Author + information
- Received October 8, 2017
- Accepted October 20, 2017
- Published online November 27, 2017.
- Yukari Kobayashi, MDa,b,∗ (, )
- Naga Lakshmi Sudini, MBBSa,b,
- June-Wha Rhee, MDa,b,
- Marie Aymami, MD, MSa,b,
- Kegan J. Moneghetti, MBBS (hons)a,b,
- Sara Bouajila, MDa,b,
- Yuhei Kobayashi, MDa,b,
- Juyong B. Kim, MD, MPHa,b,
- Ingela Schnittger, MDa,b,
- Jeffery J. Teuteberg, MDa,
- Kiran K. Khush, MD, MASa,
- William F. Fearon, MDa,b and
- Francois Haddad, MDa,b,∗∗ ()
- aDivision of Cardiovascular Medicine, Stanford University Medical Center, Stanford, California
- bStanford Cardiovascular Institute, Stanford, California
- ↵∗Address for correspondence:
Dr. Yukari Kobayashi, Division of Cardiovascular Medicine, Stanford University Medical Center, 300 Pasteur Drive, Stanford, California 94305.
- ↵∗∗Dr. Francois Haddad, Division of Cardiovascular Medicine, Stanford University Medical Center, 300 Pasteur Drive, Stanford, California 94305.
Objectives This study investigated to define graft dysfunction and to determine its incremental association with long-term outcome after heart transplantation (HT).
Background Although graft failure is an established cause of late mortality after HT, few studies have analyzed the prognostic value of graft dysfunction at 1- and 5-year follow-up of HT.
Methods Patients who underwent HT and completed their first annual evaluation with right heart catheterization and echocardiography at Stanford University between January 1999 and December 2011 were included in the study. Hierarchical clustering was used to identify modules to capture independent features of graft dysfunction at 1 year. The primary endpoint for analysis consisted of the composite of cardiovascular mortality, re-transplantation, or heart failure hospitalization within 5 years of HT. The study further explored whether changes in graft dysfunction between 1 and 5 years were associated with 10-year all-cause mortality.
Results A total of 215 HT recipients were included in the study. Using hierarchical clustering, 3 functional modules were identified; among them, left ventricular global longitudinal strain (LVGLS), stroke volume index, and right atrial pressure (RAP) or pulmonary capillary wedge pressure (PCWP) captured key features of graft function. Graft dysfunction based on pre defined LVGLS in absolute value <14%, stroke volume index <35 ml/m2, RAP >10 mm Hg, or PCWP >15 mm Hg were present in 41%, 36%, and 27%, respectively. The primary endpoint at 5 years occurred in 52 patients (24%), whereas 10-year all-cause mortality occurred in 30 (27%) of 110 patients alive at 5 years. On multivariate analysis, RAP (standardized hazard ratio: 1.63), LVGLS (standardized hazard ratio: 1.39), and a history of hemodynamically compromising rejection within 1 year (hazard ratio: 2.18) were independent predictors of 5-year outcome. RAP at 5 years, as well as change in RAP from 1 to 5 years, was predictive of 10-year all-cause mortality.
Conclusions RAP and LVGLS at the first annual evaluation provide complementary prognostic information in predicting 5-year outcome after HT.
Graft dysfunction is common after heart transplantation. In a comprehensive study to assess diastolic function, Tallaj et al. (1) observed that diastolic dysfunction (defined according to right atrial pressure [RAP] >15 mm Hg or pulmonary capillary wedge pressure [PCWP] >18 mm Hg) was observed in 22% of patients at 6 weeks and 12% of patients at 1 year. They also showed that right ventricular (RV) diastolic dysfunction, defined by the ratio of RAP to stroke volume obtained by right heart catheterization (RHC), was a strong predictor of cardiac mortality. Studies by Saleh et al. (2) and Syeda et al. (3) have also suggested that left ventricular (LV) systolic function, assessed by using left ventricular global longitudinal strain (LVGLS), is decreased even when left ventricular ejection fraction (LVEF) is maintained. Moreover, several studies have suggested the value of LVGLS in predicting post-transplant outcome. For example, several studies have shown that LVGLS may be useful in monitoring for cardiac rejection or allograft vasculopathy (4,5). Another study by Sarvari et al. (6) showed that early LVGLS at 1 to 3 weeks predicted 1-year mortality in patients with heart transplantation.
