Download Atrial fibrillation in pure rheumatic mitral valvular disease is

European Review for Medical and Pharmacological Sciences
2009; 13: 431-442
Atrial fibrillation in pure rheumatic mitral
valvular disease is expression of an atrial
histological change
N. ALESSANDRI, F. TUFANO, M. PETRASSI, C. ALESSANDRI,
C. DI CRISTOFANO*, C. DELLA ROCCA*, P. GALLO*
Department of Cuore e Grossi Vasi “A. Reale”, polo pontino, University “La Sapienza”, Rome (Italy)
*Department of Experimental Medicine, University “La Sapienza”, Rome (Italy)
Abstract. – Background: Some of theories try to explain the insurgence of atrial fibrillation (AF) in patients with acute articular rheumatism (AAR). These theories remind the close relation between AF and left atrium, or with valvular vitium degree, or monophasic action potential and histological cardiac structure. In 15
years of work in the academic Department of
Heart and Big Vessels in Rome, the Authors
studied 243 patients with mitral valvular disease
post AAR before and after surgical manoeuvres.
Materials and Methods: Patients were divided in order to monitor atrium and ventricle morphological and functional modifications of the
valve according to cardiac rhythm. Patients classification was based on surgical therapy adopted,
kind of mitral disease and cardiac rhythm. An histological examination was performed, only in patients treated with valvular replacement. During
the operation an histological examination in an
atrial tissue fragment was performed. 243 patients with mitral valvular disease post AAR with
indication in valvular adjustment were studied.
The whole population was treated with mitral
transcutaneous valvuloplasty (Group B – 130 patients) or with mitral valve replacement surgery
(Group A – 113 patients). These two groups were
divided: in Gr.A in Gr.A1 and Gr.A2, and Gr.B in
Gr.B1 and Gr.B2, according to cardiac rhythm (sinus rhythm iSR, AF). These subgroups were also
divided in Gr.A 1SR , Gr.A 1AF ; Gr.A 2SR , Gr.A 2AF ;
Gr.A3SR, Gr.A3AF, according to mitralic disease’s
kind (stenosis, stenosis/regurgitation, regurgitation). A complex screening were exerted to all patients using echocardio-doppler technology. Morphological parameters of atrium and ventricle,
and functional parameters of mitral valve, aorta
and tricuspid were evaluated. In Gr.A group patients during the operation were execute a bioptic
sampling from left atrium and a consecutive histological valuation.
Results: In Gr.A 1 mitral valve area (MtVA)
arises smaller (p<0.01) in the group with AF,
than those in SR. On the contrary, in subgroups
of population of Gr.B there isn’t statistic dis-
agreement (p>0.05). Left atrium volume arises
elder in patients in AF than in patients in SR
(p<0.01), either in patients of subgroups Gr.A1,
Gr.A 2 or in patients of the whole Gr.B before
and after valvuloplasty. In the whole population
Gr.B, either Gr.BRS or Gr.BFA, left and right atrial
volumes decrease eloquently (p<0.01) after
valvoplasty.
There’s no linear relationship (Pearson r<0.5)
between the different subgroups of Gr.A (Gr.A1,
Gr.A2, Gr.A3) and those of Gr.B according to mitral
valve area (MtVA), volume and left atrial area.
Left atrial biopsy shows in patients of SR a
normal atrial tissue in the 48% of cases and
lightly altered in remaining 52%. On the contrary
in patients of AF there are strong anomalies in
the 100% of cases.
Conclusions: According to histological view,
atrial volumes variations and valvular area variations before and after surgical treatment, and
according also to their comparisons in different
groups, authors could assume that insurgence
of AF and its chronicization could be an expression of a strong atrial myocardial histological alteration. Furthermore while starting moment of
AF genesis is characterized by histological alterations of atrial myocardium (expression of
rheumatic chronic disease), its chronicization
hands to anatomic-volumetric progressive deterioration of the atrial dysfunction.
Key Words:
Mitral valve, Atrial fibrillation, Acute articular
rheumatism, Sinus rhythm, Left atrium.
Introduction
In the latest 30 years of the last century,
rheumatic disease’s incidence in the world fortunately decreased, because of many factors like
Corresponding Author: Nicola Alessandri, MD; [email protected]
431
N. Alessandri, F. Tufano, M. Petrassi, C. Alessandri, C. Di Cristofano, C. Della Rocca, P. Gallo
scientific evolution and social-sanitary improvement. In the second half of XX century, the incidence was one case in one thousand people every
year. Between 2000 and today in some geographic areas of east Europe, in Australia and Africa a
recurrence of the rheumatic disease was noted.
So it becomes object of careful observation in
several schools1-8.
In the past the common association between
mitral valve disease and atrial fibrillation was an
argued item. The disease’s extinction didn’t answer to the most important question: if and
which physiopathology mechanisms linked these
two diseases.
The physiopathological link between the disease could be9:
• the anatomic and functional alterations and
electrophysiological modifications observable
in rheumatic disease’s history,
• the lazy and progressive blood’s stagnation in
the atrial chamber and its remoulding,
• the progressive thickening, fibrosis and calcification of the valvular system, could be
the physiopathological link between the diseases.
From this point of view, it is not already clear
if left atrium dilatation, left atrium wall alteration
and mural thrombosis formation, that are observable in rheumatic valvular disease’s history, are
the evolution of a slow subacute process of the
incipient rheumatic disease or if they are associated to hemodynamic/electrophysiological modifications9-16.
The aim of this work was to research possible
temporal and functional correlations between
cardiac electrical activity (sinus rhythm or atrial
fibrillation), atrium sizes, endangerment’s degree
of the mitralic valve system and histological conditions of the atrium wall.
