Myocardial Carnitine in End-stage Congestive Heart Failure. AJC 1989

8/10/2019 Myocardial Carnitine in End-stage Congestive Heart Failure. AJC 1989

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Myocardial Carnitine in End-Stage Congestive

Heart Failure

Mary Ella M. Pierpont, MD, PhD, Dianne Judd, BS, Irvin F. Goldenberg, MD,

W. Steves Ring, MD, Maria Teresa Olivari, MD, and Gordon L. Pierpont, MD, PhD

To test the hypothesis that camitine is decreased in

the myocardiai tissue of patients with end-stage

congestive heart failure (CHF), teft ventricular myo-

cardiai camitine was measured in 51 patients un-

dergoing erthotopic cardiac transptantation. The

study group inch&xi patients with idiopathic ditat-

ed cardiomyopathy, coronary artery disease, myo-

cardttis and riteumatic heart disease. Myocardial

camitine varied in diirent cardiac chambers. in

normal centrot hearts, the teft and right ventricular

total camitine was similar, but the ventricles had

higher levels than the atria (p


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TABLE I Clinical Characteristics o f End-Stage Congestive Heart Failure

Dilated Coronary

Rheumatic

All Pts

Cardiomyopathy Artery Disease Myocarditis

Heart Disease

(n = 51)

(n = 31) (n = 13) (n = 5) (n = 2)

Age Ws)

Dur Sx (yrs)

EF ( )

PAW (mm Hg)

CO (liters/min)

Cl (liters/min/m2)

RAP (mm Hg)

PAR (dynes s cm-s)

39f17

2.8 f 2.9

18f9

28~~7

3.6 f 1.0

2.0f0.5

14f7

234 f 126

36f17

3.0f 1.5

19flO

28zt7

3.7 f 1.0

2.0 f 0.5

15f7

225 f 120

50~8

2.6 f 4.0

16f6

27k8

3.5 f 0.8

1.9f0.4

8iz5

270 f 140

25f19

1.3f2.1

20f6

31 f 10

3.3f 1.2

2.1 f 1.0

18f2

186 f 141

47f13

4.0 f 4.2

15f6

25f4

3.3 f 1.3

1.7f0.7

9f5

261 f 111

All values are mean-f standard deviation.

l

p


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CARNITINE IN HEART FAILURE

relatively high values for myocardial carnitine (>2 stan-

dard deviations) are present n 8 (15.7 ) of the patients

in Figure 1 (4 with idiopathic dilated cardiomyopathy, 3

with coronary artery diseaseand 1 with myocarditis).

Quantitative eorrelatiatrs: As seen n Table III, total

myocardial carnitine did not correlate significantly with

any of the hemodynamic variables, age or duration of

symptoms for either the CHF group as a whole (n =

51), or the subgroup with dilated cardiomyopathy (n =

31). In the 13 patients with coronary artery disease,

myocardial total carnitine correlated with cardiac out-

put (r = 0.62, p


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TABLE III Correlation Coefficients for Myocardial Total Carnitine with Hemodynamics and Other Variables

Correlation Coefficients

Variable

All Pts

(n = 51)

Dilated Coronary

Cardiomyopathy Artery Disease

(n = 31)

(n = 13)

Myocarditis

(n = 5)

Age

0.14

0.10

Dur Sx (yrs)

0.25

0.18

EF ( ) -0.04

-0.08

PAW mm Hg) 0.17 0.17

CO (liters/min) 0.26 0.18

Cl (liters/min/m2)

0.19 0.11

RAP (mm Hg) -0.29

-0.25

PAR (dynes s cme5) 0.12

0.08

* p 2 standard

depending on the cardiac chamber sampled could ex- deviations above normal. In the group of 51 patients

plain some of the differences among previous reports, with CHF, thesemyocardial carnitine levels did not cor-

and suggest hat measurement of right ventricular car-

relate with any hemodynamic variable. Myocardial free

nitine from endomyocardial biopsiesmay not accurately

carnitine has previously been shown to be depleted in

reflect left ventricular carnitine concentration.

areas of acute myocardial infarction,1 but none of our

-0.21 0.21

0.62* 0.47

0.20 0.27

-0.17 0.99

0.62* 0.61

0.70t

0.35

-0.67

0.65

0.14

-0.03

200

160 -

160

60

20

0

NORMAL

ALL

CM

CAD

MY0

n=36

k23

n=14

n=5

t-k4

THE AMERICAN JOURNAL OF CARDIOLOGY JULY 1. 1989

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CARNITINE IN HEART FAILURE

13 patients with coronary artery diseasehad severely

depleted myocardial carnitine. Decreased myocardial

carnitine has also been reported in papillary muscle bi-

opsies9 and endomyocardial biopsiesi from patients

with chronic CHF. In the latter study by Regitz et a1,i6

the decreasedmyocardial carnitine was relatively con-

sistent, including both patients with idiopathic dilated

cardiomyopathy and coronary insufficiency. Another

study by Regitz et all7 found myocardial carnitine levels

in explanted human hearts similar to ours, but conclud-

ed they were low basedon comparison o relatively high

normal values obtained from 3 donor hearts. It is tempt-

ing to speculate that the severecarnitine deficiency in

some patients may be clinically relevant, since Ghidini

et a122 eported that L-carnitine supplementation in el-

derly patients with heart failure reduced heart rate, im-

proved diuresis, reduced edema, alleviated dyspnea and

decreaseddigitalis requirements. Our study did not ex-

amine the efficacy of dietary carnitine supplementation,

but our results suggest hat relatively few CHF patients

would benefit based on their myocardial levels.

We did not find plasma carnitine deficiency in any

of the 23 patients in whom it was measured.This is in

contrast to 6 of 27 adults with dilated cardiomyopathy

studied by Feldman et all2 and 2 of 25 patients (both

young children) reported by Tripp et al. However,

plasma total carnitine levels can be normal even in pa-

tients with systemic camitine deficiency23who can have

marked variation in plasma carnitine from day to day.

Thus, a single normal plasma camitine measurement

may not reflect deficiency of carnitine in tissues. The

poor correlation between plasma carnitine and myocar-

dial carnitine in our study and that of Regitz et all6

further supports this statement.

The mean plasma carnitine in our patients was high-

er than normal, and 12 of our patients had plasma total

carnitine >60 nmol/ml. This finding is consistent with

those of Tripp,

l1 Feldman12and co-workers in cardio-

myopathy patients, and Conte et al in patients with

dilated, hypertrophic and alcoholic cardiomyopathy and

CHF from other causes.

The cause of elevated plasma carnitine in severe

CHF is not clear. Becausecarnitine is excreted by the

kidney and can be removed by hemodialysis,25 eldman

et all2 suggested hat decreased xcretion of camitine is

a likely cause. They found a good correlation between

the natural logarithms of plasma camitine and creati-

nine clearance n 15 patients they studied, but we were

unable to confirm this finding. A correlation between

total plasma carnitine and serum creatinine was also re-

ported by Bartel et a125n a group of patients with se-

vere renal failure undergoing hemodialysis. Due to the

selection process or cardiac transplantation, renal dys-

function in our patients was minimal and thus the 2

study groups are not directly comparable. We found a

weak correlation betweenplasma total carnitine and se

rum carnitine, whereas Regitz et ali7 and Conte et a124

found no such correlation. It would appear that de-

creased enal function alone cannot account for the ele-

vated plasma carnitine, and some alterations in carni-

tine metabolism in CHF still remain unknown.

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60 THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 64

Myocardial Carnitine in End-stage Congestive Heart Failure. AJC 1989

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