To date, however, few studies have evaluated the incremental value of hemodynamic and ventricular deformation imaging for predicting long-term outcome after transplantation. Identifying which hemodynamic and echocardiographic parameters are most complementary for predicting long-term outcome can help develop a tailored approach to monitor as well as inform clinical trial design. For the present study, the hypothesis was that diastolic dysfunction assessed by using invasive hemodynamic variables and LVGLS at 1-year post-transplant would be complementary to RAP in predicting long-term outcome after heart transplantation. We further hypothesized that the worsening of diastolic dysfunction or LVGLS from 1 to 5 years would predict long-term mortality.
The first objective of the study was to define graft dysfunction based on RAP, PCWP, LVGLS, and stroke volume index (SVI) at 1 year. The relationship between graft function parameters was further assessed by using hierarchical clustering and correlation map analysis. The second objective was to determine which parameters of graft dysfunction are most predictive of the combined outcome of cardiovascular mortality, re-transplantation, or graft failure at 5 years, as well as to determine whether worsening of RAP or LVGLS would be associated with mortality or re-transplant at 10 years’ post-transplant. Finally, we explored the association between graft function at 1 year and the development of grade 2 or 3 cardiac allograft vasculopathy (CAV) according to the International Society for Heart and Lung Transplantation guidelines (7).
The study was approved by the Stanford’s institutional review board. Using the Stanford Heart Transplant Registry, we included consecutive patients who underwent heart transplantation from January 1999 to December 2011 and underwent RHC and comprehensive echocardiography at their first annual evaluation. Details of donor and recipient demographic variables, pre-transplant and post-transplant clinical variables, echocardiographic data, and hemodynamic data from the RHC were collected. Data on coronary angiogram and echocardiography at 1 year after transplant were also collected. In addition, coronary angiogram data closest to the time point of 5 years were collected.
Diabetes mellitus was defined as a fasting glucose level >7 mmol/l (126 mg/dl) or glycosylated hemoglobin level >6.5%. Chronic kidney disease was defined as a glomerular filtration rate ≤60 ml/min/1.73 m2. Pre-transplant condition under life support was defined as a condition requiring treatment with inotropes and/or mechanical devices such as extracorporeal membrane oxygenation, intra-aortic balloon pump, and ventricular assist devices.
Induction therapy was used in all patients, by either antithymocyte globulin or daclizumab. Maintenance immunosuppression consisted of a calcineurin inhibitor (cyclosporine or tacrolimus) and either mycophenolate mofetil or sirolimus. Corticosteroid therapy (methylprednisone) was initiated immediately post-operatively and progressively tapered over 1 year after transplantation in the absence of rejection. Cytomegalovirus prophylaxis consisted of valganciclovir for a total of 6 to 12 months in patients with evidence of seropositive donor or recipient status.
Right heart catheterization
RHC was performed at the time of the first annual evaluation. A balloon catheter was inserted through the internal jugular or femoral vein by using a local anesthesia in the supine position. RAP, mean pulmonary arterial pressure, PCWP, and cardiac output according to the Fick method were measured. SVI was calculated as cardiac output divided by heart rate and indexed by body surface area. Diastolic dysfunction was pre defined as RAP >10 mm Hg or PCWP >15 mm Hg. We chose a lower threshold compared with previous studies (1) because the focus of the present study was on early diastolic dysfunction rather than severe dysfunction.
Echocardiographic assessment was performed according to the American Society of Echocardiography guideline recommendations (8). Standard echocardiographic views were obtained in M-mode, 2-dimensional, and color tissue Doppler modes. LV end-systolic and end-diastolic volumes and ejection fraction (LVEF) were calculated with the biplane Simpson’s method. LV internal diameter and interventricular septal and posterior wall thicknesses were obtained at end-diastole from the 2-dimensional mode of the parasternal long-axis. Transmitral pulse Doppler velocities and tissue Doppler velocities of the mitral annulus were measured from the apical 4-chamber view, and the E/e′ ratio was obtained from the lateral annulus. LV longitudinal strain was measured by using the Lagrangian strain by manual tracing as previously described (9). Briefly, we measured the myocardial initial length in end-diastole (L0) and final length in end-systole (L1) in an Xcelera workstation (Philips Healthcare, Andover, Massachusetts) and calculated LV strain values as: 100 × (L1 − L0)/L0 (10). LV global longitudinal strain (LVGLS) represented the average of values of longitudinal strain from the apical 4-, 3-, and 2-chamber views. RV function was assessed by right ventricular fractional change (RVFAC) and right ventricular free-wall longitudinal strain (RVLS) using the Lagrangian strain. When values were indexed, adjusted body surface area was used. For longitudinal follow-up, RAP was estimated by echocardiography, as 3 mm Hg if the inferior vena cava (IVC) diameter ≤2.1 cm that collapses >50%, 15 mm Hg if IVC diameter >2.1 cm that collapses <50%, and 8 mm Hg in scenarios in which IVC diameter and collapse otherwise (11).