Materials and Methods
In Heart and Big Vessels Department of “La
Sapienza” University of Rome, Italy, a population of 243 patients hospitalized and “in-office”
followed was examined in 15 years. The patients
mean value age were 50.4±10.3 years (range 1478 years), 63 males (M) were 51.5±10.4 years,
and 180 females (F), were 50.8±9.3 years.
Inclusion’s criterions in the study were:
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1. Rheumatic disease not in active stage.
2. Isolated mitral valve disease even if “tricuspidalized” (allowed aortic insufficiency of light
degree)17.
3. Indication to valvular adjustment in dependence on mitralic valve surface indexed and
on NYHA functional class.
4. Lack of other pathologies like thyroid disease,
acute renal insufficiency or hard chronic, liver
failure, arterial hypertension, ictus or former
TIA episode.
5. Checks in patients submitted to mitral transcutaneous valvuloplasty.
6. Checks in patients submitted to mitral valve
substitution (mechanic or biological).
All patients had normal arterial pressure values and had no altered hematochemical values
about proteins, glucose and lipids.
All subjects, afterward enough information
and after received their accordance, were submitted to periodic sanitary checks (6-8 months). On
average each patient was submitted to 2 checks
before the correction and to 12±2 checks the surgical treatment.
During the check a medical examination was
accomplished. Hematochemical tests, colour
Doppler echocardiography and, if required,
transesophageal TEE, external electrocardiogram, unbloody measurement of humeral arterial
pressure were perfomed.
130 of the 243 patients were submitted on mitralic percutaneous valvuloplasty (using Inoue’s
catheter)18,19. The other 113 patients were submitted to a valve substition’s surgery with valvular
prosthesis (mechanical kind in 93 cases and biological in 20).
Indication to valvular adjustment in dependence to mitralic percutaneous valvuloplasty20-21
was choose according to clinic conditions and
TTE-TEE test22, if there was:
1. Mitralic regurgitation (higher and light-medium degree);
2. Valve anomaly and malformation and undervalvular system (Wilkins and Ried “score”) 23;
3. Presence of thrombosis in left atrium.
For statistical reasons 243 patients were mostly divided in two groups: Group A (113 patients)
submitted to mitral valve substitution surgery
(Mt.V.S), and Group B (130 patients) submitted
to mitral percutaneous valvuloplasty (Mt.P.V).
According to pre-surgery prevalent valve disease
Atrial fibrillation in rheumatic valvular disease
Gr.A group was divided in the following theree
subgroups (Gr.A1, Gr.A2, Gr.A3):
Gr.A1 → patients with isolated mitral stenosis;
Gr.A2 → patients with mitral stenosis/regurgitation;
Gr.A3 → patients with pure mitral regurgitation.
Afterward according to sinus rhythm (SR) or
atrial fibrillation (AF) each subgroups patients, according to sinus rhythm (SR) or atrial fibrillation
(AF) were divided in further two subgroups:
Gr.A1SR, Gr.A1AF; Gr.A2SR, Gr.A2AF; Gr.A3SR, Gr.A3AF
In Gr.B group were present only patients with
isolated mitral stenosis. This group was divided in
two groups Gr.B1 (before valvuloplasty) and Gr.B2
(after valvuloplasty). Each group was divided in
four subgroups according to cardiac rhythm’s kind
(Gr.B1SR, Gr.B1AF; Gr.B2SR, Gr.B2AF). Table I shows
all described groups.
After surgical treatment population from Gr.A
group wasn’t evaluated by statistical analysis.
That was because athrotomy due to the operation
and auricle’s closure should invalidated findings.
Lab Test
General chemical tests for possible phlogosis
and specific for immunity research to rheumatic
disease and evaluation of hepatic-renal function
and glucidic-lipidic complement.
Echocardiography
Transthoracic echocardiography (TTE) and
transesophageal (TEE) tests were effectuated in
each patient in quiet condition through echocardiograph ATL. Patients were invited to lie down on
the litter and to put down in left lateral decubitus
elevated in about 30°, TTE or TEE were executed
using standard projections and finding measures,
following American Society of Echocardiography
standards24.
Table I.
Gr.A → 113 pt
Gr.A1 (44 pt)
Gr.A2 (54 pt)
Gr.A3 (15 pt)
Gr.B → 130 pt
Gr.B1 (130 pt)
Gr.B2 (130 pt)
Gr.A1SR → 24 pt
Gr.A1AF → 20 pt
Gr.A2SR → 20 pt
Gr.A2AF → 34 pt
Gr.A3SR → 6 pt
Gr.A3AF → 9 pt
Gr.B1SR → 87 pt
Gr.B1AF → 43 pt
Gr.B2SR → 88 pt
Gr.B2AF → 42 pt
Intraventricular septum thickness and posterior wall thickness were evaluated in end-diastolic
and in end-systolic. Left ventricular end-diastolic and end-systolic diameters, left ventricular
end-diastolic and end-systolic volumes were
evaluated using Simpson formula. Mitral valvular area in short axis in 2D, bulb dimensions and
aortic valve’s highest gap in M-mode, left atrium transverse diameter (M-mode), left atrial
volume in atrial systole and diastole were calculated using double elliptoid formula. Ventricular
ejection fraction (EF) and shortening fraction
were evaluated. Mitral valve’s study was performed using Wilkins and Reid modalities
score23. Doppler technique was used to evaluate
trans-valvular fluxes, especially mitral and tricuspid, protodiastolic and end-diastolic peak velocity, protodiastolic deceleration time. Mitral
valve area was measured using, half-pressure
time method (PHT). Isovolumetric relaxation
time indexed for cardiac frequency, regurgitation
and its estimation were evaluated using distance
and duration technique respectively. The peak
pressure in right ventricular and pulmonary
artery were evaluated using tricuspid regurgitation. The peak systolic velocity, spectral area,
regurgitation and its estimation were evaluated
using trans-valvular aortic flow. If pregnant that
was elimination standard.
