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Prevalence and Impact of Pulmonary Hypertension on Patients With Aortic Stenosis Who Underwent Transcatheter Aortic Valve Replacement
Accepted Manuscript Prevalence and Impact of Pulmonary Hypertension on Patients With Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement Israel M. Barbash, MD, Ricardo O. Escarcega, MD, Sa’ar Minha, MD, Itsik Ben-Dor, MD, Rebecca Torguson, MPH, Steven A. Goldstein, MD, Zuyue Wang, MD, Petros Okubagzi, MD, Lowell F. Satler, MD, Augusto D. Pichard, MD, Ron Waksman, MD PII:
S0002-9149(15)00718-3
DOI:
10.1016/j.amjcard.2015.02.022
Reference:
AJC 20991
To appear in:
The American Journal of Cardiology
Received Date: 19 November 2014 Revised Date:
11 February 2015
Accepted Date: 13 February 2015
Please cite this article as: Barbash IM, Escarcega RO, Minha S’a, Ben-Dor I, Torguson R, Goldstein SA, Wang Z, Okubagzi P, Satler LF, Pichard AD, Waksman R, Prevalence and Impact of Pulmonary Hypertension on Patients With Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement, The American Journal of Cardiology (2015), doi: 10.1016/j.amjcard.2015.02.022. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Prevalence and Impact of Pulmonary Hypertension on Patients With Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement
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Israel M. Barbash, MD1,2; Ricardo O. Escarcega, MD1; Sa’ar Minha, MD1; Itsik Ben-Dor, MD1; Rebecca Torguson, MPH1; Steven A. Goldstein, MD1, Zuyue Wang, MD1, Petros Okubagzi,
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MD1; Lowell F. Satler, MD1; Augusto D. Pichard, MD1; Ron Waksman, MD1
Interventional Cardiology, MedStar Washington Hospital Center, Washington, DC; 2Leviev
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Heart Center, Sheba Medical Center, Tel Aviv University, Ramat-Gan, Israel
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Running title: Pulmonary Hypertension in TAVR Patients
Address for correspondence:
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Ron Waksman, MD
MedStar Washington Hospital Center
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110 Irving Street, NW, Suite 4B-1 Washington, DC20010 Tel: 202-877-2812
Fax: 202-877-2715
Email: [email protected]
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Abstract Limited amount of data suggests that aortic stenosis patients with pulmonary hypertension (PH) who undergo transcatheter aortic valve replacement (TAVR) experience decrease in PHTN post
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procedure. Inconsistent use of systolic pulmonary artery pressures (SPAP) cut-off values in prior studies limits our ability to draw meaningful conclusions regarding the prognostic role of PH in assessment of TAVR candidates. A total of 415 consecutive TAVR patients were included in the
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present study. Two groups were compared based on receiver-operator analysis for the best SPAP value to predict outcome, yielding two study groups of no/mild PH (≤50 mmHg) (n=172, 41%)
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versus moderate/severe PH (>50 mmHg) (n=243, 59%). Demographics and comorbidities were comparable between the two groups; however, right heart failure (35% versus 19.8%, p=0.02) and mitral regurgitation (18.4% versus 8.6%, p0.007) were more frequent among patients with moderate/severe PH. Procedural characteristics and complications were comparable between the
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groups. Although there was an early, overall decrease in SPAP post procedure, only 26% of moderate/severe PH patients experienced a significant decrease in SPAP (>10 mmHg). The 30day (14.5% versus 7.4%, p=0.02) and 1-year mortality (30.8% versus 21%, p=0.02) was higher
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among moderate/severe PH patients. In multivariate analysis, systolic pulmonary artery pressure and chronic lung disease were identified as independent predictors for mortality at 1-year. PH is
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a frequent comorbidity among patients with severe aortic stenosis undergoing TAVR. Significantly elevated pulmonary artery pressures at baseline may serve as a poor prognostic factor when performing preprocedural assessment of the patients. Keywords: pulmonary hypertension; aortic stenosis; transcatheter aortic valve replacement
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Introduction Historically, presence of pulmonary hypertension (PH) as a comorbidity in patients with severe aortic stenosis (AS) undergoing aortic valve surgery was considered as predictor for poor
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outcome.1-3 This increased risk was linked to hemodynamic challenges during the operative and postoperative period related to use of heart bypass and because of pulmonary vasculopathy and right heart failure.
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Transcatheter aortic valve replacement (TAVR) might offer several advantages for
patients with severe AS and PH because the procedure is performed without major hemodynamic
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changes that are typically associated with cardiopulmonary bypass and mechanical ventilation, which are not mandatory during TAVR. Limited amount of data suggests that AS patients with PH who undergo TAVR experience decrease in PH post procedure.4,5 However, patients with PH still suffer from worse prognosis as compared to patients without PH.4,6 Furthermore, data
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regarding the long-term hemodynamic effects of TAVR among PH patients are limited. Thus, the goals of the present study were to assess prevalence of PH among AS patients who undergo TAVR and to evaluate the long-term effects on pulmonary artery hemodynamics after TAVR.
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Methods
The study was approved by the Institutional Review Board of the MedStar Health
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Research Institute. Consecutive patients with symptomatic, severe AS who underwent TAVR from 2007 to 2013 at MedStar Washington Hospital Center were analyzed. Prespecified clinical and laboratory data were collected for all patients at baseline prior to the procedure, immediately post procedure, during the index hospitalization, and up to 1 year. Collected data included medical history, electrocardiogram, echocardiography studies, laboratory tests, and clinical outcomes.
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Patients underwent TAVR either with the balloon expandable Edwards SAPIEN or the SAPIEN-XT transcatheter heart valves (Edwards Lifesciences, Irvine, CA) or the selfexpandable Medtronic CoreValve (Medtronic, Minneapolis, MN) via the transfemoral,
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transapical, or direct aortic access routes as part of PARTNER, US, CoreValve studies or
standard clinical care, as previously described.7,8 Doppler tracings and 2-dimensional images were obtained from parasternal long- and short-axis, apical 4-chamber, and subcostal 4-chamber
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views. Transthoracic echocardiograms were reviewed to assess the pericardium, valvular
anatomy and function, and cardiac function. Tricuspid regurgitant flow was identified by color
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flow Doppler techniques. Continuous-wave Doppler measured maximum jet velocity. Right ventricular systolic pressure was estimated based on the modified Bernoulli equation and was considered equal to the systolic pulmonary artery pressure (SPAP) in the absence of right ventricular outflow obstruction. SPAP was calculated by adding trans-tricuspid pressure gradient
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to mean right atrial pressure estimated from inferior vena cava diameter and motion during respiration as follows: if the caliber of inferior vena cava was normal (1.5 to 2.5 cm), mean right atrial pressure was estimated to be 5 mmHg if there was complete collapse of the inferior vena
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cava during inspiration or was estimated to be 10 mmHg if the inferior vena cava collapse was >50%. If the inferior vena cava was dilated, mean right atrial pressure was estimated to be 15
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mmHg if the inferior vena cava collapsed by <50% with inspiration or was estimated to be 20 mmHg if there was no visible evidence of inferior vena cava collapse. Right ventricular function was assessed according to American Society of Echocardiography guidelines using the tricuspid annular plane systolic excursion (TAPSE) method.9 Right sided heart catheterization was performed with a 7Fr Swan-Ganz catheter in 199 of the patients (48%). Right atrial pressures (amplitude of a and v waves and mean pressure), right
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ventricular systolic and diastolic pressures, pulmonary artery pressures (systolic, diastolic, and mean), and pulmonary capillary wedge pressures (a and v waves and mean pressure) were measured. Cardiac output was determined by the thermodilution method.
