Download Ventricular arrhythmias late after myocardial infarction are related to

Clin. Cardiol. 16,493-496 (1993)
Ventricular Arrhytlumas Late after Myocardial Infarction Are Related to
Hypomagnesemia and Magnesium Loss: Preliminary Trial of Corrective
LESZEKCEREMUZYN
' 'SKI M.D., W.D. AND NGUYEN
VAN HAO, M.D.
Depamnent of Mology, Postgradm Medid School, Warsaw, Poland
Summary: It has been well established that in acute myocardial infamion (MI) many patients display low serum magnesium (Mg). This is associated with complex ventricular arrhythmias.The question arises whether predischargeanfiythmias occurring late after MI might also be related to Mg imbalance. In 118 patients subjected to heart rhythm 24 h Holter
monitoring in the second or third week after MI, we investigated (1) therelationship between serum Mg, urinary Mg loss,
and ventricular anfiythmias,and (2) the effect of Mg supplementationonheartrhythmdismbnces.Inpatientswithundistll&XlrhythmOr~lllO@CVen~ectopicbeats(VEB)
(Lown0-2; n = 84), mean serum Mg level (mg% f SD)was
1.83f0.21, whereasinpatientswithmultifocalVEB,paifi,or
nomustained ventricular tachycardia 0
(Lown 3 4 n = 34)
serum Mg was demasedto 1.68 f 0.27 (p <0.01). Serum Mg
n o d range in our laboratory is 1.7-2.6 mg%. The lowest
serum Mg reaching 1.55 f 0.27 was found in nonsustained VT
(Low114 b) subgroup (n= 14). Urinary Mg loss m e a s d i n 81
patients was more pronounced in those with Lown 3-4 arrhythmias (n =26) than with h w n &2 (n = 55). 'he daily values were 73 f 22 and 54.4 f 26 mg, respectively(p < 0.001).
lhirteen patients with complex arrhythmiasand low senunMg
received Mg supplementation (MgS04,8 g in 500 ml5% glucose intravenously during 24 h). This resulted in restoration
of almost undisrhythm in 10 subjects. In conclusion, a
number of patients in late phase of MI displayed hypomagne-
Address for reprints:
Prof. Leszek Ceremutydski
Department of Cardiology
Postgraduate Medical School
Grochowski Hospital
Grenadieldw 5 1/59
04-073 Warsaw, Poland
Received January 27,1993
Accepted March 9,1993
semia concomitant with augmented Mg excretion. These al-
tersltions wmrelatedtotheoccurrenceofalltlythmias:the most
threatening heart rhythm disturbanceswere accompanied by
the lowest serum Mg and the highest Mg excretion. Our preliminary observations suggest that supplementation with
MgS04 may be a reasonable approachto the treatment of predischarge complex ventricular arrhythmias after MI. This
should be verified in a conmlled trial.
Key words: myocardial infarction, ventriculararrhythmias,
magnesium
Introduction
It has been long established that magnesium ion plays an important role in the metabolism and electrophysiologyof the
heart muscle.' Several studies demonstrate a correlation between Mg depletion and complex ventricular arrhythmiasz4
which are reduced by Mg
In many patients after myowdial infamion (MI),ventricular alltlythmias are detectedjust prior to discharge and theseab
normalities have been shown to predict long-term mortality.l3>l4 Therefore, seved attempts were undertaken to suppress
arrhythmias after MI. Antiarrhythmicdrugs used for this purpose proved to be unsuccessful and even inatwed mortality,
as recently reported in the CAST study.l5 The question arises
whether at least in somepatients ventricular a
d
m
a
sin late
MI are causally related to homeostatic disturbances,in pa&ular to Mg imbalance.No data on this subject have been pm
vided so far although they may have considerableclinical significance.
The present study was undertaken (1) to measw serum Mg
and urinary Mg exmtion in patients after MI before discharge,
(2) to establish a possible relationshipbetween ventriculararrhythmias and serum Mg as well as Mg excretion,and (3) to
conduct a pilotstudy on the effect of Mg supplementationupon
ventricular arrhythrmas late after MI in patients with hypomagnesemia.
Clin. Cardiol. Vol. 16, June 1993
494
Material and Methods
The study group consisted of randomly selected consecutive patients, both male and female, admitted to the coronary
care unit, GrochowskiHospital, because of confirmed Qwave
MI and who survived the acute phase. Criteria for inclusion
in the study p u p were absence of symptoms of heart failure
and any other disease except mild hypertension. Between
October 1989and July 1991,118patients (mean age 57 years,
range 18-87) were included in the group. The majority of patients (82%) were treated with antiplateletdrugs, 63% were
given nitrates, and 47% received beta blockers. No patient r e
ceived drugs that might affect magnesium balance (e.g., diuretics, ACE inhibitors, etc.). All patients received the same
standard hospital diet.