Hystologic Test
Atrial tissue sampling was performed merely
in patients from Gr.A. In the whole population
two samplings in atrium opening, were executed.
For all the patients sampling seat was left atrium
posterior wall and left appendage. The fragment
was instantly bathed in appropriated pot comprehended formalin in 10% and sent to the Pathology Unit for investigation. The fragment, after appropriate preparation, was evaluated by two specialists in independent and different way. That
was done in order to describe the presence or the
absence of: normal endocardium, wall thickness
reduction, wall thickness accretion, rare hypertrophic cells, myocells hypertrophy, vacuolar degeneration, pigmentation degeneration, endocardial fibrosis, interstitial fibrosis, stretched fibers,
adipose displacement, colliquative myocytolisis.
Statistical Analysis
The average and respective standard deviation
was evaluated in data statistic elaboration. In
oder to compare values average it was used Student t test with two samples in discordant vari433
N. Alessandri, F. Tufano, M. Petrassi, C. Alessandri, C. Di Cristofano, C. Della Rocca, P. Gallo
ance and with two codas. A linear correlation between different groups and in the group itself
was executed (Pearson) with homogeneous and
paired parameters.
Results
The composition of groups and subgroups are
summarized in Table II to VI.
The average age is significantly (p<0.001)
higher in the patients suffering to atrial fibrillation (AF) in relation to those in sinus rithm (SR),
both in Gr.B (57 ± 8.4 vs 42.3 ± 11.4) than in
Gr.A 1 (55.8±8.4 vs 41.5±11.5) and Gr.A 2
(57.5±8.7 vs 43.1±12.3) (Table II).
In preoperatory phase of Gr.A:
• There is not statistical difference on functional
class between the various groups (p>0.05).
• In the Gr.A 1, Mitral Valve Area (MtVA) is
smaller (p<0.01) in the patients with AF than
in SR (Table III).
• The left atrium diameter is greater in patients
with AF in relation to those in both the SR
Gr.A1 and Gr.A2 (Table II).
• The area and left atrial volume are significantly (p<0.001) greater in patients with AF in relation to those in both the SR Gr.A1 and Gr.A2
, while in Gr.A3 this difference is evident only
for the area of the left atrium (Table II).
• Area and volume of the right atrium (p<0.001)
are higher in the AF group in than SR in both
the Gr.A1 and in Gr.A2 (Table II).
In the Group B it is observed that:
– the medium age of the Gr.BSR vs Gr.BAF is
statistically inferior.
– Statistically significant difference (p>0.05)
between the two subgroups (Gr.B 1SR vs
Gr.B1AF), before the valvuloplastic surgery
does not exist.
– A difference (p<0.001) between Gr.BSR and
Gr.BAF in the left atrial volume both before
the valvuloplastic and after valvuloplastic
surgery (60.6±16.8 cm3 vs 96±42 cm3), is
observed. This volume is greater in the patients with AF regarding those in SR.
– A significant (p<0.01) reduction of the left
and right atrial volumes is observed after the
valvuloplastic both in the Gr.BSR (Gr.B1SR
81.6±18.4 cm 3 vs Gr.B 2SR 60.6±16.8 cm 3)
and in Gr.B AF (Gr.B 1AF 119±45.7 cm 3 vs
Gr.B2AF 96±42 cm3) (Table II).
434
This decrement is not statistically different
between the patients in SR versus AF
(p>0.05).
– There is no significant difference (p>0.05)
between the left atrial volume of patients in
SR before the valvuloplastic and the patients
with AF after the valvuloplastic (81.6±18.4
cm3 vs 94.1±42.1 cm3). Data on the linear
correlation between the various subgroups of
the Gr.A (Gr.A1, Gr.A2, Gr.A3) undergoing
surgery and those of Gr.B undergoing valvuloplastic, divided into groups depending
from the type of rhythm (sinus rithm and
atrial fibrillation), show that the mitral valve
area (MtVA) and left atrial volume does not
have an acceptable linear correlation (r<0.5)
between them, but they show an inversely
proportional relationship: atrial volumes increase with the decline of mitral valve area
(Table II).
Data regarding patients with mitral regurgitation (Gr.A3) show that in patients suffering from
AF, right atrial volume and the severity of tricuspid regurgitation are significantly higher than in
the patients with SR (p<0.05) There is also a statistically significant linear correlation between
these two parameters (r>0.7) in patients both in
the AF and SR groups.
There is no correlation between mitral regurgitation and left atrial volume in Gr.A3AF, while
there is a correlation coefficient (r=0.7) in
Gr.A3SR (the corresponding subgroup but in SR).
Functional Class NYHA has been reduced
progressively from the preoperative value, always maintaining statistical significance; from
2.82±0.45 to 0.9±0.4 (post-surgery) (p<0.001),
from 2.82±0.45 to 0.5±0.3 (after 6 months)
(p<0.001). The cardiac rhythm has remained unchanged in all the cases with the exception of a
patient who has returned to SR after valvuloplastic surgery, maintaining this rhythm until to the
last control.
In 37% of the patients of the Gr.A in the immediate post-operative period were in SR (electrical cardioversion at the end of the EC), but
they gradually come back in AF within the 10
post-operative day in spite of the antiarrhythmic
therapy.
For the detailed results it is possible to consult
Tables II, III, IV and V.
