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Figure.
Kaplan-Meier Estimates of 30-Day to 1-Year All-Cause Mortality Among Groups A, B, and C
Kaplan-Meier Estimates of 30-Day to 1-Year All-Cause Mortality Among Groups A, B, and C

The overall log-rank P value for groups A (improvement in renal function), B (no change in renal function), and C (worsening of renal function) was .01. The log-rank P value for group A vs B was .22 (hazard ratio, 0.79; 95% CI, 0.54-1.16). The log-rank P value for group A vs C was .003 (hazard ratio, 0.55; 95% CI, 0.37-0.82). The log-rank P value for group B vs C was .07 (hazard ratio, 0.70; 95% CI, 0.47-1.03). Pairwise comparisons are also shown.

Table 1.  
Baseline and Procedural Characteristics
Baseline and Procedural Characteristics
Table 2.  
Landmark Analysis 30-Day to 1-Year Clinical Outcomesa
Landmark Analysis 30-Day to 1-Year Clinical Outcomesa
Table 3.  
Multivariable Predictors of Improved and Worsening eGFR After TAVRa,b,c
Multivariable Predictors of Improved and Worsening eGFR After TAVRa,b,c
Table 4.  
Multivariable Predictors of 30-Day to 1-Year All-Cause Mortality
Multivariable Predictors of 30-Day to 1-Year All-Cause Mortality
1.
Leon  MB, Smith  CR, Mack  M,  et al; PARTNER Trial Investigators.  Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery.  N Engl J Med. 2010;363(17):1597-1607.PubMedGoogle ScholarCrossref
2.
Smith  CR, Leon  MB, Mack  MJ,  et al; PARTNER Trial Investigators.  Transcatheter versus surgical aortic-valve replacement in high-risk patients.  N Engl J Med. 2011;364(23):2187-2198.PubMedGoogle ScholarCrossref
3.
Adams  DH, Popma  JJ, Reardon  MJ,  et al; U.S. CoreValve Clinical Investigators.  Transcatheter aortic-valve replacement with a self-expanding prosthesis.  N Engl J Med. 2014;370(19):1790-1798.PubMedGoogle ScholarCrossref
4.
Popma  JJ, Adams  DH, Reardon  MJ,  et al; CoreValve United States Clinical Investigators.  Transcatheter aortic valve replacement using a self-expanding bioprosthesis in patients with severe aortic stenosis at extreme risk for surgery.  J Am Coll Cardiol. 2014;63(19):1972-1981.PubMedGoogle ScholarCrossref
5.
Leon  MB, Smith  CR, Mack  MJ,  et al; PARTNER 2 Investigators.  Transcatheter or surgical aortic-valve replacement in intermediate-risk patients.  N Engl J Med. 2016;374(17):1609-1620.PubMedGoogle ScholarCrossref
6.
Thourani  VH, Kodali  S, Makkar  RR,  et al.  Transcatheter aortic valve replacement versus surgical valve replacement in intermediate-risk patients: a propensity score analysis.  Lancet. 2016;387(10034):2218-2225.PubMedGoogle ScholarCrossref
7.
Ferro  CJ, Chue  CD, de Belder  MA,  et al; UK TAVI Steering Group; National Institute for Cardiovascular Outcomes Research.  Impact of renal function on survival after transcatheter aortic valve implantation (TAVI): an analysis of the UK TAVI registry.  Heart. 2015;101(7):546-552.PubMedGoogle ScholarCrossref
8.
Oguri  A, Yamamoto  M, Mouillet  G,  et al; FRANCE 2 Registry investigators.  Impact of chronic kidney disease on the outcomes of transcatheter aortic valve implantation: results from the FRANCE 2 registry.  EuroIntervention. 2015;10(9):e1-e9.PubMedGoogle ScholarCrossref
9.
Yamamoto  M, Hayashida  K, Mouillet  G,  et al.  Prognostic value of chronic kidney disease after transcatheter aortic valve implantation.  J Am Coll Cardiol. 2013;62(10):869-877.PubMedGoogle ScholarCrossref
10.
Dumonteil  N, van der Boon  RM, Tchetche  D,  et al.  Impact of preoperative chronic kidney disease on short- and long-term outcomes after transcatheter aortic valve implantation: a Pooled-RotterdAm-Milano-Toulouse in collaboration Plus (PRAGMATIC-Plus) initiative substudy.  Am Heart J. 2013;165(5):752-760.PubMedGoogle ScholarCrossref
11.
Chen  C, Zhao  ZG, Liao  YB,  et al.  Impact of renal dysfunction on mid-term outcome after transcatheter aortic valve implantation: a systematic review and meta-analysis.  PLoS One. 2015;10(3):e0119817.PubMedGoogle ScholarCrossref
12.
Sinning  JM, Ghanem  A, Steinhäuser  H,  et al.  Renal function as predictor of mortality in patients after percutaneous transcatheter aortic valve implantation.  JACC Cardiovasc Interv. 2010;3(11):1141-1149.PubMedGoogle ScholarCrossref
13.
Muñoz-García  AJ, Muñoz-García  E, Jiménez-Navarro  MF,  et al; RIC Investigators.  Clinical impact of acute kidney injury on short- and long-term outcomes after transcatheter aortic valve implantation with the CoreValve prosthesis.  J Cardiol. 2015;66(1):46-49.PubMedGoogle ScholarCrossref
14.
Bagur  R, Webb  JG, Nietlispach  F,  et al.  Acute kidney injury following transcatheter aortic valve implantation: predictive factors, prognostic value, and comparison with surgical aortic valve replacement.  Eur Heart J. 2010;31(7):865-874.PubMedGoogle ScholarCrossref
15.
Nuis  RJ, van Mieghem  NM, van der Boon  RM,  et al.  Effect of experience on results of transcatheter aortic valve implantation using a Medtronic CoreValve System.  Am J Cardiol. 2011;107(12):1824-1829.PubMedGoogle ScholarCrossref
16.
Elhmidi  Y, Bleiziffer  S, Piazza  N,  et al.  Incidence and predictors of acute kidney injury in patients undergoing transcatheter aortic valve implantation.  Am Heart J. 2011;161(4):735-739.PubMedGoogle ScholarCrossref
17.
Aregger  F, Wenaweser  P, Hellige  GJ,  et al.  Risk of acute kidney injury in patients with severe aortic valve stenosis undergoing transcatheter valve replacement.  Nephrol Dial Transplant. 2009;24(7):2175-2179.PubMedGoogle ScholarCrossref
18.
Kong  WY, Yong  G, Irish  A.  Incidence, risk factors and prognosis of acute kidney injury after transcatheter aortic valve implantation.  Nephrology (Carlton). 2012;17(5):445-451.PubMedGoogle ScholarCrossref
19.
Barbash  IM, Ben-Dor  I, Dvir  D,  et al.  Incidence and predictors of acute kidney injury after transcatheter aortic valve replacement.  Am Heart J. 2012;163(6):1031-1036.PubMedGoogle ScholarCrossref
20.
Thourani  VH, Keeling  WB, Sarin  EL,  et al.  Impact of preoperative renal dysfunction on long-term survival for patients undergoing aortic valve replacement.  Ann Thorac Surg. 2011;91(6):1798-1806.PubMedGoogle ScholarCrossref
21.
Iung  B, Baron  G, Butchart  EG,  et al.  A prospective survey of patients with valvular heart disease in Europe: the Euro Heart Survey on Valvular Heart Disease.  Eur Heart J. 2003;24(13):1231-1243.PubMedGoogle ScholarCrossref
22.
Ewe  SH, Ajmone Marsan  N, Pepi  M,  et al.  Impact of left ventricular systolic function on clinical and echocardiographic outcomes following transcatheter aortic valve implantation for severe aortic stenosis.  Am Heart J. 2010;160(6):1113-1120.PubMedGoogle ScholarCrossref
23.
Saia  F, Ciuca  C, Taglieri  N,  et al.  Acute kidney injury following transcatheter aortic valve implantation: incidence, predictors and clinical outcome.  Int J Cardiol. 2013;168(2):1034-1040.PubMedGoogle ScholarCrossref
24.
Leon  MB, Piazza  N, Nikolsky  E,  et al.  Standardized endpoint definitions for transcatheter aortic valve implantation clinical trials: a consensus report from the Valve Academic Research Consortium.  J Am Coll Cardiol. 2011;57(3):253-269.PubMedGoogle ScholarCrossref
25.
Blair  JE, Brummel  K, Friedman  JL,  et al.  Inhospital and post-discharge changes in renal function after transcatheter aortic valve replacement.  Am J Cardiol. 2016;117(4):633-639.PubMedGoogle ScholarCrossref
26.
Barbanti  M, Latib  A, Sgroi  C,  et al.  Acute kidney injury after transcatheter aortic valve implantation with self-expanding CoreValve prosthesis: results from a large multicentre Italian research project.  EuroIntervention. 2014;10(1):133-140.PubMedGoogle ScholarCrossref
27.
Schnabel  RB, Seiffert  M, Wilde  S,  et al.  Kidney injury and mortality after transcatheter aortic valve implantation in a routine clinical cohort.  Catheter Cardiovasc Interv. 2015;85(3):440-447.PubMedGoogle ScholarCrossref
28.
Williams  M, Kodali  SK, Hahn  RT,  et al.  Sex-related differences in outcomes after transcatheter or surgical aortic valve replacement in patients with severe aortic stenosis: Insights from the PARTNER Trial (Placement of Aortic Transcatheter Valve).  J Am Coll Cardiol. 2014;63(15):1522-1528.PubMedGoogle ScholarCrossref
29.
Barbanti  M, Gulino  S, Capranzano  P,  et al.  Acute kidney injury with the RenalGuard System in patients undergoing transcatheter aortic valve replacement: the PROTECT-TAVI Trial (PROphylactic effecT of furosEmide-induCed diuresis with matched isotonic intravenous hydraTion in Transcatheter Aortic Valve Implantation).  JACC Cardiovasc Interv. 2015;8(12):1595-1604.PubMedGoogle ScholarCrossref
Original Investigation
July 2017

