Download Functional Assessment of Coronary Artery Disease in Patients

Coronary Physiologic Assessment and Imaging
Functional Assessment of Coronary Artery Disease in
Patients Undergoing Transcatheter Aortic Valve Implantation
Influence of Pressure Overload on the Evaluation of Lesions Severity
Gabriele Pesarini, MD; Roberto Scarsini, MD; Carlo Zivelonghi, MD; Anna Piccoli, MD;
Alessia Gambaro, MD; Leonardo Gottin, MD; Andrea Rossi, MD; Valeria Ferrero, MD;
Corrado Vassanelli, MD; Flavio Ribichini, MD
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Background—Aortic valve stenosis may influence fractional flow reserve (FFR) of concomitant coronary artery disease by
causing hypertrophy and reducing the vasodilatory reserve of the coronary circulation. We sought to investigate whether
FFR values might change after valve replacement.
Methods and Results—The functional relevance of 133 coronary lesions was assessed by FFR in 54 patients with severe
aortic valve stenosis before and after transcatheter aortic valve implantation (TAVI) during the same procedure. A linear
mixed model was used to verify the interaction of TAVI effect with the FFR values. No significant overall change in FFR
values was found before and after the aortic valve stenosis removal (0.89±0.10 versus 0.89±0.13; P=0.73). A different trend
in FFR groups (positive if ≤0.8; negative if >0.8) was found after TAVI (P for interaction <0.001). Positive FFR values
worsened after TAVI (0.71±0.11 versus 0.66±0.14). Conversely, negative FFR values improved after TAVI (0.92±0.06
versus 0.93±0.07). Similarly, FFR values in coronary arteries with lesions presenting percent diameter stenosis >50
worsened after TAVI (0.84±0.12 versus 0.82±0.16; P=0.02), whereas FFR values in arteries with mild lesions (percent
diameter stenosis <50) tended toward improvement after TAVI (0.90±0.07 versus 0.91±0.09; P=0.69). Functional FFR
variations after TAVI changed the indication to treat the coronary stenosis in 8 of 133 (6%) lesions.
Conclusions—Coronary hemodynamics are influenced by aortic valve stenosis removal. Nevertheless, FFR variations after
TAVI are minor and crossed the diagnostic cutoff of 0.8 in a small number of patients after valve replacement. Borderline
coronary lesions might become functionally significant after valve replacement, although FFR-guided interventions
were infrequent even in patients with angiographically significant lesions. (Circ Cardiovasc Interv. 2016;9:e004088.
DOI: 10.1161/CIRCINTERVENTIONS.116.004088.)
Key Words: aortic valve stenosis ◼ coronary artery disease ◼ fractional flow reserve, myocardial ◼ myocardial
revascularization ◼ transcatheter aortic valve replacement
T
he prevalence of coronary artery disease (CAD) ranges
from 25% to 50% of all patients with aortic valve stenosis (AVS).1 Observational studies reporting outcomes of
patients undergoing transcatheter aortic valve implantation
(TAVI) revealed a prevalence of CAD in the range of 40% to
75%.2–4 Current guidelines state that myocardial revascularization at the time of surgical aortic valve repair is a class I
recommendation in the presence of coronary stenosis ≥70%
and a class IIa recommendation for angiographic stenosis
50% to 70%.5 Conversely, the best management of CAD in
TAVI candidates is unclear.6 There is no evidence, at present,
of increased survival or symptoms relief with a full revascularization strategy, thus raising concerns about the real
functional meaning of coronary lesions incidentally found in
this specific subset during the routine diagnostic workout. In
this context, fractional flow reserve (FFR) measured during
diagnostic angiograms may prove useful. Nevertheless, it has
been demonstrated that AVS may influence coronary hemodynamics and represents a clinical and physiological condition in which functional indexes may vary consistently.7–9
TAVI has been demonstrated to exert an immediate effect on
coronary flow,10 and recently, the immediate improvement
in the coronary physiological reserve induced by the aortic
valve replacement has been demonstrated using wave intensity analysis.11,12 However, little is known about the functional
effects of the pressure overload on coronary stenosis and if,
and to which extent, the removal of the outflow obstruction
may influence the relation between coronary stenosis and
FFR in severe AVS.