In terms of the threshold of echocardiographic parameters, decreased LVGLS was defined as <14% in absolute value (2,3), RVLS as <17% in absolute value, and decreased RVFAC as <30%, since the longitudinal motion was reduced in patients with heart transplantation even without any complications due to post-operative change.
Intravariability and intervariability
All echocardiographic assessments were performed by a senior investigator in the Stanford Cardiovascular Institute Biomarker and Phenotypic core laboratory blinded to the study outcomes (Yukari K.). To assess the intravariability and intervariability of LVGLS, 20 patients were randomly selected, and their data were reanalyzed by the same investigator as well as by the second investigator (S.B.) 2 to 4 weeks after the first analysis without references to the initial tracings. Intraobserver and interobserver variability were assessed by using intraclass correlation analysis. The intraclass correlation was 0.97 and 0.88 for intraobserver and interobserver variability, respectively.
For the outcome analysis, the primary endpoint was defined as the composite of cardiovascular mortality, re-transplantation, and heart failure hospitalization (graft failure) within 5 years’ post-transplantation. Cardiovascular mortality was defined as death attributed to rejection, graft failure, CAV, or sudden cardiac death. We further explored all-cause mortality at 10 years by assessing the parameter that was shown to be important at 5 years. The secondary endpoint was defined as CAV at 5 years after transplantation. According to our post-transplant protocol, patients underwent a routine angiogram at 5 years. Significant CAV was defined as International Society for Heart and Lung Transplantation grade 2 or 3 according to coronary angiography (7). When a dobutamine stress echocardiography was performed instead of coronary angiography, significant CAV was defined as stress-induced wall motion abnormalities of ≥2 segments (16-segment model) or if overall systolic function decreased during dobutamine stress testing. An episode of rejection was defined as an event that led to an acute augmentation of immunosuppression (12).
Results are expressed as mean ± SD for continuous variables or as number of cases and percentage for categorical variables. Comparison of groups was performed by using the Student or Welch t-test or Mann-Whitney U test, as appropriate, for continuous variables and the chi-square test or Fisher exact test as appropriate for categorical variables. To describe graft function at 1 year, we selected RAP or PCWP, SVI obtained by catheter, and LVGLS obtained by echocardiography, which represent diastolic and systolic function parameters.
Because hemodynamic and echocardiographic parameters are associated with each other, hierarchical modeling was further used to determine if these parameters are part of different functional subsets. A heat map and dendrogram were generated from Pearson’s correlation r values and ordered according to hierarchical clustering to show distances between groupings of collected variables. The optimal number of clusters was selected by using the elbow method as provided by the R function NbClust. Univariable Cox regression analysis was performed to evaluate the association with the outcome, and the parameters with p values < 0.15 were then entered into multivariable models. Hazard ratios and 95% confidence intervals were standardized by each SD to easily compare the strength of influence. A p value < 0.05 was considered to be statistically significant. Analyses were performed by using SPSS version 21 (IBM SPSS Statistics, IBM Corporation, Armonk, New York) and MedCalc version 14.2 (MedCalc Software, Ostend, Belgium).
A total of 352 subjects were identified who underwent heart transplantation and were followed up at Stanford University Medical Center between January 1999 and December 2011. January 1999 was chosen as the initial date because it corresponds to a period when comprehensive clinical and echocardiographic data were available for each patient. Among those who underwent transplantation, 70 patients died during the first post-transplant year. Of 282 patients followed up at 1 year, 67 patients were excluded because their RHC or echocardiography data at 1-year post-transplant were not available. Finally, 215 patients were enrolled in the study. Patients included in the study did not differ from those excluded with regard to age (p = 0.12), recipient sex (p = 0.11), etiology of transplant (p = 0.16), panel reactive antibody >10% (p = 0.10), serum creatinine (p = 0.80), glycosylated hemoglobin (p = 0.09), total bilirubin (p = 0.89), or overall survival at 5 years (p = 0.89). There was, however, a small difference in donor age (30 ± 11 years vs. 33 ± 12 years; p = 0.048).