From the results of biopsies performed on the
left atrium in all patients of Gr.A during the intervention (Table VI) it has been observed that in
Gr.B2AF
Gr.B2SR
42.5 ± 11.4 57 F
31 M
57 ± 8.6
24 F
18 M
42.3 ± 11.4 56 F
31 M
57 ± 8.4
25 F
18 M
Gr.B1SR
Gr.B1AF
59 ± 11.3
Gr.A3AF
3F
3M
6F
3M
62.8 ± 10.4
43.1 ± 12.3 19 F
1M
57.5 ± 8.7 31 F
3M
41.5 ± 11.5 23 F
1M
55.8 ± 8.4 17 F
3M
Sex
Gr.A3SR
Gr.A2 FA
Gr.A2SR
Gr.A1AF
Gr.A1SR
AGE
57.5 ± 4.5
65.6 ± 15
56.4 ± 6
58.3 ± 12
63.4 ± 10.2
66.6 ± 14.8
57.3 ± 13.4
64.5 ± 9
55 ± 6.2
59.8 ± 12
EF
51.7 ± 13
39.4 ± 8.2
58.3 ± 7.4
43.9 ± 7.4
54.5 ± 7.6
46.6 ± 6.5
59 ± 10
45.7 ± 8.4
52.8 ± 8.8
46 ± 7.2
L. atrium
d.
19.1 ± 5.8
17.8 ± 4.3
14.2 ± 6
22.7 ± 10.5
16.1 ± 8
29.8 ± 10
16.4 ± 3.6
38.7 ± 16.6
23.6 ± 4.1
23 ± 7
18.7 ± 6.1
Syst.
33.4 ± 8.3
23 ± 5.8
Diast.
L. atrium area
49.7 ± 22
57.7 ± 52.8
58.6 ± 15.1
96 ± 42
60.6 ± 16.8
43.5 ± 13.3
119 ± 45.7
81.6 ± 18.4
118.2 ± 47.2
117.6 ± 59.6
14 ± 3
Diast.
13.4 ± 2.4
14 ± 2.6
–
–
–
–
21.2 ± 4.2
14 ± 3.3
27 ± 12.4
14.8 ± 3
–
–
–
–
50.3 ± 13.6
21.3 ± 8.5 9 ± 1
66 ± 39
31 ± 10.1
17.8 ± 4.4
28.5 ± 7.8 16.8 ± 6.5
Syst.
R. atrium vol.
Diast.
53 ± 25
12.8 ± 3
Syst.
R. atrium area
22.3 ± 6.8
49.6 ± 2.7
Syst.
147.4 ± 87.3
71 ± 32.2
110.5 ± 36
74 ± 33
Diast.
L. atrium vol.
SR = sinusal rhythm; AF = atrial fibrillation; EF = ejection fraction; L. atrium. d.= left atrium diameter; L. atrium area = left atrium area; L. atrium vol.= left atrium volume; R.
atrium area = right atrium area; R. atrium vol. = right atrium volume;
Syst. = atrial systole; Diast. = atrial diastole.
Gr.B2
Gr.B1
Gr.A3
Gr.A2
Gr.A1
Groups
Table II. Results.
Atrial fibrillation in rheumatic valvular disease
435
436
50.2 ± 6.7
49.4 ± 7.4
59 ± 10.3
57.7 ± 5.8
47.5 ± 5
48.8 ± 3.9
48.3 ± 4
50.3 ± 5
Gr.A2SR
Gr.A2AF
Gr.A3SR
Gr.A3AF
Gr.B1SR
Gr.B1AF
Gr.B2SR
Gr.B2AF
Gr.A2
Gr.A3
Gr.B1
Gr.B2
29.8 ± 6
34.8 ± 7
31.2 ± 7
35.2 ± 6
30.7 ± 4.5
36.8 ± 4.6
32.8 ± 6.4
33.6 ± 6.7
30.5 ± 6.1
32.5 ± 5.2
Lv. e-s. d
36.7 ± 9.2
29.5 ± 3.8
33.4 ± 7.8
28.7 ± 4
38.6 ± 12
33.8 ± 6.5
35.4 ± 6.8
31.2 ± 8.8
33.5 ± 8.6
29.8 ± 8
S.F.
2.37 ± 0.37
2.06 ± 0.25
0.95 ± 0.05
1.1 ± 0.2
3.74 ± 0.58
3.5 ± 0.9
1.6 ± 0.39
1.5 ± 0.4
1.45 ± 0.47
1.1 ± 0.26
MtVA2D
2.28 ± 0.47
2.14 ± 0.44
1.09 ± 0.23
1.05 ± 0.16
3.66 ± 0.76
3.6 ± 6.7
1.57 ± 0.46
1.38 ± 0.4
1.36 ± 0.49
1.03 ± 0.25
MtVACW
0.98 ± 0.62
0.93 ± 0.48
0.5 ± 0.2
0.5 ± 0.15
2.6 ± 0.55
3.25 ± 0.76
1.47 ± 0.47
1.89 ± 0.82
0.75 ± 0.29
0.71 ± 0.27
MtR
0.85 ± 0.4
1.05 ± 0.2
0.8 ± 0.3
1 ± 0.3
1±0
1 ± 0.71
1.29 ± 0.57
1.1 ± 0.4
0.96 ± 0.26
1.41 ± 0.3
AoR
Lv. e-d. d = left ventricular end-diastolic diameter; Lv. e-s. d = left ventricular end systolic diameter; S.F. = shortening fraction;
MtVA2D = mitral valve area 2D; MtVACW = mitral valve area CW; MtR = mitral regurgitation; AoR = aortic regurgitation; TrR = tricuspid regurgitation.
Hemodynamic grade of regurgitation: (±) = 0.5; (+) = 1; (++) = 2; (+++) = 3; (++++) = 4.
46.7 ± 4.1
45.5 ± 4.2
Gr.A1SR
Gr.A1AF
Lv. e-d. d
Gr.A1
Groups
Table III. Results.
