Discussion
The STS adult cardiac surgery database cites the operative mortality of
isolated MV replacement at 4.7%. When performing concomitant CABG, the
operative mortality increases to 9.8%, with a significantly greater
occurrence of post-operative complications and major morbidity occurring
in 7.0% to 11.6% (1). Thus, it is hypothesized that the operative risk
of combined CABG and MV surgery may be reduced by partitioning the
operation into the two lower-risk, less invasive procedures of PCI +
MVR. The present study demonstrated a low morbidity and mortality with
staged PCI + MVR for significant single coronary artery and MV disease,
compared to combined CABG and MVR.
Given the trends toward increases in minimally invasive cardiac surgery,
the broad applicability of the hybrid approach described here may be
particularly appealing. Gammie and colleagues (2) reported that from
2004 to 2008 the percentage of mitral valve operations that were done
via a minimally invasive approach increased from 11.9% to 20.1%
(P<.0001). With this progression, it is most likely that a
hybrid approach will increase as well. On the other hand, the short-term
benefits of a hybrid approach are not without potential long-term
hazards.
Fortunately, in-stent restenosis, one of the major limitations of
percutaneous revascularization, has decreased with each new generation
of coronary stent (3). PCI, however, has yet to match CABG with regard
to long-term benefits (4). Multiple studies have consistently
demonstrated that for patients with multi-vessel disease and/or left
main disease, regardless of the presence of diabetes, CABG yields better
outcomes than PCI in terms of mortality, myocardial infarction and need
for repeat coronary revascularization (5). Even when comparing CABG
versus PCI for patients with proximal LAD disease, Hannan et al., showed
that CABG patients had lower rates of repeat revascularization (6). The
benefit of CABG over PCI involves the long-term effects of Internal
Mammary Artery (IMA) to LAD anastomosis, the potential ability of bypass
grafts to ‘treat’ lesions that subsequently develop and resultant
downstream effects of cytokines on arterial disease (7). On the other
hand, PCI offers lower rates of morbidity and shorter hospital stay.
The primary purpose of a hybrid valve/PCI is to substitute PCI for
bypass grafting with saphenous vein grafts (SVGs), particularly for
lesions not in the left anterior descending (LAD) coronary artery (8).
With the current excellent performance of drug-eluting coronary stents
(DES), restenosis and thrombosis rates of DES may be less than the
estimated rate of SVG failure of 20 % at 12 months (9). The two most
common clinical objectives of hybrid procedures are to reduce overall
operative morbidity and mortality by transforming a single, high-risk
surgery into two less risky procedures, and to facilitate minimally
invasive surgery (8).
Hybrid procedures offer a reasonable alternative to traditional surgery
for patients who meet the following basic criteria: non-LAD coronary
lesions, not amenable to internal mammary bypass grafting; PCI that is
technically feasible and likely durable from a procedural standpoint;
and ability to tolerate the required antiplatelet and anticoagulation
regimens.
Our study was a prospective comparative review, of 2 years duration, of
80 patients with combined single coronary artery (requiring
revascularization in non-LAD territory) and rheumatic MV disease,
divided into two groups; Group I consisting of 40 patients who underwent
staged PCI, and mitral valve replacement 3 months later, and Group II
consisting of 40 patients who underwent combined CABG (using saphenous
venous graft) and mitral valve replacement. Our Aim was to compare
intraoperative, postoperative, and follow-up outcomes of staged PCI
versus CABG with mitral valve replacement in patients with combined
single vessel and mitral valve disease.
Reoperative coronary bypass grafting in a patient with valvular disease
poses a particular challenge in cardiac surgery. The hybrid approach is
of particular benefit in reoperative patients who have had prior CABG
with patent grafts. The technical difficulty of accessing lateral wall
targets, safely dissecting patent bypass grafts, and obtaining exposure
often precludes safe surgery, and these risks are not reflected in
traditional scoring systems. Hybrid valve/PCI may be particularly useful
in this regard and can dramatically simplify a challenging open valve
and CABG surgery by substituting PCI for reoperative bypass grafting in
lesions amenable to PCI (9). However, we excluded redo patients from our
study, as this cohort is extremely high risk, and would have affected
the results in a different way.
