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Division of Cardiology, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IllDepartment of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Ill
Division of Cardiovascular Thoracic Surgery, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IllDepartment of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Ill
Division of Cardiovascular Thoracic Surgery, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IllDepartment of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Ill
Division of Cardiovascular Thoracic Surgery, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IllDepartment of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Ill
Division of Cardiovascular Thoracic Surgery, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IllDepartment of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Ill
Address for reprints: Elfriede Pahl, MD, Heart Transplant Program, Ann & Robert H. Lurie Children's Hospital of Chicago, 225 E Chicago Ave, Box #21, Chicago, IL 60611.
Division of Cardiology, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IllDepartment of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Ill
The time course for hemodynamic normalization after pediatric heart transplantation has not been well characterized. We hypothesized that patients with a single ventricle would normalize later than those with dilated cardiomyopathy. Establishing the expected course based on the underlying pathophysiology will allow identification of patients who are outliers, requiring further investigation.
Methods
We performed a retrospective review of patients with dilated cardiomyopathy, Glenn, and Fontan who underwent heart transplantation from January 2007 to December 31, 2017, and had 6-month and 1-year catheterization data. Hemodynamic data were examined for sustained normalization of pressures. Myocardial biopsies were reviewed for clinically significant rejection within the first year.
Results
Ninety-four patients comprised the cohort (47 dilated cardiomyopathy, 18 Glenn, 29 Fontan) with a median age of 6.8 (12) years. Patients with dilated cardiomyopathy were more likely to normalize hemodynamics by 6 months (85% vs 28% Fontan, 44% Glenn, P < .05), and 96% of patients with dilated cardiomyopathy had normalized hemodynamics by 1 year (vs 62% Fontan, 78% Glenn, P < .001). The pulmonary capillary wedge pressure at 6 months was higher in patients who underwent the Fontan and Glenn (median 12.8 [8.8] mm Hg and 11.2 [5.9] mm Hg, respectively) compared with patients with dilated cardiomyopathy (7.0 [3.3] mm Hg, P < .001). Patients with dilated cardiomyopathy demonstrated normalized hemodynamics earlier (121 ± 72 days) than patients who underwent the Fontan (329 ± 62 days) and Glenn (233 ± 11 days, P < .001). Eighteen patients (19%) experienced significant rejection, which was not increased in patients with delayed hemodynamic normalization. The 6-month pulmonary capillary wedge pressure was associated with delayed normalization (hazard ratio, 1.36; 95% confidence interval, 1.16-1.60; P < .001).
Conclusions
Patients with a single ventricle demonstrated delayed hemodynamic normalization compared with dilated cardiomyopathy heart transplant recipients, without affecting survival or need for retransplantation.
Patients with a single ventricle (Glenn and Fontan) demonstrated delayed normalization of hemodynamics after heart transplant compared with patients with DCM, without differences in survival.
Establishing the expected course of hemodynamic normalization after HTx based on underlying pathophysiology allows identification of patients who are outliers requiring further intervention. We found that patients who undergo the Fontan and Glenn normalize their hemodynamics later (329 ± 62 days and 233 ± 11 days, respectively) than patients with DCM (121 ± 72 days).
Cardiac catheterization after heart transplantation (HTx) provides critical information regarding systolic and diastolic graft function, and identifies any residual hemodynamically significant lesions. Endomyocardial biopsy remains the gold standard to evaluate for rejection. However, there appears to be wide variation in the timeframe of hemodynamics normalization among pediatric patients post-HTx, even in the absence of rejection. The aim of this study was to investigate the pattern of hemodynamic normalization post-HTx depending on indication for HTx, thereby facilitating identification of patients whose course lies outside this standard time course, necessitating further investigation. We hypothesized that patients with a single ventricle, with chronically abnormal physiology including increased collateral burden, nonpulsatile pulmonary blood flow, frequent noncompliance, and repaired pulmonary arteries and aortas, would demonstrate delayed normalization relative to patients with dilated cardiomyopathy (DCM).