TAVI can be a useful clinical research model of isolated
valvular intervention to unmask underlying valvular–coronary
interactions in AVS.
Received April 9, 2016; accepted September 26, 2016.
From the Division of Cardiology, Department of Medicine, School of Medicine (G.P., R.S., C.Z., A.P., A.G., A.R., V.F., C.V., F.R.) and Department of
Anesthesia and Intensive Care (L.G.), University of Verona, Italy.
Correspondence to Flavio Ribichini, MD, Division of Cardiology, Department of Medicine, University of Verona, Piazzale Aristide Stefani 1, 37126
Verona, Italy. E-mail [email protected]
© 2016 American Heart Association, Inc.
Circ Cardiovasc Interv is available at http://circinterventions.ahajournals.org
1
DOI: 10.1161/CIRCINTERVENTIONS.116.004088
2 Pesarini et al Coronary Assessment With FFR in TAVI
What Is Known
• Coronary
artery disease has a high prevalence in
patients undergoing transcatheter aortic valve valve
implantation (TAVI).
• However, coronary hemodynamics is influenced by
the presence of severe aortic valve stenosis, and the
functional evaluation of coronary stenosis may be altered in this context.
• No recommendations are available regarding indication for myocardial revascularization in TAVI
candidates.
What the Study Adds
• Functional assessment with fractional flow reserve is
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a feasible and safe method to determine the severity
of coronary artery disease in TAVI patients.
• Overall, fractional flow reserve variations after TAVI
are minor compared with baseline measurements.
• However, post-TAVI functional assessment may
change the indication to perform percutaneous
coronary intervention in ≈15% of patients with
coronary artery disease undergoing TAVI; therefore, functional assessment with fractional flow
reserve may be more reliable after the aortic valve
replacement.
The acute improvement in ventricular mechanics and function due to the removal of severe afterload following successful
TAVI may improve coronary blood flow, possibly influencing
functional assessment of coronary lesions significance. The
purpose of the study is, therefore, to detect eventual changes of
FFR values in patients with severe AVS caused by the removal
of the aortic valve pressure overload after TAVI. To this aim,
FFR values were obtained during the same interventional procedure, before and immediately after transfemoral TAVI. Next,
we sought to observe whether functionally significant coronary
lesions present at baseline associate with the occurrence of
ischemic complications during the transfemoral TAVI procedure and the immediately after procedural period.
Methods
In this prospective, observational study, FFR measurements were attempted in the 3 major epicardial arteries before TAVI and immediately after the transcatheter valve implantation maintaining similar
hemodynamic conditions (Figure 1).
The study was approved by the ethical review board of the
University of Verona (ID CESC 2015-498), and all patients eligible
for the protocol provided their written consent.
Selection of Patients
Patients included in the study presented with severe symptomatic
AVS defined according to the current European Society of Cardiology
(ESC) Guidelines,13 showing at least 1 coronary artery stenosis and
having clinical indication to elective TAVI as jointly evaluated by the
local Heart Team. No patient had predominant aortic regurgitation.
Severe AVS was diagnosed by transthoracic echocardiogram combining the assessment of valve area (<1.0 cm2; indexed valve area
<0.6 cm2/m2 body surface area) with flow-dependent indices (mean
gradient >40 mm Hg, maximum jet velocity >4.0 m/s, and velocity
ratio <0.25).13 Aortic gradients, valvular areas, and left ventricular
function were measured before and after valve implantation.
Inclusion Criteria
1.Written informed consent
2.Diagnosis of severe AVS with preserved left ventricular function
and high transvalvular gradient, with indication to TAVI
Exclusion Criteria
1. Lack of informed consent
2. Previous myocardial infarction
3. Previous coronary intervention or tandem lesions in the same
coronary artery
4. Contraindication to adenosine administration (eg, severe asthma or chronic obstructive pulmonary disease, heart rate <50
beats/min, and systolic blood pressure <90 mm Hg)
5. Acute presentation of CAD (unstable angina or myocardial infarction) or heart failure
6. Residual aortic regurgitation greater than mild (≥grade 2) after
TAVI
All TAVI procedures, including hemodynamic and FFR measurements, were performed by the percutaneous transfemoral approach
with the use of local anesthesia and mild conscious sedation with
low-dose intravenous bolus of fentanyl or midazolam.