Although DES have shown excellent results in clinical trials, their
effectiveness in clinical practice with more complex patients and
complex lesions (high Syntax score, totally occluded coronary vessels,
bifurcated lesions, small vessels, long lesions requiring multiple
stents, ostial stenosis, calcified vessels) remains to be seen. Patients
with diabetes, who comprise 30% of the surgical population and 37.5%
of Group I in our study, have higher restenosis rates with DES (10).
Late stent restenosis and thrombosis is another concern.
The most recent data from STS (Society of Thoracic Surgeons) demonstrate
that in those undergoing isolated MV surgery, the rate of MV repair was
57.4%, and MV replacement was 42.6% (1). In the cases where MV
pathology and etiology were documented, 56.6% were identified as having
mitral regurgitation due to annular or degenerative disease, without
stenosis, of which repair was performed in 75.0% of patients. In the
present study, regarding the mitral valve lesions, mitral stenosis was
found in most of the patients; 24 patients (60%) of Group I versus 16
patients (40%) of Group II (P=0.074), mixed mitral lesions (stenosis +
regurgitation) come in the second place with 8 patients (20%) of Group
I versus 20 patients (50%) of Group II (P=0.005) (statistically
significant association between groups regarding mixed mitral valve
lesions only), and mitral regurgitation in the minority of study groups
with 8 patients (20%) of Group I versus 4 patients (10%) of Group II
(P=0.210). This means that mitral repair could have been feasible in a
minority of patients with pure mitral regurgitation, as the reparability
of other pathologies varies markedly. That encouraged us to exclude
mitral repair and standardize mitral replacement as the uniform approach
for mitral valve surgery in this study.
Although one needs to be cautious when making direct comparison with
other studies, reductions in the parameters of morbidity were noted when
compared with data from the most recent STS adult cardiac surgery
database outcomes. In patients undergoing CABG plus MV replacement, the
most common complication is new-onset atrial fibrillation, which occurs
in 44.2%, and increases peri-operative morbidity and hospital length of
stay (11). This figure is higher than the 16.1% noted in present cohort
of PCI + MIMVS (Minimally Invasive Mitral Valve Surgery) and is
consistent with prior studies suggesting a reduced incidence of
post-operative atrial fibrillation when utilizing a minimally invasive
approach for valve surgery (12). In our study, we compared staged PCI +
conventional MVR (Group I) to combined CABG + MVR (Group II). We noticed
no ECG changes in the form of arrhythmias in both groups, the AF
patients preoperatively in both groups went through several changes in
the rhythm and rate intraoperatively before returning to baseline AF
again. This may be due to the less morbid group of patients in our
study, with good EF, low median PAP, relatively good clinical status,
and nearly no comorbidities.
The staged strategy ensures optimal myocardial protection during the
mitral correction. It is our belief that myocardial protection is
greatly enhanced with hybrid procedures. By achieving 100% completeness
of revascularization before cross-clamping in all of our valve-PCI
patients, cardioplegia administration to all regions of the heart was
possible. In contrast, if surgeons are reluctant to attempt
revascularization on high-risk or technically difficult to reach
lesions, cardioprotection may be compromised, leading to low cardiac
output postoperatively, and worsened outcomes. The reduction in
cross-clamp time for a hybrid procedure also provides significant
myocardial protective benefit, as the heart is faced with a lower
overall ischemic time, and potentially less dysfunction upon
reperfusion.
By performing PCI to treat the coronary artery disease, one obviates the
necessity of performing concomitant CABG at the time of surgery,
significantly reducing the complexity of the surgery and shortening the
operative times, which was noted in our study when compared with
conventional combined CABG and MVR. In our study, the median aortic
cross-clamp and cardiopulmonary bypass times were 44 (IQR, 39-48) and 62
minutes (IQR, 59-68) for Group I, versus 60.5 (IQR, 55-65) and 82
minutes (IQR, 75-88) for Group II (P=0.001), that difference between
groups is statistically significant.