Patients and Methods
Retrospective Cohort Study: Inclusion and Exclusion Criteria
A total of 153 patients aged less than 18 underwent orthotopic HTx at our institution from January 2007 to December 31, 2017 (Figure 1). Of those patients, there were 53 with DCM, 32 who underwent the Fontan, and 21 who underwent the Glenn. Exclusion criteria included patients who did not have documentation of 6-month or 1-year catheterization (7 patients), or did not survive to 1 year (5 patients).
Figure 1Patient cohort. Flow diagram of patients for inclusion in the final cohort. Pts, Patients; OHT, orthotopic heart transplant; SV, single ventricle; CHD, congenital heart disease; HOCM, hypertrophic obstructive cardiomyopathy; DCM, dilated cardiomyopathy; op, operative; VAD, ventricular assist device.
The medical records of the remaining cohort (47 DCM, 29 Fontan, and 18 Glenn) were reviewed. Clinical data collected included standard demographic information, donor weight, organ ischemic time, and clinical outcomes.
Catheterization data were examined for sustained normalization of hemodynamics, defined as 2 consecutive catheterizations demonstrating pulmonary capillary wedge pressure less than 12 mm Hg, pulmonary vascular resistance (PVR) less than 3 indexed Woods units, and cardiac index greater than 2.5 L/min/m2.
Allen H.D. Shaddy R.E. Penny D.J. Feltes T.F. Cetta F. Moss and Adams' Heart Disease in Infants, Children, and Adolescents: Including the Fetus and Young Adult. 9th ed. Wolters Kluwer,
Philadelphia2016
Myocardial biopsies were reviewed for significant rejection within the first year (cellular grade ≥2 or treated antibody mediated rejection).
Echocardiograms of M-mode left ventricular (LV) diastolic wall thickness and systolic septal thickness measurements and z-scores from the first transthoracic echocardiography (TTE) post-HTx and 6 months post-HTx were collected to assess for LV hypertrophy. It should be noted that hearts of larger donors have thicker walls, and when these hearts are placed into smaller recipients and the LV wall thickness is normalized to the recipient's smaller body surface area, the z-scores are abnormally high, consistent with LV hypertrophy. The Institutional Review Board of Ann & Robert H. Lurie Children's Hospital of Chicago approved this study.
Institutional Protocol Catheterization and Biopsy
Our institutional protocol for routine hemodynamic catheterization and biopsy surveillance includes 2 weeks, 1 month, 3 months, 6 months, 9 months, 1 year, 18 months, and annually post-HTx. Additional hemodynamics and biopsies are performed if there is concern for rejection. If a patient had a positive cross-match, a biopsy is performed 1 week post-HTx. However, for infants weighing less than 6 kg, the first biopsy is delayed until 6 months post-HTx and the patients are followed noninvasively with echocardiograms and biomarkers until the first catheterization and biopsy.
Statistical Analysis
To take into account the differences in the frequency of catheterizations and the timing of the first catheterization, the data were analyzed in 3 ways: time to normalization based on number of days after surgery; “bin” analysis where the time of normalization was categorized as 6 months or less, 6 to 12 months, and more than 12 months (6-month and 12-month catheterizations were necessary for inclusion in the study); and longitudinal analysis. Statistical analysis was performed using commercially available software (SPSS version 23.0, IBM, Chicago, Ill). Categoric variables were analyzed using Fisher exact testing, and continuous variables were analyzed using 1-way analysis of variance for normally distributed data with post hoc Bonferroni test when appropriate, Mann–Whitney test for non-normally distributed data with 2 groups, and Kruskal–Wallis for non-normally distributed data with 3 groups. Kaplan–Meier analysis was used to assess for differences among groups in terms of time to normalization of hemodynamics and survival. Univariate analysis of differences was performed between those who had normalized hemodynamics within 1 year and those who did not. Those factors with a P value less than .10 were included in multivariate logistic regression using the Wald backward stepwise method. Data are presented as mean ± standard deviation for normally distributed data and median (interquartile range) for non-normally distributed data. Longitudinal analysis of the repeated hemodynamic measures was performed using SAS version 9.4 (SAS Institute, Inc, Cary, NC). Longitudinal mixed modeling (PROC MIXED statement) allowed for assessment of differences among the 3 cohorts (DCM, Glenn, Fontan) while accounting for within-subject effects. Cohort was modeled as a linear predictor of hemodynamic indices of interest.