Association of Transcatheter Aortic Valve Replacement With 30-Day Renal Function and 1-Year Outcomes Among Patients Presenting With Compromised Baseline Renal Function: Experience From the PARTNER 1 Trial and Registry

Author Affiliations
  • 1Columbia University Division of Cardiology, Mount Sinai Medical Center, Miami Beach, Florida
  • 2Columbia University Medical Center/New York Presbyterian Hospital, New York
  • 3Emory University, Atlanta, Georgia
  • 4Cardiovascular Research Foundation, New York, New York
  • 5Bluhm Cardiovascular Institute, Northwestern University, Chicago, Illinois
  • 6Baylor Scott & White Health, Plano, Texas
  • 7Cleveland Clinic, Cleveland, Ohio
JAMA Cardiol. 2017;2(7):742-749. doi:10.1001/jamacardio.2017.1220
Key Points

Question  What is the effect of transcatheter aortic valve replacement on renal function and clinical outcomes among high-surgical risk or inoperable patients with severe aortic stenosis and baseline impaired renal function?

Findings  In this substudy of a clinical trial, baseline renal dysfunction was present in 72% of patients, 42% of whom experienced an improvement in renal function and 24% whose renal function worsened after transcatheter aortic valve replacement, and at 1 year, a worsening estimated glomerular filtration rate (eGFR) was associated with an increased mortality trend compared with those with an unchanged eGFR. Significant predictors of an improved eGFR were being female and nonsmoking; predictors of worsening eGFR were left ventricle mass, smoking, and age; and predictors of 1-year mortality were left ventricular ejection fraction, baseline eGFR, and worsening eGFR.

