Estrogen replacement therapy and cardiovascular events: the cardiovascular health study

162A

ABSTRACTS- Cardiac Function and Heart Failure

1112-158

3

Evaluation of the Csrdloprotectlve Effect of D e x r e z o x a n e In C h i l d r e n T r e a t e d W i t h A n t h r a c y c l i n e

JACC 1113-147

March

6, 2002

Effect of Vsrdensfll, s Selective Phoephodlesterase 5

Inhibitor, on the Cardiovascular R e s p o n s e t o E x e r c i s e In Men With Coronary A r t e r y D i s e a s e

Marcelo G. Paiva. Sergio Pstrilli, Addana Cordovil. Cdstiano Mechado, Adelaide Arruda, Aden Gil, Valdir Ambroaio, Orlando Campos, Angelo DePaola, Antonio Carvaiho,

Udho ThadanL Arthur Mazzu, the Vardenafil Study Group, Oklahoma University Health

Universidade Federal de San Paulo, S,~oPaulo, Brazil, Hospital Nove de Julho. S~o Paulo, Brazil

Science Center, Oklahoma Ci~ Oklahoma, Bayer Corporation, West Haven, Connecticut.

Background: Intensive treatment of anthracycline cardiomyopathy may not have had impact on mortality as would have expected and so far cardiovascular death is the second leading cause of death in long term survivors of childhood cancer. So, demonstrating prevention of early cardiac toxicity induced by doxorrubicin may identify a population with less risk for late cardiomyopathy. Methods: 37 patients, part of Brazilian multicenter trial for treatment of ostecgenic sarcoma were studied. 19 patients (11 male, 19,7 ± 4 years) received doxorrubicin (346.47 ± 16 rag/m2) (DOXO), and 18 patients (14 male, 16,8 + 5 years) received doxorrubicin (396,53 ± 15 mg/m2) plus dexrazoxane (DOXO+DEXRA).A low dose dobutamine stress echocardiography (DSE) was performed at least I year after the last chemotherapy (OT). Left ventdcular systolic and diastolic functional parameters were evaluated at rest and after dobutamine infusion. The results were compared against a group of 21 patients (13 male, 15 ± 4 years) with osteogenic sarcoma but before QT (CONTROL). Results: No major side affects were recorded. Rest echocardiogram demonstrated no significant difference between the 3 groups. During DSE. diastolic function had the same response, but a less significant improvement was observed on systolic parameters with DOXO compared to DOXO+DEXRA and CONTROL.

Background: Erectile dysfunction (ED) is common among men with coronary artery disease (CAD). It is important to understand the cardiovascular effects of PDE5 inhibitors in man with CAD. This study evaluated the effect of vardenafU on treadmill exercise time in patients with exertional cardiac ischemia. Methods: In this double-blind, crossover, single-dose, multicenter study, 41 men (48-77 yr) with stable CAD who had reproducible exercise tests were randomized to vardenafil 10 mg or placebo, followed by exercise treadmill test (E-I-r, 5-10 METS) one hour post-dose, the time of maximal drug exposure. Nitrates were prohibited _<24 hr pre- and post-study. ReBulte: Raiati'~e to placebo, vardenafil did not alter total ETT time or time to awareness of angina pectoris, but did significantly prolon~ the time to ST-segment depression.

DOXO

DOXO+DEXRA

CONTROL

REST Fractional Shortening

34% ± 5%

36% ± 5%

36% ± 3%

DSE Fractional Shortening

42% ± 5%*

47% + 7%

47% ± 7%

* p<0,05 Conclusions: Low dose DSE was able to identify a better myocardial performance on patients treated with dexrazoxane than those who received antracycline alone. c;

POSTER SESSION

1113

Medical and Surgical Therapy in the Elderly

Monday, March 18, 2002, Noon-2:00 p.m. Georgia World Congress Center, Hall G Presentation Hour: Noon-l:00 p.m. 1113-146

Carvedilol in E l d e r l y H e a r t F a i l u r e P a t i e n t s

Chdstonher S. Allada. Anne M. Kecgh, Eugene Kotlyar, Christopher S. Hayward, Peter S. Macdonald, St Vincent's Hospital, Sydney, Australia.