Results
Patient Cohort
Patient demographics are presented in Table 1. Length-of-stay post-Htx was different among groups, with the DCM group having the shortest length of stay (22 [10] days for DCM group, 36 [43] days for Glenn group, 26 [29] days for Fontan group) (Table 2). There was no difference among the groups regarding donor:recipient weight ratio, but the DCM group had shorter ischemic times (Table 2). Significant rejection (defined as cellular rejection grade ≥2 or treated antibody mediated rejection) was present in 18 patients (19% of the cohort) and more prevalent in the Glenn group than in the DCM group (39% vs 9%, P < .05 on post hoc analysis).
Patients with DCM were substantially more likely to normalize hemodynamics by 6 months post-HTx (85% vs 28% for Fontan and 44% for Glenn, P < .05 on post hoc analysis), and all but 2 patients with DCM (96%) normalized their hemodynamics by 1 year compared with only 62% of Fontan and 78% of Glenn cases (P < .001). Elevated wedge pressure was almost exclusively the measurement preventing hemodynamic normalization. PVR occasionally was abnormally elevated; however, this was almost always in the setting of an elevated wedge pressure. The wedge pressure at 6 months was substantially higher in the Fontan and Glenn groups (median 12.8 [8.8] mm Hg for Fontan and 11.2 [5.9] mm Hg for Glenn, Table 3) compared with the DCM group (7.0 [3.3] mm Hg, P < .001). Likewise, the wedge pressure at 1 year was substantially higher in the Fontan and Glenn groups (11.0 [5.2] mm Hg for Fontan and 9.7 [4.0] mm Hg for Glenn) (Table 3) compared with the DCM group (7.0 [2.0] mm Hg, P < .001). However, the calculated PVR at 6 months was not different among groups (P = .55). Although the cardiac index was not significantly different among groups at 6 months, it was statistically significantly higher in the DCM group than in the Glenn group at 1 year (4.9 ± 1.0 vs 4.0 ± 1.0, P < .05 on post hoc testing) (Table 3). Kaplan–Meier analysis for time to hemodynamic normalization similarly revealed that the DCM group normalized significantly earlier than the Fontan and Glenn groups (Figure 2, P < .001) with a median time to normalization of 121 (159) days for the DCM group, 233 (249) days for the Glenn group, and 329 (776) days for the Fontan group. Longitudinal analysis revealed no differences among groups in terms of cardiac index or PVR (Figures 3 and 4), but significant differences among groups in wedge pressure (Figure 5). Analysis of survival of the 3 groups revealed a trend of improved survival for the Fontan group (P = .078, Figure 6).
Figure 2Time to hemodynamic normalization. Kaplan–Meier analysis of time to hemodynamic normalization post-HTx for DCM, Glenn, and Fontan cases. Groups were significantly different on log-rank analysis with P < .001. Shaded areas indicate 95% CIs for each group. DCM, Dilated cardiomyopathy.
Figure 6Transplant-free survival by group. Kaplan–Meier analysis of freedom from death or retransplantation post-HTx for DCM, Glenn, and Fontan cases. On log-rank analysis, Fontan tended to have improved freedom from death or retransplant with P = .078. Shaded areas indicate 95% CIs for each group. DCM, Dilated cardiomyopathy.
Echocardiographic Assessment of Ventricular Hypertrophy
We reviewed the first TTE, specifically diastolic wall thickness z-score and systolic septal thickness z-score, to assess the potential role of LV hypertrophy in delayed normalization. There were no differences among the 3 groups in terms of diastolic wall thickness and systolic septal thickness z-scores on first TTE or at 6 months post-HTx (Table 4). Z-scores were used rather than absolute measurements to account for growth of infant hearts.