Meaning  Baseline renal dysfunction was frequent among patients who underwent a transcatheter aortic valve replacement and those with worsening renal function after the procedure trended toward increased mortality.

Abstract

Importance  The frequency of baseline renal impairment among high-risk and inoperable patients with severe aortic stenosis undergoing a transcatheter aortic valve replacement (TAVR) and the effect of TAVR on subsequent renal function are, to our knowledge, unknown.

Objective  To determine the effect of TAVR among patients with baseline renal impairment.

Design, Setting, and Participants  This substudy of patients with baseline renal impairment (estimated glomerular filtration rate [eGFR] ≤ 60 mL/min) and paired baseline and 30-day measures of renal function undergoing TAVR in the PARTNER 1 trial and continued access registries was conducted in 25 centers in the United States and Canada.

Main Outcomes and Measures  Patients were categorized with improved eGFR (30-day follow-up eGFR≥10% higher than baseline pre-TAVR), worsened eGFR (≥10% lower), or no change in renal function (neither). Baseline characteristics, 30-day to 1-year all-cause mortality, and repeat hospitalization were compared. Multivariable models were constructed to identify predictors of 1-year mortality and of improvement/worsening in eGFR.

Results  Of the 821 participants, 401 (48.8%) were women and the mean (SD) age for participants with improved, unchanged, or worsening eGFR was 84.90 (6.91) years, 84.37 (7.13) years, and 85.39 (6.40) years, respectively. The eGFR was 60 mL/min or lower among 821 patients (72%), of whom 345 (42%) improved, 196 (24%) worsened, and 280 (34%) had no change at 30 days. There were no differences in baseline age, body mass index, diabetes, chronic obstructive pulmonary disease, coronary artery disease, peripheral arterial disease, hypertension, pulmonary hypertension, renal or liver disease, New York Heart Association III/IV symptoms, transaortic gradient, left ventricular ejection fraction, or procedural characteristics. The group with improved eGFR had more women, nonsmokers, and a lower cardiac index. Those with worsening eGFR had a higher median Society of Thoracic Surgeons score and left ventricle mass. From 30 days to 1 year, those with improved eGFR had no difference in mortality or repeat hospitalization. Those with worsening eGFR had increased mortality (25.5% vs 19.1%, P = .07) but no significant increases in repeat hospitalization or dialysis. Predictors of improved eGFR were being female (odds ratio [OR], 1.38; 95% CI, 1.03-1.85; P = .03) and nonsmoking status (OR, 1.49; 95% CI, 1.11-1.01; P = .01); predictors of worsening eGFR were baseline left ventricle mass (OR, 1.00; 95% CI, 1.00-1.01; P = .01), smoking (OR, 1.51; 95% CI, 1.06-2.14; P = .02), and age (OR, 1.03; 95% CI, 1.00-1.05; P = .05); and predictors of 1-year mortality were baseline left ventricular ejection fraction (OR, 0.98; 95% CI, 0.97-0.99; P = .003), baseline eGFR (OR, 0.98; 95% CI, 0.96-0.99; P < .001), and worsening eGFR vs no change in eGFR (OR, 1.51; 95% CI, 1.02-2.24; P = .04).

Conclusions and Relevance  Baseline renal impairment was frequent among patients who underwent TAVR. While improved eGFR did not improve 1-year outcomes, worsening eGFR was associated with increased mortality.

Trial Registration  clinicaltrials.gov Identifier: NCT00530894

Introduction

Transcatheter aortic valve replacement (TAVR) is an effective therapy for intermediate- to high-surgical risk and inoperable patients with severe symptomatic aortic stenosis.1-6 Patients undergoing TAVR often have an elevated burden of comorbidities, and 29% to 34% of those in large multicenter registries experience moderate to severe baseline renal dysfunction.7,8

It has previously been shown that severe baseline renal dysfunction predicts increased 1-year rates of morbidity and mortality among patients undergoing TAVR.9-12 Furthermore, previous studies have reported acute kidney injury among 12% to 57% of patients undergoing TAVR (the risk being higher among those with impaired baseline renal function),13 and this is associated with a 2-to-6-fold increase in short- and long-term mortality rates.14-19 Therefore, concern has been raised about offering TAVR as a treatment option to these patients. However, these patients also have an increased risk of mortality and morbidity after surgical aortic valve replacement, and 1 in 3 patients with severe valvular heart disease are refused the opportunity to undergo surgery based on the severity of their baseline renal disease.20,21

The causes of renal impairment among patients with severe symptomatic aortic stenosis (AS) are multifactorial22 and it is possible that among those with impaired baseline renal function, TAVR may improve the postoperative renal function by relieving AS and improving cardiac output, leading to improved renal perfusion, decreased renal venous pressure, and improvement in right ventricular dysfunction. However, the procedure itself may have an adverse effect on postprocedural renal function because of factors such as using iodinated contrast, hypotension during rapid pacing, athero-emboli, and procedural complications such as bleeding.17,23 To our knowledge, the effect of TAVR on subsequent renal function among patients presenting with reduced baseline renal function has not been rigorously evaluated and data are limited.

We hypothesized that among patients with severe symptomatic AS and reduced baseline renal function, TAVR may improve postprocedural renal function and affect all-cause mortality. This hypothesis was evaluated among patients undergoing TAVR in the Placement of Aortic Transcatheter Valve (PARTNER) I Trial and Continued Access (CA) Registry.

