postero-anterior chest X-rays taken at standardized distance before and after valve replacement. The cardiothoracic ratio was obtained in the usual way by dividing the transverse diameter of the heart by the internal diameter of the chest. ~ Chest X-rays were obtained within seven days prior to the oper ~ ation and on the same day as the exercise test following the operation. In some patients echocardiography was used to assess changes in left ventricular dimensions at end-systole and end-diastole. ECG evidence of changes in left ventricular hypertrophy was assessed from the resting, supine ECG. s,9 The sum of the S wave in lead V1 (SV1) and the R wave in V5 or V6 (RV5/V6), s and the sum of the largest precordial S wave and the largest R wave (max S + R), 9 w e r e measured from ECG records obtained in the week prior to operation and three to six months postoperatively. The presence of "strain pat- t e rn - -ST segment depression and T wave inversion-- on the resting ECG was noted.

Statistical analysis of the differences before and after valve replacement was done using the paired t test. Corr~ lation between the maximal ST/HR slope and other data was calculated in the usual way.

RESULTS Seven p a t i e n t s were p ro spec t i ve ly s tud ied and

the i r clinical and a n g i o g r a p h i c deta i ls are g iven in Table I. All seven p a t i e n t s m a d e a good recovery f rom surgery. C h a n g e s in the m a x i m a l S T ] H R slope

Pr io r to aor t i c va lve r e p l a c e m e n t the m a x i m a l S T / H R slope was 25.0 _+ 7.1 mm. b e a t s - l . m i n . 1 0 - 3 [13-33.3] (mean _+ S.D. [range]) (see Fig. 1 and Table II). T h u s all p a t i e n t s h a d a slope value t h a t sugges ted myocardia l i schemia which, according to previous experience wi th the max ima l S T / H R slope in p a t i e n t s w i th angina, 1 was equ iva len t to coro- n a r y h e a r t disease.

Fig. 1 i l lus t ra tes in each of the seven pa t i en t s the reduc t ion in the va lues of t he m a x i m a l S T / H R slope t h a t occur red a t l ea s t th ree m o n t h s a f t e r aor t ic va lve r ep lacemen t . Fol lowing valve replace- m e n t the m a x i m a l S T / H R slope was 6.9 _ 5.4 m m . b e a t s - - l . m i n . 1 0 - 3 [0-14.3]. A r e d u c t i o n in t h e v a l u e of t h e s lope o c c u r r e d in e a c h of t h e

JOURNAL OF ELECTROCARDIOLOGY 21 (1), 1988

ST-HR RELATION IN AORTIC VALVE DISEASE 33

TABLE I

Clinical details of the patients studied

Age & Patient Sex Valve lesion Symptoms Angiographic findings

D.W. 51 M AS/AR none Aortic valve gradient 40 mm Hg, 2/4 AR

Normal coronary arteries

S.J. 40 M AR none No gradient, 4/4 AR Normal coronary arteries

C.B. 23 M AS/AR none Aortic valve gradient 65 mm Hg, calcified aortic root, 2/4 AR

Normal coronary arteries

R.P. 52 M AR minor exertional dyspnoea

No gradient, 3/4 AR Normal coronary arteries

D.C. 35 M AR exertional dyspnoea

P.R. 28 M AS/AR exertional dyspnoea dizziness

Aortic valve gradient 70 mm Hg, 3/4 AR

Normal coronary arteries

J.W. 58 M AS none Aortic valve gradient 60 mm Hg, heavily

calcified valve, no AR Normal coronary arteries

AS = Aortic Stenosis AR = Aortic Regurgitation

seven patients, and these reductions 18.1_+3.25 mm.beats - l .min .10-3 [3-28] (mean _+ S.E. [range]) were statistically significant (P<0.005). Six pa- t ients had reductions in the value of the slope which, according to previous experience in pa- tients with angina, 1 indicated absence of coronary heart disease; the remaining pat ient continued to have slope values indicating coronary heart disease, though the slope was reduced following valve replacement. ST segment depression during exercise

Before aortic valve replacement all seven pa- t ients developed a maximal net ST segment de- pression exceeding 1 mm; only one pat ient (JW) still had such a positive response post-operat ively (see Table II). Assessment at rest

Details of the cardiothoracic ratio in each of the seven pat ients are shown in Table II; in each pa- tient there was a reduction in the cardiothoracic ratio following valve replacement (Fig. 2). Pre- operatively the cardiothoracic ratio was 52.9 _+

5.1% [45-59] (mean _+ S.D. [range]) falling to 47.9 _+4.5% (43-54) after valve replacement; group reduction 4.9 _+ 0.8% [1-8] (mean _+ S.E.) was statistically significant (P<0.005)o Left ventricular internal dimensions obtained by echocardiography in three of the seven pat ients were used to indicate whether reductions in cardiothoracic ratio included a reduction in left ventricular dimensions; their de- tails are given in Table I I. A reduction in both sys- tolic and diastolic dimensions occurred after valve replacement in each of these three patients.