Table 4Left ventricular hypertrophy
Total cohort (n = 94)
DCM (n = 47, 50%)
Glenn (n = 18, 19%)
Fontan (n = 29, 31%)
P value
First postoperative TTE
LV diastolic wall z-score
0.8 (2.8)
1.3 (3.2)
0.9 (3.6)
0.7 (1.2)
.311
LV systolic septal z-score
1.2 ± 1.9
1.1 ± 1.8
1.9 ± 2.6
1.0 ± 1.5
.303
6-mo TTE
LV diastolic wall z-score
0.1 (2.2)
−0.3 (2.0)
−0.4 (2.3)
0.4 (2.8)
.151
LV systolic septal z-score
0.4 (1.9)
0.3 (1.2)
1.0 ± 2.4
1.2 (2.3)
.12
DCM, Dilated cardiomyopathy; TTE, transthoracic echocardiogram; LV, left ventricular.
Seventeen patients (18%) had not normalized their hemodynamics by 1 year. This group was older (12.5 [10.3] years vs 5.9 [10.9] years, P = .022), had a higher 6-month wedge pressure (14.5 [7.3] vs 8.2 [4.4], P < .001), a trend toward decreased cardiac index (4.2 ± 1.0 vs 4.7 ± 1.0, P = .09), and despite no differences in LV diastolic wall and LV systolic septal wall z-score on the first postoperative echocardiogram, at 6 months had higher LV diastolic wall z-score (1.0 ± 2.1 vs −0.04 ± 1.3, P < .01) and LV systolic septal wall z-score (1.2 ± 1.5 vs 0.4 ± 1.3, P = .03). The majority (65%) of patients with delayed normalization were in the Fontan group, whereas 24% were in the Glenn group, and the remaining 2 patients were in the DCM group, both of whom had ventricular assist devices (VADs) at the time of HTx. Those in the delayed normalization group had longer length of stay after transplant (44 [34] days vs 22 [16] days, P = .015).
There were no differences between the group that normalized within 1 year and the group that did not in terms of the incidence of rejection, ischemic time, or donor:recipient mismatch. On multivariate analysis, the only factor found to be significantly associated with delayed normalization was the 6-month wedge pressure (hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.16-1.60; P < .001). The following variables were also entered into the multivariate analysis but were not found to be significant: age (P = .15), weight (P = .28), group (P = .14), 1-year cardiac index (P = .30), 6-month LV diastolic wall thickness (P = .28), and 6-month LV septal thickness (P = .21).
Ventricular Assist Devices
Twelve patients (13%) had VADs at the time of HTx (9 patients in the DCM group, 3 patients in the Glenn group, and 0 patients in the Fontan group). These patients had no differences regarding survival, rejection, or normalization of hemodynamics. Patients with VADs had more significant donor:recipient weight mismatch (median 1.6 [0.6] vs 1.2 [0.6], P = .015), with greater septal z-scores (2.4 ± 2.3 vs 1.0 ± 1.8, P = .02) and diastolic wall thickness z-scores (3.2 [3.7] vs 0.8 [2.6], P < .01) on the first postoperative echocardiogram. Additional analysis was performed in the DCM subset of patients given 9 of them had VADs placed pre-HTx. Patients in the DCM group with VADs were more likely to have delayed normalization (22% vs 0%, P = .033), without differences in ischemic times, but a trend in increased donor:recipient weight mismatch (1.6 ± 0.4 vs 1.2 ± 0.4, P = .063) and greater diastolic wall thickness on the first postoperative echocardiogram (2.9 ± 2.6 vs 0.7 ± 1.8, P = .005) was identified. However, there was no difference in survival post-HTx for the DCM with VAD pre-HTx group compared with the remaining patients in the DCM group.
Given the potential for altered flow of the patients with VAD support to affect the overall results of the study, an additional analysis was performed excluding the patients with VADs. The key results remained unchanged, with the DCM group normalizing substantially earlier than the other groups (P < .001) and all patients in the DCM group normalizing by 1 year (vs 62% Fontan and 80% of Glenn, P < .001) and 87% normalizing by 6 months (vs 28% Fontan and 47% Glenn, P < .001).