Methods
Patient Selection

The design of the PARTNER 1 trial, along with detailed selection criteria and operative methods, have been previously reported.1,2 Enrolled patients had severe, symptomatic trileaflet AS (aortic valve area of <0.8 cm2 with either a mean aortic valve gradient of ≥40 mm Hg or a peak aortic jet velocity of ≥4.0 m/s), a New York Heart Association class II or greater heart failure symptoms, and at least a high surgical risk based on the Society for Thoracic Surgeons mortality risk score and other factors determined by the heart team. In PARTNER 1A,2 high-risk patients were randomized to surgical aortic valve replacement or TAVR. In PARTNER 1B, inoperable patients were randomized to TAVR or medical treatment with or without a balloon aortic valvuloplasty.1 All patients undergoing transfemoral TAVR received either a 23- or a 26-mm balloon-expandable Edwards SAPIEN transcatheter heart valve (Edwards Lifesciences). At the time of the PARTNER 1 trial and registry, a 29-mm valve was not available. Important exclusion criteria included bicuspid aortic valve disease, left ventricular ejection fraction less than 20%, severe renal insufficiency (renal insufficiency with serum creatinine >3.0 mg/dL and/or end-stage renal disease requiring chronic dialysis), severe mitral regurgitation, severe aortic regurgitation, recent gastrointestinal bleeding, or recent neurologic event.

All patients undergoing TAVR from the PARTNER 1A, PARTNER 1B (inoperable), and both the randomized and nonrandomized CA cohorts with baseline eGFR at 60 mL/min or fewer (using the modified diet in renal disease formula9) were analyzed. (Figure). Of 2559 patients enrolled in the PARTNER 1 trial and CA registry, 1792 patients had a baseline eGFR of 60 mL/min or lower. Of these, 821 patients had paired creatinine measurements available at baseline and 30 days and composed the study population. Patients were categorized as having improved eGFR (30-day follow-up eGFR at least 10% higher than baseline preTAVR eGFR), worsened eGFR (30-day follow-up eGFR at least 10% lower than baseline preTAVR eGFR), or having experienced no change (not fitting either previous group). Since the Valve Academic Research Consortium24 criteria do not specify criteria for improvement in renal function after TAVR, we used a 10% change in eGFR as being clinically meaningful. An independent clinical events committee adjudicated all the clinical events. The institutional review board at each participating site approved the study, and all patients provided written informed consent.

Study End Points

The frequency of worsening, no change, or improvement in eGFR at 30 days following the TAVR procedure was calculated. The frequency of 30-day to 1-year all-cause mortality and cardiovascular mortality, repeat hospitalization, any stroke, major stroke, death/major stroke, aortic valve reintervention, major bleeding, and renal failure requiring dialysis were reported according to a modified version of the Valve Academic Research Consortium-1.24 These end points were prespecified and adjudicated.

Statistical Analysis

Continuous variables were summarized as mean (SD) or as medians and quartiles and were compared using t tests or Mann-Whitney rank sum tests. Categorical variables were compared using χ2 tests or Fisher exact tests. For patients who survived up to 30 days, landmark survival curves for time-to-event variables were constructed on the basis of all available follow-up data using Kaplan-Meier estimates, and comparisons were performed using the log-rank test. Univariate and multivariable analyses were performed to determine baseline clinical and echocardiographic characteristics that contributed to differences in all-cause mortality between the 3 groups. For the multivariable models predicting improvement or worsening in 30-day eGFR, we used the group who experienced no significant change in eGFR as the comparator population.

A Cox proportional hazard regression analysis was performed to determine predictors of 1-year all-cause mortality. Logistic regression models were used to determine the predictors of improvement in eGFR and of worsening in eGFR. The multivariable models were built by stepwise selection, with candidate variables being selected if they were of clinical interest or satisfied the entry criterion of P < .10 in the univariable analysis. Variables were entered with entry/stay criteria of 0.1/0.1 in a forward stepwise fashion.

A 2-sided α level of .05 was used for all statistical testing. All statistical analyses were performed using SAS, version 9.4 (SAS Institute Inc). An independent academic biostatistics group performed all data analyses.

Results

Of the 1142 patients who had paired baseline and 30-day follow-up serum creatinine levels available, 821 (72%) had impaired baseline renal function (eGFR ≤ 60 mL/min). Of these, 42% (n = 345) showed an improvement in renal function, 34% (n = 280) showed no change, and 24% (n = 196) showed worsening renal function following TAVR (eFigure in the Supplement).

Baseline Clinical, Echocardiographic, and Procedural Characteristics

Comparing baseline clinical characteristics between the 3 groups, there was no statistical difference in the mean age (mid 80s), body mass index (calculated as weight in kilograms divided by height in meters squared), or frequency of diabetes, chronic obstructive pulmonary disease, renal disease (baseline serum creatinine > 2 mg/dL), coronary artery disease, peripheral arterial disease, hypertension, pulmonary hypertension, New York Heart Association class 3/4, or liver disease. Women were more likely to have improved eGFR following TAVR (improved eGFR, 55.1%; no change in eGFR, 47.1%; worsening eGFR, 40.3%; P = .003). People who smoked were less likely to have improved eGFR following TAVR (improved eGFR, 39.4%; no change in eGFR, 48.0%; worsening eGFR, 54.4%; P = .003). The mean (SD) baseline eGFR was lowest among the people with improved GFR (39.7 [11.8] mL/min) compared with those who experienced no change in eGFR (41.6 [10.3]) and worsening GFR (41.9 [10.6]) (P = .03) (Table 1).

Baseline echocardiographic parameters revealed no difference between the groups for the mean aortic valve gradient or baseline left ventricular ejection fraction. However, the mean (SD) cardiac index was significantly different between the groups, being lowest among the group with improved eGFR (1.98 [0.61] L/min/m2) and similar among the group who experienced no change in eGFR (2.13 [0.65]) and those with worsening eGFR (2.10 [0.66]) (P = .02 across groups). Left ventricle mass was highest among the group with worsening eGFR (263.80 [72.02] g; P = .01). Stroke volume tended to be lowest among the group with improved eGFR (63.2 [20.8] mL) and highest among the group with worsening eGFR (69.3 [20.7] mL) (P = .06 across groups) (Table 1).

