Download Long-term analysis of left ventricular ejection fraction in patients with

European Heart Journal (2013) 34, 3370–3377
doi:10.1093/eurheartj/eht201
CLINICAL RESEARCH
Interventional cardiology
Long-term analysis of left ventricular ejection
fraction in patients with stable multivessel
coronary disease undergoing medicine,
angioplasty or surgery: 10-year follow-up
of the MASS II trial
Cibele Larrosa Garzillo 1, Whady Hueb 1*, Bernard J. Gersh 2, Eduardo Gomes Lima 1,
Paulo Cury Rezende 1, Alexandre Ciappina Hueb 1, Ricardo D’Oliveira Vieira1,
Desiderio Favarato 1, Alexandre Costa Pereira1, Paulo Rogério Soares1,
Carlos Vicente Serrano Jr. 1, José Antônio Franchini Ramires1, and Roberto Kalil Filho 1
1
Department of Atherosclerosis, Heart Institute of the University of São Paulo, Av. Dr. Eneas de Carvalho Aguiar 44, AB, Sala 114, Cerqueira César, São Paulo/SP 05403-000, Brazil;
and 2Mayo Clinic, Rochester, MI, USA
Received 8 February 2013; revised 11 April 2013; accepted 22 May 2013; online publish-ahead-of-print 4 July 2013
See page 3339 for the editorial comment on this article (doi:10.1093/eurheartj/eht297)
Background
Assuming that coronary interventions, both coronary bypass surgery (CABG) and percutaneous coronary intervention (PCI),
are directed to preserve left ventricular function, it is not known whether medical therapy alone (MT) can achieve this protection. Thus, we evaluated the evolution of LV ejection fraction (LVEF) in patients with stable coronary artery disease (CAD)
treated by CABG, PCI, or MT as a post hoc analysis of a randomized controlled trial with a follow-up of 10 years.
.....................................................................................................................................................................................
Methods
Left ventricle ejection fraction was assessed with transthoracic echocardiography in patients with multivessel CAD, participants of the MASS II trial before randomization to CABG, PCI, or MT, and re-evaluated after 10 years of follow-up.
.....................................................................................................................................................................................
Results
Of the 611 patients, 422 were alive after 10.32 + 1.43 years. Three hundred and fifty had LVEF reassessed: 108 patients
from MT, 111 from CABG, and 131 from PCI. There was no difference in LVEF at the beginning (0.61 + 0.07, 0.61 + 0.08,
0.61 + 0.09, respectively, for PCI, CABG, and MT, P ¼ 0.675) or at the end of follow-up (0.56 + 0.11, 0.55 + 0.11,
0.55 + 0.12, P ¼ 0.675), or in the decline of LVEF (reduction delta of 27.2 + 17.13, 29.08 + 18.77, and
27.54 + 22.74). Acute myocardial infarction (AMI) during the follow-up was associated with greater reduction in
LVEF. The presence of previous AMI (OR: 2.50, 95% CI: 1.40– 4.45; P ¼ 0.0007) and during the follow-up (OR: 2.73,
95% CI: 1.25–5.92; P ¼ 0.005) was associated with development of LVEF ,45%.
.....................................................................................................................................................................................
Conclusion
Regardless of the therapeutic option applied, LVEF remains preserved in the absence of a major adverse cardiac event
after 10 years of follow-up.
.....................................................................................................................................................................................
Clinical Trial
URL: http://www.controlled-trials.com. Registration number ISRCTN66068876.
Registration
----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords
Left ventricular ejection fraction † Coronary artery disease † Coronary bypass surgery † Percutaneous coronary
intervention † Medical therapy
* Corresponding author. Tel: +55 1126615032, Fax: +55 1126615188, Email: [email protected]
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2013. For permissions please email: [email protected]
3371
Ventricular function in MASS II trial
Introduction
Studies of ageing of the cardiovascular system in healthy subjects,
with focus on left ventricular ejection fraction (LVEF), are controversial. Some authors demonstrated that systolic function usually
remains preserved, with worsening of diastolic function1 – 3 due
mainly to adaptative mechanisms, such as myocyte hypertrophy
and changes in diastolic dynamics.