The choice of the aortic valve prosthesis was left to the operator’s discretion. The Medtronic CoreValve Evolut-R bioprosthesis
(Medtronic Inc, Minneapolis, MN) or Edwards Sapien-3 bioprosthesis (Edwards Lifesciences LLC, Irvine, CA) has been used in this
study.
Coronary Angiography and Quantitative
Coronary Analysis
Coronary angiography was performed by a standard percutaneous
femoral approach with 6F guiding catheters using the same vascular access predisposed for the valve implantation. The severity
of the CAD was graded by quantitative coronary analysis (QCA)
performed off-line using the software CASS-II QCA package (Pie
Medical Imaging, Maastricht, the Netherlands) in a previously
validated core laboratory (NBR, Verona, Italy).14 Coronary stenosis were classified after the surgical recommendations for the
treatment of CAD in surgical aortic valve repair candidates.2,11
Therefore, arteries showing minimal angiographic lesions with a
percent diameter stenosis (%DS) ≤30% were considered angiographically unobstructed; those with a %DS≥30≤50 were classified as having intermediate lesions and those with %DS>50%,
as having severe lesions. The contrast-filled catheter was used for
calibration. Reference vessel diameter (mm), minimum luminal
diameter (mm), %DS, and lesion length were calculated using enddiastolic still-frame images.
Pressure Measurements
A pressure monitoring guidewire (PrimeWire, Volcano Therapeutics,
Rancho Cordova, CA) was advanced distally to the coronary artery
stenosis after normalization. Because the continuous intravenous infusion of adenosine in severe AVS may raise hemodynamic concerns,
hyperemia was obtained after administration of intracoronary bolus
of 150 to 250 mg adenosine as previously indicated by other authors,
who reported equivalent diagnostic capabilities.9,10,15,16 The high doses
of adenosine bolus were expected to induce effective hyperemia because for clinical reasons nitroglycerin was not administered, given
the presence of severe AVS.10 An FFR value ≤0.80 was considered
pathological, whereas an FFR value >0.80 was considered negative,
that is, unlikely to induce reversible myocardial ischemia according
to current recommendations.17
3 Pesarini et al Coronary Assessment With FFR in TAVI
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Figure 1. Case example of the study methods: quantitative coronary analysis and fractional flow reserve (FFR) measurements in a
patient with 3-vessel coronary artery disease. Before transcatheter aortic valve implantation baseline analysis shows %DS=62 in the left
anterior descending artery (LAD), 46% in the left circumflex coronary artery (LCx), and 75% in the right coronary artery (RCA; A, D, G);
0.014″ pressure guidewire in each corresponding vessel and FFR values 0.86, 0.97, and 0.76 respectively (B, E, H). After valve replacement with a 26-mm Sapien-3 Edwards aortic valve, FFR values decreased to 0.77 in the LAD, 0.89 in the LCx, and 0.57 in the RCA (C,
F, I). %DS indicates percent diameter stenosis.
Clinical Follow-Up
The occurrence of any procedure-related clinical complication was
prospectively evaluated. After discharge, patients were contacted at
30 days, as per usual clinical practice to assess the clinical status
(New York Heart Association [NYHA] and Canadian Cardiovascular
Society [CCS] classes) and the eventual occurrence of major adverse
cardiovascular events: death, clinically manifested myocardial infarction, stroke, angina, or the need for hospitalization because of congestive heart failure or chest pain at rest.
Statistical Analysis
Continuous variables are presented as mean and standard deviation,
whereas categorical variables are presented as frequencies (percentages). Correlation among variables was determined by Pearson or
Spearman correlation tests as appropriate and expressed as r value.
FFR has been classified according to the basal value as positive if
the ratio was ≤0.8 or as negative if >0.8.
Comparison of variables before and after TAVI was performed using a repeated measures mixed model, with vessel nested within the
patient. The TAVI effect was considered as a binary variable (before
versus after TAVI).