Era Effect
Comparison of the earlier era (January 2007 to June 30, 2012) and recent era (July 1, 2012, to December 31, 2017) revealed no differences in age, donor:recipient weight mismatch, rejection, VAD use, time to normalization, 6-month wedge, or incidence of delayed normalization. The ischemic time in the later era was longer (225.8 ± 55.1 minutes vs 197.1 ± 50.1 minutes, P = .013). There was a trend in differences in underlying etiology, with more patients in the Fontan group in the more recent era compared with the earlier era (40% vs 17%, P = .059). As expected, follow-up was longer for the earlier era, and on Kaplan–Meier analysis of survival there was a trend of improved survival for the more recent era (P = .066, Figure 7).
Figure 7Transplant-free survival by era. Kaplan–Meier analysis of freedom from death or retransplantation post-HTx by era, where era 1 was January 2007 to June 30, 2012, and era 2 was July 1, 2012, to December 31, 2017. On log-rank analysis, there was a trend toward improved freedom from death or retransplantation in the later era with P = .066. Shaded areas indicate 95% CIs for each group.
As hypothesized, patients with a single ventricle demonstrated significantly delayed normalization of hemodynamics compared with patients with DCM, driven by delayed normalization of elevated wedge pressure. Delayed normalization was not associated with increased rejection, longer ischemic times, or donor:recipient weight mismatch. On multivariate analysis, only 6-month wedge predicted delayed normalization. However, this delayed normalization did not result in appreciable differences in mortality or need for retransplantation (Figure 8).
Figure 8Hemodynamic normalization was delayed in patients with a single ventricle after HTx. DCM, Dilated cardiomyopathy.
Although other studies have examined differences in survival among patients undergoing HTx with the Fontan or Glenn, to our knowledge this is the first study to examine the hemodynamics of these patients post-HTx. Clearly, patients requiring transplantation after a “failed Glenn” provide a different substrate than those who require transplantation after a “failed Fontan.” Patients who receive the Glenn requiring transplantation have “failed” the single ventricular palliation pathway sooner, and although the reason for failure can vary in some cases, it represents a sicker substrate, whether that is due to ventricular dysfunction, valvular dysfunction, increased PVR, or a combination of factors. These patients are also cyanotic, with a propensity of the body to create arterio-pulmonary collaterals that the new heart must be able to handle, unless these collaterals have been treated preemptively. This additional volume load to the heart would be expected to increase the wedge pressure.
In contrast, patients who undergo the Fontan have lived with completely passive flow to the lungs longer. These patients have a potpourri of indications for HTx, including protein-losing enteropathy, plastic bronchitis, decompensated systolic or diastolic dysfunction, cyanosis, and PVR issues. Many have congestive hepatopathy, and most had more operations with increased sensitization, putting the patients at increased risk for rejection. Depending on the indication for transplant and other organ dysfunction, these Fontan cases can be a higher-risk substrate for transplantation than Glenn cases.
Contributing Factors to Delayed Normalization
We postulate there are several additive factors that underlie the delayed normalization in patients with a single ventricle. First, the collateral burden that the new heart must accommodate in these chronically hypoxic patients could lead to an elevated wedge pressure. Second, donor hearts are often chosen for some degree of donor:recipient weight mismatch to help withstand elevated PVR and collateral burden in patients with a single ventricle. The patients who receive oversized hearts have elevated z-scores for LV size and wall thickness and often have postoperative hypertension due to high cardiac output that is managed medically. We hypothesize that this could contribute to some diastolic dysfunction (ie, elevated wedge), although such data are lacking with limited patients. Third, patients with small left atria may be at risk for elevated wedge pressure. Last, patients with hypoplastic left heart syndrome with restrictive atria in utero have pathophysiologic changes within the lung and pulmonary veins that could predispose these patients to elevated wedge pressure post-HTx,
and patients with significant diastolic dysfunction may be at risk for similar changes. In the Fontan cohort, years of nonpulsatile flow through pulmonary vasculature may create a less compliant pulmonary bed. These Fontan cases can also develop chronic pulmonary embolic disease with pathologic pulmonary vasculature that must remodel after restoration of pulsatile and improved pulmonary blood flow.