However, Cheng et al.,4 studying left ventricular function changes
in patients without known cardiovascular disease, found a paradoxical increase in LVEF with ageing. Another study5 demonstrated a reduction in LVEF with ageing in patients with and without diabetes,
after ruling out the presence of myocardial ischaemia.
On the other hand, in the population with coronary artery disease
(CAD), many of whom have associated comorbidities, the evolution
of LVEF is unclear. It is assumed that ventricular function deterioration could occur, if associated with the presence of continued but
unalleviated chronic myocardial ischaemia.
Since ventricular function is the most important predictor of longterm survival in patients with CAD, regardless of the number of arteries affected or the degree of arterial stenosis,6 – 10 all therapeutic
strategies that confer additional protection for the ischaemic myocardium are relevant in an attempt to improve long-term prognosis.
In this setting, revascularization procedures, percutaneous coronary
intervention (PCI) and coronary artery bypass graft (CABG), have
the potential to contribute to the reduction of myocardial ischaemia
and, in this way, possibly prevent progressive impairment of LVEF.
A post hoc substudy from the (Optimal Medical Therapy With and
Without Percutaneous Coronary Intervention) COURAGE trial11
compared the occurrence of the primary endpoint [death or acute
myocardial infarction (AMI)] in patients with CAD randomized to
optimal medical therapy (OMT) with or without PCI, according to
the presence and extent of ischaemia at baseline. Surprisingly, regardless of the ischaemic extent, even in the subgroup of patients with
moderate-to-severe ischaemia, the addition of PCI to OMT failed
to demonstrate any additional benefit in long-term prognosis.
Further study on the effectiveness of available treatments for CAD
in patients with documented myocardium ischaemia of greater extension and severity, the ongoing ISCHEMIA trial,12 will compare
the efficacy of different therapeutic strategies is patients with
moderate-to-severe ischaemia. Additionally, the role of revascularization procedures in regard to their potential to protect the function
of the ischaemic myocardium is not well established. In fact, there are
very few studies that aimed to investigate, in depth, the role of such
interventions on ventricular function during a long period of followup.13,14 Other trials comparing CABG and PCI strategies,15 – 17 or
conservative vs. interventional therapies,18 – 21 focused on primary
endpoints, such as mortality, occurrence of acute myocardial infarction, or the need of additional revascularization.
The aim of this study was to evaluate the changes in LVEF, by sequential echocardiography, in patients with chronic multivessel coronary heart disease and initially preserved ventricular function, who
underwent three therapeutic options (CABG, PCI, or MT alone) participants of the MASS II trial, during 10 years of follow-up. The second
Medical, Angioplasty, or Surgery Study (MASS II) is a single-centre
study designed to compare the long-term effects of MT, stent angioplasty, or surgical strategies among patients with multivessel CAD
with stable angina and preserved ventricular function who are appropriate candidates for all three therapies.20,21
Methods
MASS II patient selection
Briefly, patients with angiographically documented proximal multivessel
coronary stenosis of .70% by visual assessment and documented ischaemia were considered for inclusion. Patients were enrolled and randomized if the surgeons, attending physicians, and interventional
cardiologists agreed that revascularization could be attained by either
strategy.20,21
Patients gave written informed consent and were randomly assigned to
a treatment group. The Ethics Committee of the Heart Institute (InCor)
of the University of São Paulo Medical School in São Paulo, Brazil,
approved the trial, and all the procedures were performed in accordance
with the Helsinki Declaration.