Sensitivity, specificity, diagnostic accuracy, and optimal cutoff value were defined from the calculated receiver operator characteristic
curve. The optimal diagnostic cutoff value was defined based on the
Youden index. A P value <0.05 was considered statistical significant.
All statistical analyses were performed using Stata/SE 14.0 (Stata
Corp LP, College Station, TX).
Results
Patient Population
Between January 2015 and June 2016, 57 patients with
severe AVS and concomitant CAD underwent TAVI and were
included in the study. Fourteen patients received a CoreValve
Evolut-R valve, and 43 patients received an Edwards Sapien-3
valve. In 2 patients, a full assessment of the FFR before and
after TAVI could not be completed because of difficulties in
reengaging the coronary ostia after the valve implantation (1
patient) and a temporary hemodynamic instability related to
bleeding (1 patient). In 1 patient, aortic regurgitation of grade
4 Pesarini et al Coronary Assessment With FFR in TAVI
>2 was found immediately after valve replacement. These
3 patients have been excluded from this analysis; therefore,
coronary angiography and functional assessment before and
after TAVI were completed in 54 patients with 133 coronary
lesions. Baseline and angiographic characteristic of the overall patient cohort are shown in Table 1.
Effect of TAVI on Functional Assessment
of Coronary Lesions
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Table 1. Clinical and Angiographic Characteristics of the
Studied Cohort
Variable
Demographic data
Age, y
54
80±7.2
Sex male, %
41
Dyslipidemia, %
87
Hypertension, %
80
Smoke, %
48
Diabetes mellitus, %
47
Ejection fraction, %
56±14
Angiographic characteristics
Number of lesions
133
Lesion length, mm
12±6
D-Ref, mm
2.9±0.8
MLD, mm
1.8±0.6
DS, %
Mean FFR ratio
Variables
Pre-TAVI
Post-TAVI
P Value
SBP, mm Hg
130±14
135±16
0.08
DBP, mm Hg
74±12
68±14
0.01
HR, bpm
79±9
78±10
0.57
CVP, mm Hg
Mean valvular gradient pre-TAVI was 44.1±11 mm Hg, and
it dropped to 7.2±5 mm Hg after intervention (P<0.001). The
hemodynamic measures remained stable before and after
TAVI, as shown in Table 2.
TAVI effect has no significant interaction with the overall
FFR measurements (z=0.35; P=0.73). In fact, overall FFR values did not change significantly after TAVI compared with the
baseline (0.89±0.10 versus 0.89±0.13; Figure 2).
When baseline FFR group was included in the model as a
binary variable (positive if the ratio was ≤0.8 and negative if
>0.8), its interaction with TAVI effect was statistically significant (z=5.54; P<0.0001), indicating a different trend between
the 2 groups.
Positive FFR values (≤0.8) at baseline were found in 21 of
133(16%) lesions, and in these patients, a significant decrease
in the FFR ratio after aortic valve replacement was observed
(0.71±0.11 versus 0.66±0.14; Figure 3C). On the contrary,
negative FFR values at baseline improved after valve replacement (0.92±0.06 versus 0.93±0.07).
Functional FFR variations after TAVI changed the indication to treat coronary stenosis (according to the 0.80
FFR threshold) in 8 of 133 (6%) coronary lesions, that is,
15% of all patients. Seventy-three percent (97/133) of all
Number of patients
Table 2. Pre- and Postprocedural Hemodynamic and
Echocardiographic Characteristics
40±19.7
0.89±0.07
DS% indicates percent diameter stenosis; FFR, fractional flow reserve; and
MLD, minimal lumen diameter.
11±3.8
AVA, cm2
0.63±0.11
AVPG mean, mm Hg
44.1±11
AVPG max, mm Hg
68±19.2
11.8±4
0.32
1.84±0.6
<0.001
7.2±5
<0.001
17.4±9.8
<0.001
AVA indicates aortic valve area; AVPG, aortic valve pressure gradient; CVP,
central venous pressure; DBP, diastolic blood pressure; HR, heart rate; SBP,
systolic blood pressure; and TAVI, transcatheter aortic valve implantation.
coronary obstructions were classified as intermediate or severe
(%DS>30), and among these, FFR variations across the 0.80
threshold after TAVI occurred in 8% of lesions (8/97).
