Risk stratification using a combination of cardiac troponin T and brain natriuretic peptide after optimized treatment in patients with advanced heart failure

130A

ABSTRACTS

1014-155

- Cardiac Function and Heart Failure

JACC

Functional Mitral Regurgitatlon in Patlents With Chronic Heart Failure: Reiatlonship to Left Ventricular and Left Atrlai Structural and Functional Parameters

were analyzed

Klaus K. Witte, Simon D. Thackray,

Goodge.

Andrew

L. Clark, John G. Cleland,

Mohammad

The Univeraify

F. Alamgir,

Lindsey J.

of Hu//, Kingston-Upon-Hull,

Results.

61% of patients

mitral regurgitation

to explore

the relationship

(MR) in patients

with chronic

(LV) and left atriai (LA) function

echocardiographic Methoda:

between

the severity of functional

heart failure

obtained

(CHF) and indices

with the use conventional

of left

and new

(age 69ilO

tion fraction <45%) underwent (TDI). The presence

years, 13 women)

echocardlography

and magnitude

with clinically

including

coiour tissue Doppler

flow mapping,

and the MR jet area was used as a measure

annular

systolic

early diastolic

(S,),

stable CHF (LV eiec-

of MR was semi-quantitatively

Doppler

(E,)

and late diastolic

assessed

imaging by coiour

of MR severity. Miirai

(A,,,) velocities

were mea-

Patients

No significant was found

were divided

difference

between

into three subgroups

the groups.

LV ejection

MR group than in the remaining significantly

higher,

and

groups.

fraction

LA active emptying

pseudonormal

restrfctive (impaired

The severity of functional S,

and

A,.

emerged

When

remodeling

patterns

procedure, patients

and additional

in patients

to E,

filling.

predictors

only

fraction

indexes

sure using colour TDI are important

whereas

non-

with mild MR. proportional

Err,/&

to be closely

LA morphology towards

indicators

in the

to

ratio and

S,

of the severity of MR.

do not appear

reflecting

in the mild

with severe MR

and was inversely

performed,

during

exercise

patients,

Conclusion.

Rosanio,

Monica Tocchi, Vincenzo

Patients

velocities

Santlneiii,

Itzhak Shemer,

with the are signifi-

pattern of LV diastolic which are easy to mea-

cardiovascular

limitation

the importance

Technion-Israel

Institute

of Technology

Electrical

currents

have been shown to modulate of stimulated

chamber

tory cardiac

contractility

Methods: tude,

CCM

duration

applied

to the LV through

septum

endocardially

regarded

condition.

respectively,

reduction

enhanced

Moein F. Vaseghi, Casscells.,

velocity of contraction bal fractional regional

CCM stimulation similar

degree.

penit

use

enhancement

demonstrated

in experimental

Numerous

complained

With RV stimulation,

bination the sensitivity

congestive

heart failure and mortality

cles. We sought

to characterize

changes

of tO.3i

Methods. for Adults

are modest.

glo-

by significant

(PcO.05) increase

area (LV 22f5% ejection

enhanced

enhances

(UTCCCA).

which

On admission

clinical endpoints

of maximal

outcome

(N=274)

were entered

was 97.3+1.0

“F. An increase

hood of survival

tory of heart failure,

correlate

with

University

dysfunction with a single

were assessed

(193). Hospital

and the presence

Methods:

hypertension

and RV function)

predictors

because

in a cohort

We investigated

of temperature

into a multiple

regression

(T) confoundmodel.

Results:

were

Tricuspid

correlated

regurgitation

was a strong predictor

systolic

(Exp(B)=4.l,p=0.04),

“F, and in the pts who died in hospital

of 1 “F on admission

of 76% (p=O.124).

hypotension

azotemia.

and multivariate

(Exp(B)

= 37, p= 0.037). Weaker female

design have identified of in-hospital

sex

p=O.O03). but not sodium

by VT but not by AF or RR variability.

predictor

in iikeii-

used for pulmonary

p=O.O4),

(Exp(B)=1.4,

of

(N=17) T

with an increase

(marker

(Exp(B)=0.96,

and creatinine

Death was also predicted

hypothermia

or

Conciu-

as a novel, pow-

death of CHF patients.