Background: Cervedilol has been shown to improve symptoms and survival in patients with all grades of heart failure. However, exbedence is limited with the use of carvedilol in the aiderly. We wished to determine whether there are differences in tolerance of, or responses to carvedilol between people greater than or equal to, and less than 65 years of age. Methods: In a cohort of 109 elderly patients aged greater than or equal to 65 commenced on open label cervedilol between February 1996 and May 2001, 84 (77.1%) have remained on cervedilol for more than 12 months. During the same period there have been 385 patients aged less than 65 who have commenced on open label carvedilol, and of these people 308 (80.0%) have remained on carvedilol greater than 12 months. Results: Death or transplantalJon resulted in cessation of cervedilol in 11 (10.0%) and 41 (10.6%) patients in the older and younger aged groups respectively. Cessation due to other adverse side effects occurred in 14 (12.8%) and 36 (9.4%) peitents in the older and younger aged groups respectively. The 2 groups were not statistically different on chi-squared analysis. _>65 (n=84)

Baseline

3 months

6 months

12 months

NYHA

3.2 ± 0.7

2.6 + 0.6 *

2.4 ± 0.7 *

2.4 ± 0.7 *

6MW'F (m)

384 ± 117

440 ± 64 *

419 ± 57 *

434 ± 82 *

LVEDD ( m m )

71±11

69±11

57±10

66±14

LVESD (ram)

59 ± 12

58 ± 13

55 ± 12

55 ± 16

FS(%)

0.17±0.07

0.17±0.08

0.19±0.07

0.20±0.09*

EF(%)

0.29+0.10

0.31 ±0.12

0.34+_0.12"

0.33±0.12"

< 65 (n=308)

Beullne

3 months

6 months

12 months

NYHA

2.8 ± 0.8

2.2 + 0.7 *

2.1 ± 0.7 *

2.1 + 0.7 *

6MWT (m)

442 ± 66

498 ± 90 *

489 ± 105 *

483 ± 194 *

LVEDD ( m m )

74±11

72±11

71±11 *

72+12

LVEBD (ram)

63±12

59±13"

59±13"

59±14"

FS(%)

0.15+0.07

0.18±0.07"

0.18±0.07"

0.16±0.07"

EF(%) * p<0.05

0.25±0.19

0.31 + 0 . 1 0 "

0.31 ± 0 . 1 0 "

0.31 ±0.11 *

Conclusions: Elderly patients with heart failure tend to have more severe limitation at baseline. However, elderly people have a similar cessation rate due to adverse reactions or the combined end-point of death or transplantation when compared with the younger group. Where tolerated, carvedilol produces similar beneficial outcomes in both elderly and younger patients.

Parameter

Vardenafil 10 mo

Placebo

Ratio LS Means

(vardenafiVolacebo~

Treadmill Exercise Time*, sec

433 ±109 427 +105 n =39 n = 39

1.015 (NS)

"rime to Angina Pectods*, first awareness, sec

291 ±123 292 ±110 n = 34 n = 34

0.976 (NS)

Time to ST-Segment depression _>1 mm/~ from Baseline*, sec

381 ±108 334 ±108 n = 31 n = 31

1.155 (p= 0.0004)

*mean +SD Vardenafil was well tolerated. The most common events during vardenafil administration (facial flushing and headache) were mild or moderate and short-lived. Changes in BP, HR, or ECG were comparable between vardenafil and placebo groups. Conclusion: These study results show that vardenafl110 mg did not impair stable CAD patients' ability to exercise at a level exceeding that required for sexual intercourse. 1113-148