Clinical criteria for exclusion included mandatory revascularization,
ventricular aneurysm that required surgical repair, LVEF ,40%, a
history of PCI, CABG, congenital, or valvular heart disease; left main coronary artery stenosis of 50% or more, or another co-existing condition
that was a contraindication to CABG or PCI.
Treatment intervention
In MASS II, all the patients were placed on an optimal medical regimen
after randomization until the end of follow-up. Patients were randomized
to continue with aggressive MT alone or to undergo PCI or CABG in addition to MT.
Investigators were required to perform optimum coronary revascularization. For patients assigned to PCI, the procedure was available within 3
weeks after randomization and was performed according to a standard
protocol.22 Devices used for catheter-based therapeutic strategies
included stents, lasers, directional atherectomy, and balloon angioplasty.
For patients assigned to CABG, the procedures were available within 12
weeks after randomization, and revascularization performed with standard surgical techniques,23 using saphenous vein grafts, internal mammary
arteries, and other arterial conduits. No off-pump CABG was performed.
Follow-up
Adverse and other clinical events were tracked from randomization.
Patients were evaluated and angina symptoms were graduated24 with
follow-up visits every 6 months for at least 10 years at Heart Institute.
Patients underwent the treadmill exercise test according to a modified
Bruce protocol, electrocardiography and routine blood tests on
regular basis.
Myocardial infarction was defined as the presence of significant new Q
waves in at least two ECG leads or symptoms compatible with MI associated with creatine kinase-MB fraction concentrations that were more
than three times the upper limit of the reference range.
The vital status of each patient was ascertained on 28 February 2011.
The predefined primary endpoints were the incidence of total mortality,
Q-wave MI, or refractory angina that required revascularization. Secondary endpoints included angina status, death due to a cardiac cause, and
cerebrovascular accident.
Left ventricular ejection fraction assessment
Most participants of the MASS II trial underwent transtoracic echocardiography with colour Doppler before randomization. Of those, left ventricular function was evaluated at two different time periods: the first,
at the beginning of the study, and the second, after 10 years of follow-up.
3372
C.L. Garzillo et al.
Table 1 Baseline characteristics of the 350 patients with left ventricular ejection fraction reassessed according
to treatment in MASS II
PCI (n 5 131)
CABG (n 5 111)
MT (n 5 108)
P-value
...............................................................................................................................................................................
Demographic variables
Age, years
58.42 + 9.04
58.10 + 7.68
57.87 + 8.76
0.886
Age ≥65 years (%)
30.53
22.52
25
0.346
Male (%)
Current or past smoker (%)
63.36
37.61
68.47
35.45
70.37
32.82
0.485
0.738
History of MI (%)
History of hypertension (%)
50.38
58.78
43.24
57.66
37.96
49.07
0.152
0.275
Treated diabetes mellitus (%)
24.43
36.04
34.26
0.106
History of angina (%)
92.37
89.19
80.56
0.018
...............................................................................................................................................................................
Clinical history and status
...............................................................................................................................................................................
Laboratory values
Total cholesterol (mmol/L)
5.92 + 1.27
5.58 + 1.14
5.74 + 1.06
0.485
LDL cholesterol (mmol/L)
3.95 + 1.14
3.77 + 1.06
3.80 + 0.88
0.521
HDL cholesterol (mmol/L)
Triglycerides (mmol/L)
0.95 + 0.26
5.04 + 2.53
0.93 + 0.23
4.50 + 2.07
0.95 + 0.21
4.91 + 2.64
0.213
0.082
55.83
53.46
49.49
0.59
...............................................................................................................................................................................
Positive treadmill test (%)
...............................................................................................................................................................................
Angiographic profile
Double-vessel disease (%)
41.98
43.24
45.37
0.870
Triple-vessel disease (%)
Double-vessel with proximal LAD disease (%)
58.02
78.18
56.76
77.08
54.63
85.71
0.870
0.579
Coronary collateral circulation (%)
38.58
42.57
43.30
0.736
LDL, low-density lipoprotein; HDL, high-density lipoprotein; LAD, left anterior descending coronary artery. Some patients had both angina and positive treadmill tests. Unless
otherwise indicated, data are mean + SD.
