Hemodynamic effects of pacing-induced tachycardia in valvular

JOHN 0. PARKER, MD ALEXANDER L. MARK, MD VIJAY R. SANGHVI, MD ROXROY 0. WEST, MD FAREEDUDIN KHAJA, MD

The hemodynamic effects of tachycardia were studied in tension systolique dans l'art.re brachiale n'a pas change 13 patients with valvular aortic stenosis. Observations durant la stimulation, mais la tension systolique ventricu- were made during sinus rhythm (average rate 80 laire gauche tomba de 208 mm Hg . 201 mm Hg durant beats/mm) and two periods (P1 and P2) when atrial P1 (p < 0.05) et . 193 mm Hg durant P2 (p <0.001). Le pacing increased the heart rate to 109 and 131 beats! gradient systolique moyen de la valvule aortique .tait en mm respectively. The cardiac index did not change, but moyenne de 64 mm Hg sous rythme sinusal; il s'abaissa . the left ventricular stroke work index fell from 61.8 to 51 mm Hg durant P2 (p < 0.001), et le gradient 39.5 g.m/in2 (p < 0.001) as the heart rate increased. The maximum chuta de 82 . 69 mm Hg durant P2 (p < left ventricular end-diastolic pressure averaged 18 mm 0.001). La fraction d'&jection ventriculaire gauche aug- Hg during sinus rhythm and fell to about 11.5 mm Hg at menta de 26.9% sous rythme sinusal . 31.9% durant P1 P1 and P2 (p < 0.001). The brachial arterial systolic (p < 0.05) et . 34.7% durant P2 (p < 0.005). A cause de pressure did not change during pacing, but the left la prolongation de la fraction d'.jection ventriculaire ventricular systolic pressure fell from 208 mm Hg to 201 gauche et de Ia diminution du volume systolique, un plus mm Hg during P1 (p <0.05) and 193 mm Hg during P2 petit gradient de pression se manifesta dans la valvule (p < 0.001). The mean systolic aortic valve gradient st.nos&e aux rythmes cardiaques acc.l.r.s. Le test de averaged 64 mm Hg during sinus rhythm and fell to 51 stimulation contribua peu . l'.valuation de la fonction mm Hg during P2 (p < 0.001), and the peak aortic valve ventriculaire gauche et, en consequence, n'est pas utile gradient fell from 82 to 69 mm Hg during P2 (p < 0.001). lors des etudes envahissantes des r.tr&issements de The left ventricular ejection time fraction increased from l'orifice aortique. 26.9% during sinus rhythm to 31.9% during P1 (p < 0.05) and 34.7% during P2 (p < 0.005). Because of the Tachycardia, whether caused by , emotional prolonged left ventricular ejection time fraction and stimuli, or other influences, is well known smaller , a smaller pressure gradient devel- to have a deleterious effect in patients with valvular oped across the stenosed valve at higher heart rates. The heart disease, and it frequently leads to acute pulmo- pacing test was of little value in assessing left ventricular nary edema. Artificial pacing of the heart permitted us function and thus is not useful during invasive investiga- to assess the effects of controlled increments of heart tions of valvular aortic stenosis. rate in the absence of changes in or systemic ."3 Atrial pacing has been shown Les effets h.modynamiques de la tachycardie ont &t. to increase the valve gradient in mitral stenosis, demon- .tudi.s chez 13 patients souffrant de r.tr&issement de strating the importance of heart rate,4'5 but there is little l'orifice aortique. Les observations furent effectu.es sous information available on the comparable effects in rythme sinusal (rythme cardiaque moyen de 80 pulsations! valvular aortic stenosisi'7 Our study was designed to mm) et durant deux p.riodes (P1 et P2) alors que la evaluate the hemodynamic response to graded increases stimulation auriculaire acc.l&ait le rythme cardiaque . in heart rate in patients with valvular aortic stenosis. 109 et 131 pulsations/mm respectivement. L'index car- diaque n'a pas change, mais l'index de travail systolique Patients and methods ventriculaire gauche chuta de 61.8 . 39.5 g.m/in2 (p < 0.001) avec l'acc.l&ration du rythme cardiaque. Sous Thirteen patients with isolated valvular aortic steno- rythme sinusal la tension t.l.diastolique ventriculaire sis, 10 of them men, were studied. Their ages ranged gauche &tait en moyenne de 18 mm Hg; elle tomba aux from 23 to 68 years. All were symptomatic, with 11 environs de 11.5 mm Hg durant P1 et P2 (p < 0.001). La experiencing dyspnea and 5 having chest when exercising, and 3 having had episodes of . None had had congestive . All had sinus From the cardiopulmonary laboratory, department of medicine, rhythm and clinical findings indicating moderate to Queen's University, Kingston, Ont. severe valvular aortic stenosis. Informed consent was Reprint requests to: Dr. John 0. Parker, Cardiopulmonary laboratory, obtained from each patient, and there were no untoward Etherington Hall, Queen's University, Kingston, Ont. K7L 3N6 effects from this investigation. 