Two days before planned discharge (in the second or third
week of the disease, mean 16.3f 3.3 days),fastingblood samples for serum Mg and K determination were obtained. Daily
urine was collected to calculate Mg loss. Magnesium was
determined by atomic absorption specmphotometry (Opton,
type FL 6), normal values in serum were from 1.7 to 2.6 mg%.
Upper normal limit for 24-h Mg excretion was 35 mg. Serum
K was assayed by the photometric method, normal values were
from 3.5 to 5.0 mEq/l.
On the same day, all patients were subjected to 24-h Holter
heart rhythm monitoring (Medilog II, Oxford Medical Inc.).
Holter ECG tapes covering 24-h recordings were analyzed
by computer with manual overread. All tapes were reviewed
blindly by two independentinvestigatorswithout knowledge
of the biochemical data. Nonsustained ventriculartachycardia
(VT) was deiined as three or more consecutive ventricular premature complexes at a rate of > 120/min lasting c 30 s and
terminating spontaneously.
After inclusion of the first 60 patients into the study, we administered MgS04 (8 g in 500 ml5% glucose IV during 24 h)
to all subsequent subjects who displayed advanced ventricular arrhythmiasand decreased serum Mg. Infusion was given
on the next day after Holter monitoring and Mg measurement
in serum and urine. There were no other changes in the concomitant medication.The second 24-h Holter ECG recording
was made on the next day after MgS04 infusion.
The protocol was approved by the Ethical Committee of
PostgraduateMedical School in Warsaw.
Results
Serum Mg in relation to head rhythm disturbanm is shown
in Fig. 1. In the group with undisturbed sinus rhythm or with
monomorphicVEB, mean serum Mg level was normal (1.83
f 0.2 1 mg%) whereas in the presence of complex arrhythmias (multifd, pairs,nonsustained VT) serum Mg was demased (1.68 f0.27 mg%, p c 0.01). In the subgroup(n = 14) with
nonsustainedVT,mean serum Mg was as low as 1.55 f0.27
mg%.
Individual results showed that 21 of 34 patients had lowered
serum Mg with complex arrhythmias(61.8%) compared with
22 of 84 patients (26.2%) with benign arrhythmias(p c 0.01).
Serum K level was normal in all individuals. The vast majority of 81 patients in whom 24-h urine was collected displayed
increased Mg loss. This was much more pronounced in individuals with a d v a n d arhythmias (Fig. 2) than in patients with
less disturbed rhythm. Corresponding values (mg, mean f
SD) were 73 f22 and 54.4 f26 (p c 0.001)
In 13 patients with complex arrhythmias and low serum
Mg, infusion of MgS04 was administered. This resulted in
restoraton of almost undisturbed rhythm in 10 subjects. No untoward effects were observed. Details are shown in Table I.
Three patients (Nos. 8,9,13) showed little improvement. It
should be stressed, however, that serum Mg level in these patients in spite of Mg supplementation remained low. MgS04
administration led to an increase not only of serum Mg but also
of serum K levels (Table.)I In total, 10episodes of nonsustained
VT recordedin 7 patients were completely eliminated. Pairsof
VEB were reduced from 44 to 4 and multifocal VEB from
7377 to 1154 (Table lI).
I
p<0.001
Lower normal
range
pco.01
- - Q . - . U p p e r normal
Lown Lown
3-4
0-2
n=84 n=34
FIG.1 Serum magnesium in relation to heart rhythm disturbances
(mean f SD).
a
range
Lown Lown
0-2
3-4
n=55 n=26
FIG. 2 Magnesium excretionin 24-h urine in rekition to heart rhythm
disturbances(mean f SD).
L. Ceremuzyhski and N. Van Hao: Hypomagnesemia and ventricular arrhythmias late after myocardial infarction 495
TABLEI Effect of MgS04 infusion upon ventricular anhythmias, Semm magnesium (mg%), and potassium (a
in individual
) patients
Patient
No.