All echocardiographic parameters assessed were predefined and images
were analysed in a core lab, by expert physicians.
Left ventricular ejection fraction was measured by the biplane method
(Simpson) when the endocardial border of the left ventricle was welldefined and whenever regional wall-motion abnormalities were
present, or alternatively by the Teichholz method.25
Statistical analysis
Baseline characteristics were summarized for all patients as percentages
for categorical variables and as means with standard deviations for
continuous variables. Comparisons between means of the groups used
Student’s t test for parametric26 and the Mann– Whitney test for nonparametric variables.
The means of three or more groups were compared by one-way
ANOVA, followed by the Bonferroni multiple comparison test for parametric variables. For non-parametric variables, we used the Kruskal–
Wallis test, followed by multiple comparisons based on Dunn’s test.
Tests were two-sided.
The evaluation of homogeneity between proportions was performed
using the x2 or the Fisher exact test.26 To evaluate the behaviour of
groups along the evaluations (initial and 10 years) analysis of variance
with repeated measures was used.27
An additional analysis was performed using logistic regression to evaluate the association of several variables to determine LVEF dysfunction,
defined as LVEF ≤45% in 10 year survivors.
All data were analysed according to the intention-to-treat principle
and values of P , 0.05 were considered statistically significant. Statistical
analysis was performed with SPSS 15.0 for Windows.
Results
Patients characteristics
Between May 1995 and May 2000, 611 eligible patients who met all
entry criteria were randomly assigned to one of three therapeutic
strategies: PCI, MT, or CABG. After a mean follow-up of 10.32
(+1.43) years, 422 patients were alive and 350 patients had their
LVEF reassessed by echocardiography (108 patients from the MT
group, 111 from CABG, and 131 from PCI). For several reasons, 72
patients could not have their LVEF reassessed, most commonly
due to patient refusal, geographic inaccessibility and severe noncardiac illness.
Randomization created balanced treatment groups with respect
to important prognostic characteristics (Table 1), except for the
angina status (less frequent in the MT group).
Among patients eligible at 10.32 years to undergo LVEF evaluation,
baseline characteristics of those who underwent LVEF assessment
(n ¼ 350) were compared with those who did not (n ¼ 72). All variables analysed were similar in prevalence, except for diabetes, which
3373
Ventricular function in MASS II trial
Table 2 Comparison of baseline characteristics and
events between patients with and without left ventricular
ejection fraction measurements
Variable
LVEF available
(n 5 350)
LVEF missing
(n 5 72)
P-value
67.4%
57.96 + 8.7
73.6%
60 + 9
0.374
0.073
History of
55.14%
hypertension (%)
65.3%
0.146
Treated diabetes
(%)
31.4%
47.2%
0.013
Previous AMI (%)
44.28
37.5
0.353
Current or past
smoker (%)
35.14
31.9
0.701
Double-vessel
disease (%)
42.85
47.2
Triple-vessel
disease
57.14
52.8
Proximal LAD
disease
90
86.1
0.445
Total cholesterol
(mmol/L)
5.77 + 1.16
5.84 + 1.42
0.649
LDL cholesterol
(mmol/L)
3.83 + 1.03
3.90 + 1.16
0.630
HDL cholesterol
(mmol/L)
0.96 + 0.23
0.96 + 0.26
0.828
Triglycerides
(mmol/L)
PCI treatment (%)
4.86 + 2.56
5.09 + 3.36
0.554
37.42
29.2
0.278
CABG treatment
(%)
31.42
40.3
MT treatment (%)
31.14
30.6
New AMI (%)
Additional PCI (%)
12.28
15.71
6.94
8.33
0.193
0.104
Additional CABG
(%)
13.71
8.33
0.213
................................................................................