38 CAN MED ASSOC J, VOL. 129, JULY 1, 1983 We studied the patients when they were fasting. The left ventricular stroke work index (in gram- Using local anesthesia we isolated the brachial metres per square metre) was calculated with the and two in the right antecubital fossa. A no. 6 formula bipolar pacing catheter was placed with its tip against the lateral wall of the right atrium, a no. 8 Cournand LVSWI = SI X (LVs - LVEDP) X 13.6, catheter was placed with its tip in the pulmonary artery, 1000 and a no. 8 Sones catheter was introduced into the right brachial artery and advanced into the left . In where SI = stroke index (in millilitres per square three patients retrograde catheterization was unsuccess- metre), LVs = mean left ventricular systolic pressure ful, and the left ventricle was entered by the transseptal (in millimetres of mercury), LVEDP = left ventricular technique. The left brachial artery was cannulated with end-diastolic pressure (in millimetres of mercury), 13.6 a short Teflon needle by the Seldinger technique. - specific gravity of mercury and 1000 is a conversion Our first step was to rapidly increase the heart rate, factor (changing millimetres to metres). The area of the using a battery-operated external pacing unit, to deter- aortic valve was calculated in square centimetres from mine whether a ventricular response of 150 beats/mm the Gorlin formula.8 The mean systolic blood pressure could be obtained. If developed gradient across the aortic valve was determined by below that level, the maximal pacing rate with complete planimetric integration of the differences between the ventricular capture was noted. This preliminary pacing left ventricular systolic pressure and the brachial artery period lasted less than 1 minute. Following a 5-minute systolic pressure during three consecutive heart beats recovery period, and at least 15 minutes after placing all recorded at a paper speed of 100 mm/s. The interval catheters, we recorded blood pressures in the left between the onset of the upstroke of the brachial ventricle and the brachial artery as control data. We arterial pressure curve and the dicrotic notch, recorded determined the cardiac output in duplicate by injecting at a paper speed of 100 minIs, gave us the left 5 mg of indocyanine green into the pulmonary artery ventricular ejection time. This was expressed as the left and withdrawing blood from the brachial artery through ventricular ejection time fraction (LVETF), with a cuvette densitometer. We then began pacing the heart at a rate approximately half way between the sinus rate LVET x 100 and the maximal rate determined in the initial pacing LVETF- RR test. This rate (P1) was maintained for 4 minutes and then raised to the maximal rate (P2) for another 4 where RR = the interval in seconds between R waves on minutes. We recorded the during the last the electrocardiogram. 2 minutes of each pacing period. Except for The statistical significance of the differences between the patients experienced no symptoms during atrial various parameters was analysed by the paired 1-test, pacing. the p values representing the significance of the change We measured all blood pressures with P23Db trans- from the control period to the respective pacing period. ducers (Statham Instruments Division, Gould Inc., At the conclusion of the study we performed a left Oxnard, California) from a zero level 5 cm below the ventriculogram, an aortic root injection and selective angle of Louis and recorded them on a multichannel cine coronary arteriography in each of the patients. photographic recorder at a paper speed of 25 mm/s (100 None of them had significant . mm/s for determination of the left ventricular end-dias- None had hemodynamic or angiographic evidence of tolic pressure). Blood pressures were measured over two associated disease, and none had more than respiratory cycles. trivial .