However, PVR post-HTx was not elevated in the Fontan cases relative to the DCM cases, and elevated PVR was not associated with delayed normalization. Of note, organ mismatch was not found to be a factor for delayed normalization within our groups. Likewise, organ ischemic time and inadequate organ protection could lead to diastolic dysfunction and elevated wedge pressures; however, ischemic time was not found to be contributory in our data, and the relatively small differential in ischemic time among groups would be unlikely to have an effect lasting many months.
Significant rejection can affect hemodynamics by contributing to an elevated wedge pressure; however, that was not found to be significantly different between those who normalized within 1 year and those who did not. Donor LV hypertrophy could contribute to elevated wedge pressures. Although the degree of LV hypertrophy was not different between those with delayed normalization and those who normalized within 1 year on the first postoperative echocardiogram, those with 6-month echocardiogram and delayed normalization had significantly greater hypertrophy.
It is interesting that among patients with DCM, VAD placement pre-HTx was associated with delayed normalization. These patients clearly represent a sicker subset of the DCM population. Such factors as increased systemic vascular resistance, other organ dysfunction particularly kidney dysfunction, and longer time in multiorgan failure could all have contributed to the delayed normalization. Although VAD support can unload the heart before transplant, unloading is not always optimal; VAD support may be relatively brief before transplant in comparison with years of a decompensated state, and irreversible end-organ damage may have already occurred.
Despite Delayed Normalization, No Differences in Survival
Despite substantial delay in normalization for patients with a single ventricle compared with patients with DCM, there was no difference in survival or need for retransplantation at latest follow-up. This suggests that although hemodynamics may take longer to normalize, specifically the wedge pressure, overall function of the graft midterm, and survival of the patient are not affected.
Clinical Impact
On the basis of these data, Fontan and Glenn cases with elevated wedge pressures post-HTx within the normalization timeframe of these data should not require additional hemodynamic catheterizations and biopsies if they are doing well clinically. Once assessment for collaterals or pulmonary vein stenosis has been performed, medical management is continued with diuretics and sildenafil. This information on the expected course of hemodynamic normalization based on underlying pathophysiology is particularly valuable in counseling families, because an elevated wedge post-HTx causes significant anxiety to families and healthcare providers.
Survival Post-Transplant
Our results demonstrate substantially better survival in Fontan cases (no mortality over median follow-up of 40 months) than reported for patients undergoing the Fontan and HTx in other series. For instance, in a meta-analysis of patients who received the Fontan undergoing HTx, the median 1-year survival was 78%
However, more recent studies in select centers have demonstrated improved results among Fontan cases, with 85% 1-year survival and 71% 5-year survival,
The excellent outcomes from our center among Fontan cases undergoing HTx reflect improved medical management of complex patients with a single ventricle, improved perioperative care, and selection bias. Although patients with respiratory and renal failure are considered, careful thought is given to which Fontan cases will benefit from HTx. Davies and colleagues
found that renal failure was a high risk for mortality (odds ratio, 10.8). In a study from our institution, 2 of 3 patients who received the Fontan with preoperative renal failure who underwent HTx died within 30 days.
Although not statistically significant, there was a trend toward improved survival for Fontan cases compared with Glenn and DCM cases (P = .078). This is in contrast to some studies demonstrating worse outcomes for the Fontan compared with other stages of single ventricle palliation,
However, large studies based on the Pediatric Heart Transplantation Study database failed to show differences in 1-year survival between Fontan cases and other CHD cases or 5-year survival among Fontan, Glenn, and other CHD cases.
Comparison of risk factors and outcomes for pediatric patients listed for heart transplantation after bidirectional Glenn and after Fontan: an analysis from the Pediatric Heart Transplant Study.
Our data also showed a trend toward improved survival in the later era. Analysis of the International Society for Heart and Lung Transplantation database of pediatric HTx results demonstrated improved survival by era, with the most marked improvement occurring in the 1990s.
Although analysis of the Pediatric Heart Transplantation Study database found an era-dependent improvement in survival after listing for Glenn and Fontan cases, there was no improved survival after HTx.