The electrocardiographic QRS voltage was used as an index of left ventricular hypertrophy and its details are given in Table II. Reduction occurred in all pat ients in the sum of SV1 + RV5/V6 and max S + R. The reductions were in SV1 + RV5/V6, 16.4 _+ 3.5 mm [6-32] (mean _+ S.E. [range]) and in the sum of max S + R was 19.9 _ 4.6 mm [9-39]; both reductions were statist ically significant (P<0.005 and P<0.01, respectively).

The two pat ients with "strain pat tern" on their resting ECG had the largest cardiothoracic ratios

JOURNAL OF ELECTROCARDIOLOGY 21 (1), 1988

34 B ISHOP ET A L

TABLE II

Individual changes in maximal STIHR slope, measures of heart size assessed radiologically and using M-mode echocardiography and electrocardiographic features of left ventricular hypertrophy

Patient

Maximal ST/HR slope (mm. beats-l.min.10-3)

Before Post AVR

Maximal net ST segment depression (mm)

Before Post AVR

DW 13 10 - 1.1 0 SJ 25.7 7.1 - 1.2 - 0.3 CB 28 0 - 1.6 0 RP 18.1 5.9 - 1.2 - 0.3 DC 30 11 - 1.7 0 PR 27.1 0 - 1.2 0 JW 33.3 14.3 - 2.8 - 1.1

Mean (S.D.) 25 (7.1) 6.9 (5.4) - 1.54 (0.6) - 0.24 (0.4)

P value <0.005 <0.001

QRS ampl i tude (mm) Cardiothoracic Left ventr icular SV1 + RV5/V6 Max S + R Ratio (%) Dimension (mm)

Before Post AVR Before Post AVR Before Post AVR Before Post AVR

DW 50 36 50 36 55 49 SJ 42 36 56 44 59 54 73 (50) 53 (38) CB 73 41 85 46 53.5 45.5 RP 41 25 46 27 58 54 DC 39 20 47 36 51.5 46 70 (48) 50 (42) PR 39 17 54 19 48 43 53 (32) 44 (28) JW 40 34 46 37 45 44

Mean 46.3 29.9 54.9 35 52.9 47.9 S.D. 12.4 9.2 13.9 9.4 5.1 4.5

P value <0.005 <0.01 <0.005

Note: For left ventr icular dimensions, systol ic and diastol ic measurements are given with the systol ic ones in parentheses.

prior to surgery, and following valve replacement they were the only two patients with cardiothoracic ratios exceeding 50%.

There was no significant correlation between the maximal S T / H R slope values and indices of cardiac enlargement; similarly there was no corre- lation between the changes in these variables after valve replacement.

DISCUSSION In pat ients with angina the ST segment /hear t

rate relationship has been shown to correlate with the findings of coronary angiography. 1,1~ Although this technique is controversial 14-~6 it is considered to have some advantages over conventional ST seg- ment criteria. ~,~-~3,17,18 The ST segment /hear t rate relationship has been shown to be reproducible~ ~,~9 and is able to detect changes in myocardial ische- mia after revascularisation procedures2 ,4 Of rele-

vance to the present s tudy is the reported finding of '~alse positive" values of the ST segment/hear t rate relationship in pat ients with aortic regurgita- tion, cardiac enlargement or impaired pump func- tion during exercise. 2~ Similar '~alse positive" results have been reported when ST segment de- pression alone was considered. 22,23 Present findings

In each of the seven patients a maximal ST /HR slope equivalent to coronary heart disease was ob- tained in the absence of significant narrowing of the coronary arteries and symptoms of myocardial ischemia. Though a small number of selected pa- t ients with aortic valve disease were examined, it has been possible to demonstrate tha t '~alse posi- tive" values of the maximal ST /HR slope may be obtained. "False positive" results were also seen when net ST segment depression was considered.