Risk Stratification Using A Combinatlon of Cardiac Troponin T and Brain Natriuretic Peptkle After Optimized Treatment in Patients with Advanced Heart Failure

1014-158A

of

to a

with less symptoms stronger

and

contractile

Junnlchl, Toshikazu Universitv,

treatment

of Toronto, Toronto,

an increased

incidence

of

right ventri-

as well as overt heart failure

Masanori

in

Nomura,

Yuu Nakamura,

Ando, Hiroshi Kurokawa,

The aim of this study was to evaluate T (TnT) and brain natriuretic

are useful for risk stratification

Methods:

both on admission

worsening

CHF (mean age 69 yrs, NYHA

monitored

for a mean follow-up

tion rate of TnT (>O.Ol @ml), length

admission

and/or

systemic

of Toronto Congenital with gated radionuciide

records were reviewed

uptake (V02

right ventricle Cardiac Centre

max), anaerobic

angiography

for the following

threshold

of heart failure on chest radiograph

(AT), a his(CXR).

Data

Naruse, Yoshihisa Hishida,

whether

peptide

in patients

repetitive

of hospital

(detection

and on discharge

sion and discharge,

of

ejection

in 93 consecutive

heart failure

fraction

(EF) were

pts hospitalized

for

class ii in 24 pts, Iii in 46, IV in 23). Pts were

period of 272 days after discharge. TnT and BNP levels, EF and NYHA

stay 36 days)

were

improved

compared

Results:

The detec-

class on discharge with the value

on

rate of TnT: 39 YS 60%: TnT: 0.03 vs 0.07; BNP: 267 vs 725 pg/ml;

Cox regression

were independent

measurements

(pts) with congestive

During the follow-up

36 (39%) cardiac events (9 cardiac deaths and 27 readmissions stepwise

Mod,

Fujita Health

(BNP) before and after optimized

Levels of TnT and BNP and left ventricular

measured

(mean

Hiroyuki

Takeshi Kondo, Hi&hi

Toyoake, Japan.

cardiac troponin

Cardiac

in patients with single and/or systemic

oxygen

variable

the mean T of ail 291 pts was 97.3*1 .l “F. The mean T on admission

Local

global LV systolic performance

have shown

of the University

The patients

case-con-

lymphopenia,

Here we sought to examine

prognostic

Jan and Dee 96. 35 pts were excluded

ers. Factors affecting

near the CCM electrode,

may be associated

studies

adult patients

(137) or 2-D echocardiographic

by hypothermia,

records of patients (pts) with an ICD code of CHF on their last hospital admission

between

in glo-

vs. RV 23-t4%. P=NS) rate. The magnitude

in remote regions as well. Conclusions:

ventricular

from the database

We noted in a retrospective

failure, and hypotension.

EF: 45 vs 40%; NYHA class: 2.2 vs 3.0; p
193 consecutive

Texas.

but even in com-

7.2%

this population. were identified

Houston,

have been described.

CHF death was best predicted

is an independent

Madjid, $&M~J&&

(6.6* 5.4% and 6.6* 0.5%,

Gary D. Webb, Peter P. Liu, Congenital

Previous

in CHF patients

and specificity

Mohammad

of Texas-Houston,

no

and

Center of Excellence,

and Objectives.

Naghavi,

Both LV and

Ontario, Canada. Background,

at

ventricular

of

preparations.

Centre and Heart B Stroke/RL

to preserve

at 6mA in one patient,

an overall increase in the magnitude

was markedly

amplitudes,

Veldtman,

of mortality

trol study, that in-hospital

(CHF). Gruschen

strategies

right ventricles

DDD pacing was

2 patients

Heart Failure and Ventrlcuiar Dysfunction in Patients With Single and/or Systemic Right Ventricles

mPiran,

of considering

Said Siadaty, Morteza

predictors

Background: 1014-157

This study

with single or systemic

measurements

for quantifying

in time-to-peak

approach

current

right-sided

pulse pressure

expressed

of LV or RV myocardium

of higher

during

to a similar degree

improvement

The right-sided

(RV)

Echo color kinesis, a technique

motion

who in turn

ampliwere

which was abolished

in 56 of end-diastolic

systolic endocardiai

patients,

to the control population.

period

or to the right ventricular

to use 14mA CCM in all patients.

rate and shortening

with a lesser but significant

compared

patients

and heart failure symptoms

to asymptomatic

heart failure.

activity.