Comparison of risk factors and outcomes for pediatric patients listed for heart transplantation after bidirectional Glenn and after Fontan: an analysis from the Pediatric Heart Transplant Study.
In our cohort, there was a trend toward more Fontan cases in the later era, suggesting that we may be more successful in managing patients with a single ventricle to the Fontan stage, as opposed to those patients requiring HTx or dying at prior stages. This is consistent with a large single-center study that found failed single ventricular palliation as the most common indication for patients with CHD undergoing HTx, and Fontan completion was the most common cardiac surgery before HTx.
This study is limited by the relatively small number of patients in the Glenn and Fontan cohorts, the lack of data regarding pre-HTx hemodynamics, and the single institution study design. Further investigation is needed regarding causative factors underlying differences in normalization, such as quantification of collateral burden, specific pretransplant hemodynamic parameters, and anatomic/pathophysiologic differences among the patients with a single ventricle, that may predispose certain patients to delayed hemodynamic normalization post-HTx. Use of the wedge pressure does not provide an accurate assessment of end-diastolic LV pressure in patients with postcapillary obstruction (ie, significant pulmonary vein stenosis or mitral stenosis). Last, the analysis is limited by variation among patients in the timing and frequency of catheterization. Multiple statistical methods were used in the analysis to account for this.
Conclusions
Patients with a single ventricle palliated with the Fontan or Glenn demonstrated delayed normalization of hemodynamics post-HTx compared with patients with DCM, without affecting survival or need for retransplantation. The only factor on multivariate analysis predictive of delayed normalization was the pulmonary capillary wedge pressure at 6 months. Such knowledge of the natural history of hemodynamic normalization post-HTx depending on underlying pathophysiology may aid our ability to care for these complex patients.
Dr Backer is a consultant for WL Gore & Associates (no relevance to this study). All other authors have nothing to disclose with regard to commercial support.
The authors thank Sandeep Bharadwaj, BS, Grace Golan, PA, Alexa Harris, PA, and Jessica Saavedra, BS, for assistance in data collection.
References
Allen H.D. Shaddy R.E. Penny D.J. Feltes T.F. Cetta F. Moss and Adams' Heart Disease in Infants, Children, and Adolescents: Including the Fetus and Young Adult. 9th ed. Wolters Kluwer,
Philadelphia2016
Comparison of risk factors and outcomes for pediatric patients listed for heart transplantation after bidirectional Glenn and after Fontan: an analysis from the Pediatric Heart Transplant Study.
The article in the Journal by Stephens and colleagues1 astutely illustrates the concept of how poor hemodynamics as a result of passive circulation in single-ventricle (SV) patients (eg, Glenn and Fontan circulations) can impact posttransplantation management and the extended length of time to achieve “normal” hemodynamics. Conversely, most patients who undergo heart transplantation for dilated cardiomyopathy normalize in 3 months and nearly all normalize in 6 months. The article delves into the specifics of hemodynamic follow-up and illustrates the different time frames for specific cardiac hemodynamics to normalize in each cohort.
There are few existing data on expectations for hemodynamics changes following transplantation in children with failed single-ventricle (SV) palliation. Diastolic dysfunction manifested by elevated right atrial and wedge pressure (pulmonary capillary wedge pressure, or PCWP) is a known and frequent phenomenon observed during the early posttransplant period in patients.1 Filling pressures improve over time, and most patients are asymptomatic with normal systolic function even before resolution of diastolic dysfunction.
Management of single-ventricle (SV) patients remains surgically and medically challenging. With increasing proficiency and experience in patient care, there has been substantial improvement in clinical outcomes for this population over the last several decades.1 However, despite advancements, numerous learning opportunities remain as we strive to make further progress. In this issue of the Journal, Stephens and colleagues reported an interesting observation characterized by differing timetables of hemodynamic normalization (defined as 2 consecutive catheterizations exhibiting the following: pulmonary capillary wedge pressure <12 mm Hg, pulmonary vascular resistance <3 indexed Woods units, and cardiac index >2.5 L/min/m2) between patients with SV physiology (Glenn or Fontan) and those with dilated cardiomyopathy.
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