After aortic valve replacement the value of the

JOURNAL OF ELECTROCARDIOLOGY 21 (1), 1988

ST-HR RELATION IN AORTIC VALVE DISEASE 35

cO I o

d E

I .~

O .O

E E o

o CO n" -r"

I-- CO

E x

36 II

0 |

Bet;ore After AVR AVR

NSD

Fig. 1. Individual changes in the maximal ST/HR slope before and 3-6 months after aortic valve replacement (AVR). The previously described ranges for double-vessel disease (II), single-vessel disease (I) and no significant disease (NSD) are given on the right of the figure.

maximal S T / H R slope was reduced, and this was associated with a reduction in heart size as as- sessed by the cardiothoracic ratio, and a reduction in left ventricular hypertrophy as assessed by QRS amplitude. The reduction in ventricular dimensions observed on echocardiography in three pat ients suggested that changes in the cardiothoracic ratio included a reduction in left ventricular dimensions. Implications

I t was not the aim of this s tudy to investigate the possible mechanisms for the effect of aortic valve disease and subsequent valve replacement on the maximal S T / H R slope. However, the nature of the present longitudinal findings may be used to argue the following possibilities. The changes in the maximal S T / H R slope could have been associated with myocardial ischemia related to small vessel disease, hemodynamic effects at the coronary ostia, or cardiac dilatation and/or hypertrophy, or even the effect of the electrocardiographic wave form it- self. These possibilities are discussed briefly below.

V

O = m

n- o

. m

O

L -

O t--

O = m

"10 L -

t~ O

60

40 ! !

Before After AVR AVR

Fig. 2. Individual changes in heart size assessed using the cardiothoracic ratio before and 3-6 months after aor- tic valve replacement (AVR).

The changes in the maximal S T / H R slope were unlikely to have been solely related to myocardial ischemia ssociated with small vessel disease, as in every pat ient the slope was abolished or much reduced after aortic valve replacement; it is unlikely tha t a hypothetical small vessel disease resolved in all patients. Also the changes in the maximal S T / H R slope obtained were unlikely to be related to the effect of the electrocardiographic wave form itself. For instance, the resting ST segment level has been found to have no effect on the maximal S T / H R slope, as the slope depends on relative changes during exercise. 1 The changes in the QRS voltage are unlikely to affect the slope; previous studies in pat ients with angina have shown that the occurrence of myocardial infarction at least six months earlier {with consequent reduction in R

JOURNAL OF ELECTROCARDIOLOGY 21 (1), 1988

36 BISHOP ET AL

wave amplitude) did not alter the accuracy of the maximal ST/HR slope. 1,6 Similarly in the present s tudy one patient (C.B.) still fulfilled the voltage criteria of left ventricular hypertrophy three to six months following valve replacement, yet had no maximal ST/HR slope.

Support tha t subendocardial ischemia may be provoked in the presence of cardiac lesions caus- ing dilatation and hypertrophy comes from work in anim/tls 24-26 and man. 27 Similarly precordial ST segment depression, which is said to reflect suben- docardial ischemia, has been observed in the ab- sence of significant coronary artery disease in patients with aortic valve disease, mitral regurgi- tation, left ventricular hypertrophy, hypertension or hyper t rophic cardiomyopathy. 22,23,2s Aort ic regurgitation has been reported to cause "false positive" values of the maximal ST/HR slope. 2~ The values of the slope reported in this s tudy were similar to the results given above (i.e., within the range 11-60 mm/beats.min.10-3, said to be equiva- lent to moderate myocardial ischemia, single- or double-vessel disease). The effect of aortic valve replacement was not studied. 2~

Hemodynamic factors at the coronary ostia may contribute to myocardial ischemia. If these factors are of great significance similar reductions in the coronary reserve of both right and left coronary arteries of patients with aortic valve disease might be expected. However, studies in patients with aor- tic stenosis and normal coronary arteries have shown tha t the coronary reserve of vessels supply- ing the hypertrophied left ventricle was reduced, while the coronary reserve of vessels supplying the right ventricle was preserved. 29

CONCLUSION The present findings have shown aortic valve

disease may be associated with values of the max- imal ST/HR slope, which according to previous experience in patients with angina is equivalent to coronary heart disease, in the absence of angina pectoris or coronary artery disease. After correc- tion of the cardiac lesion by aortic valve replace- ment, reductions in the maximal ST/HR slope occurred. These reductions were associated with evidence of reduced left ventricular size and hyper- trophy. I t is suggested tha t these patients with aortic valve disease may have experienced myo- cardial ischemia during exercise which was related to cardiac dilatation and hypertrophy.

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ST-HR RELATION IN AORTIC VALVE DISEASE 37

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JOURNAL OF ELECTROCARDIOLOGY 21 (1), 1988