0.5 ± 0.4
1.2 ± 0.5
0.8 ± 0.4
1.45 ± 0.6
1.1 ± 0.22
1.67 ± 0.61
1.88 ± 0.64
2.37 ± 0.72
1.97 ± 0.76
2.24 ± 0.86
TrR
N. Alessandri, F. Tufano, M. Petrassi, C. Alessandri, C. Di Cristofano, C. Della Rocca, P. Gallo
p<0.001
–
–
–
Gr.B2SR ↔ Gr.B2AF
Gr.B1SR ↔ Gr.B2SR
Gr.B1AF ↔ Gr.B2AF
Gr.Abefore ↔ Gr.Aafter
p<0.001
p<0.001
p<0.001
NS
NS
NS
NS
NS
FC NYHA
–
p<0.001
p<0.001
NS
NS
NS
NS
p<0.01
MtVA
–
NS
NS
p<0.05
p<0.01
NS
p<0.001
p<0.01
LA.D
–
NS
NS
NS
NS
p<0.01
p<0.001
p<0.001
LAA
–
p<0.01
p<0.01
p<0.001
p<0.001
NS
p<0.001
p<0.001
LAV
–
p<0.001
p<0.001
NS
p<0.05
–
–
–
AV.Grad
–
–
–
–
–
p<0.05
p<0.001
p<0.,001
RAV
–
–
–
–
–
p<0.05
p<0.05
NS
TrR
FC NYHA = functional class NYHA; MtVA = mitral valve area; LA.D = left atrium diameter; LAA = left atrium area; LAV = left atrium volume; AV. Grad = atrium-ventricular
gradient; RAV = right atrium volume; TrR = tricuspid regurgitation, NS = not significant.
NS
p<0.001
p<0.001
Gr.A2SR ↔ Gr.A2AF
Gr.B1SR ↔ Gr.B1AF
p<0.001
Gr.A1SR ↔ Gr.A1AF
Gr.A3SR ↔ Gr.A3AF
AGE
Groups
Table IV.
Atrial fibrillation in rheumatic valvular disease
437
N. Alessandri, F. Tufano, M. Petrassi, C. Alessandri, C. Di Cristofano, C. Della Rocca, P. Gallo
Table V.
Gr.A1SR
Gr.A1AF
Gr.A2SR
Gr.A2AF
Gr.A3SR
Gr.A3AF
Gr.BSR
Gr.BAF
r<0.5
r<0.5
r<0.5
r<0.5
r<0.5
r=0.7
r<0.5
r<0.5
r<0.5
r<0.5
r<0.5
r<0.5
r<0.5
r<0.5
MtVA ↔ LAV
MR ↔ LAV
LAVbefore ↔ MtVAafter
LAVafter ↔ MtVAbefore
MtVA + MR ↔ LAA
MtVA + MR ↔ LAV
RAV ↔ TrR
r<0.5
r<0.5
r<0.5
r<0.5
r>0.7
r>0.7
MtVA = mitral valve area; LAV = left atrial volume; MR = mitral regurgitation; RAV = right atrial volume; TrR = tricuspid regurgitation; before = before-valvuloplastic; after = after-valvuloplastic.
the patients with SR the atrial tissue is normal in
44% of cases. The remaining 56% show a moderate increase in the parietal thickness in the 40%
of cases and a reduction of parietal thickness in
6% of cases and normal thickness in 10% of cases. It has been observed moderate myocells hypertrophy in 54% of cases, of which 44% is associated with increased parietal thickness and 10%
with normal parietal thickness, a vacuolar slight
degeneration in 6% of cases, mild interstitial fibrosis in 2% of cases, mild endocardial fibrosis
in 4% of cases.
There are anomalies in 100% of patients in
AF, including: moderate vacuolar degeneration
in 77% of cases, a strong interstitial fibrosis in
75%, moderate presence of stretched fibres
(70%), a strong adiposous replacement in 63% of
cases, a moderate myocells hypertrophy (54%),
moderate pigmentary degeneration (48%), a normal endocardium (46%), moderate endocardial
fibrosis (28%), a moderate increase in the parietal thickness (25%), a moderate colliquative
myocytolysis (24%) of cases, presence of few
but hypertrophic cellular elements (24%).
Discussion
To explain the history of the insurgence of
atrial fibrillation in rheumatic valvulopathy,
unanimously considered a pejorative device for
the disease, many observations were made.
These consideration are about morpho-functional
Table VI. Hystological atrial biopsy: results.
Normal
Gr.AAF (63 pt)
Gr.ASR (50 pt)
Normal endocardium
Reduction wall thickness
Increase wall thickness
Rare hypertrophic cells
Myocyte hypertrophy
Vacuolar degeneration
Pigmentary degeneration
Endocardial fibrosis
Interstitial fibrosis
Stretched fibers
Adipose substitution
Colliquative myocytolysis
0% (0)
46% (29 pt)
25% (16 pt)
24% (15 pt)
54% (34 pt)
77% (49 pt)
48% (30 pt)
28% (18 pt)
75% (47 pt)
70% (44 pt)
63% (40 pt)
24% (15 pt)
44% (22 pt)
6% (3 pt)
44% (22 pt)
54% (27 pt)
6% (3 pt)
4% (2 pt)
2% (1 pt)
MtVA = mitral valve area; LAV = left atrial volume; MR = mitral regurgitation; RAV = right atrial volume; TrR = tricuspid regurgitation; before = before-valvuloplastic; after = after-valvuloplastic.
438
Atrial fibrillation in rheumatic valvular disease
parameters (like left atrial increase and mitral
valve area), or exclusively dependent from
anatomopathological factors (like atrial myocardium histological ultrastructure) and from
electrophysiological factors (like ionic flows
through myocardiocites’ membrane canals).