Male sex (%)
Age (years)
0.532
Table 3
Major adverse cardiac events at 10 years
PCI
(n 5 131)
(%)
CABG
(n 5 111)
(%)
MT
(n 5 108)
(%)
P-value
13 (9.92)
36 (27.48)
9 (8.11)
10 (9.01)
16 (14.81)
15 (13.89)
0.255
,0.001
15 (11.45)
4 (3.60)
31 (28.70)
,0.001
64 (48.45)
23 (20.72)
62 (57.41)
,0.001
3 (2.29)
7 (6.31)
6 (5.56)
................................................................................
AMI
Additional
PCI
Additional
CABG
Combined
events
CVA
0.277
AMI, acute myocardial infarction; CVA, cerebrovascular accident; combined events
are the sum of AMI, additional PCI or CABG.
The overall major adverse cardiac and cerebrovascular events at
10-year follow-up of the patients who had their LVEF reassessed,
according to one of three therapeutic strategies are shown in
Table 3. The groups did not differ with respect to the occurrence of
acute myocardial infarction. However, they differ regarding the need
of additional revascularization (less frequent in the CABG group).
follow-up (P ¼ 0.675, Table 4). Regardless of the treatment strategy,
the three groups experienced the same pattern and magnitude
of ventricular function variation (P ¼ 0.641), with a decline of LVEF
(P , 0.001), represented by the reduction delta (27.2 + 17.13,
29.08 + 18.77, and 27,54 + 22.74 for PCI, CABG, and MT,
respectively, Table 4 and Figure 1).
Analysis of other variables identified a modest decline in LVEF
overall and consistent across subgroups, except for AMI during the
follow-up. Among those patients the extent of the reduction in
LVEF was statistically significantly greater (Table 5).
When those variables were correlated with the development of
ventricular dysfunction, defined as LVEF ≤45%, the presence of previous AMI and AMI during the follow-up were associated with a
greater chance of worsening of ventricular function (Figure 2).
Other demographic and anatomic factors were not different
between those with and without a decline in LVEF.
Diastolic function was re-evaluated after 10 years of follow-up
in 300 patients who had this measure obtained at baseline. One
hundred and ten patients had diastolic dysfunction at baseline and
90% of those maintained this dysfunction at re-evaluation. On the
other hand, 190 patients had normal diastolic function at baseline:
in 34 patients (17.89%) this measure remained preserved, and 155
patients (82.11%) presented diastolic dysfunction in the end of the
follow-up (47, 59, and 49 patients respectively, in the MT, PCI, and
CABG group, with no difference in evolution according to treatment
applied, P ¼ 0.331).
Of the 350 patients with LVEF reassessed after 10 years of followup, 252 had ischaemia evaluated with the treadmill exercise test
according to a modified Bruce protocol. There was no difference in
the prevalence of positive tests, irrespective of treatment applied
(Table 6). Besides, patients with ischaemia demonstrated by treadmill
tests presented the same evolution of ventricular function, compared
with the patients with no ischaemia at the end of the follow-up
(Table 6).
Left ventricular ejection fraction
assessment
Discussion
The echocardiographic assessment identified similarity of LVEF in the
three groups, both in the beginning and at the end of the 10-year
This single institution study evaluated long-term evolution of left
ventricular function, which was initially preserved, in patients with
LDL, low-density lipoprotein; HDL, high-density lipoprotein; LAD, left anterior
descending coronary artery; AMI, acute myocardial infarction. Unless otherwise
indicated, data are mean + SD.
was more frequent in patients without LVEF reassessment (Table 2).
The need of additional revascularization and new AMI was similar
between the groups.
Treatment outcomes
3374
Table 4
C.L. Garzillo et al.
Left ventricular ejection fraction evolution according the treatment assigned
PCI
CABG
MT
P-value
...............................................................................................................................................................................