CAN MED ASSOC I, VOL. 129, JULY 1, 1983 39 Results arterial pressure, resulting in a 25% increase in the aortic valve gradient.'3 The hemodynamic data for each test period are Kroetz and associates6 studied the effect of both atrial presented in Table I. The control heart rate ranged from and ventricular pacing in valvular aortic stenosis and 64 to 110 beats/mm, averaging 81 beats/mm. The showed that increases in heart rate significantly de- average heart rate increased to 109 and 131 beats/mm creased the mean systolic gradient. Linhart,7 however, during the first and second pacing periods respectively. found no change in the mean pressure gradient during pacing to an average heart rate of 135 beats/mm. Discussion The systolic gradient across the aortic valve is impor- tant in the assessment of the severity of outflow The hemodynamics in valvular aortic stenosis have obstruction. Analysis of the variables affecting the been studied during a variety of interventions. Anderson gradient has been facilitated by the development of an and coworkers9 found that exercise produced small, equation that relates the gradient to the aortic valve variable changes in the mean systolic gradient across the area, cardiac output and duration of flow across the aortic valve, the greatest being an increase of 27 mm valve.8 The Gorlin formula may be rearranged thus: Hg. Although there was no change in the average gradient between rest and exercise, the systolic blood - CO/SET2 flow increased by 30%. They suggested that the aortic AVG . X AVA valve may not behave as a fixed orifice under all hemodynamic conditions. Lee and associates'0 likewise where AVG - mean aortic valve gradient (in mil- found no significant change in the peak systolic gradient limetres of mercury), CO = cardiac output (in mil- during leg exercise while supine. lilitres per minute), SET = systolic ejection time (in The effects of an infusion of isoproterenol have been seconds per minute), 44.5 is an empiric constant for the studied in patients with valvular aortic stenosis. The aortic valve and AVA = aortic valve area (in square majority showed marked increases in the peak systolic centimetres). The mean systolic gradient is directly gradient." Perloff and colleagues'2 studied the effects of related to the square of the flow across the aortic valve increasing the afterload with an angiotensin infusion in systole (CO/SET) and inversely related to the square and reported a rise in the left ventricular and bra- of the aortic valve area. The cardiac output during chial arterial systolic pressures. The gradient fell as the pacing-induced tachycardia is unchanged, while the increase in the arterial systolic pressure exceeded the systolic ejection time per minute increases. If the aortic increase in the left ventricular pressure. Amyl nitrite valve area remains constant and the same volume of inhalation produced a regular fall in the left ventricular blood passes through a valve that is open for a longer systolic pressure but a greater decline in the brachial time, the gradient generated should decrease. This is

FIG. 1-Left ventricular stroke work index (LVSWI) plotted against left ventricular end-diastolic pressure (LVEDP) during control period and two pacing periods (Pi and Pa). Left panel shows values from patients with an LVEDP of less than 15 mm Hg during sinus rhythm, and right panel shows values from patients with an LVEDP of 15 mm Hg or more. Left ventricular filling pressures decreased during pacing-induced tachycardia. 40 CAN MED ASSOC J, VOL. 129, JULY 1, 1983 what our results show, with the mean aortic valve References gradient decreasing during tachycardia. 1. Ross J Ji., LINHART 1W, BRAUNWALD E: Effects of changing Atrial pacing at different rates has proven useful in heart rate in man by electrical stimulation of the right atrium. the evaluation of the Frank-Starling mechanism, since Studies at rest, during exercise, and with isoproterenol. Circula- cardiac output and systemic blood pressure do not tion 1965; 32: 549-558 change during pacing; there is a progressive decline 2. STEIN E, DAMATO AN, KosowsKY BD, LAU SH, LISTER 1W: in The relation of heart rate to cardiovascular dynamics. Pacing by stroke work as heart rate is increased.'4 Simultaneous atrial electrodes. Circulation 1966; 33: 925-932 changes in the left ventricular end-diastolic pressure can 3. PARKER JO, LEDWICH IR, WEST RO, CASE RB: Reversible be recorded, and by employing multiple pacing rates one cardiac failure during pectoris: hemodynamic effects of can construct a ventricular function curve. In a study of atrial pacing in coronary artery disease. Circulation 1969; 39: 10 patients with valvular aortic stenosis Linhart7 found 745-757 4. ARANI DT, CARLETON RA: The deleterious role of tachycardia in these curves to be steeper than normal, although in 3 mitral stenosis. Circulation 1967; 36: 511-516 patients the left ventricular filling pressure rose during 5. NAKHJAVAN FK, KATZ MR, MARANHAO V, GOLDBERG H: pacing. He felt that the ventricular function curve Analysis of influence of and tachycardia during obtained by pacing the heart was of help