The mean age at transplant was 49 ± 15 years, and the majority of patients (76%) were male (Table 1). Fifty-six patients (26%) underwent transplantation for ischemic cardiomyopathy. Ninety-four patients (44%) were on life support before transplantation, and 6 patients (3%) were on ventilatory support. The mean donor age was 33.1 ± 12.4 years, and ischemic time was 3.6 ± 0.9 h. Rejection during the first post-transplant year was documented in 72 patients (33%), and 24 of those patients presented with evidence of hemodynamic compromise.
Graft function profiles at 1 year post-transplant
Table 2 presents the hemodynamic and echocardiographic parameters at 1 year. Based on invasive hemodynamic variables at 1 year, 30 patients (14%) presented with increased RAP (>10 mm Hg), and 51 patients (24%) presented with increased PCWP (>15 mm Hg); 25 patients (12%) presented with both increased RAP and PCWP. Pulmonary hypertension (mean pulmonary arterial pressure ≥25 mm Hg) was observed in 34 patients (16%). Based on echocardiographic parameters, 17 patients (8%) presented with decreased LVEF (<50%), and 86 patients (41%) presented with decreased LVGLS (<14% in absolute value). Among 105 patients with E/e′ ratio data, 34 patients (32%) presented with an increased E/e′ ratio (>8). RV dysfunction assessed by reduced RVFAC (<30%) and RVLS (<17% in absolute value) was observed in 45 patients (22%) and 51 patients (25%), respectively. Patients with reduced LVGLS had a greater percentage of RV systolic dysfunction: reduced RVFAC (40% of patients) and RVLS (41%) compared with preserved LVGLS (9% and 13%, respectively) (p < 0.001).
Figure 1A presents the Venn diagrams demonstrating the overlap between the selected features to characterize graft function profiles; that is, abnormal RAP or PCWP, LVGLS, and SVI among patients who had all 3 measurements in the whole population (n = 212). Twenty-one patients (10%) had all 3 abnormal factors. To detect the clinical correlates of graft dysfunction, logistic regression analysis was performed by using covariables as age, sex, presence of diabetes mellitus, chronic kidney disease, race (African American), tacrolimus intake, panel reactive antibody >10%, history of rejection within 1 year with hemodynamic compromise, weight mismatch, donor age, and infection of cytomegalovirus mismatch. History of rejection within 1 year with hemodynamic compromise was the only independent variable associated with increased RAP or PCWP (odds ratio: 6.48; 95% confidence interval: 2.62 to 16.0; p < 0.001) and decreased LVGLS (odds ratio: 5.12; 95% confidence interval: 1.94 to 13.5; p = 0.001). No parameter was independently associated with decreased SVI.
Figure 1B shows the prevalence of graft dysfunction according to a rejection history at 1 year. More patients with a history of rejection with hemodynamic compromise presented with graft dysfunction compared with no history of rejection, whereas patients with a history without hemodynamic compromise presented with almost comparable graft dysfunction as patients without rejection.
Because several parameters of ventricular function and hemodynamic parameters are closely associated with each other, hierarchical clustering was conducted to identify the most complementary parameters. The elbow method determined that 4 clusters would be optimal to determine the different grouping of variables. As shown in Figure 2, four clusters were found that seemed to be more closely associated with each other; among them, 3 mainly reflected ventricular function parameters. The first functional cluster included LVGLS as well as LVEF and RV functional parameters; the second functional cluster highlighted hemodynamic parameters of SVI and cardiac index; and the third functional cluster mainly highlighted diastolic filling parameters. The fourth functional cluster consisted of mainly cardiac structures, which were weakly related to each other. The pre defined systolic and diastolic parameters LVGLS, SVI, and RAP or PCWP were shown to be complementary.
During the follow-up at 5 years after transplantation the primary endpoint occurred in 52 patients (24%). Of these patients, 24 patients died due to cardiovascular etiology, 2 patients underwent re-transplantation, and 26 patients were hospitalized due to heart failure. Table 3 presents the univariable Cox analysis to evaluate the association with cardiovascular mortality, re-transplantation, or heart failure hospitalization. Among hemodynamic parameters, SVI and RAP were the 2 strongest; among echocardiographic parameters, LVGLS and RVGLS were the 2 strongest. When using the predefined thresholds to define graft dysfunction profiles, the greater number of abnormal features was associated with worst outcome.