Procedural characteristics, including successful valve implantation, conversion to open heart surgery or volume of contrast used, and the need for repeat aortic valve intervention, were similar between the 3 groups. There was a trend toward an increased need for hemodynamic support during the TAVR procedure among the group with worsening eGFR as compared with the other 2 groups (improved eGFR, 5.5%; no change in eGFR, 3.6%; worsening eGFR, 8.2%; P = .09) (Table 1).

Those who had more repeat hospitalizations or had acute kidney injury, as defined by needing renal dialysis between baseline and 30 days, were more commonly found among the group with worsening eGFR. The frequency of acute kidney injury by this definition was low among the groups with improved and unchanged eGFR (1.4% each) and higher (7.6%) among the group with worsening eGFR.

Data comparing patients with paired eGFR (those included in this analysis) and those without paired eGFR (those excluded from this analysis) are shown as supplemental data (eTables 1, 2, and 3 in the Supplement). Overall, the 2 groups were similar in terms of their baseline clinical characteristics except that there were fewer patients with baseline serum creatinine at greater than 2 mg/dL in the group without paired eGFR (with paired eGFR, 20.3%; without paired eGFR, 14.6%; P < .001). There were no differences between the groups in terms of echocardiographic or procedural characteristics.

30-Day to 1-Year Outcomes

From 30 days to 1-year follow-up, the rate of all-cause mortality correlated with the 30-day change in eGFR (improved eGFR, 15.4%; no change in eGFR, 19.1%; worsening eGFR, 25.5%; P = .01), as did the rate of cardiovascular mortality (improved eGFR, 4.7%; no change in eGFR, 6.8%; worsening eGFR, 11.1%; P = .02), the composite of death or major stroke (improved eGFR, 15.2%; no change in eGFR, 25.3%; P = .01), and the occurrence of renal failure requiring dialysis (improved eGFR, 1.4%; no change in eGFR, 3.5%; worsening eGFR, 5.9%; P = .01). There was no significant difference in the rate of repeat hospitalization between 30 days and 1 year (improved eGFR, 12.3%; no change in eGFR, 15.2%; worsening eGFR, 19.0%; P = .17).

These differences were primarily driven by differences between the groups with worsening and improved eGFR. Pairwise comparisons between the group with improved eGFR and those who had experienced no change in eGFR were not significant for all-cause mortality (15.4% vs 19.1%; P = .22), the need for repeat hospitalization (12.3% vs 15.2%; P = .35), or any other clinical end points. Compared with those who experienced no change in eGFR, the group with worsening eGFR trended toward increased all-cause mortality (25.5% vs 19.1%; P = .07) and renal failure requiring dialysis (5.9% vs 3.5%; P = .19), but there were no significant differences in other end points.

However, when compared with the group with improved eGFR, the group with worsening eGFR had significantly increased all-cause mortality rates (15.4% vs 25.5%; P = .003), cardiovascular mortality rates (P = .01), composite of death or major stroke (P = .003), and renal failure (P = .002). Comparative differences in clinical end points from 30 days to 1-year are shown in Table 2 and in the Figure.

Multivariable Predictors of Change in eGFR From Baseline to 30-Days PostTAVR

To determine correlates of improvement or worsening in 30-day post-TAVR eGFR, multivariable models were constructed including age, sex, smoking status, presence of diabetes, chronic obstructive pulmonary disease, hypertension, baseline eGFR, peripheral arterial disease, anemia, baseline left ventricular mass, baseline eGFR, any aortic valve reintervention, and any major bleeding event or bleeding requiring blood transfusion. In these models, female sex was associated with improvement in eGFR (odds ratio [OR], 1.38; 95% CI, 1.03-1.85; P = .03) as was being a nonsmoker (OR, 1.49; 95% CI, 1.11-2.04; P = .01). Factors associated with worsening eGFR at 30 days post-TAVR were baseline left ventricular mass (OR [per 10 g increment], 1.03; 95% CI, 1.01-1.06; P = .02), smoking (OR, 1.51; 95% CI, 1.06-2.14; P = .02), and age (OR, 1.03; 95% CI, 1.00-1.05; P = .05) (Table 3).

Multivariable Predictors of All-Cause 1-Year Mortality

Adjustments were made for age, female sex, body mass index, Society of Thoracic Surgeons risk score, diabetes, baseline eGFR, cerebrovascular disease, chronic obstructive pulmonary disease, stroke or transient ischemic attack (last 6-12 months), baseline left ventricle ejection fraction, prior coronary artery bypass graft, changes in stroke volume index from baseline to 30 days, and changes in eGFR (in Model 1 as a continuous variable and in Model 2 as a categorical variable with no change as the reference category). In the model using change in eGFR as a continuous variable, the significant predictors of all-cause 1-year mortality were baseline left ventricle ejection fraction (hazard ratio [HR], 0.98; 95% CI, 0.97-0.99; P = .003), baseline eGFR (HR, 0.97; 95% CI, 0.96-0.99; P < .001), and delta eGFR (HR, 0.45; 95% CI, 0.25-0.81; P = .01). Examining changes in eGFR as a categorical variable revealed that worsening eGFR was significantly associated with an increased hazard of 1-year mortality (HR, 1.51; 95% CI, 1.02-2.24; P = .04), while increased eGFR showed no significant association (HR, 0.74; 95% CI, 0.50-1.09; P = .13) (Table 4).

Discussion

In a first such analysis, to our knowledge, of high-surgical risk or inoperable patients with severe symptomatic AS undergoing TAVR who had impaired baseline eGFR and paired eGFR measurements at 30 days, we found that (1) decreased baseline eGFR was frequent, being present among 72% of patients; (2) TAVR resulted in a 10% or greater improvement in eGFR among 42% of patients, an at least 10% worsening of eGFR among 24% of the patients, and no change in eGFR among 34% of patients; (3) independent baseline correlates of improvement in eGFR after TAVR were being female and nonsmoking status; (4) between 30 days and 1 year, changes in eGFR were associated with all-cause and cardiovascular mortality, the composite of death and major stroke, and the incidence of renal failure (need for dialysis); and (5) using the group who experienced no change in eGFR as a comparator arm, the group with improved eGFR showed no differences in all-cause mortality or the need for repeat hospitalization, but did trend toward a lower need for dialysis, while patients with worsening eGFR trended toward increased all-cause mortality.