in assessing supine exercise in patients with mitral stenosis and sinus rhythm. left ventricular function in cases of aortic stenosis, even Br Heart J 1969; 31: 753-761 though only one of his patients had abnormal 6. KROETZ FW, LEONARD JI, SHAVER IA, LEON DF, LANCASTER an left JF, BEAMER VL: The effect of atrial contraction on left ventricu- ventricular filling pressure during sinus rhythm. lar performance in valvular aortic stenosis. Circulation 1967; 35: Fig. 1 shows the left ventricular function curves for 852-867 our 13 patients and relates the left ventricular stroke 7. LINHART JW: Hemodynamic consequences of pacing-induced work index to the left ventricular end-diastolic pressure. changes in heart rate in valvular aortic stenosis. Circulation 1972; All the patients showed an overall decrease in the left 45: 300-309 ventricular 8. GORLIN R, GORLIN SG: Hydraulic formula for the calculation of filling pressure as stroke work declined the area of the stenotic mitral valve, other cardiac valves, and during pacing-induced tachycardia. At a higher rate, central circulatory shunts. Am Heart J 1951; 41: 1-29 however, four patients showed an increase in the left 9. ANDERSON FL, TSAGARIS TJ, TIKOFF G, THORNE IL, SCHMIDT ventricular end-diastolic pressure in spite of a further AM, KUIDA H: Hemodynamic effects of exercise in patients with decline in stroke work. This could have been secondary aortic stenosis. Am J Med 1969; 46: 872-885 to myocardial , which is known to depress 10. LEE SIK, JoNssoN B, BEVEGARD 5, KARL.F I, ASTROM H: left Hemodynamic changes at rest and during exercise in patients ventricular contractility. It is of interest that marked with aortic stenosis of varying severity. Am Heart J 1970; 79: ST-segment depression developed during pacing in two 3 18-331 of these four patients, although they experienced no 11. Moss Al, QUIVERS WW: Use of isoproterenol in the evaluation of . Patients with normal or only slightly in- aortic and pulmonic stenosis. Am J Cardiol 1963; 11: 734-737 creased left ventricular end-diastolic pressures tended to 12. PERLOFF 1K, BINNIoN PF, CAULFIELD WH, DELEON AC IR: The use of angiotensin in the assessment of left ventricular function in have steeper slopes in their ventricular function curves, fixed orifice aortic stenosis. Circulation 1967; 35: 347-357 while patients with abnormal left ventricular filling 13. HANCOCK EW, FOWKES WC: Effects of amyl nitrite in aortic pressures had flatter curves. Even in these patients, valvular and muscular subaortic stenosis. Circulation 1966; 33: though, the slope tended to steepen as the left ventricu- 383-389 lar filling pressure decreased toward normal. None of 14. PARKER JO, KHAJA F, CASE RB: Analysis of left ventricular the patients with a relatively flat ventricular function function by atrial pacing. Circulation 1971; 43: 241-252 curve had angiographic evidence of important left ventricular dysfunction, and the depressed curves may have been related to diminished left ventricular comp- RADIQIMMUNOTECHNOLOGY liance associated with long-standing pressure overload. continued from page 19 Analysis of the left ventriculograms showed no relation between left ventricular contractility, as assessed angio- 9. SHEARMAN P1, LONGENECKER BM: Clonal variation and func- graphically, and tional correlation of organ-specific metastasis and an organ- the slope of the left ventricular function specific metastasis-associated antigen. mt . Cancer 1981; 27: curve. Thus, the high left ventricular end-diastolic 387-395 pressure and the associated depression of the left 10. HAMBLIN TJ: Immune guided missiles. Br Med J 1982; 285: 461- ventricular function curve may have been primarily 463 related to decreased left ventricular compliance. 11. MEW D, CHI-KIT WAT, TOWERS GHN, LEVY IG: Photoim- Tachycardia is relatively well tolerated in aortic munotherapy: treatment of animal tumors with tumor specific stenosis, as the systolic ejection time per minute is monoclonal antibody-hematoporphyrin conjugates. J Immunol actually increased. The appearance in four of our (in press) patients of an increasing left ventrk.ular end-diastolic 12. SHARON N, LIS H: Lectins: cell agglutinating and sugar specific pressure as the pacing rate increased probably repre- proteins. Science 1972; 177: 949-959 sented a depression of ventricular function secondary to 13. BOLAND CR, MONTGOMERY CK, KIM YS: Alterations in human myocardial ischemia. With this exception we have found colonic mucin occurring with cellular differentiation and malig- a pacing test to be of little help in the assessment nant transformation. Proc Natl Acad Sci USA 1982; 79: 2051- of patients with valvular aortic stenosis. 2055 14. ZABEL PL, NOUJAIM AA, SHYSH A, BRAY 1: Radioiodinated peanut lectin: a potential radiopharmaceutical for detection of This study was supported in part by grants from the Medical tumors expressing the T-antigen. In Proceedings of the Second Research Council of Canada (MA-3062) and the Ontario International Radioimmunoimaging Symposium, Albuquerque, Heart Fund (OHF 2-13) New Mexico, Nov 1982, (in press)

CAN MED ASSOC J, VOL. 129 JULY 1, 1983 41