Negative FFR values, intended as >0.80, shifted below the
0.80 threshold in 7 of 112 (6%), whereas only 1 of 21 (5%)
positive borderline FFR value (0.79) became negative (0.86)
after TAVI. All these cases showed intermediate lesions at QCA
(%DS range, 43–63) and similar lesion length (Figure 4).
The FFR variations after TAVI stratified by different coronary vessels are shown in Table 3.
Because of the low number of lesions in the right coronary
artery and in the left circumflex coronary artery, the coronary
vessels were classified as left anterior descending (LAD)
(n=56) and non-LAD (n=77). When the coronary vessel was
added to the model, no significant interaction with TAVI
effect was evident (z=0.29; P=0.78), indicating a similar trend
between the 2 groups. Mean FFR values in LAD varied from
0.84±0.09 at baseline to 0.83±0.13 after TAVI. In non-LAD
coronary arteries, the FFR measurements were 0.92±0.09
before TAVI and 0.92±0.11 after TAVI.
Effect of TAVI on Coronary Lesions Stratified
by QCA
When DS% was included in the model as a categorical variable, its
interaction with TAVI had a mild statistical significance (χ2=6.38;
P=0.04), indicating a different trend between the groups.
The interaction of TAVI effect with FFR values was significant in coronary arteries with %DS≥50 (z=2.31; P=0.02), with
a significant worsening of the functional indexes (0.84±0.12
versus 0.82±0.16) after the AVS removal.
In coronary arteries with %DS<50, the withdrawal of
the afterload obstruction by TAVI caused a relatively small,
still constant, improvement of the FFR values both in coronary arteries with a normal angiographic aspect (%DS<30,
0.95±0.05 versus 0.96±0.06) and in the presence of intermediate coronary lesions (%DS=30–50, 0.90±0.07 versus
0.91±0.09). However, the interaction of TAVI effect did not
reach statistical significance (z=0.39; P=0.69).
Correlation Between FFR and QCA
in Patients With AVS
The %DS at QCA at baseline showed a significant correlation with the FFR measurements (r=0.58; P<0.0001) and had
5 Pesarini et al Coronary Assessment With FFR in TAVI
Figure 2. Left, the overall individual fractional flow reserve (FFR) in aortic valve
stenosis patients before and after transcatheter aortic valve implantation (TAVI).
The blue lines represent patients with FFR
>0.8 at baseline, and the dashed black
line shows the average trend of this subgroup. The red lines represent patients
with FFR pre-TAVI ≤0.8, and the dashed
red line shows their average trend. Right,
FFR values before and after TAVI in left
anterior descending (LAD), left circumflex
coronary artery (LCx), and right coronary
artery (RCA).
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a good accuracy (AUC=0.78; 95% confidence interval, 0.70–
0.84; P<0.001) in predicting positive FFR.
The best %DS cutoff value to predict a positive FFR at
receiver operator characteristic curve analysis was >39%
(Youden index=0.53), with a sensibility of 93.7% (95% confidence interval, 69.8–99.8) and a specificity of 60% (95% confidence interval, 49.4–69.8).
FFR values in intermediate coronary stenoses (%DS
30–50) located in the proximal LAD did not change significantly after TAVI (0.84±0.05 versus 0.83±0.07).
In the study cohort, 57 of 133 (43%) coronary lesions had
a %DS≥50 at QCA. Among these, 38 (67%) resulted functionally negative at FFR measurement (FFR>0.8) before TAVI
and 3 with borderline baseline FFR values became positive
(FFR≤0.8) after TAVI. The remaining 35 of 57 (61%) lesions
with %DS≥50 remained FFR negative after aortic valve
replacement.