The less traumatic nature of isolated MVR and reduced operative times in
Group I likely conferred lower bleeding and transfusion requirements,
the median bleeding loss (ml) postoperatively was 925 (IQR, 650-1200) in
group I versus 1075 (IQR, 900-1400) in group II (P= 0.021), which is
statistically significant, with a median of 2 units of packed red blood
cells (RBCs) transfused (IQR, 1–2) in group I compared to a median of 2
packed RBCs units transfused (IQR, 2-3) in group II (P= 0.002), which is
statistically significant also. However, the rate of re-exploration for
bleeding did not differ significantly between both groups, with 1 case
only (2.5%) in group I versus 2 cases (5%) in group II (P= 0.556). All
reoperation for bleeding cases were related to sternal wire placement,
and no postoperative delayed cardiac tamponade was noted in any of the
two groups.
Although, our study was not powered to detect a statistically
significant difference, shorter operative times and less blood product
use during cardiac surgery are associated with fewer infections, and a
lower morbidity and mortality (13, 14). However, composite
post-operative complications (prolonged mechanical ventilation
(>24 h), respiratory complications, wound infection,
cerebrovascular accidents, re-operation for bleeding, acute kidney
injury, and 30-day mortality) occurred less frequently in group I than
in group II.
With the goal being to optimize stent patency while minimizing the risks
of bleeding, there is concern regarding the risk of bleeding if the
surgery is performed after the PCI and the possibility of stent
thrombosis with protamine reversal. Of particular concern is the risk of
bleeding with dual antiplatelet therapy, largely based on known higher
rates of bleeding after CABG in patients receiving clopidogrel (15). In
the current study, median time of PCI to mitral valve surgery was 93
days, the patients had their antiplatelet agents stopped 5 days before
surgery and resumed their antiplatelet regimen within 24 to 48 hours
after surgery.
In the previously mentioned study by Byrne and colleagues (16), because
of the use of dual antiplatelet therapy, a high incidence of bleeding
occurred, with 22 (85%) of the 26 patients requiring blood
transfusions. In an attempt to reduce the incidence of bleeding,
Brinster and colleagues (17) performed the PCI the day of, or evening
before, the scheduled minimally invasive aortic valve replacement in 18
patients. There were no reoperations for bleeding, and only 8 (44%)
patients required blood transfusions.
Santana O, et al. compared the outcomes of patients taking clopidogrel
with those who were not taking clopidogrel. In the intraoperative
period, there were no differences in the requirement of blood products,
whereas in the postoperative period, there was a significantly higher
number of patients taking clopidogrel who required blood products
compared with those not taking clopidogrel. Out of concern for the
possible development of stent thrombosis, they prefer the continuation
of antiplatelet therapy at the time of valve operation (18).
In the study of Mihos CG, et al. (19), even though there was a higher
use of pre-operative clopidogrel in those undergoing PCI+MIMVS, there
were fewer intraoperative transfusions required, when compared with
CABG+MVS. The lower need for blood products in the PCI+MIVS group is
most likely due to the fact that, by its less traumatic nature,
minimally invasive valve surgery is associated with less blood loss.
Also, by virtue of the fact that there was no need to place bypass
grafts, the operative times were much shorter in this group, thereby
having less bleeding (20). Importantly, there were no cases of acute
stent thrombosis peri-operatively. In their previous work, they
evaluated 222 patients who had PCI+MIMVS, 183 of which were on
clopidogrel and were compared with 38 who were not (18). In the
intra-operative period, there were no differences in the requirement of
blood products between the two groups. Post-operatively, there was a
higher proportion of patients on clopidogrel requiring blood products
compared with those who did not take it (50.5% versus 26.3%, P=0.005);
however, there was no significant difference in the need for
re-operation for bleeding. Because clopidogrel use perioperatively
appears to be safe (21), their clinical practice has been to continue
anti-platelet therapy at the time of valve surgery to minimize the risk
of acute stent thrombosis.
Ideally, these patients would be best managed by either a longer staging
duration so that the clopidogrel can be stopped (three to six months
with drug-eluting stents), or by a very short staging duration (under 6
h), so that clopidogrel’s actions are just beginning to take effect once
the surgery has been completed. Our study differs from the previously
mentioned studies in that we had a significant variation on the use of
antiplatelet agents, our Group I patients had their antiplatelet agents
stopped 5 days before surgery. The median time of PCI to mitral valve
surgery in our study was 93 days, so we feel it is safe to withhold the
antiplatelet therapy.