LV and aortic pressures

with associated

in both groups,

area change

and peak ejection

right ventricles

compared

Division of Cam’iology. University

erful, univariate

Signals

With LV stimulation,

dP/dt,,,,,

bal and regional systolic function,

symptomatic

the influence

with adjustable

electrical

to 6mA was necessary.

and 10.6f. 1.4% (PcO.01 vs control).

refractory

with chronic

pulses

of local

Hemodynamics

Results:

PcO.01 vs control),

and 36.66 +/-

rate was 46% among

effect of these non-excita-

in patients

vein (12 patients)

and it was possible

RV CCM stimulation

of identifying

sion: Our two studies using different

Milano, /t&-/x

potential

and mechanical square-wave

at 10mA CCM amplitude,

occurred

the action

Simultaneous

by a Millar catheter.

Sys-

at rest and

Hypothermia as an Indicator of Imminent Death in Late Stage Congestive Heart Failure

1014-158

% lymphocytes.

David Prutchi, Waiid Haddad,

signal

sensing

an epicardial

in the other a further

symptoms

(CCM)

from

(6 patients).

as control

chest discomfort while

delay

Vicedomini,

in vitro and in viva. We assessed

were monophasic

and time

were performed

during

contractility

on the hemodynamic

signals

patients

Haifa, Israel.

applied

modulating

p < 0.00022).

vs. asymptomatic

function.

pts who sun/Ned

University Hospital,

San R&se/e

with single or systemic

have significant

medical

Yuval Mika, Gabriele

work load (496.46 +/- 265.26 vs.

patients during follow-up.

limitation

suggests

(TGA)

patients.

AT (11.3 t/- 3.5 vs. 13.2 +/- 4.9 ml/kg/min,

in symptomatic

cardiovascular

associated

of the severity of MR.

Daniel Burkhoff,

Yehuda Snir, Shiomo A. Ben-Haim,

Background:

(SVEF)

have significant

was 96.6i1.7

Salvatore

lower maximal

p&04),

and 5% among asymptomatic

right and left ventricular

function

of the great arteries

was, 33.42 +/- 15.67 vs. 46.66 +I- 13.42 (p < 0.00001)

study if temperature

Nonexcitatory Cardiac Contractility Modulation in Heart Failure: influence of Stimulated Chamber on Hemodynamic and Mechanical Response

wPaowne,

had significantly

function

indices of global LV

and pump

more restrictive

to the severity of MR. Mitral annular

1014-156

with transposition

index)

reduced

of patients

in the group of patients

was

cantly related to MR. There is a tendency filling proportional

was significantly

with CHF due to LV systolic dysfunction.

and LV ejection

severity of MR, while

analysis

MR).

and were com-

34% of patients with L-TGA, 40% of Fontan palliated

p=O.O093). and V02 max (14.69 +/- 5.03 vs. 20.29 +I- 6.75 mi/kg/min, temic ventricular

at end systoie was

of LV diastolic

prevailed

higher

LA dimension

The majority

patterns

and severe

and sphericity

was significantly

fraction

MR was proportional

multivariate

as independent

In concluafon,

or restrictive

relaxation)

(LV volumes

The maximal

severe MR group than in the two other groups. demonstrated

(mild, moderate

in indices of LV remodeling

patients

class I-II, 15% in class Ill, and 4% in class IV.

risk for heart failure and the importance

sured using TDI at six sites in three apical views and averaged. Reaulta.

and a Mustard

were in NYHA

16.71 vs. 53.33 +I- 14.06 (p < O.OCrgl). Mortality

techniques.