Mltrel Valve R e p a i r in P a t i e n t s O v e r 75 Y e a r s

Eric Braunberoer, Patrick Meimoun, Alain Deloche, Rochde Sayah, Jean-Pierre Marino, Sylvain Chauvaud, Jean-Paul Cou~til, Alain Berrebi, Jean-No~il Fabiani, Alain Carpentier, Hopita/ Europeen Georges Pompidou, Paris, France. Background : Valve repair is regarded as the gold standard in the surgery of mitrai valve insufficiency (MI). However, the results and indications in patients (pts) over 75 years of age are unknown. Methods : We reviewed 101 consecutive patients older than 75 who, between February 1995 and June 2000, underwent elective mitral valve repair for non ischamic mitral valve insufficiency (MI). Results : The cause of MI was degenerative in 56 pts, extensive annulus calcification in 6, rheumatic in 2, bacterial endocarditis in 1 and not specified in 36 pts. An associated functional thouspid annuloplasty was present in 6 pts. Mean age was 78+/-2.9 years (75-87). NYHA functional was II in 55%, til in 44% and IV in I% of the pts. Mean cardiothoracic ratio was 53+/-5 (40-70), mean ejection fraction 68+/-11 (40-90) and 23 pts (23%) were in atrial fibrillation. Valve analysis showed that 8 pts had a Carpentier functional Type I (normal leaflet motion) MI, 90 pts a Type II (leaflet prolapse) (posterior leaflet 76, anterior leaflet 9, both leaflets 5) and 3 a Type III (restricted motion) MI. A remodelling annoloplasty was performed in all cases but 2. Associated techniques comprised valve resection (83), sliding leaflet plasty (5), chordae shortening (5), chordae transposition (6), chordae fenestration (3), annulus decalcification (19) and posterior leaflet enlargement (5). During the first postoperative month, there were 8 deaths (7,9%).Death rate was much higher (5/30;16,7%) in the group of pts over 80 than in the group between 75 and 80 (3/ 71 ;4,2%) and was not correlated with the complexity of the repair.Two pts (1,9 %) were lost to follow-up. Ten died between the third to the 61th month.At the end of the study, 81 pts were still alive with a median age of 80,8 +/- 2,9 years (75-88). Follow up extended from 1 to 74 months (median 36). NYHA class I-III was 21, 53, and 7 respectively. Conclusions : 1) Mitral valve repair using Carpentier's techniques provides excellent long tem results in patients over 75 with a low pedoperative mortality. 2) Mitral valve repair should be discussed in asymptomatic patients below 80 years of age presenting with a severe MI. 3) Age is not a contreindication to valve repair in symptomatic patients beyond 80 years. 1113-149

E s t r o g e n R e p l a c e m e n t Therapy and C a r d i o v a s c u l a r Events: T h e C a r d i o v a s c u l a r H e a l t h Study

Vera Bittner. Priscilla Vaientgas, Teri A. Manolio, Bruce M. Psaty, John Robbins, Grathe S. Tell, Russell P. Tracy, University of Alabama at Birmingham, Birmingham,Alabama. Background: Obsarvational studies among middle-aged postmenopausal women suggest that estrogen-replacement therapy (ERT) reduces the risk of cardiovascular (CV) events. It is unknown whether the potential benefits of ERT extend to older women. Purpose: To assess the impact of past and current ERT use on death and CV events among women enrolled in the Cardiovascular Health Study (CHS). Methods: CHS is a prospective cohort study of participants >64 years old. Information about ERT use, CV risk factors, and CV history was obtained at baseline. CV events and mortality during follow-up were ascertained in standardized fashion and adjudicated by a committee blinded to ERT use. Relative risks (RR) of CV events with 95% CI were computed Using Cox proportional hazards modeling adjusting for age, race, diabetes, alcohol use, fibrinogen, and income. Mean follow-up was 5.8+/-1.5 years. Results: Current ERT users (n=372) had the most favorable risk profile, past users (n=860) were intermediate, and never users (n=2015) had the greatest burden of CV risk

JACC

ABSTRACTS- Cardiac Function and Heart Failure 163A

March 6, 2002

factors. RR of CV events is shown in the table. Conclusion: Current ERT use among older women was associated with fewer myocardial infarctions and "HERS endpoints", but there was no association with all cause mortality or stroke. Past ERT use was associated with lower all cause mortality, but there was no association with CV events. The observed associations may reflect a healthy-user effect. Clinical trials will be necessary to assess the effect of ERT in older women. Fully AdjustedCox Model of CV Events (RR(95%Cl)) Past ERT

Current ERT

Death

.72 (.57,.90)

1.03 (.76,1.40)

Myocardial Infarction

,90 (,66,1.23)

.44 (.23,.84)

Stroke

,84 (.62,1,13)

.94 (.60,1.45)

"HERS Endpoint" (nonfatal MI or CHD death)

.82 (.64,1.06)

.54 (.34.86)

1113-150

C h r o n i c V i t a m i n C Supplementation Improves Endothelial Function in D i a b e t i c P a t i e n t s With C o r o n a r y A r t e r y Disease

Charalambos Antoniades. Dimltris Tousoulis, Costas Tentolouris, Kyriakoula Marinou, Athanasios Trikas, Stella Brilii, Christos Pitsavos. Christodoulos Stefanadis, Pavlos Toutouzas, Cardiology Unit, Hippokration Hospital, Athens University Medical School,