1
2
3
4
5
6
7
8
9
10
11
12
13
Meall
f SD
Age
Site of infarction
66
45
66
76
37
78
45
61
72
49
69
63
53
Inferior
Anterior
Before MgS04
Day
after
MI
Anterior
Lateral
Anterior
Anterior
Anterior
Lateral
Inferior
Anterior
Anterior
Anterior
Posterior
Lawn
Low
class
16
15
14
15
18
11
15
19
26
16
19
21
20
After MgSO4
3
4a
4b
3 +4b
3+4a+4b
4a + 4b
4b
3+4a
4a + 4b
4a + 4b
3+4a
3 +4b
3
Mg
K
1S O
4.6
4.8
4.4
4.4
4.6
4.6
3.8
4.3
4.1
4.2
4.6
5.2
4.8
4.49
0.35
1.60
1S O
1.68
1.50
1.06
1.42
1.69
1.30
I .30
1.65
1.69
1.57
1S O
0.19
class
1
1
1
1
1
1
1
2+3
4a
1
1
1
3
Mg
K
1.90
1.90
1.90
2.30
2.80
2.20
2.00
1.75
1.46
1.69
2.10
2.80
1.60
2.03a
0.41
4.8
4.7
4.6
4.5
4.7
4.8
4.1
4.4
4.4
4.5
4.8
5.2
4.8
4.640
0.27
“pO.001.
TABLE
II Total number of anhythmic episodes in 24-h Holter
monitoringrecorded in 13 patients treated with MgSO4 infusion
Before MgS04
After MgSO4
Nonsustained
VT
Pairs
Multifocal
VEB
10
0
44
4
7377
1154
Abbreviations: VT = ventricular tachycardia, VEB = ventricular ec-
topic beats.
Mscussion
We have shown that 36.4%of our study p u p displayed low
serum Mg before discharge.So far the “Low-Mg” phenomenon
has been descrikd only in patients with acute MI.s5.7-12Our
observation shows that this phenomenon persists in the late
phase of the disease as well. It has also been documented in this
study that urinary Mg excretion was augmented in the vast majority of individuals (79%).Hence it may be speculatedthat low
serum Mg results from increased Mg loss. This we have previously detected in acute MI16 and suggested that augmented
Mg excretion presumably was due to an increased activity of
the renin-angiotensin-aldosterone(RAA) system.l7 There are
no data on RAA activity late after MI, but it is likely that predischarge stress stimulates both adrenergic and RAA systems
resulting in Mg loss.
The present study has demonstrated the relationship between
hypomagnesemia and arrhythmias. Of 43 patients with decreased serum Mg, 21 (48.8%) displayed advanced anhythmias, whereas advanced arrhythrmas were found in only 13
(17.3%,p c 0.001) of 75 patients with normal serum Mg. Mean
serum Mg was lowest (1.55 f0.27 mg%) in patients with nonsustained VT.
The magnitude of Mg excretion also seems to be related to
cardiac rhythm disturbanm. All cases with advanced arrhythmias showed increased Mg loss. There were only 17 patients
with normal urinary Mg excretion and all displayed normal or
mildly disturbed rhythm. The relation of Mg excretion to arrhythmias in MI has not been studied so far and in view of our
results this phenomenon deservesmore attention. Increased Mg
loss in late MI which may be the cause of hypomagnesemia
probably results from increased activity of both admergic and
RAA systems, although this concept needs further investigation.
Earlier studieshave suggested a causal relationshipbetween
Mg imbalance and arrhythmias.*“ Supplementation with
MgS04 proved to be efficacious in recent MI complicated by
heart rhythm disturbances?-12We used a similar approach in
patients presenting with complex arrhytlmuaslate after MI and
decreased serum Mg before discharge from hospital. The results achieved proved encouraging. We used relatively small
doses of MgS04, and this may be the reason why Mg infusion
was ineffective in a few cases (Nos. 8,9,13, Table I). As a matter of fact, we still do not know the best method for determination of the “magnesium status,’’ as semm Mg provides only
crude information. We recently observed six patients with complex arrhythmias after MI who were given MgS04 infusion in
spite of normal serum Mg, and in three of these undisturbed sinus rhythm was restored. Little is also known about the prop
er regimen of Mg supplementationand the length of such therapy needs to be determined.
It is worthwhile to mention that magnesium infusion also resulted in significant increase of serum potassium. This phe-
Clin. Cardiol. Vol. 16, June 1993
496
nomenon is in accordance with previous observationslE,l9
and may help reduce ventricular arrhythmias, as repletion of
Mg is necessary for repair of the cellular K loss.
Frequent and advanced arrhythmias late after MI indicate
poor progno~is.'~
Although antiarrhythmic agents may be of
theoretical benefit, no drug has been demonstrated to reduce
mortality.On the contrary, in the CAST trial there was even an
increase in m0rtality.15Our study suggeststhat predischarge arrhythmias may be triggered or at least facilitated by decreased
serum Mg. This assumption seems to be supported by the encouraging effects of MgS04 supplementationobserved in our
patients, notwithstanding that this pilot treatment on few patients was uncontrolled.The findings of our study suggest the
need for long-term controlled trial with magnesium supplementation after MI. One may speculate that beneficial effects
may be even greater than those observed so far with MgS04 infusion given only on the fmt day of acute MI.
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