LVEF baseline
LVEF 10 years
Reduction delta (%)
0.61 + 0.07
0.61 + 0.08
0.61 + 0.09
0.675
0.56 + 0.11
27.2 + 17.13
0.55 + 0.11
29.08 + 18.77
0.55 + 0.12
27.54 + 22.74
0.675
0.631
Reduction delta ¼ 100 × (LVEF 10 year – LVEF baseline)/LVEF baseline.
Table 5 Reduction of left ventricular ejection fraction
according to the presence of several variables
Variable (n)
Reduction
delta (%)
P-value
................................................................................
Male (235)
Female (115)
Figure 1 Left ventricular ejection fraction at baseline and the
10th year, according to treatment assigned: P ¼ 0.675: mean left
ventricular ejection fraction similar among groups in the beginning
and end of the follow-up; P ¼ 0.641: similar evolution among the
groups; P , 0.001: left ventricular ejection fraction decrease over
time
multivessel CAD who underwent one of three therapeutic strategies
(PCI, CABG, or MT alone), participants of the MASS II randomized
trial. Final results have shown that, regardless of the treatment
option, LVEF remained preserved at the end of follow-up, albeit
with an overall significant modest decline. This was observed
irrespective of the coronary angiographic anatomy at the time of
baseline and the need of additional revascularization.
However, patients affected by AMI had a worse outcome, with a
greater reduction of LVEF in comparison with all other subgroups.
Moreover, patients with previous AMI or with AMI during the followup had a greater chance of developing ventricular dysfunction,
characterized as LVEF ≤45%. Also, the need of CABG during the
follow-up was marginally associated with the development of LVEF
≤45% in the multivariated model (P ¼ 0.05).
Considering that our population is composed by patients with
severe CAD and other comorbidities, and that abnormalities in
endothelium-dependent vasodilation have been described in epicardial vessels and microcirculation in patients with known CAD, as well
as in those with only risk factors for atherosclerosis,28 – 30 it can be
inferred that both revascularization strategies (PCI and CABG)
were of little relevance in the protection of the ischaemic myocardium, since ventricular function remained preserved in the absence
of AMI. It is possible that the endothelial dysfunction provoked
28.71 + 20.00
26.23 + 18.36
0.278
,65 years (258)
27.51 + 19.48
0.336
≥65 years (92)
Diabetes (109)
29.00 + 19.56
27.27 + 18.96
0.779
Non-diabetes (241)
28.18 + 19.75
Smoking
Non-smoking
24.30 + 18.13
28.77 + 18.15
0.089
Previous AMI
29.25 + 14.52
0.248
No previous AMI
Double-vessel without proximal
LAD (30)
Double vessel with proximal LAD
disease (122)
Triple-vessel disease (198)
26.82 + 16.13
29.29 + 17.63
0.727
26.78 + 20.05
28.37 + 19.46
Presence of coronary collateral
circulation (144)
28.10 + 18.55
Absence of coronary collateral
circulation (206)
Additional PCI (61)
27.75 + 20.15
28.30 + 18.97
No Additional PCI (289)
27.81 + 19.62
0.825
0.884
Additional CABG (50)
No additional CABG (300)
211.15 + 23.08
27.36 + 18.81
0.152
New AMI (38)
218.29 + 21.22
0.001
No AMI during follow-up (312)
26.63 + 18.91
Reduction delta ¼ 100 × (LVEF 10 year– LVEF baseline)/ LVEF baseline.
by the epicardial vessel atherosclerosis in our patients could be
responsible for the slight decrease in LVEF observed in all subgroups,
irrespective of the treatment option and the presence of other risk
profiles.
In fact, the results shown by LVEF analysis demonstrate that,
regardless of the therapeutic option, ventricular function was
significantly impaired only when there was a history of AMI (prior
to randomization or during the follow-up). One possible explanation
for this result is that the subgroup with previous AMI included
patients with LVEF slightly .45%, so that any decline in ventricular
function, as a continuous variable, would led to LVEF value ,45%.