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In-hospital outcomes were collected according to the Valve Academic Research
Consortium (VARC)-2 consensus document.10 Out-of-hospital adverse events were assessed up to 1 year by means of outpatient clinic visit or a standardized telephone interview. All suspected
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events were adjudicated by a blinded interventional cardiologist.
Statistical analysis was performed using SAS version 9.1 (SAS Institute Inc., Cary, NC).
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Continuous variables are expressed as mean ± standard deviation or median (25th-75th interquartile range) as appropriate according to variable distribution. Categorical variables are expressed as percentages. Student’s t test was used to compare continuous variables, and the chisquare test or Fisher’s exact test was used to compare categorical variables. Pearson Correlation
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Coefficients were used to assess correlation between pulmonary pressure measurements by echocardiography and right heart study.
Receiver-operating-characteristic curve was analyzed to assess the discriminatory ability
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of baseline SPAP to predict 30-day mortality and to determine the best cut-off value to predict this end point. For that purpose, the best prognosticator in receiver-operating-characteristic curve
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analysis was considered to be the value that gave the highest product of sensitivity and specificity for predicting 30-day mortality. Survival rates up to 1 year were computed using the Kaplan-Meier method, and
differences in parameters were assessed using the log-rank test. A Cox proportional hazards analysis was performed to assess the independent influence of baseline PH on 1-year mortality in each group. Variables of the baseline and clinical characteristics associated with the outcome of
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interest were adjusted in the multivariable analysis: age, prior myocardial infarction, chronic renal failure, left ventricular ejection fraction, Society of Thoracic Surgeons (STS) score, chronic lung disease, and peripheral vascular disease. A p value <0.05 was considered statistically
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significant.
RESULTS
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A total of 415 patients were included in the present study. The average age was 84±8 years, and 47% of the patients were male. The study population comprised a high-risk patient
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population with an average STS risk score of 10±5 and Logistic euroSCORE of 30±24. A large proportion of the patients had significant comorbidities, such as diabetes (31%), chronic lung disease (31%), renal insufficiency (55%), prior coronary bypass surgery (31%), and left ventricular ejection fraction (LVEF) lower than 40% (23%).
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By receiver-operator curve analysis, baseline SPAP demonstrated intermediate prognostic power as a single parameter to predict 30-day mortality (AUC 0.62) (Figure 1). Based on these findings, a SPAP cut-off value of 50 mmHg was selected to predict 30-day mortality for
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TAVR patients, yielding sensitivity and specificity of 57% and 60%, respectively. This cut-off value was used to determine the study groups of no/mild PH (≤50 mmHg) versus
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moderate/severe PH (>50 mmHg). The majority of the patients were included in the moderate/severe PH group (243 of 415, 59% of the entire cohort). Overall, as shown in Table 1, baseline characteristics and comorbidities of patients in
both groups were comparable between patients with no/mild versus moderate/severe PH. Average SPAP was significantly higher in moderate/severe PH group (61±12 mmHg) as compared to no/mild PH group (36±9 mmHg, p<0.001). This finding was corroborated also by
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pre-TAVR right heart catheterization with intermediate correlation to the echocardiographic assessment of SPAP (r=0.46) (Table 2). Baseline echocardiographic evaluation showed that the average left ventricular function of the patients is preserved with only 16% and 12% of the
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patients that have LVEF lower than 30% in both groups (Table 2). Conversely, patients with moderate/severe PH had higher rates of concomitant valve disease and right ventricular failure. Similarly, rates of moderate/severe mitral regurgitation and moderate/severe tricuspid
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regurgitation were significantly higher and nearly twice as frequent as right ventricular dysfunction (Table 2).
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The procedural characteristics did not differ significantly between patients with no/mild and moderate/severe PH (Table 3). There was a large majority for the transfemoral access and for the use of the SAPIEN transcatheter heart valve . Nearly two-thirds of the patients underwent the procedure with conscious sedation, thus avoiding the need for mechanical ventilation. VARC
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in-hospital complications were mostly comparable between the groups; however, acute kidney injury rates tended to be higher (nearly double) among patients with moderate/severe PH as compared to patients with no/mild PH, although mostly driven by the grade-1 acute kidney
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injury rates. Interestingly, in-hospital infection rates, typically respiratory, were higher among moderate/severe PH patients. Finally, moderate/severe PH patients had longer stay in intensive
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care; however this did not translate to a longer hospitalization period (Table 4). As demonstrated in Figure 2, the elevated SPAP in the moderate/severe PH group tended
to decrease after TAVR procedure. Interestingly, the decrease in SPAP occurred early, during the index hospitalization, and was maintained up to 1 year follow-up. However, SPAP values remained higher than the SPAP values among the patients in the no/mild PH group throughout follow-up and did not return at any stage to normal values (Figure 2). Subgroup analysis of the
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moderate/severe PH group (n=243) according to whether SPAP decreased early after procedure (defined as a decrease of >= 10 mmHg) showed that although there is an early decrease in SPAP after procedure, the majority (n=180, 74%) of the patients do not experience a significant
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improvement (that is, >= 10 mmHg). Furthermore, outcome was not different for the patients who experienced decrease in SPAP compared to those who did not with 7.4% versus 8% 30-day mortality (p=1) and 22.2% versus 28% 1-year mortality (p=0.56), respectively.
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The prevalence of moderate or severe mitral regurgitation decreased from 18.4% at
baseline to 6.2% at 1-year follow-up. Similar trends were observed also in the prevalence of
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moderate or severe tricuspid regurgitation (from 23% to 9.1%) and moderate or severe right ventricular dysfunction (from 35% to 18% at 1 year) (Table 5).
Despite the improvement in the post-procedure echocardiographic parameters (Table 5, Figure 2), the early and late mortality of patients with moderate/severe PH was higher than
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patients with no/mild PH. In-hospital mortality (Table 4) is nearly 2-fold higher (13.5% versus 7%, p=0.03), and the mortality difference is maintained at 30-days (14.5% versus 7.4%, p=0.02) and up to 1-year follow-up (30.8% versus 21%, p=0.02) (Figure 3). As shown in Table 6, in uni-
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variate analysis moderate/severe PH, the STS score and moderate/severe lung disease were associated with poor 1 year outcome. Similarly, among the sub-group of patients that underwent
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right heart study, pulmonary vascular resistance (hazard ratio (HR) of 1.1, 95% confidence interval (CI) of 1.01-1.2) but not diastolic pulmonary vascular pressure gradient (HR of 0.99, 95% CI of 0.93-1.06) were associated with poor outcome. By multivariable analysis, baseline SPAP and moderate or severe lung disease were independent predictors of poor outcome (Table 6).
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DISCUSSION The main findings of the present study that aimed to assess the impact of PH on TAVR results indicate that a large amount of the patients have concomitant PH. This study shows that
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overall SPAP decreases after TAVR but does not normalize. Finally, similar to cardiac surgery, the presence of PH is indeed an independent predictor of poor short- and long-term outcome after TAVR; however, by itself, it has low power to predict poor outcome as indicated by the
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intermediate sensitivity and specificity.