A multivariable analysis was then conducted to determine which factors were more strongly related to outcome. Parameters with p values < 0.15 in univariable analysis, as well as age and sex, were included in the multivariable analysis. RAP and LVGLS, as well as history of rejection with hemodynamic compromise, were independent associates of outcome. Using only echocardiographic parameters in multivariable analysis, RAP according to echocardiography and LVGLS, as well as history of rejection with hemodynamic compromise, were independent associates with the outcome in patients with transplantation. Figure 3A shows the crude incidence rates of cardiovascular death, re-transplantation, and heart failure hospitalization according to the number of abnormal parameters in these 3 factors; as the number of abnormal factors increased, the incidence of events significantly increased (p < 0.001). Kaplan-Meier curve analysis also differentiated the outcome according to the number of abnormal factors (log-rank test, p < 0.001) (Figure 3B). Receiver operating characteristic curve analysis identified an LVGLS threshold of −13% and a RAP threshold of 7 mm Hg as the one with the most balanced sensitivity and specificity for the combined outcome. These parameters were also associated with all-cause mortality at 5 years (standardized hazard ratio: 1.61 [p = 0.002] for RAP and 1.69 [p = 0.002] for LVGLS worsening). Furthermore, RAP at 5 years and change in RAP from 1 to 5 years were associated with all-cause mortality in 110 patients who underwent heart transplantation before 2006 and were alive at 5 years, among whom 30 patients died at 10 years after transplantation; LVGLS at 5 years and the change in LVGLS were not associated with all-cause mortality (Table 4).
CAV at 5 years
In terms of the secondary outcome, among 186 patients who were alive and evaluated on CAV at 5 years after transplantation, 36 patients (19%) met the diagnosis of severe CAV as defined previously. As shown in Table 5, LV mass index and SVI at 1 year were independent associates with severe CAV at 5 years. Using only echocardiographic parameters, LV mass index was an independent associate of the outcome.
The main finding of the present study is that RAP and LVGLS at 1 year were complementary in assessing 5-year outcome after heart transplantation. This outcome was further supported by the fact that worsening of RAP at 5 years was associated with increased mortality at 10 years after transplantation. Moreover, the presence of LV hypertrophy was associated with the development of significant allograft vasculopathy. To our knowledge, this study is the largest to date that combines simultaneous hemodynamic and comprehensive echocardiographic data at 1 year post-transplant.
Graft failure is an important cause of late mortality after heart transplantation, accounting for >15% of deaths (13). There has been an interest in the field to evaluate the value of markers of both diastolic and systolic graft dysfunction. In the 1990s, several studies had suggested the importance of diastolic dysfunction in heart transplantation using deceleration time and isovolumic relaxation time on outcome (14). More recently, the comprehensive study by Tallaj et al. (1) focused on RAP and PCWP as well as the combined index of RAP to stroke volume (diastolic elastance parameter) to assess the impact of diastolic dysfunction on outcome. Their study was the first to show the importance of RV diastolic function in predicting outcome; alternatively, RAP/stroke volume could also be viewed as a combined index of systolic and diastolic performance.
LVGLS has also gathered more attention as several studies focused on its prognostic importance. For example, Sarvari et al. (6) described systolic function assessed by LVGLS as a good predictor for short-term outcome (during the first year) when assessed at 1 to 3 weeks after heart transplantation. Although LVGLS is currently recommended for diagnosing subclinical allograft dysfunction (15), few studies have investigated the association between LVGLS and other outcomes such as long-term graft failure or mortality. LV hypertrophy is the marker of cardiac remodeling that is reportedly associated with adverse outcome after heart transplantation (16–18). For example, Patel et al. (16) investigated LV mass by using cardiac magnetic resonance in 140 patients with heart transplantation and found that LV mass, particularly of a concentric phenotype, is an independent risk factor for cardiovascular and all-cause mortality.