The present analysis underscores the high prevalence of baseline renal insufficiency among high-risk and inoperable patients with severe symptomatic AS, the cause of which is likely to be multifactorial,22 including type 2 cardiorenal syndrome (decreased renal perfusion because of cardiac dysfunction) related to AS-induced reduced cardiac output, right ventricular dysfunction, and elevated renal venous pressure, all of which contribute to decreased renal perfusion. Additionally, these patients have frequent comorbidities such as hypertension, dyslipidemia, peripheral arterial disease, and older age, all of which contribute to renal dysfunction and are associated with elevated operative risk.20,21

It is interesting that among this cohort of high-risk or inoperable patients with compromised baseline renal function undergoing TAVR, 76% of patients experienced either improvement (42%) or no change (34%) in their renal function after TAVR. It appears, therefore, that among these patients, the salutary hemodynamic effects of TAVR resulting in improved renal perfusion may have outweighed the adverse procedural features, such as using iodinated contrast, drops in blood pressure during rapid pacing at the time of valve deployment, and embolic debris. In the present analysis, those with improved eGFR after TAVR were more likely to have a lower baseline cardiac index and eGFR, suggesting that among these patients relief of AS with TAVR had a beneficial impact on type 2 cardiorenal syndrome. We found no differences between the groups in procedural characteristics such as the volume of contrast used, the rate of successful valve implantation, or the use of transfemoral or transapical access. There was a trend toward an increased need for hemodynamic support among the group with worsening eGFR compared with the group who experienced no change in eGFR, suggesting a more hemodynamically compromised group.

These results also suggest a more frequent rate of improvement in renal function (42% in the present study) than previously reported in a smaller single center study, which reported improvement in renal function among 15% of patients at 30 days (defined as an absolute decrease in serum creatinine ≥0.3 mg/dL) and included all patients irrespective of baseline renal function.25 In contrast, in the present study, we specifically studied patients who presented with compromised baseline renal function and found a substantial percentage with improved or stable postTAVR renal function. A selection bias may exist in the present analysis because we excluded patients without 30-day eGFR or those that had early mortality within 30 days. Because the Valve Academic Research Consortium definitions do not specify criteria to determine improvement in renal function after TAVR, we used a clinically meaningful change in eGFR of 10% rather than specifying a decline of serum creatinine of 0.3 mg/dL or more as in the other recent analysis.25

Patients that had improvement in eGFR after TAVR showed no difference in all-cause mortality or the need for repeat hospitalization as compared with the group who experienced no change in eGFR. These results are surprising and may be because of the present study being underpowered to detect this difference. However, patients with worsening eGFR trended toward an increased 1-year all-cause mortality compared with those who experienced no change in eGFR. These results confirm the adverse effects of worsening renal function after TAVR.13,14,18,23,25-27

We attempted to determine the predictors of improved eGFR and found that the predictive ability was limited. Our modeling did not reveal procedural characteristics such as repeat aortic valve interventions, major hemorrhage, or the need for a transfusion as being predictive beyond baseline clinical characteristics. Women were 38% more likely to have an improvement in post-TAVR eGFR. It has been previously shown in an analysis from the PARTNER trial that women undergoing TAVR in the PARTNER trial had a lower prevalence of comorbidities, including peripheral vascular disease, diabetes, and baseline renal dysfunction.28 Therefore, it is possible that the relief of type 2 cardiorenal syndrome is a dominant effect of TAVR among women, whereas among men this competes with baseline renal dysfunction driven by the more frequent occurrence of comorbidities. Smoking was predictive of worsening renal function (people who smoked were 51% more likely to worsen than people who did not). This was likely because of an increased incidence of peripheral arterial disease, endothelial dysfunction, baseline renal dysfunction, and possibly an increased risk of embolic debris during the procedure among people who smoked. While procedural characteristics are expected to affect post procedural eGFR,16,23,26 we found no significant difference between the groups in terms of procedural characteristics such as the volume of contrast used, procedural success, needing aortic valve reinterventions, major bleeding, vascular complications, or needing transfusions.

Careful preprocedural hydration, minimizing the duration of rapid pacing and associated hypotension at time of transcatheter valve deployment, bringing the blood pressure up if patient is hypotensive before placing the transcatheter valve across the aortic valve, and possibly using newer techniques such as the RenalGuard system (RenalGuard Solutions Inc)29 and renal embolic protection devices, among others, may all help to avoid post-TAVR worsening of renal function.

Of interest, independent predictors of worsening eGFR included history of smoking, baseline left ventricle mass and patient age. The association between smoking status and change in eGFR was commented on earlier. A higher baseline left ventricle mass was likely the result of longer standing AS and associated risk factors such as hypertension, while older patients were more likely to have a higher burden of comorbidities and renal dysfunction at baseline. The independent association of worsening eGFR at 30-day postprocedure with elevated 1-year mortality confirms results from previous studies.12,16,23,25-27

Limitations

This study is a retrospective subanalysis of the PARTNER trial and is subject to the limitations inherently present in such analyses. A survival bias may exist in the present analysis because we excluded patients without 30-day eGFR or those that had early mortality within 30-day. Those with severe renal insufficiency (baseline serum creatinine >3 mg/dL) and those on dialysis were not included in the present analysis since they were excluded from the PARTNER trial and nonrandomized continued access registries. The impact of TAVR in those with baseline serum creatinine greater than 3.0 mg/dL is therefore unclear. The study is likely not adequately powered to detect differences in some clinical end points among the groups with improved or worsened eGFR compared with the group who experienced no change, despite event rates that follow a consistent pattern of being lowest among the group with improved eGFR, intermediate among the group who experienced no change, and highest among the group with worsened eGFR. We used a clinically meaningful definition of improvement or worsening of eGFR, but other definitions such an absolute increase or decrease of serum creatinine of 0.3 mg/dL could be used as an extrapolation from the Valve Academic Research Consortium definitions.