3375
Ventricular function in MASS II trial
Figure 2 Association of several variables and development of left ventricular ejection fraction dysfunction (LVEF ≤45%). Double/triple indicates
double vs. triple-vessel disease; Col. Circ., presence of coronary collateral circulation; MT/Revasc., medical treatment vs. revascularization
(either PCI or CABG), according to treatment assigned from randomization; Add. PCI, additional PCI; Add CABG, additional CABG.
Table 6 Ischaemia assessment with treadmill test after
10 years follow-up
Ischaemic
changes present
Ischaemic
changes absent
P-value
PCI (n)
MT (n)
17
17
79
56
0.728
CABG (n)
16
67
Reduction
delta
25.18 + 17.83
27.27 + 18.31
................................................................................
0.468
Reduction delta ¼ 100 × (LVEF 10 year– LVEF baseline)/ LVEF baseline.
In this subgroup, as well as in all other patients in the MASS II trial, a
slight decrease in LVEF was observed independently of the occurrence of AMI during the follow-up, but in the presence of this
event the magnitude was greater.
In this same way, investigators of the Bypass Angioplasty Revascularization Investigation (BARI) trial evaluated the LVEF (initially preserved) in 1220 subjects with multivessel coronary heart disease,
5 years after randomization for balloon PCI or CABG. They found
a similarity in LVEF at that time period between the groups.
However, attention was not drawn to the slight reduction in
ventricular function observed in the comparison of baseline values
of LVEF and the 5th year evaluation.13 Despite the similarity of
those results with the present study, the BARI trial did not analyse
a group with optimal medical treatment alone. In MASS II, LVEF of
patients from the MT group demonstrated the same pattern of
changes as those who underwent revascularization procedures.
Another subset analysis of 100 of the 988 patients from the SoS
trial (Stent or Surgery trial) evaluated the LVEF 30 days, 4 and 10
years after CABG or PCI with bare metal stents. They found an
initial improvement in ventricular function after 30 days in both
groups that was sustained at 4 and 10 year’s revaluation. It is important to note, however, that those results represent only one of the 53
sites of the trial and were confined to only 68 of the original 100
patients from that specific site.14
The COURAGE nuclear substudy31 also assessed ventricular function measurements at baseline and 6– 18 months after interventions.
Results identified a similarity in rest and post-stress LVEF between
patients in OMT, with or without PCI. Despite the short follow-up
period, those results indicated that, similar to the findings of the
present study, PCI did not confer any additional protection to the
ventricular function. However, the nuclear substudy of COURAGE
included only 314 of the 2287 participants of the original trial and additionally, measurements of ventricular function were missing in 141
patients at baseline and in 26 at follow-up. It is possible that the population selected for this substudy does not represent the entire population of the COURAGE trial.
In the present study, of the 422 patients alive with a mean follow-up
of 10 years and eligible for LVEF reassessment, echocardiography was
not performed in 17% (72 patients). Although the prevalence of diabetes was greater in the group without revaluation of the ventricular
function, this variable did not impact on poorer evolution of ventricular function in those with LVEF reassessed, and the variables responsible for worst outcome (AMI prior to randomization and during the
3376
follow-up) were similar between patients with and without LVEF
revaluated. This would suggest that results presented here, i.e. the
absence of a difference according to initial treatment assignment
can probably be extrapolated to those patients who did not
undergo LVEF reassessment.
Noteworthy, this analysis of measurements performed at 10 years
did not include any patient who died before that time. These results
therefore apply only to patients alive at 10 years. It is possible that
patients with lower LVEF died before our evaluation.