Several parameters can be theoretically used to evaluate different profiles of graft dysfunction, including filling pressure, stroke volume or cardiac index, cardiac remodeling parameters, or cardiac strain parameters. Our hierarchical clustering analysis suggests that RAP, LVGLS, and SVI may be the most complementary in assessing graft dysfunction. This question of complementarity is important to consider, as there may be strong collinearity between factors. An important clinical question is to determine which threshold should be used to define subclinical dysfunction in patients with transplantation. Based on our outcome analysis, LVGLS <13% in absolute value, RAP >7 mm Hg, and SVI based on the assumed Fick method of 32 ml/min/m2 provided the best discrimination; the best thresholds to use will vary, however, depending on methodology of assessment. Although RAP can only be used as categorical variables by echocardiography, RAP assessed by echocardiography was still shown to be similarly predictive of outcome, using only echocardiographic parameters. In short, elevated RAP either by transthoracic echocardiogram or catheter is associated with worse outcome as well as any episode of rejection with hemodynamic compromise. The importance of RAP was also supported by our result that RAP at 5 years and the change in RAP from 1 to 5 years assessed by using echocardiography predicted 10-year all-cause mortality. These simple parameters and their combination can easily be integrated into our patient care as a risk stratification tool. Although we validated that RAP is strongly related to outcome, we could not validate that RAP/stroke volume is a better predictor, as suggested by Tallaj et al. (1). Not surprisingly, a history of rejection with hemodynamic compromise is the strongest correlate of early graft dysfunction defined by abnormal RAP/PCWP, LVGLS, or SVI. Conversely, patients with a history of rejection without hemodynamic compromise had an incidence of graft dysfunction comparable to those patients without a history of rejection without hemodynamic compromise.
Although LV mass index and hypertrophy have been related to mortality after transplantation (16–18), the present study is the first to suggest its possible association with allograft vasculopathy at 5 years. Patients with heart transplantation may be at increased risk of developing LV hypertrophy, possibly due to an increased prevalence of hypertension, adverse effects of immunosuppressive therapy, and/or immunologic injury (19,20). Although the mechanism of CAV has not been well established, it is initiated and propagated by both immunologic (i.e., inflammation) and nonimmunologic (i.e., hypertension, donor age, cytomegalovirus infection) insults, which overlap with the contributing factor of LV hypertrophy (21). Therefore, future studies will be needed to determine whether LV hypertrophy early after heart transplantation is predictive of future development of CAV.
First, this study was a single-center observation, and further examination across multiple centers would therefore be warranted to validate the present findings. In addition, the total number of study objects was relatively small, and approximately 25% of patients had to be excluded from the study due to unavailable RHC data. However, when baseline characteristics were compared between patients who were included and excluded, we found no significant differences in these characteristics. Second, B-type natriuretic peptide levels were not routinely measured in our cohort, which would represent another important profile to incorporate (22). However, this study was designed to focus on hemodynamic and imaging parameters. Investigating the association between these echocardiographic and hemodynamic parameters and important biomarkers may help to further risk stratify patients post-transplantation. Third, incorporating graft dysfunction analysis with early allograft vasculopathy data would lead to a more comprehensive assessment of graft adaptation (23,24). Finally, some events may have not been captured, especially those that occurred outside of our institution. However, all patients except for 2 in the cohort were routinely followed up at our institute for their annual evaluation, where a comprehensive review of hospitalization history was performed even when the patients were hospitalized at outside institutions.
Early graft dysfunction at 1 year based on RAP and LVGLS may help better risk stratify patients for long-term outcome after heart transplantation. Furthermore, the presence of LV hypertrophy could be an emerging risk factor for allograft vasculopathy.
COMPETENCY IN MEDICAL KNOWLEDGE: Our study showed that several simple echocardiographic parameters of graft dysfunction, such as RAP or LVGLS at 1 year, are useful for risk stratification after heart transplantation, which expands the applicability of noninvasive testing as a screening tool in this population.
TRANSLATIONAL OUTLOOK: Integration of these parameters into clinical practice will help detect the high-risk population. Future clinical trials are warranted to investigate whether patients with subclinical diastolic or systolic dysfunction will benefit from spironolactone or angiotensin-converting enzyme inhibitor treatment.
The authors thank Dr. Sharon A. Hunt for her help to this study, and Stanford Cardiovascular Institute and the Pai Chan Lee Research Fund for their support.
Dr. Fearon has received a research grant from Edwards Lifesciences. The other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- coronary allograft vasculopathy
- inferior vena cava
- left ventricular
- left ventricular global longitudinal strain
- pulmonary capillary wedge pressure
- right atrial pressure
- right heart catheterization
- right ventricular
- right ventricular fractional change
- right ventricular free-wall longitudinal strain
- stroke volume index
- Received October 8, 2017.
- Accepted October 20, 2017.
- 2017 American College of Cardiology Foundation
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