73 patients

and asymptomatic

in 24% of patients

567.24 +/- 199.31 kilopond-meters,

This study was designed ventricular

occurred

Symptomatic

United Kingdom.

for symptomatic

pared with normal controls. Head failure

s,

separately

March 6,2002

analysis

including

of cardiac

for worsening

CHF). In a

TnT, log BNP, EF and NYHA class on admis-

age and sex, TnT (p=O.o003) predictors

period, there were

event.

and log BNP (p=O.O4) on discharge

Using

discharge

0.01: T+ or T-) and BNP (> or < 160: B+ or B-) determined

values

of TnT (> or <

by ROC curves, the pts were

JACC

ABSTRACTS

March 6, 2002

divided

into 4 subgroups

BNP after optimized and morbiditv

(Table).

treatment

Conclusion:

Measuring

may be valuable

the combination

for risk assessment

of TnT and

of cardiac

Function and Heart Failure

(179N) Mutation

I (T-/8-)

using

n=37

discharge

II (l-/B+)

values

of TnT

Ill (T+/B-)

n=20

and BNP IV (T+/B+)

n=9

n=27

Bioern C. Knollmann, Weissman,

Cardiac death

0 (0%)

0 (0%)

2 (22%)

7 (26%)

Cardiac event

5 (14%)

6 (30%)

4 (44%)

21 (78%)

Syevda G. Sirenko,

Georgelow

Washington

Hospital

Cyclosporine

Universify

James D. Potter, Kenneth

School of Medicine,

Center, Washington,

A (CyA) prevents

been proposed

as treatment

cardiac

POSTER

SESSION

a mouse doned.

Cardiomyopathy Models and Hypertrophic Cardiomyopathy

Sunday, March 17, 2002, 9:00 a.m.-11:OO Georgia World Congress Center, Hall G Presentation Hour: 9:00 a.m.-IO:00 a.m.

model

for Familial

Troponin

Methods:

for 4 weeks.

serial echocardiography LV wall thickness

Compensated Cardiac Hypertrophy in Endothelial Nitric Oxide Synthase Knockout Mice

1015-137

Michael

P. Fl&&y,

Maria Brown, Hitoshi Takano,

lngrid L. Grupp, Jo El Schultz,

University of Cincinnati,

Murphree,

W. Keith Jones,

Louisville,

LouisviNe. Kentucky

Cincinnati,

Ohio, University

Sidney

Tg-l79N

mice, (3.3ztt.lmg/S

histology

were found.

mice expressing

a a-myosin

mass in mice expressing

of

treatment

should

heavy

chain

a FHC-linked

not be generalized

FHC

Troponin

gous knockout

mice (eNOS+)

develop

troversy over the development investigate

that endothelial

We examined

and biochemical

age. Histological

examination

and control

heart preparation mice exhibited

fibrosis and evidence

of atrial natriuretic

necrosis

Sarcoplasmic decreased strated

factor-a

reticulum

were perlormed

of myocyie

SERCA2a

hearts of eNOS’.

function,

there was a blunted

and

heads slightly

hypertrophy,

increases

correlated

Conclusions:

eNOS+

fetal genes

were

mice 52 weeks

decreased

phospholamban

mice exhibit

myocardial of TNF-a

ratio of SERCA2a

protein

indicative

remodeling,

levels.

of reduced

including

and SERCA2a,

gests a mechanism

protein to phospholamban

for the long-term

physiological

re-induc-

there is no pro-

protein at this timepoint

compensation

sug-

that occurs in eNOS”.

hearts.

Treatment

New Mutation in Lamin A/C Gene Associated Severe Dilated Cardiomyopathy Lorenzo

Marisa Crespo. Alfonso lnstituto

Monserrat,

Castro-Beiras,

Sandra

cases.

Idiopathic

Lamin

associated

AJC mutations

with conduction

with features Methods:

Dilated

72+4”

7

Vehicle

85t6

116*4

Tg-WT

6

CYA

1 oot3

11255

Non-Ta

6

CvA

67*3

111*6

1015-140

Effect of Estrogen on Angiotensin Receptors, Matrix Metalloproteinases, and Left Ventricular Mass in a Transgenic Mouse Model of Human Hypertrophic Cardiomyopathy

Edith Speir, zurxiylc, Fananapazir,

Kazuyo Takeda, Victor J. Ferrans. Mariappan

National

Heart, Lung and Blood Institute,

Univarsify, Co//ege Station, Background:

Mutahons

Estrogen

eases. This study was designed can modify left ventricular metalloproteinases

identified

system disease.