Recent randomized clinical trials confirm equivalent long-term
clinical outcomes for stable CAD patients treated with intensive
medical management with or without coronary revascularization.18,19 In the MASS II trial, patients in CABG and PCI groups
were under medication therapy as aggressive as patients of the MT
group. The current findings indicate that an initial conservative strategy is effective for the prevention of MACE, as well as for the preservation of ventricular function in patients with stable CAD. Besides, it
is possible that the intensive treatment for all other comorbidities
could protect ventricular function of those patients. Additionally,
the potential benefit of revascularization procedures over ventricular
function could be lost after 10 years follow-up, considering graft
patency and stent stenosis, as well as progression of atherosclerosis
in native arteries.
Clinical implications and
conclusions
Since LVEF is a major predictor of prognosis in patients with stable
CAD, the impact of strategies on ventricular function is of interest
and relevance.6,7,9 In this way, revascularization techniques were
believed to be of greater importance.
The MASS II trial has already shown similar survival of MT patients,
when compared with PCI and CABG after a follow-up of 10 years.21
The current study demonstrated that initial medical treatment was
equivalent to revascularization procedures in respect to long-term
evolution of LVEF. Also, we have found that the occurrence of AMI
was the only variable associated with deterioration of LVEF.
Thus, aggressive MT and lifestyle prescriptions with comprehensive risk factor control are valuable and should not be underestimate
in the treatment of patients with stable multivessel CAD.
Acknowledgements
Medical writing support was provided by Ann Conti Morcos of
MorcosMedia during the preparation of this paper, supported by
Zerbini Foundation.
Funding
This work was supported by a research grant from the Zerbini Foundation, São Paulo, Brazil. There is no relationship with industry. Funding
was provided by the Zerbini Foundation.
Conflict of interest: none declared.
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CARDIOVASCULAR FLASHLIGHT
doi:10.1093/eurheartj/eht229
Online publish-ahead-of-print 3 October 2013
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Unruptured sinus valsalva aneurysm in bicuspid aortic valve as an unusual
cause of seasonal dyspnoea
Kyung Hwa Kim*, Jong Bum Choi, and Jah Hong Kuh
Department of Thoracic and Cardiovascular Surgery, Research Institute of Clinical Medicine, Chonbuk National University Medical School, 20 Geonji-Ro, Geumam-dong,
Deokjin-gu, Jeonju 561-180, Republic of Korea
* Corresponding author. Tel: +82 632502522, Fax: +82 632501480, Email: [email protected]
A 44-year-old woman presented with an intracardiac cystic mass. She has been taking inhaled
steroid during 2 years because of seasonal dyspnoea, with positive response to the methacholine
bronchial provocation test. The chest X-ray
showed no abnormal finding (Panel A). The echocardiogram showed a thin-walled saccular lesion in the
right atrium and its’ cystic mass was extended from
the ascending aorta and protruded into the right
atrium (Panel B). A cardiac MRI revealed that the
cystic mass was connected to the non-coronary
sinus and was not located in the right atrium and
confirmed the presence of an unruptured 30-mm
diameter sinus valsalva aneurysm (SVA) (Panel C).
We performed a bidirectional approach, in which
both the aorta and the right atrium were opened
and both the ends of the defect were separately
repaired. The intra-operative exploration revealed
a bicuspid aortic valve type 1, L/R with a thin-walled SVA (Panel D, left upper). First, following the excision of the aneurismal sac at its
base in the low-pressure cardiac chamber (right atrium), the aortic end of the non-coronary sinus fistula was patched by means of a
semi-circular-shaped prosthetic patch, tailored on a 21 aortic valve sizer, through aortotomy (Panel D, left lower). Then the resultant
defect at its base in the right atrium was repaired by vascular patch (Panel D, right lower).
She remains asymptomatic 2 years without any inhaled steroid after surgery. Also follow-up MRI demonstrate good geometric aortic
sinus without aortic dilatation (Panel E). This case showed unruptured SVA association with the bicuspid aortic valve as an unusual cause of
seasonal dyspnoea.
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2013. For permissions please email: [email protected]