Conclusions

Decreased baseline eGFR was frequent among high-risk and inoperable patients with severe symptomatic AS. After undergoing TAVR, 76% of patients experienced either improved (42%) or unchanged (34%) renal function, diminishing the concern about offering this otherwise beneficial therapy to such patients. At 1 year, after adjusting for baseline risk factors, worsening eGFR was associated with an increased hazard of all-cause mortality.

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Article Information

Corresponding Author: Nirat Beohar, MD, Columbia University Division of Cardiology, Mount Sinai Medical Center, 4300 Alton Rd, Miami Beach, FL 33140 (nbeohar3@gmail.com).

Accepted for Publication: March 16, 2017.

Published Online: May 3, 2017. doi:10.1001/jamacardio.2017.1220

Author Contributions: Dr Beohar had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Beohar, Thourani, McCarthy, Kirtane.

Acquisition, analysis, or interpretation of data: Beohar, Doshi, Jensen, Kodali, F. Zhang, Y. Zhang, Davidson, Mack, Kapadia, Leon, Kirtane.

Drafting of the manuscript: Beohar, Jensen.

Critical revision of the manuscript for important intellectual content: Beohar, Doshi, Thourani, Kodali, F. Zhang, Y. Zhang, Davidson, McCarthy, Mack, Kapadia, Leon, Kirtane.

Statistical analysis: Beohar, Jensen, F. Zhang, Y. Zhang, Kirtane.

Administrative, technical, or material support: Doshi, Jensen, Leon, Kirtane.

Supervision: Thourani, Kapadia.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Thourani receives consulting fees from Edwards Lifesciences and Abbott Vascular. Dr Kodali receives consulting fees from Edwards Lifesciences and holds equity in Thubrikar Aortic Valve, Inc. Drs Davidson and McCarthy receive grant support from Edwards Lifesciences. Drs Mack and Leon are members of the PARTNER Trial Executive Committee, for which they receive no direct compensation. Dr Kirtane receives grant support from Edwards Lifesciences, Medtronic, Boston Scientific, Abiomed, St. Jude Medical, Eli Lilly, and CathWorks. No other disclosures are reported.

Funding/Support: The PARTNER Trial was funded by Edwards Lifesciences.

Role of the Funder/Sponsor: Edwards Lifesciences was involved in the design and conduct of the study and the collection and management of data, but had no role in the analysis and interpretation of data, preparation, review, or approval of the manuscript, or the decision to submit the manuscript for publication.