Procedural and 30-Day Outcome
In no patient, the administration of intracoronary adenosine
caused hemodynamic or clinical adverse effects. No clinical
complication was observed in relation to the catheterization of
the coronary arteries for FFR measurements before and after
TAVI. Most importantly, no patient with FFR-positive values
at baseline experienced clinical consequences related to the
valve positioning procedure (sustained angina or hypotension,
myocardial infarction, or heart failure) during the procedure
or within the 30 days that followed the intervention, despite
Figure 3. Fractional flow reserve (FFR)
variations in patients with aortic valve stenosis before and after transcatheter aortic
valve implantation (TAVI) of coronary
lesions with percent diameter stenosis
(%DS) <50 (A) and ≥50 (B) at quantitative coronary analysis (QCA). FFR values
pre- and post-TAVI of coronary lesions
with %DS≥50% at QCA. FFR values preand post-TAVI of functionally significant
coronary lesions (FFR ≤0.8) at baseline
(C). Coronary lesions with significant
functional stenosis found at post-TAVI
FFR and treated with percutaneous coronary intervention (PCI) are presented with
the postprocedural FFR controls (D). The
dashed black lines show the average
trends of each subgroup.
6 Pesarini et al Coronary Assessment With FFR in TAVI
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Figure 4. Subgroup of coronary lesions
that crossed through the 0.8 fractional
flow reserve (FFR) threshold after transcatheter aortic valve implantation (TAVI).
LAD indicates left anterior descending
artery; LCx, left circumflex coronary
artery; QCA, quantitative coronary analysis; and RCA, right coronary artery.
the presence of at least 1 critical coronary stenosis, including
the proximal LAD in 6 lesions and the unprotected left main
in 1 patient (Figure 5).
In 17 (31%) patients, 19 percutaneous coronary interventions (PCIs) were performed during the same TAVI procedure because of FFR values ≤0.8 after the valve replacement
(1 unprotected left main, 9 LAD, 5 right coronary artery,
and 4 left circumflex coronary artery). In all cases, the PCI
was successful, and no complications occurred. In all treated
lesions, FFR values normalized after stenting (Figure 3D).
The remaining 3 positive lesions located in distal LAD (1
lesion) and in distal right coronary artery (2 lesions) were
left on medical therapy because of angiographic complexity,
distal location, and advanced age of the patients. In addition, these patients remained asymptomatic during the study
period observation.
Discussion
The main finding of our study is that FFR variations after
TAVI performed with the 2 more commonly used types of
valves are minor, confirming the validity of FFR in this
specific clinical setting. However, significant changes may
occur after TAVI in patients with different degrees of CAD.
Therefore, FFR values measured after valve replacement
may be more accurate to evaluate the need for myocardial revascularization compared with values obtained during preintervention diagnostic examinations. In particular,
Table 3. Functional Assessment of Coronary Lesions
Stratified by Coronary Segment Pre-TAVI vs Post-TAVI
Subset of Patients
at Baseline
Number of Lesions
Pre-TAVI
Post-TAVI
FFR≤0.8
15
0.72±0.12
0.69±0.13
FFR>0.8
41
0.88±0.12
0.89±0.13
LAD
Coronary segment other than LAD
FFR≤0.8
6
0.69±0.12
0.62±0.14
FFR>0.8
71
0.94±0.12
0.95±0.13
When the coronary artery (LAD vs non-LAD) was included in the mixedmodel, no significant interaction with TAVI effect was evident (z=0.29; P=0.78),
indicating a similar trend between the groups (see text for details). Values are
mean±SD. Coronary segments other than LAD include left circumflex coronary
artery and right coronary artery. FFR indicates fractional flow reserve; LAD, left
anterior descending; and TAVI, transcatheter aortic valve implantation.
7 Pesarini et al Coronary Assessment With FFR in TAVI
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Figure 5. Case example of a significant unprotected left main lesion. At the quantitative coronary analysis, a 57%DS in the left main trunk was
evident (A, F). Pressure guidewire was advanced in the left anterior descending (LAD) and left circumflex coronary artery (LCx) before (B, G) and
after (D, I) a 29-mm CoreValve Evolute-R implantation. Fractional flow reserve (FFR) values worsened after transcatheter aortic valve implantation both in the LAD (from 0.65 to 0.57; C, E) and in the LCx territory (from 0.66 to 0.62; H, J). %DS indicates percent diameter stenosis.