PH is frequently associated with AS. PH rates among AS patients were reported with
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prevalence of up to half of the patients.11-13 More recently, Ben-Dor, et al. reported that nearly 70% of TAVR candidates have concomitant PH.14 Several studies have shown that the prognosis of these patients is poor if left untreated.13-15 Conversely, the prognostic role of baseline SPAP before aortic valve surgery is unclear.3,13,15 There is also a large body of evidence to suggest that
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patients with PH and right ventricular dysfunction are particularly at a higher risk for adverse events after cardiac surgery.16
Similar ambiguity is present with regard to the limited number of studies that analyzed
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the pre-procedural effect of PH on AS patients who undergo TAVR. These studies suffer from one major limitation—the inconsistent use of SPAP cut-off values for grouping the patients.2,15
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This inconsistency limits our ability to draw meaningful conclusions from these studies. In the present study, we attempted to assess the independent prognostic power of SPAP to predict patient outcome. Although SPAP had intermediate power to determine prognosis, we based our analysis on the optimal cut-off value as determined by specificity/sensitivity analysis. Our study indicates that patients with significant PH at baseline do not have higher incidence of procedural complications. However, the mortality of patients with significant PH is
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higher than patients with no/mild PH. This mortality hazard is present early after the procedure (that is, in-hospital mortality) and continues up to 1- year follow-up. Although one recent registry indicated that PH is associated with late but not early mortality hazard, the findings from
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the present analysis as well as others2,4 suggest that the mortality hazard for these patients begins early after the procedure. A possible explanation for the early mortality after TAVR might be related to factors that are not directly related to the procedure itself but to other complications,
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such as higher in-hospital infection rates and sepsis as shown in this and other 2 analyses and reflected by the need for prolonged stay in intensive care as shown in the present study.
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Similarly, the long-term mortality hazard is probably related to the fact that a large proportion of the patients do not decrease significantly the SPAP, and perhaps PH is associated with other noncardiac factors that are responsible for late mortality.
Several hemodynamic patterns of SPAP that were identified in the present study should
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be emphasized: Median SPAP tended to decrease from baseline to post-procedure (60 to 48 mmHg). Second, the change in SPAP occurred early after the procedure, and the effect was maintained in the long run. These findings might be explained by the documented improvement
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in mitral regurgitation post procedure in this (18.4% at baseline to 10.6% post-procedure moderate/severe mitral regurgitation) and other studies.17 A similar trend of improvement in
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tricuspid regurgitation and right ventricular function (Table 5) in long term follow up was also documented. As the majority of the patients had normal or near normal left ventricular function at baseline, these changes might be related to the decrease in diastolic pressures after the procedure, as was also shown in surgical aortic valve studies. 18 However, despite these encouraging data, only a minority of the patients (26%) experienced a significant (>10 mmHg) decrease in SPAP. Previously published data suggested
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that post-operative SPAP was an independent predictor of improved outcome.4,15 Interpretation of the results from this study in light of this previously published data indicates that the lack of extensive improvement in SPAP following TAVR may explain the poor prognosis of these
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patients in the early and late follow-up. Alternatively, the higher mortality among patients with persistent PH may be related to residual paravalvular leak.4 A potential approach that might be considered in patients with severe PH is to perform balloon aortic valvuloplasty and to assess
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response to the procedure. It is plausible the patients who will experience decrease in PH with improvement in right ventricular function will also respond favorably to the TAVR procedure.
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There are several limitations to this study. This study was a post hoc analysis and, as such, is subject to the limitations of retrospective analyses; results may possibly have been affected by unknown confounders. In the present study, echocardiography was used as the main technique for assessment of SPAP. Although right ventricular systolic pressure is a calculated
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value, use of echocardiography allowed for a consistent measurement that we could follow over time, allowing high rates of echocardiographic follow-up. Furthermore, although SPAP from right heart catheterization was available for only about half of the patients, we, as well as data
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from prior studies,19 found good correlation between the right heart catheterization and echo measurements among this sample of patients. The cutoff of SPAP = 50 mmHg used for grouping
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the patients in this study was based on ROC analysis, however, the discriminative power was relatively low and other SPAP values may be proven to be as good as the one used in this paper. Additionally, the higher rates of in-hospital infections found among PH patients could not be further assessed due to lack of data regarding etiology of infection.
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Figure legend: Figure 1. Receiver-operator curve for predictive power of systolic pulmonary artery pressure to predict 30-
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day outcome among patients undergoing transcatheter aortic valve replacement.
Figure 2.
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1-year follow-up. PHTN=pulmonary hypertension.
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Change in median and range of pulmonary artery systolic pressure over time, from baseline up to
Figure 3.
Kaplan-Meier survival estimate of patients with no/mild versus moderate/severe pulmonary
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hypertension following transcatheter aortic valve replacement. PHTN=pulmonary hypertension.
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Table 1. Baseline characteristics of patients with no/mild versus moderate/severe pulmonary hypertension undergoing transcatheter aortic valve replacement Pulmonary hypertension No/mild (n=172)
p Value
80 (47%)
0.8
10.2±5
0.6
28.3±24.9
0.4
218 (94%)
152 (92%)
0.5
69 (30%)
55 (33%)
0.5
73 (31%)
53 (33%)
0.8
119 (53%)
95 (58%)
0.3
4 (1.8%)
4 (2.4%)
0.7
86 (38%)
51 (32%)
0.3
History of coronary artery disease*
137 (78%)
95 (75%)
0.5
Prior myocardial infarction
48 (21%)
23 (14%)
0.09
Prior percutaneous coronary intervention
76 (33%)
44 (27%)
0.2
Prior coronary artery bypass surgery
76 (33%)
48 (29%)
0.5
Prior valve surgery