Athens, Greece. Background: Coronary artery disease (CAD) as well as diabetes mellltus (DM), are both known to be associated with endothelial dysfunction. Oxidative stress is considered to be one of the most important mechanisms involved in the pathogenesis of endothelial dysfunction in CAD and DM. In this study we investigated whether treatment with the antioxidant vitamin C improves endothelial function in patients with type ~or II DM and CAD. Methods: In a double-blind placebo-controlled study, 48 patients (42 males, 6 females, aged 66±1.3 years) with CAD and DM, were enrolled. 22 of them were of type I DM and 26 of type I1.18 diabetic patients (7 with type I DM (group A) and 11 with type II DM (group B)) were treated with vitamin C 2g/day for 4 weeks. The remaining (15 with type I DM (group C) and 15 with type II DM (group D)) received placebo for 4 weeks. Forearm blood flow was measured using venous occlusion strain-gauge plethysmography, at baseline and after treatment. Endothelium dependent flow mediated vasodilation (FMD) was expressed as the % change from baseline to post reactive hyperemia blood flow. Endothelium independent flow (NTG%) was expressed as the % change from baseline to pest sublingual nitroglycerin administration flow. Results: Baset blood pressure, heart rate, body weight, basal forearm blood flow and NTG% remained unchanged in all groups. All values are expressed as msan±SEM. FMD was similar between patients with type I (53.9±3.3%) and type II (57.8±6.0%, p=NS) DM. After treatment, RH% was significantly increased in groups A (from 54.2±7.3 to 73.1±7.1% p<0.05) and B (from 66.5±11.7 to 84.3±15.1% p<0.05) while remained unchanged in groups C (from 53.1 ±4.2 to 50,1±8.2% p=NS) and D (from 55.8±11.6 to 58.3±10.1% p=NS). Conclusions: Chronic administration of vitamin C seems to improve endothelial function in patients with combined coronary artery disease and diabetes mellitus of type I or II. These findings indicate a possible beneficial role of antioxidant vitamin C in diabetic patients with coronary artery disease.

Insulin use did not further stratify asymptomatic diabetics for abnormal SPECT (57% insulin vs 60% no insulin, p=0.15) or high-dsk SPECT images (20% insulin vs 19% no insulin, p=0,59). In asymptomatic diabetics who underwent exercise stress (52%), a positive ECG occurred in 29%. Conclusions: In asymptomatic patients referred for screening stress SPECT imaging, diabetics are slightly younger and more frequently female than nondiabetics but have a significantly higher prevalence of abnormal and high-risk SPECT scans. Both abnormal and high-risk scans are more common in asymptomatic diabetics than even in symptomatic nondiabetics. 2:30 p.m. C o m p a r i s o n o f Noninvaslve Cardiac Testing in 903 Asymptomatic Men: C o r r e l a t i o n W i t h C o r o n a r y Angiography and W i t h C l i n i c a l E v e n t s s t Two and Five

830FO-3

Years Patrick J. Fitzsimmons. Ants Palm-Leis, William T. Thompson, William B. Kruyer, USAF

School of Aerospace Medicine, Brooks AFB, Texas. Background: Noninvasive techniques may be used to screen asymptomatic subjects for coronary artery disease (CAD). However, the accuracy of these tests is significantly influenced by the low prevalence of CAD in asymptomatic populations. We sought to define the accuracy of three noninvasive tests for predicting significant CAD and cardiac events in a population of asymptomatic men. Methods: From a database of 1487 asymptomatlc military aviators who had coronary angiography performed for occupational indications and had clinical follow-up, we identified 903 who had all three noninvasive tests prior to angiography - treadmill, stress thallium imaging and coronary artery fluoroscopy for detection of coronary calcification. Sensitivity, specificity and positive and negative predictive values were calculated for each test for the presence of significant CAD (maximum lesion >50% stenosis). Cardiac event rates at two and five years were determined for abnormal versus normal test. Cardiac events considered were cardiac death, nonfatal myocardial infarction and coronary revascularization. Results: Mean age at coronary angiography was 43.7 (+/-6.2) years and mean follow-up was 11.8 (+/-3.8) years. Sensitivity, specificity and positive and negative predictive values for the presence of significant CAD were: treadmill 54%, 49%, 16% and 86%; thallium 55%, 62%, 21% and 89%; and fluoroscopy 68%, 71%, 29% and 93%. Average annual cardiac event rates at two and five years for abnormal test were: abnormal treadmill 1.0%/yr and 0.5%/yr, abnormal thanium 1.0%/yr and 0.6% /yr, and positive coronary artery fluoroscopy 1.6%/yr and 1.3%/yr. For normal test, event rates at two and five years were: normal treadmill 0.3%/yr and 0.5%/yr, normal thanium 0.5%/yr and 0.5%/yr, and negative fluoroscopy 0.2%/yr and 0.1%/yr, Conclusion: As expected, all three noninvasive tests were independently poor predictors of significant CAD and cardiac events in this low CAD prevalence population. For all parameters examined, detection of coronary calcification by routine fluoroscopy performed better than treadmill and thallium, both for prediction of anatomic disease and for cardiac events at two and five years of fonow-up. 2:45 p.m.