Whereas rheumatic disease is the main etiologic factor of mitral valvulopathy, in this study
it has been investigated the eventual role of
histopathological substrate of rheumatic disease in atrial fibrillation’s genesis, starting
from an accurate analysis of atrial and valvular
morphology.
Synthesizing different research’s streaks in literature about atrial fibrillation’s genesis, it has
been observed a slow evolution from the idea of
the exclusive attention on left and right atrium
dimensions (diameter over 45 mm or 65 mm)25-26
to a largest vision. This point of view alternates
taking in exame either atrial wall histological
structure or microelectrophysiological cells’ alteration, in particular a modification in myocardiocites’ monophasic action potential 15,16,27-28.
Completing know how about atrial volume increase interfere hemodynamic factors, like mitral
valvular area, left medium atrial pressures, pulmonary wedging pressures or Wedge and right
medium atrial pressure, that determine an incessant stress in atrial wall.
In our study it was possible to observe:
• Left and right atrial dimensions, according to
literatures, are significantly larger in AF patients than in SR patients.
• There’s no linear relationship between valvular alteration amount, stenosis (Gr.A1; Gr.B1),
regurgitation (Gr.A3) or stenosis/regurgitation
(Gr.A2), and left atrium increase.
• The seriousness of mitral stenosis is major in
AF patients than in SR patients (group Gr.A1
and group with stenosis-regurgitation)
• In patients from Gr.B there’s no difference between AF and SR, in valvular area before and
after valvuloplasty.
In patients from Gr.B there’s no statistically
difference between AF and SR, in left atrial volume reduction before and after valvuloplasty.
Different behavior of the two groups in re-distribution of atrial volume according to valvular
defect, could mean that straight nexus described
in literature between AF and atrial volume, or
between A and MtVA, or between AF and
pathology degree is not so clear.
It’s important to remind that all patients in
AF were submitted, following classic standards,
to antiarrhythmic therapy to reinstate sinus
rhythm. One patient in AF, submitted to percutaneous mitralic valvuloplasty, came back 5
days after sinus rhythm correction. All patients
submitted to valvular substitution with prosthesis, egresses from operating room with a SR induced by cardioversion (37% in 113 patients),
gradually returned in atrial fibrillation in 10
days after the surgery, despite antiarrhythmic
therapy.
Atrial dimensions after surgery were not
charged, because athrotomy and its mending
determine an artificial modification in left atrial dimensions. This modification is not ponderable and could invalidate the measurement
about the probable reduction induced. Instead,
only by the MtVA modification or relate it with
the atrial volumes of valvuloplasty group. The
outcomes of histological analysis in 113 patients submitted to operation show in patients
in AF more than a histological alteration in all
microscope slides (100%). The most frequent
was a vacuolar degeneration of the myocardiocite (77%), whereas in 75% of the cases
there was an interstitial fibrosis; sprained fibers
(70%) and ample adipose degeneration (63%)
were less frequent.
In SR just the 56% of the microscope slides
showed a modest alteration that consisted in cellular hypertrophy (54%). Fibrosis or vacuolar
degeneration were slightly referred and present
respectively in 2 and 6% of the group. From
these data it can been deduced that atrial volume, significantly larger in patients in AF, can’t
be considered strictly related to mitralic valve
alteration’s entity, neither as the primary cause
of arrhythmia. The cause of atrial fibrillation
genesis have to be researched other where, instead atrial dimensions assume a function in a
sequent step of physiopathological frame25,28,29.
It is possible to suppose that an essential role as
primum movens in establishing of arrhythmia
could be played by histological alterations found
in this study of atrial myocardium of patients in
AF, despite atrial biopsies belonging to patients
in sinus rhythm bare of considerable and expressive alterations. The structural subversion found
in presence of AF, and particularly cellular degeneration with a marked increase of interstitial
fibrosis, can influence and impulse generation
and propagation potential in atrial chamber15,16,27.
And electrophysiological modifications able to
439
N. Alessandri, F. Tufano, M. Petrassi, C. Alessandri, C. Di Cristofano, C. Della Rocca, P. Gallo
cause the arrhythmia can intervene. The presence of substitutive fibrosis, joined with a structural modification of myocardiocites, can explain the possible reduction of L canals of calcium and consequently the reduction of the calcium corrent (Ica) through the same canals. Ica’s
reduction is been considered in several studies
like the most important ionic modification present in myocardiocites of fibrillant atrium30-32.
To confirm this idea there are all those patients
in chronic AF submitted to mitral valvoplasty:
despite they improve their conditions with mitral
valvular area’s increase, with right and left atrial
volume’s reduction and with an enhancement in
functional class (regressed from II-III to barely
belonging to Ia), they rested in atrial fibrillation.
Furthermore, it can been assumed, that histological alterations can cause the aberrations described and it can determine AF. Besides once
AF is established it alters systolic-diastolic cardiac cycle, it produces a progressive modification in blood stagnation and in average atrial
pressure, that determines a progressive aggravation of atrial volume. This thesis is supported by
that there’s not a significant relationship between stenosis entity or mitral regurgitation and
atrial dimensions. This evidences that hemodynamic factors are not the exclusive agents of
atrial increasing33-36. The only patient (Gr.B) in
atrial fibrillation of recent insurgence (less than
two weeks) before valvuloplasty, re-entered in
sinus rhythm after five days. Before the dilatation with balloon, he was in anti-arrhythmic
therapy (amiodarone in dosage 200 mg × 2 daily
for 7 days, then 200 mg × 2 for 7 days and then
200 mg daily) and actually (after two years) still
in SR and in treatment with amiodarone 200 mg
daily for five days a week37-39. The data related
to left atrial volume, before and after valvuloplasty and valvular area before and after valvuloplasty, were in the average of the values related to belonging group. Respectively atrium was
80 cm3 vs 119±45.7 cm3 before valvoplasty and
60 cm3 vs 96±42 cm3 after. Whereas MtVA was
1,1cm2 before valvuloplasty 1.05±0.16 cm2 and
1,9 vs 2.06±0.25 cm2 after. Maybe the return of
this patient (Gr.B) firstly fibrillant in SR after
valvuloplasty is a consequence of two factors.
