natural history of unoperated aortic stenosis: hemodynamic progression

1
ABSTRACTS HYDRALAZINE EFFECTS ON HEMODYNAMICS, CARDIAC CONTRACTILE FUNCTION AND MYOCARDIAL ENERGETICS IN ISOLATED MYOCARDIUM Leigh D. Segel, PhD; Stephen V. Rendig, MS: Ezra A. Amsterdam, MD, FACC; Dean T. Mason, MD, FACC, University of California, Davis, California. There is relatively little information regarding the di- rect cardiac effects of hydralazine (H), a vasodilator drug that has been applied in the treatment of cardiac failure. To clarify the direct cardiac effects of H, dose-response curves for this agent were evaluated in (1) isolated, working rat heart (IWRH); (2) isometric cat right ventricular papillary muscle (PM); and (3) isolated rabbit right atrium (RA). IWRH (n=6): there was a marked increase in coronary flow (72199 ml/min/g, pc.05) at lo-'M H, which remained significantly elevated at lo-'M and 10m4M H. Heart rate, cardiac output, left ventricular (LV) end-diastolic pressure and myocardial oxygen consum tion (MvO2) were not altered from control at 10-8M - 1 lo- M H. Cat PM (n=7): maximum developed tension (T), dT/dtmax and time to peak tension were unaltered by lo-7M, 10-6M and lo-5M H but dT/dtmax was significantly elevated (34.+36 g/sec/mm2 , pc.05) at 10m4M and both T and dT/dtmax were increased (6.7+9.2 g/mmz, 34+62 b pc.02) at 10-3M. Pre- treatment with propranolol (lo- M, n=7) abolished this positive inotropic effect. Isolated RA (n=S): spontaneous contraction rate was unaltered by lo-7M - 10w5M H, and di- minished by lo-4M and 10v3M H (87+80~+68 beats/min, pc.005). Thus, H was associated with unaltered pump performance and WO2, accompanied by augmented coronary flow in IWRH, while high concentration of H induced a positive inotropic effect mediated by beta-adrenergic stimulation in cat PM and elicited a negative chronotropic effect in rabbit myo- cardium. These data indicate that H has a primary coronary vasodilator effect and that at concentrations utilized clinically, its salutary circulatory actions are primarily related to extracardiac vasodilator actions. TUESDAY, MARCH 11, 1980 PM AORTIC VALVE DISEASE 2:00-3:30 ATURAL HISTORY OF UNOPERATED AORTIC STENOSIS: HEMO- YNAMIC PROGRESSION. Stephen Wagner, MD, FACC; Arthur elrer, MD, FACC, Pacific Medical Center, San Francisco, A. n order to examine factors that might predict progression ate in valvular aortic stenosis (AS) we reviewed serial emodynamic studies in 50 adult pts of whom 7 had con- enital, 22 rheumatic and 21 degenerative calcific aortic tenosis (CAS). Compared with the others those with CAS ere older (62 f 6 vs. 51 + 9 yrs, p i .OOl) and had onset f murmur laterin life (In+ 4 yrs before first cath vs. 7 + 9 yrs, p < ,001). For all pts average values at irst cath include age 54 + 4 yrs, peak gradient 38 + 7 mmHg, calculated aortic-valve area (AVA) 1.3 I .7 cm2. mean 3.5 + 3 yrs later gradient was 57 + 30 mmHg and VA .8 + .4cm2. Peak left ventricular (TV) pressure rose + 33 mmHg and cardiac output (CO) fell .5 + .2 L/min. t? appeared to distribute into rapid (n = 2i) and slow n = 29) progressors with respective rates of a change in VA of .30 + .21 vs. .02 + .08 cm2/yr. 76% of RP had CAS 5. 21% of 3P (p i .OOl);-they also differed in that 484 P had serial fall in CO > 1 L/min vs. 17? of J P (p c .05) /21 RP developed criticaT AS with AVA 5 .5 c and severe V failure, all had CAS. t is concluded that pts with CAS progress more rapidly han those with congenital or rheumatic etiology and in ome reduction of calculated AVA is due to an impaired bility of the failing LV to move calcified leaflets /rather than an anatomic reduction in valve orifice area. THE ERGONOVINE STRESS TEST: A PROVOCATIVE TEST FOR DIFFUSE ESOPHAGEAL SPASM OR VARIANT ANGINA? Kenneth L. Koch, MD, Ann Long, RN, R. Charles Curry, MD, and John R. Mathias, MD. University of