TAVI may unmask functionally significant coronary lesions
among angiographically intermediate stenosis because
borderline or positive FFR values at baseline decrease significantly after the AVS removal, in particular in the LAD
territory. However, in our series that includes also FFR measurements in mild CAD, such functional variations changed
the indication to treat the coronary stenosis in a relatively
low percentage of lesions (6%). A percentage that rises
to 8% when only angiographically intermediate to severe
lesions (DS%>30) is considered.
Interestingly, in the absence of significant CAD, FFR
improved after TAVI in our series, and in angiographically
normal arteries, it tended toward normalization.
Moreover, our findings support the feasibility and the
safety of assessing angiographically and functionally coronary stenosis in patients undergoing TAVI before and after
the aortic valve replacement. In fact, no ischemic complication related to the administration of intracoronary adenosine
or the use of the pressure wire during the procedure and at 30
days of follow-up was observed, even in patients with angiographically severe lesions with confirmed positive FFR ratios
at baseline in the LAD territory.
In summary, our findings demonstrate the usefulness of
FFR in this clinical setting and suggest that angiographically
intermediate lesions may become functionally significant after
TAVI, while FFR variations would not affect the diagnostic
8 Pesarini et al Coronary Assessment With FFR in TAVI
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decision based on the 0.80 cutoff in patients at the extremes of
the QCA spectrum (unobstructed arteries or severe lesions).
Fifty-seven of 133 (43%) coronary lesions presented angiographically significant stenosis (%DS≥50) at QCA, a percentage in agreement with previous observations.1,3 However,
the majority of these lesions were functionally negative before
(66%) and after TAVI (61%), strongly supporting the need for
physiological evaluation before attempting revascularization
of lesions incidentally found during a workout AVS examination. Safety and clinical reliability of FFR-guided revascularization in AVS has been recently demonstrated.18
The relationship among QCA, FFR, and inducible myocardial ischemia assessed by imaging or metabolic studies in
patients with AVS is unknown. Therefore, the capability of
inducing ischemia of the QCA–FFR interaction observed in
our patients using the standard 0.80 cutoff cannot be interpreted. Keeping in adherence with current knowledge, the
number of functionally guided PCI required in TAVI patients
may be quite limited, even in patients with coronary lesions
showing %DS≥50 at QCA. This observation is important for
the management of TAVI patients in the near future because,
by downgrading the severity of CAD, FFR may reduce the
need for (useless) myocardial revascularizations in analogy
with the observations of the SYNTAX functional study.19
Such a less-invasive approach would make the AVS population even more suitable for transcatheter treatments.
Recently, the introduction of TAVI has expanded the
opportunity of treating much older and fragile patients that
drive significant survival benefit from valve implantation.3,20,21
Few studies have, however, evaluated the impact of CAD
on outcomes of patients after TAVI with conflicting results.1
Indeed, unlike CABG at the time of surgical aortic valve
repair,22,23 there is no agreement about the real benefit of treating coronary stenosis before or after TAVI in the absence
of clear signs of ischemia.24 In a group of 730 consecutive
patients who underwent transapical TAVI, a single-stage
combined treatment of severe AVS and CAD with PCI has
been shown safe and feasible. Early and 3-year survival was
comparable with that observed in patients without CAD who
received TAVI only.25 Conversely, others analyzed the clinical
outcome of 411 TAVIs, 16% of which had significant CAD
and received PCI. Incidence of myocardial infarction and
30-day mortality were much higher in the TAVI+PCI group
compared with the TAVI alone group (P=0.01). Synchronous
versus staged approach for PCI had comparable early mortality (P=1.0).26
The management of CAD in TAVI patients represents an
important challenge in the immediate future of transcatheter
therapeutics, and the precise identification of the functional
significance of coronary stenosis may reveal fundamental for
the risk stratification and the safe and effective management
of TAVI candidates. This observation may acquire particular
importance in view of the expanding indications for TAVI in
younger and lower risk patients.