First is that the AF was of recent insurgence
(less than six months) and second is that the patient had a left atrial volume (before and after
operation) clearly inferior compared to the average. So it can be assumed that in this patient all
the actions described were still inexistent or in
440
an early stage. Particularly that histological alteration is able to start AF and the vicious circle
of structural subversion and atrial wall straining
(that determines the persistent of arrhythmia)
was not yet determined, so the antiarrhythmic
action of the drug had worked. Finally it can be
deduced that the initial moment in AF genesis
can be recognized by histological alterations of
atrial myocardium, that represent cardiac manifestation of rheumatic disease. This disease is
rheumatic cardiopathy which concerns myocardium, endocardium and (in less proportion)
pericardium40.
Once it is established, AF concurs to progressive deterioration of atrial myocardium, already
started for rheumatic cardiopathy, and so to progressive straining and increase of the atrium.
References
1) TIBAZARWA KB, VOLMINK JA, MAYOSI BM. The incidence of acute rheumatic fever in the world: A
systematic review of population-based studies.
Heart 2008; 94: 1534-1540.
2) ROBERTSON KA, MAYOSI BM. Rheumatic heart disease: social and economic dimensions. S Afr
Med J 2008; 98: 780-781.
3) NORDET P, LOPEZ R, DUENAS A, SARMIENTO L. Prevention and control of rheumatic fever and
rheumatic heart disease: the Cuban experience
(1986-1996-2002). Cardiovasc J Afr 2008; 19:
135-140.
4) BRYANT PA, ROBINS-BROWNE R, CARAPETIS JR, CURTIS N.
Some of the people, some of the time :susceptibility to acute rheumatic fever. Circulation 2009;
119: 742-753.
5) MOVAHED MR, AHMADI-KASHANI M, KASRAVI B, SAITO Y.
Increased prevalence of mitral stenosis in
women. J Am Soc Echocardiogr 2006; 19: 911913.
6) E S S O P MR, N K O M O VT. Rheumatic and nonrheumatic valvular heart disease: epidemiology,
management and prevention in Africa. Circulation
2005; 112: 3584-3591.
7) SCHAFFER WL, GALLOWAY JM, ROMAN MJ, PALMIERI V,
LIU JE, LEE ET, BEST LG, FABSITZ RR, HOWARD BV,
D E V E R E U X RB. Prevalence and correlates of
rheumatic heart disease in American Indians
(the Strong Heart Study). Am J Cardiol 2003;
91: 1379-1382.
8) NARULA J, CHANDRASEKHAR Y, RAHIMTOOLA S. Diagnosis of active rheumatic carditis: the echoes of
change. Circulation 1999; 100: 1576-1581.
Atrial fibrillation in rheumatic valvular disease
9) K U M A R A, S I N H A M, A N D S I N H A DN. Chronic
rheumatic heart disease in Ranchi. Angiology
1982; 33: 141-145.
10) CHOPRA P, GULWANI H. Pathology and pathogenesis
of rheumatic hearth disease. Indian J Pathol Microbiol 2007; 50: 685-697.
CD, WAGGONER A. American Society of Echocardiography Sonographer Training and Education
Commitee: Guidelines for cardiac sonographer
education: recommendation of the American Society of Echocardiography Sonographer Training
and Education Commitee. J Am Soc Echocardiogr 2001; 14: 77-84.
11) DARE AJ, HARRITY PJ, TAZELAAR HD, EDWARDS WD,
MULLANCY CJ. Evalutation of surgically excised mitral valves: Revised recommendations, based on
changing operative procedures in the 1990s.
Hum Pathol 1993; 24: 1286-1293.
24) HENRY WL, MORGANROTH J, PEARLMAN AS, CLARK CE,
REDWOOD DR, ITSCOITZ SB, EPSTEIN SE. Relation between echocardiographically determined left atrial
size and atrial fibrillation. Circulation 1976; 53:
273-279.
12) RAJAKARUNA C, MHANDU P, GHOSH-DASTIDAR M, DESAI
J. Giant left atrium secondary to severe mixed mitral valve pathology. Eur J Cardiothorac Surg
2007; 32: 932.
25) UNVERFERTH DV, FERTHEL RH, UNVERFERTH BJ, LEIER
CV. Atrial fibrillation in mitral stenosis: histologic,
hemodynamic and metabolic factors. Int J Cardiol
1984; 5: 143-152.
13) ATES M, SENSOZ Y, ABAY G, AKCAR M. Giant left atrium with rheumatic mitral stenosis. Tex Heart Inst
J 2006; 33: 389-391.
26) ALESSIE M, AUSMA J, SCHOTTEN U. Electrical, contractile and structural remodelling during atrial fibrillation. Cardiovasc Res 2002; 54: 230-246.
14) JOHN B, STILES MK, KUKLIK P,CHANDY ST, YOUNG GD,
M ACKENZIE L, S ZUMOWSKY L, J OSEPH G, J OSE J,
WORTHLEY SG, KALMAN JM, SANDERS P. Electrical
remodelling of the left and right atria due to
rheumatic mitral stenosis Eur Heart J 2008; 29:
2234-2243.