Florida and the Veterans Administration Medical Center, Gainesville, Florida. Intravenous ergonovine maleate (EM) during cardiac cathe- terization (CC) is used to evoke coronary artery spasm, resulting in chest pain (CP) and ST segment shifts. We have observed patients who experience CP in response to EM in the absence of spasm. The purpose of this study was to determine if EM produced esophageal dysfunction and CP. 15 patients were evaluated by routine esophageal manometry - 7 with CP(Croup 1) and 8 without CP(Group 2). All pa- tients had normal CCs. During esophageal manometry IV infusions of saline 10 ml or EM .2-.4 mg/lO ml were given. Following each infusion 25 dry swallows were analyzed. Means of the manometric responses are below: Group 1:Saline vs EM Group 2:Saline vs EM LESP' mmHg 18 28 19 20 % LESP f w.EM 57a 6 % LESP relax 79 54)) 48 49 % Repetitive 9 20h 10 16 !=Lower Esoohaaeal Sohincter Pressure U=oc.05 EM vs EM D= ._ . pc.05 Saline vs EM During EM infusion Group 1 patients developed CP and sig- nificantly increased LESP, increased repetitive contract- ions, and decreased % LESP relaxation which resembled dif- fuse esophageal spasm. In contrast 4/8 Group2 patients had CP with EM infusion but no changes in responses studied. In conclusion: 1) EM infusion induced both CP and esophageal motor dysfunction in Group 1 patients indi- cating esophageal disease. 2) Esophageal manometry with EM challenge may be a useful clinical test for angina- like CP by unmasking latent DES. LATE SURVIVAL AFTER VALVE REPLACEMENT FOR SEVERE ISOLATED AORTIC INCOMPETENCE. John Greves,MD; David Clark,MD; Barry Greenberg,MD,FAmhfi McAnulty,MD,FACC; Albert Starr,MD,FACC;Shahbudin Rahimtoola,MD,FACC, University of Oregon Health Sciences Center, Portland, Oregon Twenty-nine patients (pts) underwent aortic valve re- placement (AvR) for severe, isolated aortic incompetence (AI) from 1973 to '78. Average (avg) age of the 23 men and 6 women was 42 yrs. Etiology for AI was aortic root dis- ease in 11, congenital in 6, previous bacterial endocardi- tis in 6 and unknown in 6. Four had associated coronary artery disease; all received bypass grafts. There were no hospital deaths; 5 yr survival is 61510% (meanfSE). Of all 9 late deaths (LD), 5 (55%) were due to non-anticoagulation of mechanical prostheses. In 24 anticoagulated pts, the 5 yr survival is 82+8%, avg mortality 3.6%/yr; 4 LD were due to heart failure, arrhythmia, sudden death, and unknown in 1 each. The 5 yr survival of pts with cardiac index (CT) >2.5 L/min/m2 was 92!7% vs 57i19% in pts with CI <2.5 (P<.OZ);with mean Vcf >0.75 drc/sec was 9158% vs 54i20% in mean Vcf<0.75(P<.05) and with left ventricularTLV) ejection fraction (EF)>0.45 was 94+6% vs 33_ClY% for EF co.45 (Pc.001). There were-no deaths in pts with EF >0.50 at an avg followup of 5 yrs. There were no significant differences in late survival between pts in Functional Class I & II vs III & IV, LV end-diastolic pressure of ~20 vs ~20 mmHg, LV end-diastol- ic volume of >210 vs ~210 ml/m? , LV end-systolic volume of 1110 vs <Ii0 mlm and LV mass of ,240 s ~240 g/me. These data suggest that in pts with severe AI, AVR should be undertaken: 1) in all pts with impaired LV func- tion at rest. The results will be better in those with mild impairment (e.g. EF as low as 0.45);and 2) in all symptomatic pts with normal LV function, even if symptoms are mild. 440 February 1980 The American Journal of CARDIOLOGY Volume 45

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Page 1: Natural history of unoperated aortic stenosis: Hemodynamic progression

ABSTRACTS

HYDRALAZINE EFFECTS ON HEMODYNAMICS, CARDIAC CONTRACTILE FUNCTION AND MYOCARDIAL ENERGETICS IN ISOLATED MYOCARDIUM Leigh D. Segel, PhD; Stephen V. Rendig, MS: Ezra A. Amsterdam, MD, FACC; Dean T. Mason, MD, FACC, University of California, Davis, California.