5 (2.8%)
6 (4.4%)
0.5
Atrial fibrillation
92 (40%)
73 (44%)
0.4
Prior stroke or transient ischemic attack
43 (19%)
28 (18%)
0.7
42 (23%)
22 (18%)
0.3
Age (years±SD)
83±8
Men
116 (48%)
Risk assessment 9.9±4.5
Log EuroSCORE risk (%±SD)
31±23.6
Systemic hypertension Diabetes mellitus Chronic obstructive lung disease Renal failure
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Peripheral vascular disease
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Hemodialysis
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Co-morbidities
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Society of Thoracic Surgeons score risk (%±SD)
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Moderate /severe (n=243) 84±8
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Variable
Permanent pacemaker/ implantable cardioverter defibrillator
*Defined as any coronary artery stenosis ≥50%, prior PCI or CABG
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Table 2. Baseline echocardiography and right sided heart catheterization of patients with no/mild versus moderate/severe pulmonary hypertension undergoing transcatheter aortic valve replacement Pulmonary hypertension
Variable
Echocardiogrpahy Left ventricular ejection fraction (%±SD)
53±17
Moderate /severe (n=243)
p Value
53±14
0.9
21 (12%)
0.3
0.65±0.1
0.5
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No/mild (n=172)
38 (16%)
Aortic valve area (cm2±SD)
0.65±0.1
Mean gradient (mmHg±SD)
48±13
48±13
0.9
Peak velocity
4.4±0.6
4.4±0.6
0.7
1.3±0.2
1.3±0.2
0.6
1.2±0.2
1.2±0.2
0.5
Left ventricular end systolic diameter (cm±SD)
3.1±0.9
3.2±0.9
0.2
Left ventricular end diastolic diameter (cm±SD)
4.4±0.8
4.4±0.8
1.0
19 (8.6%)
29 (18.4%)
0.007
Moderate or severe tricuspid regurgitation
13 (5.9%)
38 (23%)
<0.001
Moderate or severe RV dysfunction*
21 (19.8%)
29 (35.3%)
0.02
6 (2.6%)
12 (7.3%)
0.047
4.5±0.7
4.7±0.8
0.04
36±9
61±12
<0.001
8.9±7.9
8.9±5.5
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Septal thickness (cm±SD) Posterior wall thickness (cm±SD)
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Moderate or severe mitral regurgitation
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Left ventricular ejection fraction <30%
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Moderate or severe RV dilatation Left atrial diameter (cm±SD)
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Systolic pulmonary artery pressure (mmHg±SD) Right sided heart catheterization** Right atrial pressure; mean (mmHg±SD) Pulmonary artery pressure (mmHg±SD)
<0.01
Systolic
44.9±13
57±16
Diastolic
18.9±6
22.8±7
28±8
34±9
19±8
21±8
Mean Pulmonary capillary wedge pressure; mean
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(mmHg±SD) Cardiac output (L/min±SD)
4.2±1.2
4.6±1.5
0.3
Cardiac index (L/min/m2±SD)
2.5±0.7
2.4±0.8
0.9
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*n=188; **n=199
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Table 3. Procedural characteristics and complications of patients undergoing transcatheter aortic valve replacement stratified by degree of PHTN undergoing transcatheter aortic valve replacement Pulmonary hypertension
Variable
Moderate /severe (n=243)
Transfemoral
179 (75%)
134 (78%)
Transapical
61 (25%)
37 (22%)
Valve type 167 (67%)
SAPIEN XT
41 (17%)
110 (65%)
CoreValve
0.3
0.6
31 (18%)
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SAPIEN
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Approach
p Value
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No/mild (n=172)
33 (13%)
24 (14%)
129 (52%)
88 (52%)
90 (36%)
66 (39%)
23 (9%)
12 (7%)
6 (2.4%)
4 (2.4%)
154 (63%)
112 (65%)
89 (37%)
61 (35%)
Fluoroscopy time (min. ± SD)
22±21
19±10
0.1
Contrast volume (ml ± SD)
123±79
118±60
0.5
227 (98%)
159 (98%)
0.7
Tamponade
1 (0.4%)
3 (1.7%)
0.3
Balloon post dilatation
19 (7.8%)
8 (4.7%)
0.2
Need for second valve
4 (1.8%)
1 (0.7%)
0.7
Valve size (mm) 23 26
29
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31 Sedation Conscious sedation
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General anesthesia
Successful valve delivery
0.8
0.7
Complications
AF, atrial fibrillation
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Table 4. In-hospital complications and outcome of patients undergoing transcatheter aortic valve replacement stratified by degree of pulmonary hypertension Pulmonary hypertension
Variable
Life threatening bleed
19 (7.9%)
18 (10.6%)
0.3
Myocardial infarction
1 (0.4%)
1 (0.6%)
1
Ischemic stroke
12 (5%)
0
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Hemorrhagic stroke
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Stroke
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Moderate /severe (n=243) 16 (9.4%)
p Value
Major vascular complications
No/mild (n=172) 23 (9.5%)
Acute kidney injury Any
10 (5.8%)
0.9
0.7
0
22 (10.1%)
26 (17.2%)
0.5
15 (6.9%)
18 (11.9%)
0.09
2 (0.9%)
2 (1.3%)
1
5 (2.3%)
6 (4%)
0.4
Mechanical ventilation post-procedure
44 (18.2%)
34 (20%)
0.6
Heart failure
43 (17.9%)
40 (23.4%)
0.2
14 (5.9%)
12 (7%)
0.6
24 (10%)
29 (17.1%)
0.04
Intensive care unit stay (days ± SD)
2.7±3.7
3.9±6.3
0.03
Post-procedure length of stay (days ± SD)
6.3±7.4
7.8±8
0.5
17 (7%)
23 (13.5%)
0.03
Stage 1 Stage 2
New pacemaker
Death
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Any infection
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Stage 3
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Table 5. Echocardiography of patients undergoing transcatheter aortic valve replacement stratified by degree of pulmonary hypertension 1-month
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1-year
Pulmonary hypertension No/mil Modera d te /severe 54±12 54±12 0.7
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Pulmonary hypertension No/mil Modera d te /severe 54±13 54±14 0.9
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Left ventricular ejection fraction (%±SD)
Pulmonary hypertension No/mil Modera d te /severe 53±17 53±14
In-hospital
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Baseline
Pulmonary hypertension No/mil Modera d te /severe 54±12 56±11 0.2
19 (8.6%)
29 (18.4%)
0.007
13 (6%)
15 (10.6%)
0.2
14 (8.6%)
13 (13.4%)
0.3
13 (10.2%)
4 (6.2%)
0.4
Moderate or severe tricuspid regurgitation
13 (5.9%)
38 (23%)
<0.001
19 (9%)
25 (18%)
0.01
10 (6.2%)
20 (21.3%)
<0.001
6 (5.5%)
6 (9.1%)
0.4
Moderate or severe RV dysfunction*
21 (19.8%)
29 (35.3%)
0.02
Moderate or severe RV dilatation
6 (2.6%)
12 (7.3%)
0.047
Systolic pulmonary artery pressure (mmHg±SD)
36±9
61±12
<0.001
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Moderate or severe mitral regurgitation
28 (32.5%)
0.6
21 (21%)
11 (18.6%)
0.7
15 (23%)
7 (18%)
0.6
7 (3.3%)
8 (5.6%)
0.4
5 (3.1%)
7 (7.7%)
0.13
2 (2%)
3 (5%)
0.4
42±13
50±19
<0.001
40±13
48±14
<0.001
40±11
48±18
0.003
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24 (22.9%)
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Table 6. Univariate and multivariable cox regression analysis for clinical predictors of 1-year mortality after transcatheter aortic valve replacement Univariate
Multivariate
Lower HR
Upper HR
P value
Moderate/severe pulmonary hypertension*
1.6
1.07
2.32
0.02
Age
1.00
0.98
1.03
0.984
Prior myocardial infarction
1.21
0.74
1.97
0.451
Baseline renal failure
1.44
0.96
2.17
0.076
Left ventricular ejection fraction
0.98
0.91
1.05
0.590
STS score
1.05
1.01
1.10
Moderate/Severe chronic lung disease
1.86
1.07
Peripheral vascular disease
1.34
0.89
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Lower HR
Upper HR
P value
1.16
2.87
0.010
1.00
0.97
1.03
0.948
1.27
0.69
2.35
0.446
1.16
0.71
1.89
0.556
1.00
0.92
1.09
0.946
0.007
1.04
0.99
1.09
0.122
3.21
0.026
1.79
0.98
3.28
0.059
2.00
0.158
1.23
0.77
1.99
0.386
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1.82
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* Versus no/mild pulmonary hypertension.
