Download Alexandra Gonçalves and Scott D. Solomon Multivalvular Disease

Mitral Regurgitation in Transcatheter Aortic Valve Replacement: The Complexity of
Multivalvular Disease
Alexandra Gonçalves and Scott D. Solomon
Circulation. 2013;128:2101-2103; originally published online October 2, 2013;
doi: 10.1161/CIRCULATIONAHA.113.006196
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Editorial
Mitral Regurgitation in Transcatheter
Aortic Valve Replacement
The Complexity of Multivalvular Disease
Alexandra Gonçalves, MD, PhD; Scott D. Solomon, MD
T
ranscatheter aortic valve replacement (TAVR) has
emerged as an alternative treatment for patients with
symptomatic aortic stenosis (AS) who are at an unacceptably
high risk for conventional surgical aortic valve replacement
(AVR).1,2 Approximately 60 000 patients worldwide have
undergone TAVR in the 11 years since it was introduced.3
Although good procedural success and favorable clinical outcomes have been reported,4,5 issues remain regarding the best
patient selection for the procedure. Risk calculators commonly
used to estimate the risk of valvular surgery, such as the logistic EuroSCORE and the Society of Thoracic Surgeons model,
are not considered accurate in patients undergoing TAVR
because they do not account for all clinical characteristics
that may significantly affect procedural and postprocedural
mortality. The current selection criteria are based on those
used in randomized trials, and, in conjunction with the clinical evaluation, echocardiography is a mainstay in the assessment of candidates for this procedure. Beyond the clinical and
anatomic exclusion criteria, severe pulmonary hypertension
with right ventricular dysfunction, very severe left ventricular
(LV) systolic dysfunction (ejection fraction <20%), and severe
mitral regurgitation (MR) are among the echocardiographic
exclusions.6 Moreover, each of the commercially available
prosthesis manufacturers presents its own recommendations
for the procedure, with the CoreValve being more restrictive
with respect to concomitant valvular disease.
Article see p 2145
Nevertheless, the criteria for patient selection are still open
to debate and are not considered binding. As a consequence,
patients found in TAVR registries often have characteristics
that go beyond the recommended criteria, and this procedure
is being considered in a wider array of patients with off-label
indications. TAVR in patients with significant MR is one example, and several large series have reported up to 48% of patients
with moderate or severe MR.7,8 Nevertheless, until recently, the
prognostic impact of MR among patients undergoing TAVR
was unknown, and conflicting results have been reported.9
The opinions expressed in this article are not necessarily those of the
editors or of the American Heart Association.
From the Cardiovascular Division, Brigham and Women’s Hospital,
Boston, MA.
Correspondence to Scott D. Solomon, MD, Brigham and Women’s
Hospital, Cardiovascular Division, 75 Francis St, Boston, MA 02115.
E-mail [email protected]
(Circulation. 2013;128:2101-2103.)
© 2013 American Heart Association, Inc.
Circulation is available at http://circ.ahajournals.org
DOI: 10.1161/CIRCULATIONAHA.113.006196
Previous studies have shown that patients with moderate
or severe MR undergoing TAVR exhibit a worse baseline
clinical profile, including advanced age, higher EuroSCORE
and Society of Thoracic Surgeons scores, higher prevalence
of atrial fibrillation, and previous myocardial infarction. On
echocardiography, they have lower LV ejection fraction,
larger LV volumes, smaller aortic valve area, and higher systolic pulmonary pressure.8,10,11 In this issue of Circulation,
Bedogni et al12 highlight the prognostic significance of MR
in patients undergoing TAVR. This study included 1007 consecutive patients from the Italian nationwide registry, 33.4%
with moderate/severe MR, treated with the third-generation
the 18-Fr CRS CoreValve Revalving System device. As with
previous studies, patients with moderate or severe MR had
higher logistic EuroSCORE and Society of Thoracic Surgeons
scores, higher rate of New York Heart Association class 3 to
4, and higher frequency of pulmonary hypertension and atrial
fibrillation, and those with severe MR had lower mean estimated glomerular filtration rate compared with patients with
mild baseline MR. At 1 month and 1 year after TAVR, the cardiac mortality rates in patients with moderate/severe MR were
significantly higher compared with those with none to mild
MR. At 1 year, they observed a stepwise increase in the risk
of mortality across the MR groups (none to mild, 10%; moderate, 12%; severe 17%), but the difference between patients
with moderate/severe MR was not statistically significant.
Most patients presented with functional MR, and a substantial percentage demonstrated MR improvement (47% with
severe MR and 35% with moderate MR) at 1 year, whereas
MR severity worsened in only 8.4%. However, in this registry,
the improvement in MR severity was not associated with a
beneficial effect on survival. Importantly, severe pulmonary
hypertension and atrial fibrillation were more frequently
found among patients whose MR severity worsened and were
also independent predictors of mortality.12
Other registries and observational studies have previously
reported similar findings concerning the effect of MR on mortality among patients undergoing TAVR. Toggweiler et al,8
using the Edwards SAPIEN valve, reported a doubling of
mortality at 1 month after TAVR among patients with moderate/severe MR compared with mild or less MR. Nevertheless,
those patients had similar mortality rates at 1 year. In addition, the Canadian13 and the Italian CoreValve registries have
reported a higher frequency of severe MR among patients who
died at 30 and 69 days after the procedure, respectively.14 The
German registry recently showed that, among 1385 patients
undergoing TAVR, 33.8% presented with MR ≥ grade 2.