After informed

consent,

with familial

Results:Three

members

developed

severe

years old respectively.

familial

30% of the

DCM, frecuently

DCM and required

in the twins.

A new mutation

(Arg349Leu)

was identified

was not present

in 22 unaffected

mutation

a highly

Rattus norvegicus

relatives

conserved

region

cardiac

and her two female

transplantation

with slow ventricular

identical

of daily treadmill

exercise.

LV mass was assessed

and some hearts were perfusion-fixed

and immunoblotting

for frozen sections and were performed.

had LV masses of 77 and 49 mg. and placebo-treated

AT-1 receptors,

MMP-3 and MMP-13

to estrogen-treated Estrogen

were increased

(p-zO.05, for

in untreated

ov

OY TGM.

replacement

significantly

reduced

in a model of FHCM. These findings

of genes involved

of clinical importance

the

in awake mice at 2 weeks

others were processed

staining

(0~).

in 10 mice of each group;

OY TGM had LV masses of 79 and 60 mg. respectively

both comparisons).

1015-l 59

in matrix metabolism

in human patients

LV mass, AT-1 receptors suggest that estrogen

and

can reg-

and cardiac fibrosis, which are

with FHCM.

Determinants of Exercise Capacity in Hypertrophic Cardiomyopathy: The Role of Left Ventricular Outflow Tract Obstruction

at 52 years old. At

response.

No conduc-

MunmohanS.Virdee,Yoshihisa Matsumura, in exon 6 in the three patients.

This mutation

and in more than 100 healthy

controls.

identical

(AT,) in a transgenic

(20 each) were ovariectomized

were performed

Mice were then euthanized

Intact TGM and NTGM

at 36, 18, and 20

in Xenopus

laevis. Gallus

This

gallus.

and humans.

The Arg349Leu

and after 3 months

lmmunohistochemical

ulate expression

receptors

doses

release of matrix

by SSCP and cycle sequenced.

(mother

The father of the index case had died suddenly

was present

affects

studied

of one of the families

and cod-

in physiological

by attenuating

were implanted

Echocardiograms

in paraffin, for sectioning;

Conclusions:

estrogen

angiotensin

cohorts (NTGM) pellets

tissue extracts.

TGM compared

hypertrophic in several dis-

Aspl75Asn.

(90 days) estrogen

MMP-3 and MMP-13

we studied the lamin A/C gene in 17 patients of 14 dif-

tion disturbance

Conclusions:

for causing

in about

DCM. DNA was isolated from frozen blood samples

the mother was on atrial fibrillation

form of DCM.

is familial

whether

(MMPs) and by regulating

tracings.

Lameh

Texas ABM

can cause familial

and hypertrophy

and embedded Results:

We repon here a novel lamin A/C mutation

ing regions of lamin A/C were PCR amplified,

diagnosis,

Spain,

of severe dilated cardiomyopathy.

ferent families

twins)

q ouzas,

(Aspl75Asn)

to determine

TGM and nontransgenic

from M-mode

Muthuchamy, Maryland,

has been shown to be cardioprotective

(LV) function

mouse model (TGM) expressing Methods:

Bethesda,

Texas.

in a-tropomyosin

(FHCM).

and estrogen-treated

(DCM)

4 weeks (ma)

Tg-l79N

after ov (baseline)

Spain.

Cardiomyopathy

have been

With

Barral, Rafael Laredo, Beatriz

Hospital Juan Canalejo, A Corufia,

de Ciencias de la Salud, A Corufia,

Background:

(ma)

84t3

other 10 received placebo.

B.

Baseline

CYA

Slow-release

1015-138

or models.

(means+ee)

markedly

of age demon-

to failure before 52 weeks of age and in fact these hearts are hypercontractile.