Hazard Ratio
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Hazard Ratio
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Figure 1
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Figure 2
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Log-Rank p= 0.02
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EP
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Figure 3
Mod/Severe
243
211
187
169
154
No/Mild
171
132
119
104
94
S0002-9149(15)00718-3
DOI:
10.1016/j.amjcard.2015.02.022
Reference:
AJC 20991
To appear in:
The American Journal of Cardiology
Received Date: 19 November 2014 Revised Date:
11 February 2015
Accepted Date: 13 February 2015
Please cite this article as: Barbash IM, Escarcega RO, Minha S’a, Ben-Dor I, Torguson R, Goldstein SA, Wang Z, Okubagzi P, Satler LF, Pichard AD, Waksman R, Prevalence and Impact of Pulmonary Hypertension on Patients With Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement, The American Journal of Cardiology (2015), doi: 10.1016/j.amjcard.2015.02.022. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Prevalence and Impact of Pulmonary Hypertension on Patients With Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement
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Israel M. Barbash, MD1,2; Ricardo O. Escarcega, MD1; Sa’ar Minha, MD1; Itsik Ben-Dor, MD1; Rebecca Torguson, MPH1; Steven A. Goldstein, MD1, Zuyue Wang, MD1, Petros Okubagzi,
1
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MD1; Lowell F. Satler, MD1; Augusto D. Pichard, MD1; Ron Waksman, MD1
Interventional Cardiology, MedStar Washington Hospital Center, Washington, DC; 2Leviev
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Heart Center, Sheba Medical Center, Tel Aviv University, Ramat-Gan, Israel
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Running title: Pulmonary Hypertension in TAVR Patients
Address for correspondence:
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Ron Waksman, MD
MedStar Washington Hospital Center
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110 Irving Street, NW, Suite 4B-1 Washington, DC20010 Tel: 202-877-2812
Fax: 202-877-2715
Email: [email protected]
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Abstract Limited amount of data suggests that aortic stenosis patients with pulmonary hypertension (PH) who undergo transcatheter aortic valve replacement (TAVR) experience decrease in PHTN post
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procedure. Inconsistent use of systolic pulmonary artery pressures (SPAP) cut-off values in prior studies limits our ability to draw meaningful conclusions regarding the prognostic role of PH in assessment of TAVR candidates. A total of 415 consecutive TAVR patients were included in the
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present study. Two groups were compared based on receiver-operator analysis for the best SPAP value to predict outcome, yielding two study groups of no/mild PH (≤50 mmHg) (n=172, 41%)
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versus moderate/severe PH (>50 mmHg) (n=243, 59%). Demographics and comorbidities were comparable between the two groups; however, right heart failure (35% versus 19.8%, p=0.02) and mitral regurgitation (18.4% versus 8.6%, p0.007) were more frequent among patients with moderate/severe PH. Procedural characteristics and complications were comparable between the
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groups. Although there was an early, overall decrease in SPAP post procedure, only 26% of moderate/severe PH patients experienced a significant decrease in SPAP (>10 mmHg). The 30day (14.5% versus 7.4%, p=0.02) and 1-year mortality (30.8% versus 21%, p=0.02) was higher
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among moderate/severe PH patients. In multivariate analysis, systolic pulmonary artery pressure and chronic lung disease were identified as independent predictors for mortality at 1-year. PH is
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a frequent comorbidity among patients with severe aortic stenosis undergoing TAVR. Significantly elevated pulmonary artery pressures at baseline may serve as a poor prognostic factor when performing preprocedural assessment of the patients. Keywords: pulmonary hypertension; aortic stenosis; transcatheter aortic valve replacement
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Introduction Historically, presence of pulmonary hypertension (PH) as a comorbidity in patients with severe aortic stenosis (AS) undergoing aortic valve surgery was considered as predictor for poor
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outcome.1-3 This increased risk was linked to hemodynamic challenges during the operative and postoperative period related to use of heart bypass and because of pulmonary vasculopathy and right heart failure.
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Transcatheter aortic valve replacement (TAVR) might offer several advantages for
patients with severe AS and PH because the procedure is performed without major hemodynamic
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changes that are typically associated with cardiopulmonary bypass and mechanical ventilation, which are not mandatory during TAVR. Limited amount of data suggests that AS patients with PH who undergo TAVR experience decrease in PH post procedure.4,5 However, patients with PH still suffer from worse prognosis as compared to patients without PH.4,6 Furthermore, data
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regarding the long-term hemodynamic effects of TAVR among PH patients are limited. Thus, the goals of the present study were to assess prevalence of PH among AS patients who undergo TAVR and to evaluate the long-term effects on pulmonary artery hemodynamics after TAVR.
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Methods
The study was approved by the Institutional Review Board of the MedStar Health
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Research Institute. Consecutive patients with symptomatic, severe AS who underwent TAVR from 2007 to 2013 at MedStar Washington Hospital Center were analyzed. Prespecified clinical and laboratory data were collected for all patients at baseline prior to the procedure, immediately post procedure, during the index hospitalization, and up to 1 year. Collected data included medical history, electrocardiogram, echocardiography studies, laboratory tests, and clinical outcomes.
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Patients underwent TAVR either with the balloon expandable Edwards SAPIEN or the SAPIEN-XT transcatheter heart valves (Edwards Lifesciences, Irvine, CA) or the selfexpandable Medtronic CoreValve (Medtronic, Minneapolis, MN) via the transfemoral,
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transapical, or direct aortic access routes as part of PARTNER, US, CoreValve studies or
standard clinical care, as previously described.7,8 Doppler tracings and 2-dimensional images were obtained from parasternal long- and short-axis, apical 4-chamber, and subcostal 4-chamber
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views. Transthoracic echocardiograms were reviewed to assess the pericardium, valvular
anatomy and function, and cardiac function. Tricuspid regurgitant flow was identified by color
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flow Doppler techniques. Continuous-wave Doppler measured maximum jet velocity. Right ventricular systolic pressure was estimated based on the modified Bernoulli equation and was considered equal to the systolic pulmonary artery pressure (SPAP) in the absence of right ventricular outflow obstruction. SPAP was calculated by adding trans-tricuspid pressure gradient
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to mean right atrial pressure estimated from inferior vena cava diameter and motion during respiration as follows: if the caliber of inferior vena cava was normal (1.5 to 2.5 cm), mean right atrial pressure was estimated to be 5 mmHg if there was complete collapse of the inferior vena
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cava during inspiration or was estimated to be 10 mmHg if the inferior vena cava collapse was >50%. If the inferior vena cava was dilated, mean right atrial pressure was estimated to be 15
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mmHg if the inferior vena cava collapsed by <50% with inspiration or was estimated to be 20 mmHg if there was no visible evidence of inferior vena cava collapse. Right ventricular function was assessed according to American Society of Echocardiography guidelines using the tricuspid annular plane systolic excursion (TAPSE) method.9 Right sided heart catheterization was performed with a 7Fr Swan-Ganz catheter in 199 of the patients (48%). Right atrial pressures (amplitude of a and v waves and mean pressure), right
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ventricular systolic and diastolic pressures, pulmonary artery pressures (systolic, diastolic, and mean), and pulmonary capillary wedge pressures (a and v waves and mean pressure) were measured. Cardiac output was determined by the thermodilution method.