27) VOLGMAN AS, SOBLE JS, NEUMANN A, MUKHTAR KN,
IFTIKHAR F, VALLESTEROS A, LIEBSON PR. Effect of left
atrial size on recurrence of atrial fibrillation after electrical cardioversion: atrial dimension
versus volume. Am J Card Imaging 1996; 10:
261-265.
15) THIEDEMANN KU, FERRANS VJ. Left atrial ultrastructure in mitral valvular disease. Am J Pathol 1977;
89: 575-604.
28) KEREN G, ETZION T, SHEREZ J, ZELCER AA, MEGIDISH R,
MILLER HI, LANIADO S. Atrial fibrillation and atrial enlargement in patients with mitral stenosis. Am
Heart J 1987; 114: 1146-1155.
16) SANCHEZ-LEDESMA M, CRUZ-GONZALES I, SANCHEZ PL,
M ARTIN -M OREIRAS J, J NEID H, R ENGIFO -M ORENO P,
CUBEDDU RJ, INGLESSIS I, MAREE AO, PALACIOS IF. Impact of concomitant aortic regurgitation on percutaneous mitral valvuloplasty: immediate results,
short-term, and long-term outcome. Am Heart J
2008; 156: 361-366.
17) FATKIN D, ROY P, MORGAN JJ, FENELEY MP. Percutaneous balloon mitral valvotomy with the Inoue
single-balloon catheter: commissural morphology
as a determinant of outcome. J Am Coll Cardiol
1993; 21: 390-397.
18) CHENG TO. Long-term results of percutaneous balloon mitral valvuloplasty with the Inoue balloon
catheter in elderly patients. Am J Cardiol 2002;
90: 686-687.
19) VAHANIAN A, PALACIOS IF. Percutaneous approaches to valvular disease. Circulation 2004; 109:
1572-1579.
20) DELABAYS A, GOY JJ. Images in clinical medicine.
Percutaneous mitral valvuloplasty. N Engl J Med
2001; 345: e4.
21) RODRIGUEZ L. Echocardiography in mitral valve disease. Arch Cardiol Mex 2005; 75: 188-196.
22) WANG YC, TSAI FC, CHU JJ, LIN PJ. Midterm outcomes of rheumatic mitral repair versus replacement. Int Heart J 2008; 49: 565-576.
23) EHLER D, CARNEY DK, DEMPSEY AL, RIGLING R, KRAFT
C, WITT SA, KIMBALL TR, SISK EJ, GEISER EA, GRESSER
29) LE GRAND B L, HATEM S, DEROUBAIX E, COUETIL J P,
CORABOEUF E. Depressed transient outward and
calcium currents in dilated human atria. Cardiovasc Res 1994; 28: 548-556.
30) VAN WAGONER DR, POND AL, LAMORGESE M, ROSSIE
SS, M C C ARTHY PM, N ERBONNE JM. Atrial L-type
Ca2+ currents and human atrial fibrillation. Circ
Res 1999; 85: 428-436.
31) NATTEL S. Atrial electrophysiological remodeling
caused by rapid atrial activation: underlying
mechanism and clinical relevance to atrial fibrillation. Cardiovasc Res 1999; 42: 298-308.
32) PHAM TD, FENOGLIO JJ Jr. Right atrial ultrastructure
in chronic rheumatic heart disease. Int J Cardiol
1982; 1: 289-304.
33) FRUSTACI A, CHIMENTI C, BELLOCCI F, MORGANTE E, RUSSO MA, MASERI A. Histological substrate of atrial
biopsies in patients with lone atrial fibrillation. Circulation 1997; 96: 1180-1184.
34) MOREYRA AE, WILSON AC, DEAC R, SUCIU C, KOSTIS JB,
ORTAN F, KOVACS T, MAHALINGHAM B. Factors associated with atrial fibrillation in patients with mitral
stenosis: a cardiac catherization study. Am Heart
J 1998; 135: 138-145.
35) KRAHN AD, MANFREDA J, TATE RB, MATHEWSON FA,
CUDDY TE. The natural history of atrial fibrillation:
incidence, risk factors, and prognosis in the Manitoba follow-up study. Am J Med 1995; 98: 476484.
441
N. Alessandri, F. Tufano, M. Petrassi, C. Alessandri, C. Di Cristofano, C. Della Rocca, P. Gallo
36) ROY D, TALAJIC M, DORIAN P, CONNOLLY S, EISENBERG
MJ, GREEN M, KUS T, LAMBERT J, DUBUC M, GAGNÉ P,
NATTEL S, THIBAULT B. Amiodarone to prevent recurrence of atrial fibrillation. Canadian Trial of
Atrial Fibrillation Investigators. N Engl J Med
2000; 342: 913-920.
37) NACCARELLI GV, WOLBRETTE DL, KHAN M, BHATTA L,
HYNES J, SAMII A, LUCK J. Old and new antiarrhythmic drugs for converting and maintaining sinus
rhythm in atrial fibrillation: comparative efficacy
and result of trials. Am J Cardiol 2003; 91: 15D26D.
442
38) S LAVIK RS, T ISDALE JE, B ORZAK S. Pharmacologic
conversion of atrial fibrillation: a systematic review of available evidence. Prog Cardiovasc Dis
2001; 44: 121-152.
39) LIU TJ, HSUEH CW, LEE WL, LAI HC, WANG KY, TING
CT. Conversion of rheumatic atrial fibrillation by
amiodarone after percutaneous ballon mitral
commisurotomy. Am J Cardiol 2003; 92: 12441246.
40) NATTEL S, SHIROSHITA-TAKESHITA A, BRUNDEL BJ, RIVARD L.
Mechanism of atrial fibrillation: lessons from animal
models. Prog Cardiovasc Dis 2005; 48: 9-28.