There is relatively little information regarding the di- rect cardiac effects of hydralazine (H), a vasodilator drug that has been applied in the treatment of cardiac failure. To clarify the direct cardiac effects of H, dose-response curves for this agent were evaluated in (1) isolated, working rat heart (IWRH); (2) isometric cat right ventricular papillary muscle (PM); and (3) isolated rabbit right atrium (RA). IWRH (n=6): there was a marked increase in coronary flow (72199 ml/min/g, pc.05) at lo-'M H, which remained significantly elevated at lo-'M and 10m4M H. Heart rate, cardiac output, left ventricular (LV) end-diastolic pressure and myocardial oxygen consum tion

(MvO2) were not altered from control at 10-8M - 1 lo- M H. Cat PM (n=7): maximum developed tension (T), dT/dtmax and time to peak tension were unaltered by lo-7M, 10-6M and lo-5M H but dT/dtmax was significantly elevated (34.+36

g/sec/mm2 , pc.05) at 10m4M and both T and dT/dtmax were increased (6.7+9.2 g/mmz, 34+62

b pc.02) at 10-3M. Pre-

treatment with propranolol (lo- M, n=7) abolished this positive inotropic effect. Isolated RA (n=S): spontaneous contraction rate was unaltered by lo-7M - 10w5M H, and di- minished by lo-4M and 10v3M H (87+80~+68 beats/min, pc.005). Thus, H was associated with unaltered pump performance and

WO2, accompanied by augmented coronary flow in IWRH, while high concentration of H induced a positive inotropic

effect mediated by beta-adrenergic stimulation in cat PM and elicited a negative chronotropic effect in rabbit myo- cardium. These data indicate that H has a primary coronary vasodilator effect and that at concentrations utilized clinically, its salutary circulatory actions are primarily related to extracardiac vasodilator actions.

TUESDAY, MARCH 11, 1980 PM AORTIC VALVE DISEASE 2:00-3:30

ATURAL HISTORY OF UNOPERATED AORTIC STENOSIS: HEMO- YNAMIC PROGRESSION. Stephen Wagner, MD, FACC; Arthur elrer, MD, FACC, Pacific Medical Center, San Francisco, A. n order to examine factors that might predict progression ate in valvular aortic stenosis (AS) we reviewed serial emodynamic studies in 50 adult pts of whom 7 had con- enital, 22 rheumatic and 21 degenerative calcific aortic tenosis (CAS). Compared with the others those with CAS ere older (62 f 6 vs. 51 + 9 yrs, p i .OOl) and had onset f murmur laterin life (In+ 4 yrs before first cath vs. 7 + 9 yrs, p < ,001). For all pts average values at irst cath include age 54 + 4 yrs, peak gradient 38 + 7 mmHg, calculated aortic-valve area (AVA) 1.3 I .7 cm2. mean 3.5 + 3 yrs later gradient was 57 + 30 mmHg and VA .8 + .4cm2. Peak left ventricular (TV) pressure rose + 33 mmHg and cardiac output (CO) fell .5 + .2 L/min. t? appeared to distribute into rapid (n = 2i) and slow n = 29) progressors with respective rates of a change in VA of .30 + .21 vs. .02 + .08 cm2/yr. 76% of RP had CAS 5. 21% of 3P (p i .OOl);-they also differed in that 484 P had serial fall in CO > 1 L/min vs. 17? of

J P (p c .05)

/21 RP developed criticaT AS with AVA 5 .5 c and severe V failure, all had CAS. t is concluded that pts with CAS progress more rapidly han those with congenital or rheumatic etiology and in ome reduction of calculated AVA is due to an impaired bility of the failing LV to move calcified leaflets

/rather than an anatomic reduction in valve orifice area.