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In-hospital outcomes were collected according to the Valve Academic Research
Consortium (VARC)-2 consensus document.10 Out-of-hospital adverse events were assessed up to 1 year by means of outpatient clinic visit or a standardized telephone interview. All suspected
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events were adjudicated by a blinded interventional cardiologist.
Statistical analysis was performed using SAS version 9.1 (SAS Institute Inc., Cary, NC).
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Continuous variables are expressed as mean ± standard deviation or median (25th-75th interquartile range) as appropriate according to variable distribution. Categorical variables are expressed as percentages. Student’s t test was used to compare continuous variables, and the chisquare test or Fisher’s exact test was used to compare categorical variables. Pearson Correlation
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Coefficients were used to assess correlation between pulmonary pressure measurements by echocardiography and right heart study.
Receiver-operating-characteristic curve was analyzed to assess the discriminatory ability
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of baseline SPAP to predict 30-day mortality and to determine the best cut-off value to predict this end point. For that purpose, the best prognosticator in receiver-operating-characteristic curve
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analysis was considered to be the value that gave the highest product of sensitivity and specificity for predicting 30-day mortality. Survival rates up to 1 year were computed using the Kaplan-Meier method, and
differences in parameters were assessed using the log-rank test. A Cox proportional hazards analysis was performed to assess the independent influence of baseline PH on 1-year mortality in each group. Variables of the baseline and clinical characteristics associated with the outcome of
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interest were adjusted in the multivariable analysis: age, prior myocardial infarction, chronic renal failure, left ventricular ejection fraction, Society of Thoracic Surgeons (STS) score, chronic lung disease, and peripheral vascular disease. A p value <0.05 was considered statistically
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significant.
RESULTS
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A total of 415 patients were included in the present study. The average age was 84±8 years, and 47% of the patients were male. The study population comprised a high-risk patient
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population with an average STS risk score of 10±5 and Logistic euroSCORE of 30±24. A large proportion of the patients had significant comorbidities, such as diabetes (31%), chronic lung disease (31%), renal insufficiency (55%), prior coronary bypass surgery (31%), and left ventricular ejection fraction (LVEF) lower than 40% (23%).
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By receiver-operator curve analysis, baseline SPAP demonstrated intermediate prognostic power as a single parameter to predict 30-day mortality (AUC 0.62) (Figure 1). Based on these findings, a SPAP cut-off value of 50 mmHg was selected to predict 30-day mortality for
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TAVR patients, yielding sensitivity and specificity of 57% and 60%, respectively. This cut-off value was used to determine the study groups of no/mild PH (≤50 mmHg) versus
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moderate/severe PH (>50 mmHg). The majority of the patients were included in the moderate/severe PH group (243 of 415, 59% of the entire cohort). Overall, as shown in Table 1, baseline characteristics and comorbidities of patients in
both groups were comparable between patients with no/mild versus moderate/severe PH. Average SPAP was significantly higher in moderate/severe PH group (61±12 mmHg) as compared to no/mild PH group (36±9 mmHg, p<0.001). This finding was corroborated also by
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pre-TAVR right heart catheterization with intermediate correlation to the echocardiographic assessment of SPAP (r=0.46) (Table 2). Baseline echocardiographic evaluation showed that the average left ventricular function of the patients is preserved with only 16% and 12% of the
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patients that have LVEF lower than 30% in both groups (Table 2). Conversely, patients with moderate/severe PH had higher rates of concomitant valve disease and right ventricular failure. Similarly, rates of moderate/severe mitral regurgitation and moderate/severe tricuspid
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regurgitation were significantly higher and nearly twice as frequent as right ventricular dysfunction (Table 2).
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The procedural characteristics did not differ significantly between patients with no/mild and moderate/severe PH (Table 3). There was a large majority for the transfemoral access and for the use of the SAPIEN transcatheter heart valve . Nearly two-thirds of the patients underwent the procedure with conscious sedation, thus avoiding the need for mechanical ventilation. VARC
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in-hospital complications were mostly comparable between the groups; however, acute kidney injury rates tended to be higher (nearly double) among patients with moderate/severe PH as compared to patients with no/mild PH, although mostly driven by the grade-1 acute kidney
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injury rates. Interestingly, in-hospital infection rates, typically respiratory, were higher among moderate/severe PH patients. Finally, moderate/severe PH patients had longer stay in intensive
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care; however this did not translate to a longer hospitalization period (Table 4). As demonstrated in Figure 2, the elevated SPAP in the moderate/severe PH group tended
to decrease after TAVR procedure. Interestingly, the decrease in SPAP occurred early, during the index hospitalization, and was maintained up to 1 year follow-up. However, SPAP values remained higher than the SPAP values among the patients in the no/mild PH group throughout follow-up and did not return at any stage to normal values (Figure 2). Subgroup analysis of the
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moderate/severe PH group (n=243) according to whether SPAP decreased early after procedure (defined as a decrease of >= 10 mmHg) showed that although there is an early decrease in SPAP after procedure, the majority (n=180, 74%) of the patients do not experience a significant
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improvement (that is, >= 10 mmHg). Furthermore, outcome was not different for the patients who experienced decrease in SPAP compared to those who did not with 7.4% versus 8% 30-day mortality (p=1) and 22.2% versus 28% 1-year mortality (p=0.56), respectively.
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The prevalence of moderate or severe mitral regurgitation decreased from 18.4% at
baseline to 6.2% at 1-year follow-up. Similar trends were observed also in the prevalence of
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moderate or severe tricuspid regurgitation (from 23% to 9.1%) and moderate or severe right ventricular dysfunction (from 35% to 18% at 1 year) (Table 5).
Despite the improvement in the post-procedure echocardiographic parameters (Table 5, Figure 2), the early and late mortality of patients with moderate/severe PH was higher than
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patients with no/mild PH. In-hospital mortality (Table 4) is nearly 2-fold higher (13.5% versus 7%, p=0.03), and the mortality difference is maintained at 30-days (14.5% versus 7.4%, p=0.02) and up to 1-year follow-up (30.8% versus 21%, p=0.02) (Figure 3). As shown in Table 6, in uni-
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variate analysis moderate/severe PH, the STS score and moderate/severe lung disease were associated with poor 1 year outcome. Similarly, among the sub-group of patients that underwent
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right heart study, pulmonary vascular resistance (hazard ratio (HR) of 1.1, 95% confidence interval (CI) of 1.01-1.2) but not diastolic pulmonary vascular pressure gradient (HR of 0.99, 95% CI of 0.93-1.06) were associated with poor outcome. By multivariable analysis, baseline SPAP and moderate or severe lung disease were independent predictors of poor outcome (Table 6).
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DISCUSSION The main findings of the present study that aimed to assess the impact of PH on TAVR results indicate that a large amount of the patients have concomitant PH. This study shows that
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overall SPAP decreases after TAVR but does not normalize. Finally, similar to cardiac surgery, the presence of PH is indeed an independent predictor of poor short- and long-term outcome after TAVR; however, by itself, it has low power to predict poor outcome as indicated by the
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intermediate sensitivity and specificity.