These patients had high procedural success but lower survival
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2101
2102 Circulation November 5, 2013
rates at 30 days and 1 year, although the improvement in quality of life at 30 days was similar in both groups.11
There is limited information regarding the effect of TAVR
on MR, but, after aortic valve gradient relief, the immediate decrease in afterload and LV pressure would be expected
to result in improvement in MR. Moreover, the longer-term
effects of TAVR may, similarly to AVR, lead to regression of
hypertrophy or reversal of LV dilation, improving ventricular
geometry with resultant reduction in MR severity over time.
However, functional MR can be a maladaptive consequence
of AS, and it is found in patients with greater LV dilation and
worse LV function15 and thus is a marker of LV disease that
reflects underlying LV dysfunction. In this study, patients
with AS and severe MR presented with higher end-diastolic
LV volumes, but LV ejection fraction was not significantly
different in patients with varying degrees of MR severity.
Considering that MR enhances LV ejection fraction, which
may mask subclinical myocardial dysfunction, the similarity
of LV ejection fraction between patients with moderate/severe
MR and those with mild MR might indicate the absence of
myocardial functional compensation in the former group.
This may help explain the higher mortality and hospitalization rates for heart failure of patients with moderate/severe
MR, despite MR improvement. Additional insights into LV
myocardial contractility and function in patients with AS and
MR referred to TAVR might be obtained with strain analysis,
which is a less load-dependent measure of cardiac function
than ejection fraction.
Parallels can be drawn with surgical AVR, because MR is
recognized as an independent risk factor influencing longterm survival in elderly patients undergoing AVR,16 and concomitant MR surgery is selectively considered in symptomatic
patients undergoing AVR. Mitral valve (MV) repair has been
associated with improved late survival in patients with double
valve disease, including the elderly and those with depressed
LV function; however, simultaneous replacement of the aortic
valve and MV significantly increases surgical morbidity and
mortality. Thus, echocardiographic MV morphologic evaluation is critical for the assessment of mechanism and reparability. MR improvement after AVR is more likely in patients
with lesser degrees of MR or in the presence of normal MV
morphology, because it usually reflects the functional nature
of MR. In patients with myxomatous, calcific, and ischemic
MR, the decrease in MR severity should not be expected.16 In
contrast to surgical AVR, concurrent MV repair has not been
an option for patients undergoing TAVR. However, bivalvular
transcatheter treatment of concomitant AS and MR has been
reported previously from a very experienced center,9 using
TAVR and mitral clip in a single session. Additional studies
showing efficacy and safety of bivalvular transcatheter treatments are needed for future recommendations.
The effect of TAVR on the degree of MR may be different
depending on the type of prosthesis used. It has been suggested
that the effects of the 2 commercially available transcatheter
valves could differ because of the potential for increased risk
of MV anterior leaflet restriction or secondary chordae disruption by the longer CoreValve prosthesis.17 In the current study,
CoreValve MV function impairment was ruled out, because
the low implant had no effect on MR.
If left untreated, patients with severe AS and concomitant
moderate/severe MR have a very poor prognosis. Although
patients with moderate/severe MR undergoing TAVR have
higher overall morbidity and mortality compared with those
with lower degrees of MR, the benefit of TAVR may indeed be
higher in this group. The randomized trials PARTNER A and
B suggested that patients with MR may experience an even
greater benefit from TAVR compared with both medical management and surgical AVR.1,7 In the PARTNER 1B trial, MR
was a marker of higher TAVR procedural mortality but also
of greater procedural benefit compared with medical management. Likewise, in the PARTNER 1A study, patients with MR
had a lower risk with TAVR than with surgical AVR (24.2%
versus 35%).2
Nevertheless, the PARTNER trial was not designed to
determine whether patients with more substantial MR would
benefit from TAVR. Even with the best attempts to minimize
confounding, registries and observational studies have limited
ability to determine the potential benefit of this intervention
in clinical practice and only provide incentive for designing
properly powered trials. Considering the high prevalence of
MR and the frequency of events in patients undergoing TAVR
with significant MR, additional trials to determine whether
patients with moderate to severe MR will benefit from TAVR
are certainly warranted to support the best medical decision.
Sources of Funding
Dr Gonçalves receives funds from Portuguese Foundation for Science
and Technology Grant HMSP-ICS/007/2012.
Disclosures
None.
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Key Words: Editorials ◼ aortic stenosis ◼ mitral valve insufficiency ◼
percutaneous aortic valve replacement
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