References
1.
Leon  MB, Smith  CR, Mack  M,  et al; PARTNER Trial Investigators.  Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery.  N Engl J Med. 2010;363(17):1597-1607.PubMedGoogle ScholarCrossref
2.
Smith  CR, Leon  MB, Mack  MJ,  et al; PARTNER Trial Investigators.  Transcatheter versus surgical aortic-valve replacement in high-risk patients.  N Engl J Med. 2011;364(23):2187-2198.PubMedGoogle ScholarCrossref
3.
Adams  DH, Popma  JJ, Reardon  MJ,  et al; U.S. CoreValve Clinical Investigators.  Transcatheter aortic-valve replacement with a self-expanding prosthesis.  N Engl J Med. 2014;370(19):1790-1798.PubMedGoogle ScholarCrossref
4.
Popma  JJ, Adams  DH, Reardon  MJ,  et al; CoreValve United States Clinical Investigators.  Transcatheter aortic valve replacement using a self-expanding bioprosthesis in patients with severe aortic stenosis at extreme risk for surgery.  J Am Coll Cardiol. 2014;63(19):1972-1981.PubMedGoogle ScholarCrossref
5.
Leon  MB, Smith  CR, Mack  MJ,  et al; PARTNER 2 Investigators.  Transcatheter or surgical aortic-valve replacement in intermediate-risk patients.  N Engl J Med. 2016;374(17):1609-1620.PubMedGoogle ScholarCrossref
6.
Thourani  VH, Kodali  S, Makkar  RR,  et al.  Transcatheter aortic valve replacement versus surgical valve replacement in intermediate-risk patients: a propensity score analysis.  Lancet. 2016;387(10034):2218-2225.PubMedGoogle ScholarCrossref
7.
Ferro  CJ, Chue  CD, de Belder  MA,  et al; UK TAVI Steering Group; National Institute for Cardiovascular Outcomes Research.  Impact of renal function on survival after transcatheter aortic valve implantation (TAVI): an analysis of the UK TAVI registry.  Heart. 2015;101(7):546-552.PubMedGoogle ScholarCrossref
8.
Oguri  A, Yamamoto  M, Mouillet  G,  et al; FRANCE 2 Registry investigators.  Impact of chronic kidney disease on the outcomes of transcatheter aortic valve implantation: results from the FRANCE 2 registry.  EuroIntervention. 2015;10(9):e1-e9.PubMedGoogle ScholarCrossref
9.
Yamamoto  M, Hayashida  K, Mouillet  G,  et al.  Prognostic value of chronic kidney disease after transcatheter aortic valve implantation.  J Am Coll Cardiol. 2013;62(10):869-877.PubMedGoogle ScholarCrossref
10.
Dumonteil  N, van der Boon  RM, Tchetche  D,  et al.  Impact of preoperative chronic kidney disease on short- and long-term outcomes after transcatheter aortic valve implantation: a Pooled-RotterdAm-Milano-Toulouse in collaboration Plus (PRAGMATIC-Plus) initiative substudy.  Am Heart J. 2013;165(5):752-760.PubMedGoogle ScholarCrossref
11.
Chen  C, Zhao  ZG, Liao  YB,  et al.  Impact of renal dysfunction on mid-term outcome after transcatheter aortic valve implantation: a systematic review and meta-analysis.  PLoS One. 2015;10(3):e0119817.PubMedGoogle ScholarCrossref
12.
Sinning  JM, Ghanem  A, Steinhäuser  H,  et al.  Renal function as predictor of mortality in patients after percutaneous transcatheter aortic valve implantation.  JACC Cardiovasc Interv. 2010;3(11):1141-1149.PubMedGoogle ScholarCrossref
13.
Muñoz-García  AJ, Muñoz-García  E, Jiménez-Navarro  MF,  et al; RIC Investigators.  Clinical impact of acute kidney injury on short- and long-term outcomes after transcatheter aortic valve implantation with the CoreValve prosthesis.  J Cardiol. 2015;66(1):46-49.PubMedGoogle ScholarCrossref
14.
Bagur  R, Webb  JG, Nietlispach  F,  et al.  Acute kidney injury following transcatheter aortic valve implantation: predictive factors, prognostic value, and comparison with surgical aortic valve replacement.  Eur Heart J. 2010;31(7):865-874.PubMedGoogle ScholarCrossref
15.
Nuis  RJ, van Mieghem  NM, van der Boon  RM,  et al.  Effect of experience on results of transcatheter aortic valve implantation using a Medtronic CoreValve System.  Am J Cardiol. 2011;107(12):1824-1829.PubMedGoogle ScholarCrossref
16.
Elhmidi  Y, Bleiziffer  S, Piazza  N,  et al.  Incidence and predictors of acute kidney injury in patients undergoing transcatheter aortic valve implantation.  Am Heart J. 2011;161(4):735-739.PubMedGoogle ScholarCrossref
17.
Aregger  F, Wenaweser  P, Hellige  GJ,  et al.  Risk of acute kidney injury in patients with severe aortic valve stenosis undergoing transcatheter valve replacement.  Nephrol Dial Transplant. 2009;24(7):2175-2179.PubMedGoogle ScholarCrossref
18.
Kong  WY, Yong  G, Irish  A.  Incidence, risk factors and prognosis of acute kidney injury after transcatheter aortic valve implantation.  Nephrology (Carlton). 2012;17(5):445-451.PubMedGoogle ScholarCrossref
19.
Barbash  IM, Ben-Dor  I, Dvir  D,  et al.  Incidence and predictors of acute kidney injury after transcatheter aortic valve replacement.  Am Heart J. 2012;163(6):1031-1036.PubMedGoogle ScholarCrossref
20.
Thourani  VH, Keeling  WB, Sarin  EL,  et al.  Impact of preoperative renal dysfunction on long-term survival for patients undergoing aortic valve replacement.  Ann Thorac Surg. 2011;91(6):1798-1806.PubMedGoogle ScholarCrossref
21.
Iung  B, Baron  G, Butchart  EG,  et al.  A prospective survey of patients with valvular heart disease in Europe: the Euro Heart Survey on Valvular Heart Disease.  Eur Heart J. 2003;24(13):1231-1243.PubMedGoogle ScholarCrossref
22.
Ewe  SH, Ajmone Marsan  N, Pepi  M,  et al.  Impact of left ventricular systolic function on clinical and echocardiographic outcomes following transcatheter aortic valve implantation for severe aortic stenosis.  Am Heart J. 2010;160(6):1113-1120.PubMedGoogle ScholarCrossref
23.
Saia  F, Ciuca  C, Taglieri  N,  et al.  Acute kidney injury following transcatheter aortic valve implantation: incidence, predictors and clinical outcome.  Int J Cardiol. 2013;168(2):1034-1040.PubMedGoogle ScholarCrossref
24.
Leon  MB, Piazza  N, Nikolsky  E,  et al.  Standardized endpoint definitions for transcatheter aortic valve implantation clinical trials: a consensus report from the Valve Academic Research Consortium.  J Am Coll Cardiol. 2011;57(3):253-269.PubMedGoogle ScholarCrossref
25.
Blair  JE, Brummel  K, Friedman  JL,  et al.  Inhospital and post-discharge changes in renal function after transcatheter aortic valve replacement.  Am J Cardiol. 2016;117(4):633-639.PubMedGoogle ScholarCrossref
26.
Barbanti  M, Latib  A, Sgroi  C,  et al.  Acute kidney injury after transcatheter aortic valve implantation with self-expanding CoreValve prosthesis: results from a large multicentre Italian research project.  EuroIntervention. 2014;10(1):133-140.PubMedGoogle ScholarCrossref
27.
Schnabel  RB, Seiffert  M, Wilde  S,  et al.  Kidney injury and mortality after transcatheter aortic valve implantation in a routine clinical cohort.  Catheter Cardiovasc Interv. 2015;85(3):440-447.PubMedGoogle ScholarCrossref
28.
Williams  M, Kodali  SK, Hahn  RT,  et al.  Sex-related differences in outcomes after transcatheter or surgical aortic valve replacement in patients with severe aortic stenosis: Insights from the PARTNER Trial (Placement of Aortic Transcatheter Valve).  J Am Coll Cardiol. 2014;63(15):1522-1528.PubMedGoogle ScholarCrossref
29.
Barbanti  M, Gulino  S, Capranzano  P,  et al.  Acute kidney injury with the RenalGuard System in patients undergoing transcatheter aortic valve replacement: the PROTECT-TAVI Trial (PROphylactic effecT of furosEmide-induCed diuresis with matched isotonic intravenous hydraTion in Transcatheter Aortic Valve Implantation).  JACC Cardiovasc Interv. 2015;8(12):1595-1604.PubMedGoogle ScholarCrossref
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