In these hybrid procedures, the optimal timing of the valve operation
once PCI has been performed is not known. At our institution, the time
delay between PCI and the valve operation is mainly driven by a desire
to reduce the incidence of acute kidney injury counterbalanced with the
urgency of the operation. It has been noted that the closer the 2
procedures are in time, the higher the incidence of acute kidney injury.
Data from 4,440 patients undergoing coronary angiography and cardiac
operation on the same day demonstrated this approach to be an
independent predictor for the development of acute kidney injury (22).
Another study evaluated the incidence of acute kidney injury in patients
who had cardiac catheterization and cardiac operations during the same
admission and compared it with a group of patients who had cardiac
catheterization followed by operation at a later admission (23). The
incidence of acute kidney injury in the patients who had same-admission
cardiac catheterization and operations was 50.2% compared with 33.7%
in those who had operations at a later date (p = 0.009). To reduce the
incidence of acute kidney injury, several institutes prefer to wait at
least 3 weeks after PCI to perform valve operations (22, 23).
We decided to wait 3 months after PCI to perform MVR, to avoid renal
failure, and to be able to stop the antiplatelet therapy safely. We have
got 2 patients (5%) in group I versus 1 (2.5%) in group II of acute
kidney injury (P= 0.556), in the form of elevated creatinine levels,
which resolved medically, without the need for dialysis. This difference
was not statistically significant. We attribute this to the period of 3
months between PCI & MVR, which provide us with the protection window
against acute kidney injury.
Santana O, et al (24) compared 65 patients who had a hybrid approach
with 52 matched control patients who underwent conventional bypass
grafting and valve operation. The results demonstrated a significant
reduction in composite complications and hospital lengths of stay in the
hybrid group when compared with conventional group. This is similar to
the results per our study which showed fewer composite complications in
Group I, as well as statistically significant lower median intensive
care unit (ICU) length of stay (hours) and hospital length of stay
(days); 39 hours (IQR, 32-45) and 5.5 days (IQR, 5-6), versus 56.5 hours
(IQR, 49-69) and 8.5 days (IQR, 7-13) for Group II (P=0.001),
respectively.
The postoperative complications were comparable with no statistically
significant difference for groups I and II, with less prolonged
mechanical ventilation (>24 h) 0 (0%) versus 3 (7.5%),
and less respiratory complications 0 (0%) versus 1 (2.5%) for group I.
This may be due to less aggressive and less time consuming is the
isolated MVR than the combined CABG + MVR, which paves the way for
faster extubation with less respiratory complications. The 3 patients of
Group II eventually got extubated, one of them got chest infection which
has been resolved using appropriate antibiotics. However, both
approaches did include a sternotomy.
By virtue of avoiding a sternotomy, minimally invasive surgery results
in less thoracic surgical trauma and alterations in pulmonary physiology
and biomechanics, which contributes to an enhanced post-operative
recovery and faster extubation, with a reported significantly lower
incidence of prolonged mechanical ventilation occurring in 18.3% of the
PCI + MIMVS cohort, and 29% in CABG plus MV replacement, leading to
shorter intensive care unit length of stay with the PCI + MIMVS
approach, when compared with sternotomy. We don’t see this significant
difference in our study, because both groups were approached through a
median sternotomy, with low incidence of prolonged mechanical
ventilation, most probably due to exclusion of any lung disease or other
comorbidities from our study groups.
Our present study showed slightly less wound infection in group I; 0
(0%) versus 2 (5%), most probably due to less operative time, ICU &
hospital stay, blood transfusion requirements, & other postoperative
complications which usually encourage infection. However, this
difference is not significant, probably due to the similar approach used
in both groups; sternotomy, and similar baseline characteristics between
both groups.
The cerebrovascular accidents encountered in our study was one stroke
patient in group II without any residual deficit. No other cases were
reported in both groups, probably due to relatively good baseline
characteristics of the patients included in our study, with good carotid
duplex preoperatively, and exclusion of old patients above 60 years old
with any central or peripheral vascular disease.