From a physiological standpoint, the reduction of the wall
stress and the end-diastolic pressure that follows the removal
of the left ventricle afterload causes a rapid increase in the coronary flow,27 independent of the presence of CAD in patients
with preserved contractile function.28 Recently, wave intensity
analysis, derived from simultaneously acquired measures of
coronary pressure and velocity using invasive intracoronary
wires, has been used to investigate changes in coronary physiology before and after TAVI. Normal coronary perfusion is
maintained by coupling between the pressure originating
from the proximal (aortic) and the distal (microcirculatory)
ends of the coronary circulation.11 At wave intensity analysis,
the microcirculatory decompression (suction) was found to
decrease and the forward compression wave to increase after
TAVI, reflecting the reduction in myocardial work required
to eject blood past a stenosed aortic valve and the immediate
improvement in the coronary physiological reserve induced
by the aortic valve replacement.11,12,29
TAVI, inducing an immediate decrease in hyperemic
microvascular resistance and an increase in hyperemic flow
velocity, is associated with an immediate improvement in
the reserve vasodilator capacity of the coronary microcirculation.10 Increased extravascular compression and reduced
diastolic perfusion time, rather than vascular remodeling,
influence coronary microvascular dysfunction in AVS. After
aortic valve replacement, the improvement in coronary
microcirculatory function and the consequent improvement in transmural myocardial perfusion have been related
to a combination of reduction in extravascular compressive forces, as well as improved hyperemic diastolic perfusion time.30,31 The pathophysiologic explanations for these
changes may be multiple and complex, and their interactions
may be involved in the FFR changes after TAVI observed in
our study. These, however, go beyond the aims of this observational study and warrant further investigation in dedicated
study models.
Limitations
Given the global complexity of the TAVI patients and the
study protocol, the present analysis was conducted on a still
limited number of patients, and this may induce some analytic
drawbacks. For example, grouping the coronary lesions per
coronary segment, our results were not confirmed in vessels
other than LAD. Because the coronary obstructions investigated were located in the LAD in a majority of cases (56/133;
42%), it is plausible that the limited sample size influenced the
analysis in left circumflex coronary artery and right coronary
artery. The general trends are in fact maintained in vessels
other than LAD, but larger studies are needed to further investigate the complex crosstalk between QCA and FFR in AVS.
Hemodynamic variables, such as the left ventricular filling
pressures or the central venous pressure, were not analyzed
because, recently, it has been demonstrated that these have no
implications in the measurement of FFR while limited within
normal values.32 Not administering nitrates in patients with
AVS is a limitation to optimal FFR measuring, but this was
a request of the reviewers of the study protocol; large doses
of adenosine were used in an attempt to optimize hyperemia,
however.
Conclusions
Our findings suggest that FFR measurements are influenced
by the presence of AVS. Positive FFR values at baseline will
likely decrease further after TAVI, whereas negative FFR
9 Pesarini et al Coronary Assessment With FFR in TAVI
values at baseline may not change or tend to improve. Borderline lesions might differ significantly after valve replacement,
potentially changing patients’ management in a relatively
small percentage of high-risk TAVI procedures. FFR assessment in patients with severe AVS undergoing TAVI is safe,
provides reliable information about the functional relevance
of coronary lesions, and should be ideally obtained after AVS
removal by transcatheter valve implantation.
Acknowledgments
We thank Dr Luisa Zanolla, from the Biostatistical Department, for
her valuable contribution to the statistical analysis of the manuscript.
Sources of Funding
This study was partially supported by a scholarship grant from
Volcano Corp.
Downloaded from http://circinterventions.ahajournals.org/ by guest on May 2, 2017
Disclosures
None.
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Functional Assessment of Coronary Artery Disease in Patients Undergoing Transcatheter
Aortic Valve Implantation: Influence of Pressure Overload on the Evaluation of Lesions
Severity
Gabriele Pesarini, Roberto Scarsini, Carlo Zivelonghi, Anna Piccoli, Alessia Gambaro,
Leonardo Gottin, Andrea Rossi, Valeria Ferrero, Corrado Vassanelli and Flavio Ribichini
Circ Cardiovasc Interv. 2016;9:
doi: 10.1161/CIRCINTERVENTIONS.116.004088
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