830FO Featured Oral Session...Stress Testing and Prognosis: Non-ST Segment Parameters Monday, March 18, 2002, 2:00 p.m.-3:30 p.m. Georgia World Congress Center, Room 367W 2:15 p.m. 830FO-2

Ventrlcular Ectopic Activity Predicts Mortality When It Occurs During Recovery, but Not Just During Exercise

830FO-4

FEATURED ORALPRESENTATION

T h e Y i e l d o f Screening Stress Myocardial Perfusion

Imaging in Asymptomatic Diabetics Todd D. Miller. Navin Rajagopalan, David O. Hodge, Robert L Frye, Raymond J. Gibbons, Mayo Clinic, Rochester, Minnesota.

Background: Diabetics have a higher prevalence of silent coronary artery disease (CAD) than nondiabetics and a prognosis similar to that of patients with established CAD. Nonetheless, screening stress testing in asymptomatic persons without known CAD including diabetics is not well established according to the ACC/AHA Guidelines for Exercise Testing. Methods: The results of exercise and pharmacologic single photon emission computed tomography (SPECT) imaging were analyzed in 27,179 patients without known CAD who underwent testing between January 1986 and December 2000. Patients were grouped by symptom and diabetes status. SPECT scans were categorized as abnormal or not and "high-dsk" (on the basis of previously published critaria) or not.

Joseph Frolkis, Claire E. Pothier Snarler, Eugene H. Blackstone, Michael S. Lauer.

Cleveland Clinic Foundation, Cleveland, Ohio.

Background:Ventdcular ectopy (VEA) induced by exercise predicts death in populationbased cohorts. We examined the prognostic importance of VEA dudeg exercise and recovery, when reactivation of parasympathetic activity occurs. We hypothesized that VEA dudng recovery would predict death better than VEA during exemise. Methods:We followed for 5.3 years 28,976 patients (age 56+11, 70% male) who underwent treadmill exercise testing and were without heart failure, valve disease, atrial fibdllation, VEA history, or pacemakers. VEA was defined as: > 7 VPCs/minuta, ventricular bigeminy or trigeminy, ventricular tachycardia, or veetricular fibdllation. Results:VEA during exercise only occurred in 923 patients (3%), during recovery only in 577 (2%), and during exercise and recovery in 483 (2%). There were 1801 deaths (6%). In univariate analyses, VEA dudng exercise predicted death (11% vs. 6%, hazard ratio [HR] 1.9, 95% CI 1.6-2.2, P<0.0001), but VEA during recovery was a stronger predictor (13% vs. 6%, HR 2.4, 95% CI 2.1-2.9, P<0.0001) (Figure), Klplan

Moklr Curve o f

VQnf~cublr Ect ¢py DUdl~ S~ell

Testing

Results: Subset

Number

Symptomatic, nondiabetic 16,196 Symptomatic, diabetic 2994 Asymptomatic, nondiabetic 6248 Asymptomatic, diabetic 1741 •p _<0.004 vs asymptomatic diabetic

Age Male (%) Abnormal (yrs_+ SD) SPECT (%) 62_+15" 53* 44* 63_+11" 53* 59 63_+11* 73* 46* 60~__13 70 59

High-risk SPECT (%) 13" 22 11* 20

o

2

4

6

e

YelNAfter~ u l Test

No~ml~ Nether ~ess

26993 923

26077 ~78

403

441

22701 767

19406 ~6

16547 57B

13B~ 479

~1105 396

3O9

252

~S

177

91~ 327 14

~05 251