Several groups have investigated hybrid approaches of PCI combined with
valve operations. In 2014, Santana et al., published the results of over
200 patients who underwent PCI for coronary revascularization followed
by a minimally invasive valve procedure. They found a mortality rate of
3.6% and an all-cause mortality rate of 12% at 4.5 years. They also
demonstrated a decreased complication rate and length of stay for the
hybrid group compared to those undergoing conventional sternotomy (24).
In 2015, George et al. described a series of 26 patients who underwent a
single-stage hybrid procedure involving PCI of a non-LAD vessel followed
by a valve operation (21). Recalculating the STS risk after the PCI was
performed, they found a 35% risk reduction in the re-operative group
and a 17% risk reduction in the non-reoperative group. In addition,
they had no in-hospital mortalities and very few complications. No
coronary-stent thromboses were noted during a follow-up period of two
years.
Specific to mitral valve, Umakanthan et al. described the Vanderbilt
experience with 32 consecutive patients who underwent a hybrid
procedure, including PCI and mitral valve surgery. Of these procedures,
28 (89 %) were performed as a single-stage procedure in a hybrid
operating room (25). The observed in-hospital mortality rate was 3 %
(1/32) and survival at one and two years was 96 % and 89 %,
respectively. The series was expanded to 39 patients and reported by
Solenkova et al., noting a predicted mortality for conventional CABG/
mitral of 14.1 % versus an observed in-hospital mortality of only
2.6 % (1/39). (26)
This is different from our study which showed no operative/30-day
mortality in both groups. This may be attributed to the baseline
characteristics of our group of elective patients who are low risk
patients with few or no comorbidities.
As demonstrated by 5-year outcomes from the Synergy Between Percutaneous
Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) trial
(27), a strong argument can now be made for PCI in patients with left
main or multivessel disease with low SYNTAX scores (less than 23).
However, the SYNTAX trial also clearly demonstrates a survival benefit
of CABG for patients with a higher burden of disease, as reflected by a
high SYNTAX score (greater than 33), and in specific patient subsets,
such as patients with diabetes mellitus (28). The benefit of CABG is
primarily attributable to left IMA grafting to the LAD, and the patency
of IMA grafting consistently exceeds 95% at 10 years, setting the gold
standard with which other revascularization strategies should be
compared. Yet, significant limitations of both PCI and CABG persist.
Whereas PCI is burdened by the need for repeat target lesion
interventions, saphenous vein graft failure for non-LAD targets in CABG
can reach 30% at 1 year, and at 10 to 15 years, only 50% to 60% of
the SVGs have been reported to be patent (29). Conversely, the early
restenosis and thrombosis rate of the drug-eluting stents (DES) in
non-LAD vessels is lower than that reported for SVG failure (30).
This is to a great extent in line with the results per our study.
Postoperative routine trans-thoracic echo (TTE) follow-up was done upon
discharge, as well as after 3 months, 6 months, and 1 year for all
patients in both groups. Follow-up was completed after one year.
Regional wall motion abnormalities were noted in 15 patients (37.5%) of
group I versus 17 patients (42.5%) of group II (P=0.648), who all
undergone stress ECG, of whom 9 patients (22.5%) in group I versus 11
patients (27.5%) in group II showed positive results (P=0.606), and
qualified for diagnostic coronary angiography, which confirmed the need
for reoperation for myocardial ischemia/infarction within the first year
of follow up post-operatively in 4 patients (10%) of group I versus 8
patients (20%) of group II (P=0.210). However, all these follow up
outcomes showed no significant difference between both groups within the
first year of follow up. None of the patients in both groups had major
cardiac events or CCU admission. We attribute this to the nature of our
patients in both groups, who have single non-LAD vessel disease
supplying limited heart territories with good functional reserve. Long
term data are needed for more informative conclusion.
As more hybrid PCI/valve procedures are being performed, many questions
remain unanswered, including the optimal order for the procedures, their
timing, the management of dual antiplatelet therapy, and the optimal
costs and logistics of the procedures (8).