An increased

LV

any effect of CyA

mutation

n

posi-

no deficit of baseline

stimulation

and dysregulation

Thus,

in

reduced

7

cardiomyopathy

Although

in tissue Unlike

Genotwe

at 27-30 weeks.

levels

of eNOS”-

to P-adrenergic

differences

Tg-l79N

in cardiac expression

were detected

transcript

multi-

As mice aged,

mRNA

mice at 52 weeks of age demonstrated response

using

reserve.

tion of cardiac gression

(SERCA2a)

whereas

analysis

degeneration/death.

and protein

heart to

to vehicle-treated

at 52 weeks of age.

left ventricular

Significant

mANA

Ca’+-ATPase

Although contractile

of cardiac hypeltrophy

factor (ANF) and a-skeletal-actin

(TNF-a)

at 27-40 weeks,

normalized

markers

concentric

tively with the degree of cardiac hypertrophy. of tumor

to

affects of chronic eNOS ablation.

at 40 weeks of age and cardiac functional

Results: Hearts from eNOS+ re-induction

of con-

mice at 18-20, 27-30, 40 and 52 weeks of

the isolated work performing focal replacement

Because

in these mice, we undertook

steady state levels of molecular

and heart failure in male eNOS.”

on LV-mass

mice corn-

Conclusion:

FHC-linked

with

(eNOS) homozy-

arterial hypertension.

of cardiac pathophysiology

the cardiac functional

Methods:

sustained

nitric oxide synthase

Tg-l79N

CyA treatment

T mutation.

across different

Effect of CyA treatment Background’. It is well documented

mutation,

T

CyA treatment.

compared nglml.

we

mutant (Tg-l79N)

On sacrifice,

No significant

were 453+124

model,

with CyA (18mqkgl

in CyA-treated

pc.05).

CyA levels

in

a troponin

were measured

was unchanged.

in CyA-treated

vs. 3.6M.lmg/g.

Blood

(Tg-WT),

All mice tolerated

decreased

decreased

mouse

expressing

and function

Results:

and mortality

with CyA were aban-

were treated

mass

(table). Systolic function

body weight ratio was significantly

wild-type

(Non-Tg)

fashion.

studies

FHC model

human

littermates

and mass significantly

pared to all other groups

But with

to this particular

murine

LV dimensions,

in blinded

and has

(FHC).

clinical

be specific

Mice expressing

T and non-transgenic

day) or vehicle

models,

Cardiomyopathy

cardiac hypertrophy

proposed

the effect of CyA in a different

(179N) mutation.

a.m.

increased

the CyA effect could

Neil J.

Dist. of Columbia,

in several animal

Hypertrophic

of FHC (aMHC+/403),

Because

examined

Horton,

Washington,

Dist. of Columbia. hypertrophy

the recent report that CyA administration

1015

131A

Cyclosporine A Treatment Decreases Left Ventricular Mass in Mice Expressing a FHC-Linked Troponin T

1015-139

mortality

in CHF pts. -Risk etr&cation

Subgroup

- Cardiac

McKenna,

St George’s

Sami Firoozi, Perry M. Elliott, William

J.

Hospital Medical School, London, United Kingdom.

Background:

The influence

cise capacity

in patients

of left ventricular

outflow

(pts) with Hypertrophic

tract obstruction

Cardiomyopathy

(LVOTO)

on exer-

(HCM) is poorly under-

stood. mutation

in LMNA

A/C gene is associated

with a severe

Methods:

86 pts with HCM

ergomehy

with expiratory

peak exercise pulse),

(pkVOP),

anaerobic

age of predicted Results:

anaerobic

threshold

73% symptomatic)

threshold

(at02

underwent

and echocardiography.

pulse);

(atV02);

Oxygen

upright

bicycle

consumption

02 pulse at peak exercise

and peak workload

are expressed

at

(pkO2

as percent-

values.

37 pts with resting

pkVO2

than those without

resting

LVOTO,

change

in LVOTO during

16 developed

(43 +14yrs,

gas analysis

pkVO2

LVOTO resting

exercise

LVOTO >SOmmHg

>=30mmHg LVOTO,

correlated

(58 *2OmmHg,

65 219 vs 74 *19%,

with peak

exercise

LVOTO

group A), had a lower p=O.O3. In pts without (wO.43,

(r=O.44, p=O.O02). Of 49 pts without during exercise

p=O.O03) and resting

(group Bi), 33 did not (group

exercise LVOTO was lower in group Bi than group A (48 i21 vs 81 r27mmHg.

LVOTO. Bn). Peak p
Table 1. There was no difference

between

the 3 groups

for peak heart rate and respiratory

quo-