THE ERGONOVINE STRESS TEST: A PROVOCATIVE TEST FOR DIFFUSE ESOPHAGEAL SPASM OR VARIANT ANGINA? Kenneth L. Koch, MD,

Ann Long, RN, R. Charles Curry, MD, and John R. Mathias,

MD. University of Florida and the Veterans Administration

Medical Center, Gainesville, Florida.

Intravenous ergonovine maleate (EM) during cardiac cathe- terization (CC) is used to evoke coronary artery spasm, resulting in chest pain (CP) and ST segment shifts. We

have observed patients who experience CP in response to EM in the absence of spasm. The purpose of this study was to

determine if EM produced esophageal dysfunction and CP. 15 patients were evaluated by routine esophageal manometry - 7 with CP(Croup 1) and 8 without CP(Group 2). All pa-

tients had normal CCs. During esophageal manometry IV infusions of saline 10 ml or EM .2-.4 mg/lO ml were given. Following each infusion 25 dry swallows were analyzed. Means of the manometric responses are below:

Group 1:Saline vs EM Group 2:Saline vs EM LESP' mmHg 18 28 19 20

% LESP f w.EM 57a 6

% LESP relax 79 54)) 48 49 % Repetitive 9 20h 10 16

!=Lower Esoohaaeal Sohincter Pressure U=oc.05 EM vs EM D=

._ . pc.05 Saline vs EM

During EM infusion Group 1 patients developed CP and sig- nificantly increased LESP, increased repetitive contract- ions, and decreased % LESP relaxation which resembled dif- fuse esophageal spasm. In contrast 4/8 Group2 patients had CP with EM infusion but no changes in responses studied. In conclusion: 1) EM infusion induced both CP and esophageal motor dysfunction in Group 1 patients indi- cating esophageal disease. 2) Esophageal manometry with EM challenge may be a useful clinical test for angina- like CP by unmasking latent DES.

LATE SURVIVAL AFTER VALVE REPLACEMENT FOR SEVERE ISOLATED AORTIC INCOMPETENCE. John Greves,MD; David Clark,MD;

Barry Greenberg,MD,FAmhfi McAnulty,MD,FACC; Albert Starr,MD,FACC;Shahbudin Rahimtoola,MD,FACC, University of Oregon Health Sciences Center, Portland, Oregon

Twenty-nine patients (pts) underwent aortic valve re- placement (AvR) for severe, isolated aortic incompetence (AI) from 1973 to '78. Average (avg) age of the 23 men and 6 women was 42 yrs. Etiology for AI was aortic root dis- ease in 11, congenital in 6, previous bacterial endocardi- tis in 6 and unknown in 6. Four had associated coronary artery disease; all received bypass grafts.

There were no hospital deaths; 5 yr survival is 61510% (meanfSE). Of all 9 late deaths (LD), 5 (55%) were due to non-anticoagulation of mechanical prostheses.

In 24 anticoagulated pts, the 5 yr survival is 82+8%, avg mortality 3.6%/yr; 4 LD were due to heart failure, arrhythmia, sudden death, and unknown in 1 each. The 5 yr survival of pts with cardiac index (CT) >2.5 L/min/m2 was

92!7% vs 57i19% in pts with CI <2.5 (P<.OZ);with mean Vcf >0.75 drc/sec was 9158% vs 54i20% in mean Vcf<0.75(P<.05) and with left ventricularTLV) ejection fraction (EF)>0.45 was 94+6% vs 33_ClY% for EF co.45 (Pc.001). There were-no deaths in pts with EF >0.50 at an avg followup of 5 yrs.

There were no significant differences in late survival between pts in Functional Class I & II vs III & IV, LV end-diastolic pressure of ~20 vs ~20 mmHg, LV end-diastol- ic volume of >210 vs ~210 ml/m? , LV end-systolic volume of 1110 vs <Ii0 mlm and LV mass of ,240 s ~240 g/me.

These data suggest that in pts with severe AI, AVR should be undertaken: 1) in all pts with impaired LV func- tion at rest. The results will be better in those with mild impairment (e.g. EF as low as 0.45);and 2) in all symptomatic pts with normal LV function, even if symptoms are mild.

440 February 1980 The American Journal of CARDIOLOGY Volume 45