PH is frequently associated with AS. PH rates among AS patients were reported with
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prevalence of up to half of the patients.11-13 More recently, Ben-Dor, et al. reported that nearly 70% of TAVR candidates have concomitant PH.14 Several studies have shown that the prognosis of these patients is poor if left untreated.13-15 Conversely, the prognostic role of baseline SPAP before aortic valve surgery is unclear.3,13,15 There is also a large body of evidence to suggest that
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patients with PH and right ventricular dysfunction are particularly at a higher risk for adverse events after cardiac surgery.16
Similar ambiguity is present with regard to the limited number of studies that analyzed
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the pre-procedural effect of PH on AS patients who undergo TAVR. These studies suffer from one major limitation—the inconsistent use of SPAP cut-off values for grouping the patients.2,15
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This inconsistency limits our ability to draw meaningful conclusions from these studies. In the present study, we attempted to assess the independent prognostic power of SPAP to predict patient outcome. Although SPAP had intermediate power to determine prognosis, we based our analysis on the optimal cut-off value as determined by specificity/sensitivity analysis. Our study indicates that patients with significant PH at baseline do not have higher incidence of procedural complications. However, the mortality of patients with significant PH is
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higher than patients with no/mild PH. This mortality hazard is present early after the procedure (that is, in-hospital mortality) and continues up to 1- year follow-up. Although one recent registry indicated that PH is associated with late but not early mortality hazard, the findings from
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the present analysis as well as others2,4 suggest that the mortality hazard for these patients begins early after the procedure. A possible explanation for the early mortality after TAVR might be related to factors that are not directly related to the procedure itself but to other complications,
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such as higher in-hospital infection rates and sepsis as shown in this and other 2 analyses and reflected by the need for prolonged stay in intensive care as shown in the present study.
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Similarly, the long-term mortality hazard is probably related to the fact that a large proportion of the patients do not decrease significantly the SPAP, and perhaps PH is associated with other noncardiac factors that are responsible for late mortality.
Several hemodynamic patterns of SPAP that were identified in the present study should
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be emphasized: Median SPAP tended to decrease from baseline to post-procedure (60 to 48 mmHg). Second, the change in SPAP occurred early after the procedure, and the effect was maintained in the long run. These findings might be explained by the documented improvement
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in mitral regurgitation post procedure in this (18.4% at baseline to 10.6% post-procedure moderate/severe mitral regurgitation) and other studies.17 A similar trend of improvement in
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tricuspid regurgitation and right ventricular function (Table 5) in long term follow up was also documented. As the majority of the patients had normal or near normal left ventricular function at baseline, these changes might be related to the decrease in diastolic pressures after the procedure, as was also shown in surgical aortic valve studies. 18 However, despite these encouraging data, only a minority of the patients (26%) experienced a significant (>10 mmHg) decrease in SPAP. Previously published data suggested
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that post-operative SPAP was an independent predictor of improved outcome.4,15 Interpretation of the results from this study in light of this previously published data indicates that the lack of extensive improvement in SPAP following TAVR may explain the poor prognosis of these
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patients in the early and late follow-up. Alternatively, the higher mortality among patients with persistent PH may be related to residual paravalvular leak.4 A potential approach that might be considered in patients with severe PH is to perform balloon aortic valvuloplasty and to assess
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response to the procedure. It is plausible the patients who will experience decrease in PH with improvement in right ventricular function will also respond favorably to the TAVR procedure.
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There are several limitations to this study. This study was a post hoc analysis and, as such, is subject to the limitations of retrospective analyses; results may possibly have been affected by unknown confounders. In the present study, echocardiography was used as the main technique for assessment of SPAP. Although right ventricular systolic pressure is a calculated
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value, use of echocardiography allowed for a consistent measurement that we could follow over time, allowing high rates of echocardiographic follow-up. Furthermore, although SPAP from right heart catheterization was available for only about half of the patients, we, as well as data
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from prior studies,19 found good correlation between the right heart catheterization and echo measurements among this sample of patients. The cutoff of SPAP = 50 mmHg used for grouping
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the patients in this study was based on ROC analysis, however, the discriminative power was relatively low and other SPAP values may be proven to be as good as the one used in this paper. Additionally, the higher rates of in-hospital infections found among PH patients could not be further assessed due to lack of data regarding etiology of infection.
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2. Roselli EE, Abdel Azim A, Houghtaling PL, Jaber WA, Blackstone EH. Pulmonary hypertension is associated with worse early and late outcomes after aortic valve replacement: Implications for transcatheter aortic valve replacement. J Thorac Cardiovasc Surg 2012;144:1067-1074 e1062.
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19. Janda S, Shahidi N, Gin K, Swiston J. Diagnostic accuracy of echocardiography for
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Figure legend: Figure 1. Receiver-operator curve for predictive power of systolic pulmonary artery pressure to predict 30-
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day outcome among patients undergoing transcatheter aortic valve replacement.
Figure 2.
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1-year follow-up. PHTN=pulmonary hypertension.
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Change in median and range of pulmonary artery systolic pressure over time, from baseline up to
Figure 3.
Kaplan-Meier survival estimate of patients with no/mild versus moderate/severe pulmonary
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hypertension following transcatheter aortic valve replacement. PHTN=pulmonary hypertension.
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Table 1. Baseline characteristics of patients with no/mild versus moderate/severe pulmonary hypertension undergoing transcatheter aortic valve replacement Pulmonary hypertension No/mild (n=172)
p Value
80 (47%)
0.8
10.2±5
0.6
28.3±24.9
0.4
218 (94%)
152 (92%)
0.5
69 (30%)
55 (33%)
0.5
73 (31%)
53 (33%)
0.8
119 (53%)
95 (58%)
0.3
4 (1.8%)
4 (2.4%)
0.7
86 (38%)
51 (32%)
0.3
History of coronary artery disease*
137 (78%)
95 (75%)
0.5
Prior myocardial infarction
48 (21%)
23 (14%)
0.09
Prior percutaneous coronary intervention
76 (33%)
44 (27%)
0.2
Prior coronary artery bypass surgery
76 (33%)
48 (29%)
0.5
Prior valve surgery
5 (2.8%)
6 (4.4%)
0.5
Atrial fibrillation
92 (40%)
73 (44%)
0.4
Prior stroke or transient ischemic attack
43 (19%)
28 (18%)
0.7
42 (23%)
22 (18%)
0.3
Age (years±SD)
83±8
Men
116 (48%)
Risk assessment 9.9±4.5
Log EuroSCORE risk (%±SD)
31±23.6
Systemic hypertension Diabetes mellitus Chronic obstructive lung disease Renal failure
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Peripheral vascular disease
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Hemodialysis
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Co-morbidities
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Society of Thoracic Surgeons score risk (%±SD)
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Moderate /severe (n=243) 84±8
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Variable
Permanent pacemaker/ implantable cardioverter defibrillator
*Defined as any coronary artery stenosis ≥50%, prior PCI or CABG
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Table 2. Baseline echocardiography and right sided heart catheterization of patients with no/mild versus moderate/severe pulmonary hypertension undergoing transcatheter aortic valve replacement Pulmonary hypertension
Variable
Echocardiogrpahy Left ventricular ejection fraction (%±SD)
53±17
Moderate /severe (n=243)
p Value
53±14
0.9
21 (12%)
0.3
0.65±0.1
0.5
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No/mild (n=172)
38 (16%)
Aortic valve area (cm2±SD)
0.65±0.1
Mean gradient (mmHg±SD)
48±13
48±13
0.9
Peak velocity
4.4±0.6
4.4±0.6
0.7
1.3±0.2
1.3±0.2
0.6
1.2±0.2
1.2±0.2
0.5
Left ventricular end systolic diameter (cm±SD)
3.1±0.9
3.2±0.9
0.2
Left ventricular end diastolic diameter (cm±SD)
4.4±0.8
4.4±0.8
1.0
19 (8.6%)
29 (18.4%)
0.007
Moderate or severe tricuspid regurgitation
13 (5.9%)
38 (23%)
<0.001
Moderate or severe RV dysfunction*
21 (19.8%)
29 (35.3%)
0.02
6 (2.6%)
12 (7.3%)
0.047
4.5±0.7
4.7±0.8
0.04
36±9
61±12
<0.001
8.9±7.9
8.9±5.5
1
Septal thickness (cm±SD) Posterior wall thickness (cm±SD)
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Moderate or severe mitral regurgitation
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Left ventricular ejection fraction <30%
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Moderate or severe RV dilatation Left atrial diameter (cm±SD)
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Systolic pulmonary artery pressure (mmHg±SD) Right sided heart catheterization** Right atrial pressure; mean (mmHg±SD) Pulmonary artery pressure (mmHg±SD)
<0.01
Systolic
44.9±13
57±16
Diastolic
18.9±6
22.8±7
28±8
34±9
19±8
21±8
Mean Pulmonary capillary wedge pressure; mean
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(mmHg±SD) Cardiac output (L/min±SD)
4.2±1.2
4.6±1.5
0.3
Cardiac index (L/min/m2±SD)
2.5±0.7
2.4±0.8
0.9
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*n=188; **n=199
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Table 3. Procedural characteristics and complications of patients undergoing transcatheter aortic valve replacement stratified by degree of PHTN undergoing transcatheter aortic valve replacement Pulmonary hypertension
Variable
Moderate /severe (n=243)
Transfemoral
179 (75%)
134 (78%)
Transapical
61 (25%)
37 (22%)
Valve type 167 (67%)
SAPIEN XT
41 (17%)
110 (65%)
CoreValve
0.3
0.6
31 (18%)
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Approach
p Value
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No/mild (n=172)
33 (13%)
24 (14%)
129 (52%)
88 (52%)
90 (36%)
66 (39%)
23 (9%)
12 (7%)
6 (2.4%)
4 (2.4%)
154 (63%)
112 (65%)
89 (37%)
61 (35%)
Fluoroscopy time (min. ± SD)
22±21
19±10
0.1
Contrast volume (ml ± SD)
123±79
118±60
0.5
227 (98%)
159 (98%)
0.7
Tamponade
1 (0.4%)
3 (1.7%)
0.3
Balloon post dilatation
19 (7.8%)
8 (4.7%)
0.2
Need for second valve
4 (1.8%)
1 (0.7%)
0.7
Valve size (mm) 23 26
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31 Sedation Conscious sedation
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General anesthesia
Successful valve delivery
0.8
0.7
Complications
AF, atrial fibrillation
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Table 4. In-hospital complications and outcome of patients undergoing transcatheter aortic valve replacement stratified by degree of pulmonary hypertension Pulmonary hypertension
Variable
Life threatening bleed
19 (7.9%)
18 (10.6%)
0.3
Myocardial infarction
1 (0.4%)
1 (0.6%)
1
Ischemic stroke
12 (5%)
0
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Hemorrhagic stroke
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Stroke
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Moderate /severe (n=243) 16 (9.4%)
p Value
Major vascular complications
No/mild (n=172) 23 (9.5%)
Acute kidney injury Any
10 (5.8%)
0.9
0.7
0
22 (10.1%)
26 (17.2%)
0.5
15 (6.9%)
18 (11.9%)
0.09
2 (0.9%)
2 (1.3%)
1
5 (2.3%)
6 (4%)
0.4
Mechanical ventilation post-procedure
44 (18.2%)
34 (20%)
0.6
Heart failure
43 (17.9%)
40 (23.4%)
0.2
14 (5.9%)
12 (7%)
0.6
24 (10%)
29 (17.1%)
0.04
Intensive care unit stay (days ± SD)
2.7±3.7
3.9±6.3
0.03
Post-procedure length of stay (days ± SD)
6.3±7.4
7.8±8
0.5
17 (7%)
23 (13.5%)
0.03
Stage 1 Stage 2
New pacemaker
Death
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Any infection
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Table 5. Echocardiography of patients undergoing transcatheter aortic valve replacement stratified by degree of pulmonary hypertension 1-month
0.9
1-year
Pulmonary hypertension No/mil Modera d te /severe 54±12 54±12 0.7
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Pulmonary hypertension No/mil Modera d te /severe 54±13 54±14 0.9
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Left ventricular ejection fraction (%±SD)
Pulmonary hypertension No/mil Modera d te /severe 53±17 53±14
In-hospital
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Baseline
Pulmonary hypertension No/mil Modera d te /severe 54±12 56±11 0.2
19 (8.6%)
29 (18.4%)
0.007
13 (6%)
15 (10.6%)
0.2
14 (8.6%)
13 (13.4%)
0.3
13 (10.2%)
4 (6.2%)
0.4
Moderate or severe tricuspid regurgitation
13 (5.9%)
38 (23%)
<0.001
19 (9%)
25 (18%)
0.01
10 (6.2%)
20 (21.3%)
<0.001
6 (5.5%)
6 (9.1%)
0.4
Moderate or severe RV dysfunction*
21 (19.8%)
29 (35.3%)
0.02
Moderate or severe RV dilatation
6 (2.6%)
12 (7.3%)
0.047
Systolic pulmonary artery pressure (mmHg±SD)
36±9
61±12
<0.001
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Moderate or severe mitral regurgitation
28 (32.5%)
0.6
21 (21%)
11 (18.6%)
0.7
15 (23%)
7 (18%)
0.6
7 (3.3%)
8 (5.6%)
0.4
5 (3.1%)
7 (7.7%)
0.13
2 (2%)
3 (5%)
0.4
42±13
50±19
<0.001
40±13
48±14
<0.001
40±11
48±18
0.003
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Table 6. Univariate and multivariable cox regression analysis for clinical predictors of 1-year mortality after transcatheter aortic valve replacement Univariate
Multivariate
Lower HR
Upper HR
P value
Moderate/severe pulmonary hypertension*
1.6
1.07
2.32
0.02
Age
1.00
0.98
1.03
0.984
Prior myocardial infarction
1.21
0.74
1.97
0.451
Baseline renal failure
1.44
0.96
2.17
0.076
Left ventricular ejection fraction
0.98
0.91
1.05
0.590
STS score
1.05
1.01
1.10
Moderate/Severe chronic lung disease
1.86
1.07
Peripheral vascular disease
1.34
0.89
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Lower HR
Upper HR
P value
1.16
2.87
0.010
1.00
0.97
1.03
0.948
1.27
0.69
2.35
0.446
1.16
0.71
1.89
0.556
1.00
0.92
1.09
0.946
0.007
1.04
0.99
1.09
0.122
3.21
0.026
1.79
0.98
3.28
0.059
2.00
0.158
1.23
0.77
1.99
0.386
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1.82
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* Versus no/mild pulmonary hypertension.
Hazard Ratio
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Hazard Ratio
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Figure 2
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Log-Rank p= 0.02
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Figure 3
Mod/Severe
243
211
187
169
154
No/Mild
171
132
119
104
94